Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (338 unread)

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Merkel cell carcinoma, melanoma, metastatic mimics of breast cancer.

Fetched: June 26th, 2017, 1:00am EDT

Merkel cell carcinoma, melanoma, metastatic mimics of breast cancer.

Semin Diagn Pathol. 2017 May 31;:

Authors: Troxell ML

Abstract
Merkel cell carcinoma and melanoma can each occur primarily in breast skin, or metastasize to the breast. The breast is a rare site of metastasis of essentially any and every type of tumor, including carcinomas, sarcomas, and hematolymphoid neoplasms, and 10-30% of breast metastases may represent the initial presentation of disease. Although metastases generally recapitulate histologic features of the primary tumor, they are diagnostically challenging given their rarity and morphologic overlap with breast carcinoma, including special types of breast cancer. Histologic clues may include lack of carcinoma in situ, lack of central elastosis, pattern of infiltration around normal breast structures, yet none of these are specific. Careful correlation with clinical history and judicious use of immunostain panels is essential in approaching these cases.

PMID: 28645508 [PubMed - as supplied by publisher]

ICTV Virus Taxonomy Profile: Polyomaviridae.

Fetched: June 25th, 2017, 1:01am EDT

ICTV Virus Taxonomy Profile: Polyomaviridae.

J Gen Virol. 2017 Jun 22;:

Authors: Moens U, Calvignac-Spencer S, Lauber C, Ramqvist T, Feltkamp MCW, Daugherty MD, Verschoor EJ, Ehlers B, Ictv Report Consortium

Abstract
The Polyomaviridae is a family of small, non-enveloped viruses with circular dsDNA genomes of approximately 5 kbp. The family includes four genera whose members have restricted host range, infecting mammals and birds. Polyomavirus genomes have also been detected recently in fish. Merkel cell polyomavirus and raccoon polyomavirus are associated with cancer in their host; other members are human and veterinary pathogens. Clinical manifestations are obvious in immunocompromised patients but not in healthy individuals. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Polyomaviridae, which is available at www.ictv.global/report/polyomaviridae.

PMID: 28640744 [PubMed - as supplied by publisher]

Tumor vascularization and clinicopathologic parameters as prognostic factors in merkel cell carcinoma.

Fetched: June 25th, 2017, 1:01am EDT

Tumor vascularization and clinicopathologic parameters as prognostic factors in merkel cell carcinoma.

J Cancer Res Clin Oncol. 2017 Jun 21;:

Authors: Bob A, Nielen F, Krediet J, Schmitter J, Freundt D, Terhorst D, Röwert-Huber J, Kanitakis J, Stockfleth E, Ulrich C, Weichenthal M, Egberts F, Lange-Asschenfeldt B

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine tumor of the skin with an increasing incidence. The clinical course is variable and reliable prognostic factors are scarce. Tumor angiogenesis has been shown to have prognostic impact in different types of cancer. The aim of our study was to determine potential prognostic factors, including tumor vascularization, for clinical outcome of MCC.
METHODS: The medical records of 46 patients with MCC diagnosed between 1997 and 2010 were analyzed retrospectively. Tissue samples were immune-stained for the lymphatic endothelial vessel marker podoplanin/D2-40 and the panvascular marker CD31. These immunostained sections were analyzed using computer-assisted morphometric image analyses. Aside from the parameters of tumor vascularization, clinicopathologic features were investigated, and progression-free survival (PFS) and tumor-specific survival (TSS) were assessed. Univariate and multivariate analyses were performed to determine prognostic factors.
RESULTS: Male sex of the MCC patients and a high cross-sectional whole vessel area (WVA) in relation to the entire tumor area as determined on CD31-stained tumor sections were found to be negative prognostic factors for PFS in a univariate and multivariate regression analysis. Ulceration of the primary tumor was significantly associated with both impaired PFS and TSS.
CONCLUSIONS: Our results indicate a high prognostic impact of tumor vascularization on the clinical outcome of MCC patients. Male sex and ulceration of the primary MCC were identified as independent unfavorable prognostic markers for the clinical outcome. As an outlook, MCC patients with increased angiogenesis might be identified and subjected to a targeted anti-angiogenic treatment.

PMID: 28639083 [PubMed - as supplied by publisher]

Merkel cell carcinoma occurring in a black woman: a case report.

Fetched: June 25th, 2017, 1:01am EDT

Merkel cell carcinoma occurring in a black woman: a case report.

J Med Case Rep. 2017 Jan 31;11(1):25

Authors: Kadiri S, Aissa A, Berhili S, Khmou M, Elmajjaoui S, Kebdani T, El Khannoussi B, Elkacemi H, Benjaafar N

Abstract
BACKGROUND: Merkel cell carcinoma is a rare, very aggressive neuroectodermal tumor of the skin. It is typically located on sun-exposed skin and frequently found in white men aged between 70 and 80 years.
CASE PRESENTATION: We report a case of a 58-year-old black woman diagnosed with Merkel cell carcinoma of the posterior face of the right elbow. She had biopsy excision and was lost to follow-up. Four months later, she presented with recurrent disease on the inferior third of the right arm with three ipsilateral axillary lymph node metastases. Amputation of the right arm and ipsilateral axillary lymph node dissection were performed, followed by adjuvant radiotherapy. Six months later, the patient died as a result of respiratory failure caused by lung metastasis. To the best of our knowledge, no specific studies have been done comparing the course and the characteristics of Merkel cell carcinoma in white and black populations, and no similar case has been reported in the literature.
CONCLUSIONS: The Merkel cell carcinoma is very rare in black people. As described elsewhere in the literature, our patient had a poor outcome despite radical management. To date, to the best of our knowledge, there has been no comparison of the prognosis of this tumor in white and black populations.

PMID: 28143624 [PubMed - indexed for MEDLINE]

Permalink for 'Recurrence and Survival in Patients With Merkel Cell Carcinoma Undergoing Surgery Without Adjuvant Radiation Therapy to the Primary Site.'

Recurrence and Survival in Patients With Merkel Cell Carcinoma Undergoing Surgery Without Adjuvant Radiation Therapy to the Primary Site.

Fetched: June 22nd, 2017, 1:00am EDT

Recurrence and Survival in Patients With Merkel Cell Carcinoma Undergoing Surgery Without Adjuvant Radiation Therapy to the Primary Site.

JAMA Dermatol. 2016 Sep 01;152(9):1001-7

Authors: Frohm ML, Griffith KA, Harms KL, Hayman JA, Fullen DR, Nelson CC, Wong SL, Schwartz JL, Bichakjian CK

Abstract
IMPORTANCE: The use of adjuvant radiation therapy (RT) to the primary site in Merkel cell carcinoma (MCC) is not uncommon. However, the need for adjuvant RT to the primary site in patients at low risk for local recurrence is questionable.
OBJECTIVES: To examine the occurrence of true local, satellite, in-transit, regional, and distant recurrences in patients undergoing surgery alone without adjuvant RT to the primary site. To establish overall survival (OS), MCC-specific survival (MCCSS), and disease-free survival (DFS) relationships in a cohort of patients with MCC.
DESIGN, SETTING, AND PARTICIPANTS: Our University of Michigan Multidisciplinary MCC Program database was used to obtain characteristics and outcome measures for 104 patients (105 primary MCCs) with tumors less than 2 cm in diameter. The majority of patients were treated between July 2006 and November 2012.
MAIN OUTCOMES AND MEASURES: Outcome measures included the occurrence of true local, satellite, in-transit, regional, and distant recurrences. End points included OS, MCCSS, and DFS.
RESULTS: Overall, information for 55 men and 49 women with 105 primary MCCs was obtained; 19 patients developed recurrent disease, and the mean time to first recurrence was 10.7 months. True local recurrence occurred in 1 patient with concurrent in-transit recurrence. Satellite recurrence occurred in 1 patient with concurrent regional recurrence. Four additional patients developed in-transit metastases. Thirteen patients had a regional recurrence component, 4 patients had distant metastases, and 6 patients developed subsequent regional and/or distant recurrences. Stratified by initial pathologic stage, the OS and MCCSS at 48 months were estimated to be 85.0% (95% CI, 71.8%-92.3%) and 94.4% (95% CI, 83.4%-98.2%) for patients with stage 1A/B disease and 63.2% (95% CI, 36.6%-81.1%) and 78.1% (95% CI, 50.0%-91.5%) for patients with stage 3A disease. The OS and MCCSS at 24 months for patients with stage 3B disease were both 50.0% (95% CI, 5.8%-84.5%).
CONCLUSIONS AND RELEVANCE: In selected MCC patients with primary tumors less than 2 cm in diameter treated with surgery alone without adjuvant RT to the primary site, we found a low occurrence of true local recurrences and satellite recurrences. This relatively low rate of local recurrence questions the need for adjuvant RT to the primary tumor site in patients with small low-risk lesions.

PMID: 27248515 [PubMed - indexed for MEDLINE]

PDQ Cancer Information Summaries

Fetched: June 22nd, 2017, 1:00am EDT

PDQ Cancer Information Summaries

Book. 2002

Authors:

Abstract
This PDQ cancer information summary has current information about the treatment of merkel cell carcinoma. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Adult Treatment Editorial Board.

PMID: 26389202

Avelumab: First Global Approval.

Fetched: June 21st, 2017, 1:00am EDT

Avelumab: First Global Approval.

Drugs. 2017 May;77(8):929-937

Authors: Kim ES

Abstract
Avelumab (Bavencio(®)) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of avelumab leading to this first approval for mMCC.

PMID: 28456944 [PubMed - indexed for MEDLINE]

Frequent detection of Merkel cell polyomavirus DNA in tissues from 10 consecutive autopsies.

Fetched: June 16th, 2017, 1:00am EDT

Frequent detection of Merkel cell polyomavirus DNA in tissues from 10 consecutive autopsies.

J Gen Virol. 2017 Jun 14;:

Authors: Mancuso G, Antona J, Sirini C, Salvo M, Giacometti L, Olivero C, Trisolini E, Indellicato R, Boldorini R

Abstract
Merkel cell polyomavirus (MCPyV) has been identified in samples of Merkel cell carcinoma (MCC), an aggressive skin cancer. Seroepidemiologic studies indicated a high frequency of MCPyV infection in humans, suggesting respiratory and faecal-oral routes, or transmission by skin contact. Since MCC is more frequent in immunocompromised patients, a reactivation of MCPyV latently infecting target cells has been proposed. However, neither definite ways of transmission nor specific target organs have been identified with certainty. Ten autopsies with an extensive organ sampling for a total of 121 specimens (tissue and blood samples) were collected. All tissue specimens were fixed in formalin and embedded in paraffin. Real-time PCR was performed to quantify the copy number of the large T antigen (LT) gene and the capsid VP1 gene of MCPyV. MCPyV LT and/or VP genes were detected in all of the collected specimens. A high prevalence of MCPyV was found in the blood (six cases) and lung (five cases); the brain was positive in three cases. The highest viral copy number was detected in blood from two autopsies (21 610 570.09 copies per 105 cells and 380 413.25 copies per 105 cells), whereas the viral copy number in the other organs was low. Our data confirm the high frequency of MCPyV infection in the general population, which seems to indicate that the respiratory tract is a possible route for viral transmission and viral persistence in the brain. The frequent detection of MCPyV DNA in blood suggests that circulating leukocytes could be one of the reservoirs of MCPyV, whereas the high viral copy number also seems to indicate the possibility of viral reactivation in immunocompetent adults.

PMID: 28613147 [PubMed - as supplied by publisher]

Complete spontaneous regression of Merkel cell carcinoma (1986-2016): a 30 year perspective.

Fetched: June 14th, 2017, 4:26pm EDT

Complete spontaneous regression of Merkel cell carcinoma (1986-2016): a 30 year perspective.

J Cutan Pathol. 2016 Dec;43(12):1150-1154

Authors: Walsh NM

PMID: 27596690 [PubMed - indexed for MEDLINE]

Permalink for 'Age and gender associations of virus positivity in Merkel cell carcinoma characterized using a novel RNA in situ hybridization assay.'

Age and gender associations of virus positivity in Merkel cell carcinoma characterized using a novel RNA in situ hybridization assay.

Fetched: June 14th, 2017, 4:26pm EDT

Age and gender associations of virus positivity in Merkel cell carcinoma characterized using a novel RNA in situ hybridization assay.

Clin Cancer Res. 2017 Jun 12;:

Authors: Wang L, Harms PW, Palanisamy N, Carskadon S, Cao X, Siddiqui J, Patel RM, Zelenka-Wang S, Durham AB, Fullen DR, Harms K, Su F, Shukla S, Mehra R, Chinnaiyan AM

Abstract
Purpose: Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin. Merkel cell polyomavirus (MCPyV) plays an oncogenic role in the majority of MCCs. Detection of MCPyV in MCCs has diagnostic utility and prognostic potential. We investigated whether RNAscope, an RNA in situ hybridization (ISH) assay for detection of RNA transcripts in tissues, is useful for MCPyV detection. Experimental Design: We applied an RNAscope probe targeting MCPyV T antigen transcripts on tissue microarrays (TMAs) and whole tissue sections encompassing 87 MCCs from 75 patients, 14 carcinomas of other types, and benign tissues. For comparison, quantitative PCR (qPCR) was performed on 57 cases of MCC from 52 patients. Results: RNA-ISH demonstrated the presence of MCPyV in 37/75 (49.3%) cases. Notably, tumors from younger patients (< 73 years) had a significantly higher virus positivity than those from elderly patients (≥ 73 years) (64.9% vs. 34.2%, P =0.011). Female patients had a higher positive rate of MCPyV than male patients (66.7% vs. 39.6%, P =0.032). Data from both RNA-ISH and qPCR were available for 57 samples. Considering MCPyV qPCR as the gold standard for determining MCPyV status, RNAscope had 100% sensitivity and 100% specificity. There was a strong correlation between qPCR copy number and RNA-ISH product score (Spearman's correlation coefficient R(2) = 0.932, P < 0.0001). Conclusions: RNA-ISH is comparably sensitive to qPCR for detection of MCPyV and allows for correlation with tissue morphology. This study also reveals a significant association between age, gender, and MCPyV positivity.

PMID: 28606924 [PubMed - as supplied by publisher]

Constitutive and acquired mechanisms of resistance to immune checkpoint blockade in human cancer.

Fetched: June 14th, 2017, 4:26pm EDT

Constitutive and acquired mechanisms of resistance to immune checkpoint blockade in human cancer.

Cytokine Growth Factor Rev. 2017 Jun 02;:

Authors: Bellone M, Elia AR

Abstract
Cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes has been revolutionizing medical oncology, and the clinical success of monoclonal antibodies targeting either cytotoxic T lymphocyte antigen-4 (CTLA-4) or program death-1 (PD-1) in patients affected by melanoma, Hodgkin's lymphoma, Merkel cell carcinoma, and head and neck, bladder, renal cell or non-small cell lung cancer is way beyond the most optimistic expectation. However, immune checkpoint blockade (ICB) has failed to arrest progression in a consistent amount of patients affected by those tumors, and various histological types, including breast, colon and prostate cancer, are less sensitive to this therapeutic approach. Such clinical findings have fueled massive research efforts in the attempt to identify pre-existing and acquired mechanisms of resistance to ICB. Here we focus on evidences emerging from studies in humans on how tumor cells and the tumor microenvironment contribute to the heterogeneous clinical responses, and we propose strategies stemming from pre-clinical models that might improve clinical outcomes for patients.

PMID: 28606732 [PubMed - as supplied by publisher]

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA.

Fetched: June 14th, 2017, 4:26pm EDT

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA.

Future Oncol. 2017 Jun 13;:

Authors: Cowey CL, Mahnke L, Espirito J, Helwig C, Oksen D, Bharmal M

Abstract
AIM: This retrospective study of patients in the USA with metastatic Merkel cell carcinoma (mMCC) aimed to assess patient responses to second-line and later (2L+) and first-line (1L) chemotherapy.
PATIENTS & METHODS: Out of 686 patients with MCC identified in The US Oncology Network, 20 and 67 patients with mMCC qualified for the 2L+ and 1L study, respectively; the primary analysis population was restricted to immunocompetent patients.
RESULTS: In the 2L+ primary analysis population, objective response rate (ORR) was 28.6%, median duration of response (DOR) was 1.7 months and median progression-free survival was 2.2 months. In the 1L primary analysis population, ORR was 29.4%, median DOR was 6.7 months and median progression-free survival was 4.6 months.
CONCLUSION: The low ORR and brief DOR underscore the need for novel therapies.

PMID: 28605939 [PubMed - as supplied by publisher]

Permalink for 'Cytokeratin-positive fibroblastic reticular cell: a pitfall for dermatopathologists assessing lymph nodes for Merkel cell carcinoma.'

Cytokeratin-positive fibroblastic reticular cell: a pitfall for dermatopathologists assessing lymph nodes for Merkel cell carcinoma.

Fetched: June 14th, 2017, 4:26pm EDT

Cytokeratin-positive fibroblastic reticular cell: a pitfall for dermatopathologists assessing lymph nodes for Merkel cell carcinoma.

J Cutan Pathol. 2016 Dec;43(12):1231-1233

Authors: Olson NJ, Perry AE, Linos K

PMID: 27640340 [PubMed - indexed for MEDLINE]

Pharmaceutical Approval Update.

Fetched: June 7th, 2017, 1:00am EDT

Pharmaceutical Approval Update.

P T. 2017 Jun;42(6):366-371

Authors: Choy M

Abstract
Ribociclib (Kisqali) for HR+/HER2- advanced or metastatic breast cancer in postmenopausal women; safinamide (Xadago) as adjunctive treatment for patients with Parkinson's disease; and avelumab (Bavencio) for metastatic Merkel cell carcinoma.

PMID: 28579722 [PubMed - in process]

Permalink for 'Factors influencing radiation treatment recommendations in early-stage Merkel cell carcinoma: a survey of US-based radiation oncologists.'

Factors influencing radiation treatment recommendations in early-stage Merkel cell carcinoma: a survey of US-based radiation oncologists.

Fetched: June 7th, 2017, 1:00am EDT

Factors influencing radiation treatment recommendations in early-stage Merkel cell carcinoma: a survey of US-based radiation oncologists.

Expert Rev Anticancer Ther. 2017 Mar;17(3):281-287

Authors: Tseng YD, Apisarnthanarax S, Liao JJ, Bhatia S, Nghiem PT, Parvathaneni U

Abstract
BACKGROUND: It is unclear which subgroups of Merkel cell carcinoma (MCC) patients benefit the most from radiation. We surveyed radiation oncologists (RO) that regularly see and treat MCC to understand how they approach the treatment of early-stage MCC.
METHODS: A web-based survey was emailed to 63 ROs, who were identified through publications, guideline panel membership, and/or affiliation with institutions of high MCC volume. ROs provided treatment recommendations for two hypothetical case scenarios of early stage MCC.
RESULTS: Among 28 respondents (45%), 26 regularly saw and treated MCC patients for a median 7 years (range, 0-30). While all ROs recommended adjuvant radiation for a stage II upper extremity MCC, only 48% recommended adjuvant radiation for stage I head and neck MCC.
CONCLUSION: Among US-based MCC RO 'specialists,' there is equipoise on the role of radiotherapy for stage I MCC. Ideally, prospective studies are needed to identify which patients may benefit from radiation.

PMID: 28103445 [PubMed - indexed for MEDLINE]

Merkel cells are long-lived cells whose production is stimulated by skin injury.

Fetched: June 1st, 2017, 9:26am EDT

Merkel cells are long-lived cells whose production is stimulated by skin injury.

Dev Biol. 2017 Feb 01;422(1):4-13

Authors: Wright MC, Logan GJ, Bolock AM, Kubicki AC, Hemphill JA, Sanders TA, Maricich SM

Abstract
Mechanosensitive Merkel cells are thought to have finite lifespans, but controversy surrounds the frequency of their replacement and which precursor cells maintain the population. We found by embryonic EdU administration that Merkel cells undergo terminal cell division in late embryogenesis and survive long into adulthood. We also found that new Merkel cells are produced infrequently during normal skin homeostasis and that their numbers do not change during natural or induced hair cycles. In contrast, live imaging and EdU experiments showed that mild mechanical injury produced by skin shaving dramatically increases Merkel cell production. We confirmed with genetic cell ablation and fate-mapping experiments that new touch dome Merkel cells in adult mice arise from touch dome keratinocytes. Together, these independent lines of evidence show that Merkel cells in adult mice are long-lived, are replaced rarely during normal adult skin homeostasis, and that their production can be induced by repeated shaving. These results have profound implications for understanding sensory neurobiology and human diseases such as Merkel cell carcinoma.

PMID: 27998808 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus is Not Detected in Lung Adenocarcinomas by Immunohistochemistry.

Fetched: June 1st, 2017, 9:26am EDT

Merkel Cell Polyomavirus is Not Detected in Lung Adenocarcinomas by Immunohistochemistry.

Appl Immunohistochem Mol Morphol. 2016 Jul;24(6):427-30

Authors: Trejo Bittar HE, Pantanowitz L

Abstract
Merkel cell polyomavirus (MCPyV) is an oncogenic DNA virus that causes Merkel cell carcinoma. Recently, MCPyV has been identified in other noncutaneous tumors including lung non-small cell carcinoma. However, the true role of this virus in lung carcinogenesis is unclear. We aimed to determine the efficacy of immunohistochemistry for detecting MCPyV in a series of lung adenocarcinomas. Nuclear expression of the MCPyV large T antigen was evaluated by immunohistochemistry (CM2B4 antibody) in formalin-fixed paraffin-embedded lung adenocarcinomas of different histologic subtypes. Of a total of 90 lung adenocarcinomas that were examined, none of the tumors (0%) were positive for MCPyV T antigen expression by immunohistochemistry. These data suggest that MCPyV immunohistochemistry alone might not be a sensitive method for detection of MCPyV in lung adenocarcinomas or that these tumors do not harbor MCPyV. Further studies are needed to correlate these data with molecular studies for MCPyV DNA integration and to similarly evaluate other types of lung carcinomas.

PMID: 26317307 [PubMed - indexed for MEDLINE]

Skin Cancers in Organ Transplant Recipients.

Fetched: June 1st, 2017, 1:00am EDT

Skin Cancers in Organ Transplant Recipients.

Am J Transplant. 2017 May 29;:

Authors: Mittal A, Colegio OR

Abstract
Long-term utilization of immunosuppression in organ transplant recipients (OTRs) leads to decreased immune-mediated tumor surveillance and development of malignant tumors. A delicate balance needs to be maintained in the intensity of immunosuppression to keep the risk of malignancy low without jeopardizing life-saving graft function. OTRs are prone to developing skin cancers which exhibit unique epidemiologic, pathophysiologic and prognostic characteristics. In this review, we discuss the most commonly reported skin cancers in OTRs: squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Kaposi's sarcoma, Merkel cell carcinoma and malignant melanoma (MM). Tumors in this high-risk population are aggressive and may respond poorly to standard therapies. However, new targeted therapies are promising. Checkpoint inhibitor antibodies have been used for treatment of cutaneous SCC, Merkel cell carcinoma, and MM; epidermal growth factor receptor inhibitors for cutaneous SCC; hedgehog pathway inhibitors for BCC; and BRAF and MEK inhibitors are being used increasingly in the management of MM. Guidelines for dermatologic screening is variable and primarily based on expert opinion. Prospective evidence-based trials by multidisciplinary groups are needed to better define surveillance schedules for pre-transplant and post-transplant cutaneous malignancies. This article is protected by copyright. All rights reserved.

PMID: 28556451 [PubMed - as supplied by publisher]

Overview of the 8th Edition TNM Classification for Head and Neck Cancer.

Fetched: June 1st, 2017, 1:00am EDT

Overview of the 8th Edition TNM Classification for Head and Neck Cancer.

Curr Treat Options Oncol. 2017 Jul;18(7):40

Authors: Huang SH, O'Sullivan B

Abstract
OPINION STATEMENT: The main purpose of the TNM system is to provide an anatomic-based classification to adequately depict cancer prognosis. Accurate cancer staging is important for treatment selection and outcome prediction, research design, and cancer control activities. To maintain clinical relevance, periodical updates to TNM are necessary. The recently published 8th edition TNM classification institutes the following changes to the staging of head and neck (excluding thyroid cancer): new stage classifications [HPV-related oropharyngeal cancer (HPV+ OPC) and soft tissue sarcoma of the head and neck (HN-STS)] and modification of T and N categories [T and N categories for nasopharyngeal cancer (NPC), T categories for oral cavity squamous cell carcinomas (OSCC), N categories for non-viral related head and neck cancer and unknown primary (CUP), and T categories for head and neck cutaneous carcinoma]. These changes reflect better understanding tumor biology and clinical behavior (e.g., HPV+ OPC and HN-STS), improved outcomes associated with technical advances in diagnosis and treatment (e.g., NPC), evolving knowledge about additional prognostic factors and risk stratification from research and observation (e.g., inclusion of depth of invasion variable for OSCC, inclusion of extranodal extension variable for all non-viral head and neck cancer, and reintroduction of size criteria for non-Merkel cell cutaneous carcinoma of the head and neck). This review summarizes the changes and potential advantages and limitations/caveats associated with them. Further evidence is needed to evaluate whether these changes would result in improvement in TNM stage performance to better serve the needs for clinical care, research, and cancer control.

PMID: 28555375 [PubMed - in process]

Permalink for 'Association of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma.'

Association of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma.

Fetched: May 31st, 2017, 1:00am EDT

Association of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma.

Hum Pathol. 2017 May 24;:

Authors: Kuromi T, Matsushita M, Iwasaki T, Nonaka D, Kuwamoto S, Nagata K, Kato M, Akizuki G, Kitamura Y, Hayashi K

Abstract
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that mostly occurs in the elderly. Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of MCCs and is associated with carcinogenesis. Hedgehog signaling pathway plays a role in human embryogenesis and organogenesis. In addition, reactivation of this pathway later in life can cause tumors. 29 MCPyV-positive and 21 MCPyV-negative MCCs were immunohistochemically stained with primary antibodies for hedgehog signaling (SHH, IHH, PTCH1, SMO, GLI1, GLI2, and GLI3) and evaluated using H-score. PCR and sequence analysis for SHH and GLI1 exons were also performed. Expression of SHH was higher in MCPyV-positive MCCs than in MCPyV-negative MCCs (P<.001). Higher expression of GLI1, MCPyV-infection, male, and Japanese ethnicity were associated with better overall survival (P=.034, P=.001, P=.042, P=.036, respectively). Higher expression of SHH and MCPyV infection were associated with improved MCC-specific survival (P=.037, P=.002, respectively). The mutation analysis of prognosis-related GLI1 and SHH genes in our study revealed a low frequency of mutations in the 10 exons examined, except GLI1 exon 5, (18/22 cases) all having the same silent mutation of c.576G>A. Only two mutations with amino acid changes were detected in MCPyV-negative MCCs only: one missense mutation in GLI1 exon 4 and one nonsense mutation in SHH-3B. Expression of SHH and GLI1 may be useful prognostic markers of MCC because increased expression was associated with better prognosis. The high rate of c.576G>A silent mutation in GLI1 exon 5 was a feature of MCC.

PMID: 28551328 [PubMed - as supplied by publisher]

Intraepidermal Merkel cell carcinoma: a case series of a rare entity with clinical follow-up.

Fetched: May 27th, 2017, 1:00am EDT

Intraepidermal Merkel cell carcinoma: a case series of a rare entity with clinical follow-up.

J Cutan Pathol. 2017 May 23;:

Authors: Jour G, Aung PP, Rozas-Muñoz E, Curry JL, Prieto V, Ivan D

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous carcinoma. MCC involves typically dermis and although epidermotropism has been reported, MCC strictly intraepidermal or in situ (MCCIS) is exceedingly rare. Most of the cases of MCCIS described so far have associated other lesions, such as squamous or basal cell carcinoma, actinic keratosis, etc. Herein, we describe three patients with MCC strictly in situ, without a dermal component.
METHODS: Our patients were elderly, two of the lesions involved the head and neck area and one was on a finger. All tumors were strictly intraepidermal in the diagnostic biopsies, had histomorphologic features and an immunohistochemical profile supporting the diagnosis of MCC. Excisional biopsies were performed in two cases and failed to reveal dermal involvement by MCC or other associated malignancies.
RESULTS AND CONCLUSION: Our findings raise the awareness that MCC strictly in situ does exist and it should be included in the differential diagnosis of Paget's or extramammary Paget's disease, pagetoid squamous cell carcinoma, melanoma, and other neoplasms that typically show histologically pagetoid extension of neoplastic cells. Considering the limited number of cases reported to date, the diagnosis of isolated MCCIS should not warrant a change in management from the typical MCC.

PMID: 28543532 [PubMed - as supplied by publisher]

Frequency and locations of systemic metastases in Merkel cell carcinoma by imaging.

Fetched: May 27th, 2017, 1:00am EDT

Frequency and locations of systemic metastases in Merkel cell carcinoma by imaging.

Acta Radiol Open. 2017 Mar;6(3):2058460117700449

Authors: Kouzmina M, Koljonen V, Leikola J, Böhling T, Lantto E

Abstract
BACKGROUND: The primary neuroendocrine skin cancer, Merkel cell carcinoma (MCC), has a well-known predilection to metastasize systemically. However, the experience of systemic metastases in MCC is mainly disseminated through case reports due to the rarity of MCC.
PURPOSE: To elucidate the frequency and locations of systemic metastasis in MCC by reviewing the imaging of patients with metastatic MCC in a national cohort.
MATERIAL AND METHODS: Patients with diagnosed metastatic MCC by imaging studies in Finland during 1999-2012 were included in this study. We reviewed their imaging studies to evaluate the most frequent sites for systemic metastasis and determined the latency between the primary tumor diagnosis and systemic metastasis. The material includes 30 MCC patients with complete imaging series and 187 examinations, of which 102 (54%) were CT images.
RESULTS: The mean latency from the primary tumor diagnosis to systemic metastasis was 2.1 years and the mean latency between the radiologic diagnosis of the metastases and death was 299 days. Metastases were recorded in several organ systems in most of the cases, and at least two separate metastatic sites in 63% of the cases. Metastatic spread was noted in 60% of the cases in distant lymph nodes. Liver and lungs were the most affected solid organs.
CONCLUSION: Systemic metastasis in MCC has no predilection site, basically every organ system can be involved. Most of the systemic metastases were recorded during the first two years after the MCC diagnosis.

PMID: 28540062 [PubMed]

Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma.

Fetched: May 27th, 2017, 1:00am EDT

Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma.

Sci Rep. 2017 May 23;7(1):2290

Authors: Ritter C, Fan K, Paschen A, Reker Hardrup S, Ferrone S, Nghiem P, Ugurel S, Schrama D, Becker JC

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host's immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2. Notably, experimental provisions of HLA class-I binding peptides restored HLA class-I surface expression on MCC cells. Silencing of the HLA class-I APM is due to histone deacetylation as inhibition of histone deacetylases (HDACs) not only induced acetylation of histones in the respective promoter regions but also re-expression of APM components. Thus, HDAC inhibition restored HLA class-I surface expression in vitro and in a mouse xenotransplantation model. In contrast to re-induction of HLA class-I by interferons, HDAC inhibitors did not interfere with the expression of immuno-dominant viral proteins. In summary, restoration of HLA class-I expression on MCC cells by epigenetic priming is an attractive approach to enhance therapies boosting adaptive immune responses.

PMID: 28536458 [PubMed - in process]

Merkel cell carcinoma associated with stable chronic hemodialysis: A report of two cases.

Fetched: May 24th, 2017, 1:00am EDT

Merkel cell carcinoma associated with stable chronic hemodialysis: A report of two cases.

J Dermatol. 2016 Nov;43(11):1336-1339

Authors: Nagase K, Kimura H, Ogawa S, Tara-Hashimoto A, Koba S, Inoue T, Narisawa Y

Abstract
Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy associated with the Merkel cell polyomavirus (MCPyV). Multiple studies have shown that the incidence of MCC is higher among immunocompromised individuals than among the general population. In fact, immunosuppressed individuals account for approximately 10% of the MCC patient population. In this report, we describe two cases of MCPyV-related MCC in Japanese patients on hemodialysis. In both the cases, MCC was present on the face. Both cellular and humoral immunities have been shown to be decreased in uremic patients, and dialysis patients have a high risk of viral-mediated cancers, including human papillomavirus-associated cancers. Immune dysfunction related to uremia and dialysis may be associated with a high risk of developing MCC.

PMID: 27334898 [PubMed - indexed for MEDLINE]

Merkel cell polyomavirus small T antigen initiates Merkel cell carcinoma-like tumor development in mice.

Fetched: May 19th, 2017, 1:00am EDT

Merkel cell polyomavirus small T antigen initiates Merkel cell carcinoma-like tumor development in mice.

Cancer Res. 2017 May 16;:

Authors: Verhaegen ME, Mangelberger D, Harms PW, Eberl M, Wilbert DM, Meireles J, Bichakjian CK, Saunders TL, Wong SY, Dlugosz AA

Abstract
Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a non-proliferative population of neuroendocrine cells which arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of pre-term transgenic mice, we show that epidermis-targeted co-expression of sT and the cell fate determinant atonal bHLH transcription factor 1 (Atoh1) leads to development of widespread cellular aggregates with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Co-expression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with Atoh1. MCPyV sT, when co-expressed with Atoh1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice.

PMID: 28512245 [PubMed - as supplied by publisher]

Comparison of the incidence of skin cancers in patients on dialysis and after kidney transplantation.

Fetched: May 18th, 2017, 1:00am EDT

Comparison of the incidence of skin cancers in patients on dialysis and after kidney transplantation.

Postepy Dermatol Alergol. 2017 Apr;34(2):138-142

Authors: Sułowicz J, Wojas-Pelc A, Ignacak E, Krzanowska K, Kuźniewski M, Sułowicz W

Abstract
INTRODUCTION: Kidney transplant (KTx) patients on immunosuppressive therapy are predisposed to the development of infections and cancers.
AIM: To compare the incidence and type of malignant skin lesions in kidney transplant patients and the dialyzed population based on the initiated dermatologic screening.
MATERIAL AND METHODS: The study included 598 patients: 486 kidney transplant recipients and 112 patients on maintenance dialysis. All the patients underwent dermatological examination. Only histologically confirmed cancers were included in this study. Age, gender and immunosuppressive therapy administration were also considered. Patients were followed up by a dermatologist for a period of 5 years.
RESULTS: Fifty-eight skin cancers; 39 basal cell carcinomas (BCC), 13 squamous cell carcinomas (SCC), 1 Bowen disease, 2 Kaposi sarcoma, 1 malignant melanoma, 1 Merkel cell carcinoma, and 1 fibrosarcoma protuberans were diagnosed in 30 (6.2%) kidney transplant patients, and 8 lesions (7 BCC and 1 SCC) were found in 4 (3.6%) patients on dialysis.
CONCLUSIONS: The initiated dermatologic screening program indicates that the risk of skin cancer incidence in post kidney transplant patients receiving immunosuppressive therapy was significantly higher than in patients on dialysis.

PMID: 28507493 [PubMed - in process]

Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.

Fetched: May 17th, 2017, 1:00am EDT

Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.

J Eur Acad Dermatol Venereol. 2017 May 14;:

Authors: Longo C, Benati E, Borsari S, Bombonato C, Pampena R, Moscarella E, Piana S, Pellacani G

Abstract
Merkel cell carcinoma (MCC) is an uncommon skin tumour with aggressive behaviour. Clinically, MCC usually appear as a fast growing red cherry nodule on the leg or face of elderly patients (1-4). Dermoscopically, it might reveal a reddish background with arborizing not in focus vessels, a pattern that is rather aspecific. Thus, the final diagnosis is routinely made by histopathologic examination and specific immunohistochemical stainings. This article is protected by copyright. All rights reserved.

PMID: 28502121 [PubMed - as supplied by publisher]

Skin manifestations of endocrine and neuroendocrine tumors.

Fetched: May 17th, 2017, 1:00am EDT

Skin manifestations of endocrine and neuroendocrine tumors.

Semin Oncol. 2016 Jun;43(3):335-40

Authors: Leventhal JS, Braverman IM

Abstract
The skin signs of benign and malignant endocrine and neuroendocrine tumors are manifold and early identification of these dermatologic features is crucial in initiating timely diagnosis and management. This article reviews the salient cutaneous features of these tumors that arise in the classic endocrine glands, lung and gastrointestinal tract either as individual neoplasms or as part of a syndrome.

PMID: 27178685 [PubMed - indexed for MEDLINE]

Permalink for 'Definitive radiotherapy for Merkel cell carcinoma confers clinically meaningful in-field locoregional control: A review and analysis of the literature.'

Definitive radiotherapy for Merkel cell carcinoma confers clinically meaningful in-field locoregional control: A review and analysis of the literature.

Fetched: May 14th, 2017, 1:00am EDT

Definitive radiotherapy for Merkel cell carcinoma confers clinically meaningful in-field locoregional control: A review and analysis of the literature.

J Am Acad Dermatol. 2017 May 08;:

Authors: Gunaratne DA, Howle JR, Veness MJ

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon radiosensitive, neuroendocrine malignancy. Treatment often involves surgery; however, older, sicker patients may not be candidates for an operation. Institutions have published data favoring the role of definitive radiotherapy for macroscopic locoregional disease.
OBJECTIVE: Our objective was to report the outcome of patients treated with definitive radiotherapy.
METHODS: We performed a systematic review of Medline, PubMed, and Embase databases for reported cases or series of definitive radiotherapy for macroscopic locoregional MCC.
RESULTS: The mean radiation dose did not significantly differ between primary and regional sites (48.7 ± 13.2 vs 49.4 ± 10.1 Gy, P = .74). The rate of recurrence was calculated on the basis of the site of disease (11.7%) and per patient (14.3%). Recurrence was significantly more likely to occur at regional than at primary irradiated sites (16.3% vs 7.6%, P = .02). There was no association between radiotherapy dose and incidence of recurrence or nonrecurrence; primary (42.7 ± 23 vs 49.3 ± 11.8 Gy, P = .197) and regional (48.6 ± 10 vs 49.5 ± 10.3 Gy, P = .77).
LIMITATIONS: A limitation of this report is that most publications were retrospective; heterogeneity was present in the size of MCC and in radiotherapy details.
CONCLUSIONS: Definitive radiotherapy for locoregional macroscopic MCC was found to confer clinically meaningful local and regional in-field control.

PMID: 28495499 [PubMed - as supplied by publisher]

The plasma virome of febrile adult Kenyans shows frequent parvovirus B19 infections and a novel arbovirus (Kadipiro virus).

Fetched: May 14th, 2017, 1:00am EDT

The plasma virome of febrile adult Kenyans shows frequent parvovirus B19 infections and a novel arbovirus (Kadipiro virus).

J Gen Virol. 2016 Dec;97(12):3359-3367

Authors: Ngoi CN, Siqueira J, Li L, Deng X, Mugo P, Graham SM, Price MA, Sanders EJ, Delwart E

Abstract
Viral nucleic acids present in the plasma of 498 Kenyan adults with unexplained fever were characterized by metagenomics analysis of 51 sample pools. The highest to lowest fraction of plasma pools was positive for parvovirus B19 (75 %), pegivirus C (GBV-C) (67 %), alpha anellovirus (59 %), gamma anellovirus (55 %), beta anellovirus (41 %), dengue virus genotype 2 (DENV-2) (16 %), human immunodeficiency virus type 1 (6 %), human herpesvirus 6 (6 %), HBV (4 %), rotavirus (4 %), hepatitis B virus (4 %), rhinovirus C (2 %), Merkel cell polyomavirus (MCPyV; 2 %) and Kadipiro virus (2 %). Ranking by overall percentage of viral reads yielded similar results. Characterization of viral nucleic acids in the plasma of a febrile East African population showed a high frequency of parvovirus B19 and DENV infections and detected a reovirus (Kadipiro virus) previously reported only in Asian Culex mosquitoes, providing a baseline to compare with future virome studies to detect emerging viruses in this region.

PMID: 27902331 [PubMed - indexed for MEDLINE]

Recurrent Merkel cell carcinoma of the testis with unknown primary site: a case report.

Fetched: May 14th, 2017, 1:00am EDT

Recurrent Merkel cell carcinoma of the testis with unknown primary site: a case report.

J Med Case Rep. 2016 Nov 05;10(1):314

Authors: Mweempwa A, Tan A, Dray M

Abstract
BACKGROUND: Merkel cell carcinoma is a rare and aggressive neuroendocrine tumor that commonly arises in the skin. It is rare for it to occur in the testes. There are only seven cases of testicular Merkel cell carcinoma reported in the literature.
CASE PRESENTATION: A 66-year-old Maori man presented to our hospital with left testicular swelling. His alpha-fetoprotein and beta-human chorionic gonadotrophin levels were within normal limits. His lactate dehydrogenase concentration was elevated to 267 U/L. Ultrasound imaging confirmed a large testicular mass, and he underwent left orchiectomy. His histological examination revealed a neuroendocrine tumor with an immunostaining pattern suggesting Merkel cell carcinoma. He presented to our hospital again 3 months later with right testicular swelling that was confirmed on ultrasound sonography to be a tumor. He underwent a right orchiectomy, and his histological examination revealed metastatic Merkel cell carcinoma. A primary lesion was not identified, and computed tomographic imaging did not reveal spread to other organs. He received six cycles of adjuvant carboplatin and etoposide chemotherapy and remained disease-free 18 months after completion of chemotherapy.
CONCLUSIONS: Given the paucity of studies, standard adjuvant treatment for testicular Merkel cell carcinoma remains uncertain, although platinum-based chemotherapy seems to be an appropriate option.

PMID: 27814751 [PubMed - indexed for MEDLINE]

Virus-Induced Cancers of the Skin and Mucosa: Are We Dealing with "Smoking Guns" or "Smoke and Mirrors" in the Operating Theatre?

Fetched: May 11th, 2017, 1:00am EDT

Virus-Induced Cancers of the Skin and Mucosa: Are We Dealing with "Smoking Guns" or "Smoke and Mirrors" in the Operating Theatre?

Dermatol Ther (Heidelb). 2017 May 08;:

Authors: Goon PKC, Goon PKY, Tan EKH, Crawford RAF, Levell NJ, Sudhoff H

Abstract
INTRODUCTION: Human papillomavirus (HPV) alone is thought to cause ~610,000 cases of cancer per year, and is the dominant aetiological agent for ano-genital (esp. cervical) and head and neck cancers (esp. oropharyngeal). Merkel cell polyomavirus (MCV) is a more recently discovered virus which causes Merkel cell carcinoma, a rare but highly aggressive skin malignancy.
METHODS: We explored the available published evidence to see if transmission of live HPV or MCV virus in smoke generated by laser or diathermy was feasible, and would pose an infection risk. Long-term infection with such carcinogenic viruses would then pose an increased risk for the development of virus-induced cancers in medical personnel.
RESULTS: The morphological structures of both HPV and MCV are very similar, and the size, external capsids and genomic structures show striking similarity. Both viruses have a non-enveloped external protein capsid consisting of 72 capsomeres, and a double-stranded DNA core. Sizes of both viruses range from 50 to 60 nm. There are now recent data demonstrating live and infectious HPV in smoke, and that these viruses can be used to infect cells in vitro. Further, anecdotal reports of virus transmission leading to disease causation in the production of respiratory airway viral warts (benign disease), and, finally, reports of HPV-induced oropharyngeal carcinoma (malignant disease) in two gynaecological surgeons as an occupational health hazard have been published recently.
CONCLUSION: There is now sufficient evidence to support the hypotheses that live infectious carcinogenic viruses can be transmitted via smoke generated from surgical procedures, and, in rare instances, actually cause significant disease. Protective measures such as smoke extraction and airway protection should be instituted for all healthcare personnel, particularly those with multiple repeated exposures such as gynaecological surgeons.

PMID: 28484898 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma.

Fetched: May 11th, 2017, 1:00am EDT

Merkel Cell Carcinoma.

Surg Pathol Clin. 2017 Jun;10(2):399-408

Authors: Pulitzer M

Abstract
Merkel cell carcinoma (MCC) encompasses neuroendocrine carcinomas primary to skin and occurs most commonly in association with clonally integrated Merkel cell polyomavirus with related retinoblastoma protein sequestration or in association with UV radiation-induced alterations involving the TP53 gene and mutations, heterozygous deletion, and hypermethylation of the Retinoblastoma gene. Molecular genetic signatures may provide therapeutic guidance. Morphologic features, although patterned, are associated with predictable diagnostic pitfalls, usually resolvable by immunohistochemistry. Therapeutic options for MCC, traditionally limited to surgical intervention and later chemotherapy and radiation, are growing, given promising early results of immunotherapeutic regimens.

PMID: 28477888 [PubMed - in process]

Phospho-STAT5B Expression Is a Prognostic Marker for Merkel Cell Carcinoma.

Fetched: May 11th, 2017, 1:00am EDT

Phospho-STAT5B Expression Is a Prognostic Marker for Merkel Cell Carcinoma.

Anticancer Res. 2017 05;37(5):2335-2341

Authors: Fujimura T, Furudate S, Kambayahsi Y, Kakizaki A, Yamamoto Y, Okuhira H, Fujimoto N, Aiba S

Abstract
BACKGROUND/AIM: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Although recent reports suggest that tumor-infiltrating leukocytes (TILs), especially CD8(+) T-cells, contribute to the pathogenesis of MCC, it is difficult for a single Institute with a small number of patients with MCC to determine the threshold number of CD8(+) cells. Therefore, clearer and easier methods of evaluating prognostic factors of MCC are needed.
PATIENTS AND METHODS: In order to identify the prognostic factors of 24 cases of MCC, we employed immuno histochemical staining of phospho-signal transducer and activator of transcription 5B (pSTAT5B), which has been reported to be a prognostic marker for several types of cancers.
RESULTS: All MCC cases with a good outcome (n=16) expressed pSTAT5B, whereas all MCC cases with a poor outcome (n=8) did not express pSTAT5B. Moreover, we additionally employed immunohistochemical staining of periostin (POSTN) and interleukin-4, as well as sub-populations of TILs (granulysin-bearing cells, regulatory T-cells, CD163(+) cells, and CD206(+) cells), and the deposition of matrix metalloproteinase 12 in the lesional skin of patients with MCC. The results suggested that there is no significant difference in stromal factors between MCC cases with a good and those with a poor outcome.
CONCLUSION: pSTAT5B expression may be an indicator of positive prognosis in patients with MCC.

PMID: 28476799 [PubMed - in process]

Protein-mediated viral latency is a novel mechanism for Merkel cell polyomavirus persistence.

Fetched: May 5th, 2017, 1:00am EDT

Protein-mediated viral latency is a novel mechanism for Merkel cell polyomavirus persistence.

Proc Natl Acad Sci U S A. 2017 May 01;:

Authors: Kwun HJ, Chang Y, Moore PS

Abstract
Viral latency, in which a virus genome does not replicate independently of the host cell genome and produces no infectious particles, is required for long-term virus persistence. There is no known latency mechanism for chronic small DNA virus infections. Merkel cell polyomavirus (MCV) causes an aggressive skin cancer after prolonged infection and requires an active large T (LT) phosphoprotein helicase to replicate. We show that evolutionarily conserved MCV LT phosphorylation sites are constitutively recognized by cellular Fbw7, βTrCP, and Skp2 Skp-F-box-cullin (SCF) E3 ubiquitin ligases, which degrade and suppress steady-state LT protein levels. Knockdown of each of these E3 ligases enhances LT stability and promotes MCV genome replication. Mutations at two of these phosphoreceptor sites [serine (S)220 and S239] in the full viral genome increase LT levels and promote MCV virion production and transmission, which can be neutralized with anti-capsid antibody. Virus activation is not mediated by viral gene transactivation, given that these mutations do not increase late gene transcription in the absence of genome replication. Mechanistic target of rapamycin inhibition by either nutrient starvation or use of an active site inhibitor reduces Skp2 levels and stabilizes LT, leading to enhanced MCV replication and transmission. MCV can sense stresses in its intracellular environment, such as nutrient loss, through SCF E3 ligase activities, and responds by initiating active viral transmission. Protein-mediated viral latency through cellular SCF E3 ligase targeting of viral replication proteins is a unique form of latency that may promote chronic viral persistence for some small DNA and RNA viruses.

PMID: 28461484 [PubMed - as supplied by publisher]

A Review of the Global Guidelines on Surgical Margins for Nonmelanoma Skin Cancers.

Fetched: May 3rd, 2017, 1:00am EDT

A Review of the Global Guidelines on Surgical Margins for Nonmelanoma Skin Cancers.

J Clin Aesthet Dermatol. 2017 Apr;10(4):37-46

Authors: Nahhas AF, Scarbrough CA, Trotter S

Abstract
Background: Adequate treatment and follow-up of a patient with nonmelanoma skin cancer is of utmost concern for a clinician. However, there is a lack of international consensus on recommendations for surgical excision margins. Furthermore, lack of familiarity of the published guidelines leads to a variety in practice styles. Objective: To compare the consistency in global recommendations for surgical excision margins for basal cell carcinoma, cutaneous squamous cell carcinoma, dermatofibrosarcoma protuberans, and Merkel cell carcinoma. Methods: A review of the current literature and global guidelines for surgical excision margins for basal cell carcinoma, cutaneous squamous cell carcinoma, dermatofibrosarcoma protuberans, and Merkel cell carcinoma. Results: Upon review of international guidelines, variations do exist among guidelines for peripheral and deep surgical margins. Guideline recommendations were found to be more globally consistent in margin selection for low-risk basal cell carcinoma and low-risk cutaneous squamous cell carcinoma, however, least consistent when concerning margin selection for dermatofibrosarcoma protuberans and Merkel cell carcinoma. Conclusion: Although guidelines exist, there is a need for international collaboration and consensus to determine a more unified and evidence-based approach to surgical excision as a treatment for nonmelanoma skin cancer.

PMID: 28458773 [PubMed - in process]

Somatostatin receptor positron emission tomography/computed tomography imaging in Merkel cell carcinoma.

Fetched: May 3rd, 2017, 1:00am EDT

Somatostatin receptor positron emission tomography/computed tomography imaging in Merkel cell carcinoma.

J Eur Acad Dermatol Venereol. 2016 Sep;30(9):1507-11

Authors: Sollini M, Taralli S, Milella M, Erba PA, Rubagotti S, Fraternali A, Roncali M, Moscarella E, Perotti G, Rufini V, Versari A

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon aggressive primary cutaneous carcinoma with neuroendocrine differentiation. However, literature data about the use of somatostatin receptor positron emission tomography/computed tomography (PET/CT) imaging in MCC are limited and its role is not clearly stated.
OBJECTIVE: To investigate the role of PET/CT using somatostatin analogues radiolabelled with gallium-68 in patients with MCC.
METHODS: All patients affected by MCC who performed a somatostatin receptor PET/CT imaging from October 2007 to May 2014 were retrospectively analysed. The diagnostic performances of PET/CT were evaluated on a patient-based analysis and compared to final diagnosis (histology = 3 or clinical/radiological follow-up = 20).
RESULTS: We evaluated 23 consecutive MCC patients [18 men; median age 71 years (range 47-87)]. Primary tumour was located in ear (1/23), cheek (3/23), arm (2/23), hand (1/23), back (1/23), anal canal (1/23), gluteus (4/23), thigh (3/23) and popliteal fossa (1/23). In 6/23 patients, the site of primary tumour was unknown. PET/CT was performed to detect primary tumour site (4/23) or to stage (8/23) or re-stage (11/23) patients. PET/CT resulted positive in 14/23 patients and according to the final diagnosis was defined true positive, true negative, false positive (FP) and false negative in 11/23, 8/23, 3/23 and 1/23 cases respectively. FP PET/CT results were due to unspecific liver uptake, post-surgical inflammation and pancreatic neuroendocrine tumour. PET/CT was unable to detect primary tumour site in all patients with unknown primary MCC. Sensitivity, specificity and diagnostic accuracy of PET/CT were 92%, 73% and 83% respectively.
CONCLUSIONS: In our experience, somatostatin receptor PET/CT imaging resulted useful in patients with MCC and presented high diagnostic performances with a significant impact in disease management although in patients with unknown primary MCC, it was unable to identify the primary tumour site.

PMID: 26446694 [PubMed - indexed for MEDLINE]

Evaluation of Merkel cell polyomavirus in non-small cell lung cancer and adjacent normal cells.

Fetched: May 1st, 2017, 1:00am EDT

Evaluation of Merkel cell polyomavirus in non-small cell lung cancer and adjacent normal cells.

Microb Pathog. 2017 Apr 25;:

Authors: Behdarvand A, Zamani MS, Sadeghi F, Yahyapour Y, Vaziri F, Jamnani FR, Nowruzi B, Fateh A, Siadat SD

Abstract
Several risk factors have been linked to lung cancer (LC). Nevertheless, a viral etiology has been mentioned for a subset of patients developing LC. The aim of this study was to evaluate the effect of Merkel cell polyomavirus (MCPyV) on developing non-small cell lung cancer (NSCLCs). In total, 96 paraffin-embedded NSCLC biopsies and 96 adjacent non-LC normal specimens were analyzed by quantitative real-time polymerase chain reaction (PCR) for the existence of the MCPyV DNA and the expressions of RNA transcripts. Among the 96 enrolled participants, 42 patients were adenocarcinomas (ADs) and 54 patients were squamous cell carcinoma (SCC). Of the 42 ADs, MCPyV DNA was determined in 15 (35.7%) samples and of the 54 SCC, MCPyV DNA was detected in 22 (40.7%) samples. Only one non-cancerous sample in SCC subjects was positive for MCPyV LT-Ag DNA load (0.216 × 10(-3)). In MCPyV-positive subjects, the median MCPyV copy number was higher in the patients with ADs (0.016 × 10(-3) copies/cell) compared to SCCs (0.005 × 10(-3) copies/cell); but this difference was not statistically significant (P = 0.913). In the seven stages of LC, the MCPyV LT-Ag was quantified in stage IV (0.204 × 10(-3) copies/cell) more than in other stages. There was statistically significant difference between stages of cancer and MCPyV LT-Ag DNA load (P = 0.002). These results revealed for the first time the presence of MCPyV in a subset of patients with NSCLCs in Iran. Further studies should be carried out to clarify the role of MCPyV in lung carcinogenesis.

PMID: 28455138 [PubMed - as supplied by publisher]

The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.

Fetched: April 29th, 2017, 1:00am EDT

The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.

Oncotarget. 2017 Apr 11;8(15):25418-25432

Authors: Abdul-Sada H, Müller M, Mehta R, Toth R, Arthur JSC, Whitehouse A, Macdonald A

Abstract
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.

PMID: 28445980 [PubMed - in process]

A population-based cohort study on the association of dermatologist density and Merkel cell carcinoma survival.

Fetched: April 29th, 2017, 1:00am EDT

A population-based cohort study on the association of dermatologist density and Merkel cell carcinoma survival.

J Am Acad Dermatol. 2017 Mar;76(3):570-572

Authors: Criscito MC, Martires KJ, Stein JA

PMID: 28212766 [PubMed - indexed for MEDLINE]

Talimogene laherparepvec for regionally advanced Merkel cell carcinoma: A report of 2 cases.

Fetched: April 28th, 2017, 1:00am EDT

Talimogene laherparepvec for regionally advanced Merkel cell carcinoma: A report of 2 cases.

JAAD Case Rep. 2017 May;3(3):185-189

Authors: Blackmon JT, Dhawan R, Viator TM, Terry NL, Conry RM

PMID: 28443305 [PubMed - in process]

Avelumab Impresses in Merkel Cell Carcinoma.

Fetched: April 27th, 2017, 1:00am EDT

Avelumab Impresses in Merkel Cell Carcinoma.

Cancer Discov. 2017 Apr 24;:

Authors:

Abstract
The PD-L1 inhibitor avelumab-approved by the FDA in March for the treatment of Merkel cell carcinoma-demonstrated a high number of durable responses in an international, open-label, prospective phase II study. The results of the study, which supported the FDA's decision, were presented in April at the American Association for Cancer Research (AACR) Annual Meeting 2017.

PMID: 28438774 [PubMed - as supplied by publisher]

Potential Activity of Amrubicin as a Salvage Therapy for Merkel Cell Carcinoma.

Fetched: April 26th, 2017, 1:00am EDT

Potential Activity of Amrubicin as a Salvage Therapy for Merkel Cell Carcinoma.

Intern Med. 2017;56(5):567-570

Authors: Sakaida E, Ebata T, Iwasawa S, Kurimoto R, Yonemori S, Ota S, Nakatani Y, Sekine I, Takiguchi Y

Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin with an aggressive clinical course. Although anthracycline- and platinum-based regimens are empirically used as first-line treatments for metastatic or unresectable cases, no salvage therapy has been established. A 73-year-old man with platinum-refractory recurrent MCC was treated with amrubicin. The symptoms improved soon, and a partial response was achieved. A total of nine cycles of amrubicin were administered in nine months with manageable adverse events until disease progression was finally observed. The present findings suggest the potential of amrubicin monotherapy as a second-line therapy for patients with advanced/recurrent MCC.

PMID: 28250307 [PubMed - indexed for MEDLINE]

A population-based cohort study of the influence of socioeconomic factors and race on survival in Merkel cell carcinoma.

Fetched: April 26th, 2017, 1:00am EDT

A population-based cohort study of the influence of socioeconomic factors and race on survival in Merkel cell carcinoma.

J Am Acad Dermatol. 2017 Jan;76(1):166-167

Authors: Madankumar R, Criscito MC, Martires KJ, Stein JA

PMID: 27986144 [PubMed - indexed for MEDLINE]

Permalink for 'A high neutrophil-to-lymphocyte ratio as a potential marker of mortality in patients with Merkel cell carcinoma: A retrospective study.'

A high neutrophil-to-lymphocyte ratio as a potential marker of mortality in patients with Merkel cell carcinoma: A retrospective study.

Fetched: April 26th, 2017, 1:00am EDT

A high neutrophil-to-lymphocyte ratio as a potential marker of mortality in patients with Merkel cell carcinoma: A retrospective study.

J Am Acad Dermatol. 2016 Oct;75(4):712-721.e1

Authors: Zaragoza J, Kervarrec T, Touzé A, Avenel-Audran M, Beneton N, Esteve E, Wierzbicka Hainaut E, Aubin F, Machet L, Samimi M

Abstract
BACKGROUND: The prognostic relevance of a high blood neutrophil-to-lymphocyte ratio (NLR) has been reported in many cancers, although, to our knowledge, not investigated in patients with Merkel cell carcinoma (MCC) to date.
OBJECTIVE: We assessed whether the NLR at baseline was associated with specific survival and recurrence-free survival in MCC.
METHODS: We retrospectively included MCC cases between 1999 and 2015 and collected clinical data, blood cell count at baseline, and outcome. A Cox model was used to identify factors associated with recurrence and death from MCC.
RESULTS: Among the 75 patients included in the study, a high NLR at baseline (NLR ≥4) was associated with death from MCC in univariate (hazard ratio 2.76, 95% confidence interval 1.15-6.62, P = .023) and multivariate (hazard ratio 3.30, 95% confidence interval 1.21-9.01, P = .020) analysis, but not with recurrence.
LIMITATIONS: Because of the retrospective design, we excluded patients with missing data and not all confounding factors that may influence the NLR were available.
CONCLUSION: A high NLR at baseline was independently associated with specific mortality in patients with MCC. The NLR seems to constitute an easily available and inexpensive prognostic biomarker at baseline.

PMID: 27544490 [PubMed - indexed for MEDLINE]

Permalink for 'An increased risk of non-Hodgkin lymphoma and chronic lymphocytic leukemia in US patients with Merkel cell carcinoma versus Australian patients: A clinical clue to a different mechanism of pathogenesis?'

An increased risk of non-Hodgkin lymphoma and chronic lymphocytic leukemia in US patients with Merkel cell carcinoma versus Australian patients: A clinical clue to a different mechanism of pathogenesis?

Fetched: April 26th, 2017, 1:00am EDT

An increased risk of non-Hodgkin lymphoma and chronic lymphocytic leukemia in US patients with Merkel cell carcinoma versus Australian patients: A clinical clue to a different mechanism of pathogenesis?

Australas J Dermatol. 2016 Aug;57(3):e114-6

Authors: Bloom R, Amber KT, Nouri K

Abstract
The US and Queensland populations both demonstrate an increased risk of secondary malignancies following the diagnosis of Merkel cell carcinoma (MCC). A recent Queensland study failed to demonstrate a significantly increased risk of developing non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukaemia (CLL) in these patients. In contrast, using the US Surveillance, Epidemiology, and End Results database, we demonstrate there is an increased risk in CLL and NHL following the diagnosis of MCC in the USA. We hypothesise that this difference may be a result of a differing pathogenesis.

PMID: 25801041 [PubMed - indexed for MEDLINE]

Permalink for 'RE: Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base.'

RE: Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base.

Fetched: April 22nd, 2017, 1:00am EDT

RE: Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base.

J Natl Cancer Inst. 2017 Oct 01;109(10):

Authors: Vargo JA, Ghareeb ER, Balasubramani GK, Beriwal S

PMID: 28423400 [PubMed - in process]

Non-melanoma skin cancer: new and future synthetic drug treatments.

Fetched: April 19th, 2017, 12:13am EDT

Non-melanoma skin cancer: new and future synthetic drug treatments.

Expert Opin Pharmacother. 2017 Apr 17;:1-11

Authors: Amaral T, Garbe C

Abstract
INTRODUCTION: Non-melanoma skin cancers (NMSC) mainly comprise two different entities: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC); beneath these two entities, Merkel cell carcinoma, adnexal tumors, dermatofibrosarcoma protuberans, angiosarcoma, and cutaneous lymphoma belong to NMSC. These rare skin tumors are not the topic of this review. BCC and SCC are the most common cancers diagnosed in humans. The preferred treatment is surgery, which in most cases is curative. Although a high recurrence rate is seen, these cancers rarely metastasize. Therefore, systemic treatments were not a priority for these patients. It is long known that the abnormal activation of Hedgehog and epidermal growth factor receptor pathways were involved in BCC and SCC. In the last decade, metastatic disease became an important area of research, mostly because new therapies that targeted components of these two pathways became available. Areas covered: Here we cover the available therapeutic options for patients diagnosed with BCC and SCC, focus on systemic and targeted therapies. Expert opinion: BCC and SCC are common cancers, with good prognosis. More than the metastatic disease, advanced local disease and recurrent disease pose clinicians a great challenge. Albeit there are promising results with targeted therapies, resistance development has already been described.

PMID: 28414587 [PubMed - as supplied by publisher]

Merkel cell carcinoma in a vein graft donor site.

Fetched: April 19th, 2017, 12:13am EDT

Merkel cell carcinoma in a vein graft donor site.

Cutis. 2016 May;97(5):364-7

Authors: Ranario JS, Wolthoff AJ, Hope RH, Stetson CL, Ronaghan CA

Abstract
The development of malignancies in graft donor sites is rare and may be caused by de novo malignancies as well as metastatic and iatrogenic spread. Malignancies in graft donor sites are distinguished from Marjolin ulcers by some investigators because they occur in healed surgical wounds rather than in chronic wounds or unstable scars and tend to occur sooner after injury. We present a unique case of Merkel cell carcinoma (MCC) developing in a vein graft donor site 18 years after vein harvesting.

PMID: 27274546 [PubMed - indexed for MEDLINE]

MGMT promoter methylation status in Merkel cell carcinoma: in vitro versus invivo.

Fetched: April 15th, 2017, 1:00am EDT

MGMT promoter methylation status in Merkel cell carcinoma: in vitro versus invivo.

J Cancer Res Clin Oncol. 2017 Apr 12;:

Authors: Improta G, Ritter C, Pettinato A, Vasta V, Schrama D, Fraggetta F, Becker JC

Abstract
PURPOSE: Expression of O6-methylguanine-DNA methyltransferase (MGMT) in Merkel cell carcinoma (MCC) is very variable; thus, we tested whether this may be due to differential methylation of the MGMT gene promoter.
METHODS: Quantitative analysis of MGMT mRNA and protein expression, as well as MGMT promoter methylation status, was performed in a series of tissue samples of MCC tumors, representing both primary and metastatic lesions, as well as in six MCC cell lines.
RESULTS: These analyses revealed a very heterogeneous MGMT mRNA and protein expression in MCC both in vivo and in vitro. However, neither the MGMT mRNA nor protein expression correlated with the sensitivity of MCC cell lines toward the alkylating agent dacarbazine in vitro. Notably, increased methylation at the promoter of the MGMT gene was observed in 2/6 (33%) of the MCC cell lines; however, MGMT promoter methylation was absent in all MCC tissue samples. According to our results, albeit aberrant methylation of MGMT gene promoter can be observed in in vitro propagated MCC cell lines, it seems to be absent or very rare in MCC lesions in situ.
CONCLUSION: Thus, the evaluation of this marker has no or only little significance for predicting response to therapy or for improving efficacy of demethylating agents in the treatment of MCC. Microenvironmental factors may play a role in explaining the different results between MCC cell lines and MCC samples.

PMID: 28405827 [PubMed - as supplied by publisher]

Permalink for 'Molecular Profiling of Multiple Primary Merkel Cell Carcinoma to Distinguish Genetically Distinct Tumors From Clonally Related Metastases.'

Molecular Profiling of Multiple Primary Merkel Cell Carcinoma to Distinguish Genetically Distinct Tumors From Clonally Related Metastases.

Fetched: April 15th, 2017, 1:00am EDT

Molecular Profiling of Multiple Primary Merkel Cell Carcinoma to Distinguish Genetically Distinct Tumors From Clonally Related Metastases.

JAMA Dermatol. 2017 Apr 12;:

Authors: Harms KL, Lazo de la Vega L, Hovelson DH, Rahrig S, Cani AK, Liu CJ, Fullen DR, Wang M, Andea AA, Bichakjian CK, Johnson TM, Tomlins SA, Harms PW

Abstract
Importance: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. In rare cases, the development of an additional cutaneous MCC tumor is clinically consistent with a second primary MCC tumor rather than a cutaneous metastasis, which has important treatment and prognostic implications.
Objective: To evaluate genetic relatedness in 4 cases with the clinical diagnosis of multiple primary MCCs.
Design, Setting, and Participants: In this case series, 7 cases of clinically designated multiple primary MCC were identified; 4 cases met inclusion criteria for next-generation sequencing (NGS) analysis. Mutations, copy number alterations, and Merkel cell polyomavirus (MCPyV) sequence were analyzed and compared between clinically designated multiple primary tumors to characterize genetic relatedness and hence assess clonality. Patients with clinically designated multiple primary MCC were identified from the multidisciplinary MCC Program at the University of Michigan, a tertiary care center.
Main Outcomes and Measures: Four cases of clinically designated multiple primary MCC were characterized by tumor sequencing and targeted MCPyV sequencing to distinguish independent primary tumors from related metastases.
Results: Overall, 4 patients in their 70s or 80s were included and analyzed. Cases 1 and 4 were verified as genetically distinct primary tumors and did not harbor similar copy number alterations or demonstrate significant mutational overlap. Cases 2 and 3 were designated as clonally related based on overlapping copy number alterations. In clonally related tumors, chromosomal copy number changes were more reliable than mutations for demonstrating clonality. Regardless of clonality, we found that MCPyV status was concordant for all tumor pairs and MCPyV positive tumors harbored predominatly subclonal mutations.
Conclusions and Relevance: Our findings suggest that patients with MCC may develop a second genetically distinct primary tumor; in this case, the subsequent tumor is likely to develop through similar mechanisms of pathogenesis, either MCPyV-mediated or ultraviolet light-mediated. Next-generation sequencing analysis of chromosomal copy number changes and mutations is useful in distinguishing multiple primary MCCs from progression of MCC clinically resembling multiple primaries, allowing appropriate staging of the patient.

PMID: 28403382 [PubMed - as supplied by publisher]

What's New in Eyelid Tumors.

Fetched: April 13th, 2017, 1:00am EDT

What's New in Eyelid Tumors.

Asia Pac J Ophthalmol (Phila). 2017 Mar-Apr;6(2):143-152

Authors: Silverman N, Shinder R

Abstract
Eyelid malignancies represent between 5% and 10% of all skin cancers. Basal cell carcinoma is the most common, followed by squamous cell carcinoma, sebaceous cell carcinoma, Merkel cell carcinoma, and melanoma. The gold standard treatment for periocular epithelial malignancies is surgical excision. Given the constraints of the anatomy and function of the eyelids, excision with negative margins and reconstruction can be challenging. In cases of significant tissue invasion or metastasis, complete tumor removal may not be possible. This review examines the management of periocular skin cancer from diagnosis and staging, including the role of sentinel lymph node biopsy, to both surgical and nonsurgical treatment. The development of targeted drug therapy against specific genetic mutations in cutaneous malignancies has allowed for the treatment of specific cancer cells with less systemic toxicity than more traditional treatments.

PMID: 28399340 [PubMed - in process]

Merkel cell carcinoma: a review.

Fetched: April 12th, 2017, 1:00am EDT

Merkel cell carcinoma: a review.

Cutis. 2016 Apr;97(4):290-5

Authors: Oram CW, Bartus CL, Purcell SM

Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of unknown origin that usually presents in the elderly population. A novel polyomavirus has been associated with a large percentage of tumors. Immune response plays an important role in pathogenesis of MCC. This article reviews the history, pathogenesis, presentation, and treatment of MCC. Future treatments also are discussed briefly.

PMID: 27163912 [PubMed - indexed for MEDLINE]

Sentinel lymph node biopsy and survival in Merkel cell carcinoma: A 10 year review.

Fetched: April 9th, 2017, 1:00am EDT

Sentinel lymph node biopsy and survival in Merkel cell carcinoma: A 10 year review.

J Plast Reconstr Aesthet Surg. 2016 Oct;69(10):1450-1

Authors: Dunne JA, Steele J, Woods E, Odili J

PMID: 27544843 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma: new insights into pathogenesis.

Fetched: April 8th, 2017, 1:00am EDT

Merkel cell carcinoma: new insights into pathogenesis.

Eur J Dermatol. 2017 Feb 03;:

Authors: Curzio G, Paolini F, Cota C, Donati P, Di Mattia C, Mariani L, Migliano E, Venuti A

PMID: 28382918 [PubMed - as supplied by publisher]

Metastatic Merkel cell carcinoma of the face.

Fetched: April 8th, 2017, 1:00am EDT

Metastatic Merkel cell carcinoma of the face.

Indian J Dermatol Venereol Leprol. 2016 Sep-Oct;82(5):562-4

Authors: Vaccaro M, Magaudda E, Brianti P, Licata L, Cardia R, De Ponte FS

PMID: 27212280 [PubMed - indexed for MEDLINE]

Spontaneous lung metastasis formation of human Merkel cell carcinoma cell lines transplanted into scid mice.

Fetched: April 7th, 2017, 1:00am EDT

Spontaneous lung metastasis formation of human Merkel cell carcinoma cell lines transplanted into scid mice.

Int J Cancer. 2017 Apr 05;:

Authors: Knips J, Czech-Sioli M, Spohn M, Heiland M, Moll I, Grundhoff A, Schumacher U, Fischer N

Abstract
Merkel cell carcinoma (MCC) is an aggressive skin cancer entity that frequently leads to rapid death due to its high propensity to metastasize. The etiology of most MCC cases is linked to Merkel cell polyomavirus (MCPyV), a virus which is monoclonally integrated in up to 95% of tumors. While there are presently no animal models to study the role of authentic MCPyV infection on transformation, tumorigenesis or metastasis formation, xenograft mouse models employing engrafted MCC derived cell lines (MCCL) represent a promising approach to study certain aspects of MCC pathogenesis. Here, the two MCPyV positive MCC cell lines WaGa and MKL-1 were subcutaneously engrafted in scid mice. Engraftment of both MCC cell lines resulted in the appearance of circulating tumor cells and metastasis formation, with WaGa-engrafted mice showing a significantly shorter survival time as well as increased numbers of spontaneous lung metastases compared to MKL-1 mice. Interestingly, explanted tumors compared to parental cell lines exhibit an upregulation of MCPyV sT-Antigen expression in all tumors, with WaGa tumors showing significantly higher sT-Antigen expression than MKL-1 tumors. RNA-Seq analysis of explanted tumors and parental cell lines furthermore revealed that in the more aggressive WaGa tumors, genes involved in inflammatory response, growth factor activity and Wnt signaling pathway are significantly upregulated, suggesting that sT-Antigen is the driver of the observed differences in metastasis formation. This article is protected by copyright. All rights reserved.

PMID: 28380668 [PubMed - as supplied by publisher]

Permalink for 'Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.'

Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.

Fetched: April 6th, 2017, 1:00am EDT

Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.

Lancet Oncol. 2017 Mar 31;:

Authors: Gulley JL, Rajan A, Spigel DR, Iannotti N, Chandler J, Wong DJ, Leach J, Edenfield WJ, Wang D, Grote HJ, Heydebreck AV, Chin K, Cuillerot JM, Kelly K

Abstract
BACKGROUND: Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC).
METHODS: In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or non-squamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or expression of other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received infusional avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary objective was to assess safety and tolerability. This trial is registered with ClinicalTrials.gov, number NCT01772004; enrolment in this cohort is closed and the trial is ongoing.
FINDINGS: Between Sept 10, 2013, and June 24, 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (IQR 7·2-11·9). The most common treatment-related adverse events of any grade were fatigue (46 [25%] of 184 patients), infusion-related reaction (38 [21%]), and nausea (23 [13%]). Grade 3 or worse treatment-related adverse events occurred in 23 (13%) of 184 patients; the most common (occurring in more than two patients) were infusion-related reaction (four [2%] patients) and increased lipase level (three [2%]). 16 (9%) of 184 patients had a serious adverse event related to treatment with avelumab, with infusion-related reaction (in four [2%] patients) and dyspnoea (in two [1%]) occurring in more than one patient. Serious adverse events irrespective of cause occurred in 80 (44%) of 184 patients. Those occurring in more than five patients (≥3%) were dyspnoea (ten patients [5%]), pneumonia (nine [5%]), and chronic obstructive pulmonary disease (six [3%]). Immune-related treatment-related events occurred in 22 patients (12%). Of 184 patients, 22 (12% [95% CI 8-18]) achieved a confirmed objective response, including one complete response and 21 partial responses. 70 (38%) had stable disease. Overall, 92 (50%) of 184 patients achieved disease control (they had a confirmed response or stable disease as their best overall response). One patient was initially thought to have died from grade 5 radiation pneumonitis during the study; however, this adverse event was subsequently regraded to grade 3 and the death was attributed to disease progression.
INTERPRETATION: Avelumab showed an acceptable safety profile and antitumour activity in patients with progressive or treatment-resistant NSCLC, providing a rationale for further studies of avelumab in this disease setting.
FUNDING: Merck KGaA and Pfizer.

PMID: 28373005 [PubMed - as supplied by publisher]

Impact of total radiotherapy dose on survival for head and neck Merkel cell carcinoma after resection.

Fetched: April 5th, 2017, 1:00am EDT

Impact of total radiotherapy dose on survival for head and neck Merkel cell carcinoma after resection.

Head Neck. 2017 Mar 29;:

Authors: Patel SA, Qureshi MM, Mak KS, Sahni D, Giacalone NJ, Ezzat W, Jalisi S, Truong MT

Abstract
BACKGROUND: Head and neck Merkel cell carcinoma (MCC) is commonly treated with surgery and adjuvant radiotherapy (RT) for high-risk features. The optimal radiation dose is unknown.
METHODS: One thousand six hundred twenty-five eligible patients with head and neck MCC were identified in the National Cancer Data Base (NCDB). Radiation dose was divided into 3 groups: 30 to <50 Gray (Gy), 50-55 Gy, and >55-70 Gy. Cox regression was used to compare overall survival (OS) between groups, accounting for age, sex, stage, surgery type, margin status, comorbidities, and use of chemotherapy.
RESULTS: With a median follow-up of 33.5 months, 3-year OS was 48.9%, 70.3%, and 58.7% for 30 to <50 Gy, 50-55 Gy, and >55-70 Gy, respectively (P < .001). Compared to 50-55 Gy, doses between 30 to <50 Gy (adjusted hazard ratio [HR] 1.53; 95% confidence interval [CI] 1.17-1.99; P = .002) and >55-70 Gy (adjusted HR 1.21; 95% CI 1.0-1.46; P = .06) were associated with worse survival.
CONCLUSION: Adjuvant radiation doses within 50-55 Gy may be optimal for head and neck MCC.

PMID: 28370725 [PubMed - as supplied by publisher]

Erythema ab igne: new technology rebounding upon its users?

Fetched: April 5th, 2017, 1:00am EDT

Erythema ab igne: new technology rebounding upon its users?

Int J Dermatol. 2017 Mar 30;:

Authors: Salgado F, Handler MZ, Schwartz RA

Abstract
Erythema ab igne (EAI) is a persistent, chronic skin condition resulting from prolonged exposure to infrared radiation, experienced as heat. Once associated with traditional warming sources like wood burning stoves or open fires, modern, infrared exposure originates also from newer sources like laptops and heating pads and may be creating a rebound of EAI. The epidemiology may be different too, with younger patients than previously seen. Localized EAI over an area of pain in the abdomen or lower back can be a sign of an underlying disorder, including cancer. Prognosis of EAI is good, with removal of the heat source resulting in complete remission. In chronic cases in which premalignant cutaneous dysplasia has resulted, additional treatments may be necessary including topical retinoids, 5-fluorouracil cream, and laser treatments. Rarely, cancers such as squamous cell carcinoma, Merkel cell carcinoma, and cutaneous marginal zone B cell lymphoma have been associated with longstanding EAI.

PMID: 28369761 [PubMed - as supplied by publisher]

Mohs Micrographic Surgery for the Treatment of Merkel Cell Carcinoma.

Fetched: April 5th, 2017, 1:00am EDT

Mohs Micrographic Surgery for the Treatment of Merkel Cell Carcinoma.

Dermatol Surg. 2016 Aug;42(8):945-51

Authors: Kline L, Coldiron B

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive malignant neoplasm. Traditionally, wide local excision has been used for local control. However, the tissue-sparing capability of Mohs micrographic surgery (MMS) and the greater certainty of complete tumor removal offer a potential advantage over wide local excision if MMS offers acceptable cure rates.
OBJECTIVE: This study aims to help elucidate management of MCC and includes one of the largest groups of patients from a single institution.
MATERIALS AND METHODS: This study is a retrospective chart review of 22 patients with cutaneous MCC treated with MMS at our practice over 20 years. Clinical characteristics and outcomes were examined. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in the approval by our institution's human research review committee.
RESULTS: The overall local recurrence rate was 5% (1/22). The overall rate of biopsy-proven metastasis to regional lymph nodes was 14% (3/22). No cases of distant metastases were documented.
CONCLUSION: To our knowledge, this is the largest group of patients with MCC treated with MMS from a single institution and indicates that MMS may be a useful treatment modality for this rare aggressive disease.

PMID: 27467228 [PubMed - indexed for MEDLINE]

Aberrant expression of ALK and EZH2 in Merkel cell carcinoma.

Fetched: April 2nd, 2017, 1:00am EDT

Aberrant expression of ALK and EZH2 in Merkel cell carcinoma.

BMC Cancer. 2017 Mar 31;17(1):236

Authors: Veija T, Koljonen V, Bohling T, Kero M, Knuutila S, Sarhadi VK

Abstract
BACKGROUND: Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA level in MCC tumors. In this study, we studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC.
METHODS: RNA expression of 50 cancer-related genes in 26 MCC tumors was analyzed by targeted amplicon based next-generation sequencing using the Ion Torrent technology and the expression compared with that of normal, non-cancerous skin samples. Sequencing data were processed using Torrent Suite™ Software. Expression profiles of MCV-negative and MCV-positive tumors were compared. Fluorescence in situ hybridization was performed to study ALK rearrangements and immunohistochemistry to study ALK expression in tumor tissue.
RESULTS: ALK, CDKN2A, EZH2 and ERBB4 were overexpressed, and EGFR, ERBB2, PDGFRA and FGFR1 were underexpressed in MCC tumors compared to normal skin. In the MCV-negative tumors, MET, NOTCH1, FGFR3, and SMO were overexpressed and JAK3 and NPM1 were under-expressed compared to the MCV-positive tumors.
CONCLUSIONS: High expression of ALK, CDKN2A and EZH2 was recorded in MCC tumors. No ALK fusion was seen by FISH analysis. Overexpression of EZH2 suggests its potential as a drug target in MCC.

PMID: 28359267 [PubMed - in process]

A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development.

Fetched: April 1st, 2017, 1:00am EDT

A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development.

PLoS Genet. 2016 07;12(7):e1006150

Authors: Xiao Y, Thoresen DT, Miao L, Williams JS, Wang C, Atit RP, Wong SY, Brownell I

Abstract
The Sonic hedgehog (Shh) signaling pathway regulates developmental, homeostatic, and repair processes throughout the body. In the skin, touch domes develop in tandem with primary hair follicles and contain sensory Merkel cells. The developmental signaling requirements for touch dome specification are largely unknown. We found dermal Wnt signaling and subsequent epidermal Eda/Edar signaling promoted Merkel cell morphogenesis by inducing Shh expression in early follicles. Lineage-specific gene deletions revealed intraepithelial Shh signaling was necessary for Merkel cell specification. Additionally, a Shh signaling agonist was sufficient to rescue Merkel cell differentiation in Edar-deficient skin. Moreover, Merkel cells formed in Fgf20 mutant skin where primary hair formation was defective but Shh production was preserved. Although developmentally associated with hair follicles, fate mapping demonstrated Merkel cells primarily originated outside the hair follicle lineage. These findings suggest that touch dome development requires Wnt-dependent mesenchymal signals to establish reciprocal signaling within the developing ectoderm, including Eda signaling to primary hair placodes and ultimately Shh signaling from primary follicles to extrafollicular Merkel cell progenitors. Shh signaling often demonstrates pleiotropic effects within a structure over time. In postnatal skin, Shh is known to regulate the self-renewal, but not the differentiation, of touch dome stem cells. Our findings relate the varied effects of Shh in the touch dome to the ligand source, with locally produced Shh acting as a morphogen essential for lineage specification during development and neural Shh regulating postnatal touch dome stem cell maintenance.

PMID: 27414798 [PubMed - indexed for MEDLINE]

Permalink for 'Prognostic Value of the Staging System for Eyelid Tumors in the 7th Edition of the American Joint Committee on Cancer Staging Manual.'

Prognostic Value of the Staging System for Eyelid Tumors in the 7th Edition of the American Joint Committee on Cancer Staging Manual.

Fetched: March 31st, 2017, 1:00am EDT

Prognostic Value of the Staging System for Eyelid Tumors in the 7th Edition of the American Joint Committee on Cancer Staging Manual.

Ophthal Plast Reconstr Surg. 2017 Mar 27;:

Authors: Ford J, Thakar S, Thuro B, Esmaeli B

Abstract
PURPOSE: To determine the prognostic value of the staging criteria for eyelid tumors in the 7th edition of the American Joint Committee on Cancer (AJCC) staging manual and to determine, for each type of eyelid tumor, which AJCC T categories are associated with increased risk of nodal metastasis and thus potential usefulness of sentinel lymph node biopsy.
METHODS: Systematic review and analysis of articles found by searching PubMed and Google Scholar using the search terms "AJCC," "eyelid," "carcinoma," and "melanoma."
RESULTS: Rates of local recurrence, regional nodal metastasis, and distant metastasis were approximately 7% to 10%, 1% to 9%, and 0% to 0.8%, respectively, for eyelid squamous cell carcinoma; 5% to 6%, 8% to 23%, and 2% and 14%, respectively, for eyelid sebaceous carcinoma; 10%, 10% to 22%, and 19% to 22%, respectively, for eyelid Merkel cell carcinoma (when staged according to the criteria for eyelid carcinoma as opposed to Merkel cell carcinoma), 14%, 5%, and 0%, respectively, for eyelid sweat gland carcinoma; and 2%, 9%, and 6%, respectively, for eyelid melanoma. Overall, the risks of local recurrence and regional nodal and distant metastasis appeared to increase with increasing AJCC T category, although not statistically significant in all studies. Clinical T2b or greater T category was significantly associated with increased risk of nodal metastasis for eyelid squamous cell carcinomas, sebaceous carcinomas, Merkel cell carcinomas (staged with eyelid carcinoma criteria), sweat gland carcinomas, and melanomas. Clinical T3 or greater T category was significantly associated with distant metastasis for eyelid carcinomas and melanomas.
CONCLUSION: For eyelid carcinomas and eyelid melanomas, AJCC 7th edition T category correlates with the risks of nodal and distant metastasis, with T2b and larger tumors associated with highest risk of nodal metastasis. Patients with T2b or larger tumors may be candidates for sentinel lymph node biopsy or close nodal surveillance.

PMID: 28350693 [PubMed - as supplied by publisher]

Permalink for 'Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma.'

Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma.

Fetched: March 31st, 2017, 1:00am EDT

Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma.

Future Oncol. 2017 Mar 28;:

Authors: Nghiem P, Kaufman HL, Bharmal M, Mahnke L, Phatak H, Becker JC

Abstract
AIM: Merkel cell carcinoma (MCC) is a rare neuroendocrine, cutaneous malignancy with poor prognosis once metastasized. The aim of this study was to conduct a systematic literature review to assess clinical outcomes associated with chemotherapy regimens in metastatic MCC.
MATERIALS & METHODS: Embase(®), MEDLINE(®), MEDLINE(®)-In-Process and CENTRAL were searched for studies published in January 2016.
RESULTS & CONCLUSION: Overall, the literature on chemotherapy in patients with metastatic MCC is sparse, with most studies being case series/reports. Across all studies, response rates ranged from 20 to 61%, with higher response rates in first-line setting (53-61%) versus second-line setting (23-45%). Among responders, duration of response was short (≤8 months) in both first- and second-line settings. There is a need for novel agents that can induce durable responses in metastatic MCC.

PMID: 28350180 [PubMed - as supplied by publisher]

[Skin cancers in kidney transplant recipients].

Fetched: March 29th, 2017, 1:00am EDT

[Skin cancers in kidney transplant recipients].

Wiad Lek. 2017;70(1):68-73

Authors: Bieryło A, Brzósko S, Laudańska E, Naumnik B

Abstract
Kidney transplantation is the best treatment for end-stage renal failure. It prolongs the patient's life, improves quality of life and reduces costs associated with renal replacement therapy. Increasingly, newer immunosuppressive regimens allow for the proper functioning of the transplanted organ for many years. The progress in transplantation, qualification patients in older age for the procedure and longer survival of kidney graft lead to an increase in the number of patients receiving immunosuppressive drugs. They are exposed to various side effects associated with long-term suppression of the immune system, including an increased risk of cancer development. The most common malignancies (40- 50%) diagnosed in renal transplant recipients are skin cancers. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most common types of tumors occurring in this population. The use of immunosuppression resulted in the increase of the incidence of tumors that in the general population are relatively rare such as melanoma, Merkel cell cancer, Kaposi's sarcoma, anogenital cancer as well as sebaceous carcinoma.

PMID: 28343197 [PubMed - in process]

Seeking Standards for the Detection of Merkel Cell Polyomavirus and its Clinical Significance.

Fetched: March 29th, 2017, 1:00am EDT

Seeking Standards for the Detection of Merkel Cell Polyomavirus and its Clinical Significance.

J Invest Dermatol. 2017 Apr;137(4):797-799

Authors: Eid M, Nguyen J, Brownell I

Abstract
Merkel cell carcinoma is a rare skin cancer associated with Merkel cell polyomavirus in most cases. Prior studies associating Merkel cell carcinoma viral status with prognosis have inconsistent findings. Moshiri et al. used multimodal virus detection to determine that the 81% of patients with virus-positive Merkel cell carcinoma tumors had earlier stage disease and better outcomes relative to virus-negative cases.

PMID: 28340681 [PubMed - in process]

Myroides bacteremia: A case report and concise review.

Fetched: March 25th, 2017, 1:00am EDT

Myroides bacteremia: A case report and concise review.

IDCases. 2017;8:34-36

Authors: Beharrysingh R

Abstract
Myroides species are bacteria found commonly in environmental sources, such as water and soil. Despite this, they are historically uncommon pathogens, tending to affect primarily immunocompromised hosts. Based on a review of the current cases listed in the U.S. National Institutes of Health's National Library of Medicine (Table 1), there have been 48 reported cases of infection to date, one third of which have been reported in only the last seven years. This report outlines a case of bacteremia caused by Myroides species occurring in a diabetic male on chemotherapy for Merkel cell cancer. Myroides species can be difficult to treat, many strains are resistant to several antibacterial classes, this patient was treated successfully with meropenem.

PMID: 28331806 [PubMed - in process]

Rapidly growing gastric metastasis of Merkel cell carcinoma, an unusual cause of melena.

Fetched: March 25th, 2017, 1:00am EDT

Rapidly growing gastric metastasis of Merkel cell carcinoma, an unusual cause of melena.

Acta Clin Belg. 2016 Aug;71(4):263-6

Authors: Hulstaert E, Smith V, Mielants H, Van Praet L, De Kock J, Lambrecht V, Rasschaert G, Van Belle S

Abstract
Merkel cell carcinoma (MCC) is an uncommon, highly aggressive neuroendocrine skin carcinoma that has a tendency for local recurrence and metastatic disease. We report a rare case of recurrent melena in a 77-year-old Caucasian male. Three years earlier, the patient had undergone a radical resection of a para-umbilical MCC. A repeat esophagogastroduodenoscopy proved necessary to identify rapidly proliferating gastric metastasis of MCC as the cause of bleeding.

PMID: 27075789 [PubMed - indexed for MEDLINE]

The role of imaging in the management of patients with nonmelanoma skin cancer: When is imaging necessary?

Fetched: March 24th, 2017, 1:00am EDT

The role of imaging in the management of patients with nonmelanoma skin cancer: When is imaging necessary?

J Am Acad Dermatol. 2017 Apr;76(4):591-607

Authors: Humphreys TR, Shah K, Wysong A, Lexa F, MacFarlane D

Abstract
When treating aggressive skin cancers, pre- and postoperative imaging provides important information for treatment planning and multidisciplinary cooperation of care. It is important for dermatologists to recognize the clinical scenarios where imaging is indicated in the management of skin cancer. We here address the most common indications for imaging in cutaneous oncology and how to best utilize the modalities available.

PMID: 28325389 [PubMed - in process]

The role of imaging in the management of patients with nonmelanoma skin cancer: Diagnostic modalities and applications.

Fetched: March 24th, 2017, 1:00am EDT

The role of imaging in the management of patients with nonmelanoma skin cancer: Diagnostic modalities and applications.

J Am Acad Dermatol. 2017 Apr;76(4):579-588

Authors: MacFarlane D, Shah K, Wysong A, Wortsman X, Humphreys TR

Abstract
While uncomplicated cases of nonmelanoma skin cancer can be treated with surgery, destruction, or topical therapy alone, advanced or neglected cases require more complex management decisions. Dermatologists and dermatologic surgeons should be familiar with the imaging techniques relevant to cutaneous oncology and their value in different clinical scenarios. Herein we review imaging modalities used in management of nonmelanoma skin cancer.

PMID: 28325388 [PubMed - in process]

Permalink for 'Copy number analysis by low coverage whole genome sequencing using ultra low-input DNA from formalin-fixed paraffin embedded tumor tissue.'

Copy number analysis by low coverage whole genome sequencing using ultra low-input DNA from formalin-fixed paraffin embedded tumor tissue.

Fetched: March 22nd, 2017, 1:00am EDT

Copy number analysis by low coverage whole genome sequencing using ultra low-input DNA from formalin-fixed paraffin embedded tumor tissue.

Genome Med. 2016 11 15;8(1):121

Authors: Kader T, Goode DL, Wong SQ, Connaughton J, Rowley SM, Devereux L, Byrne D, Fox SB, Mir Arnau G, Tothill RW, Campbell IG, Gorringe KL

Abstract
Unlocking clinically translatable genomic information, including copy number alterations (CNA), from formalin-fixed paraffin-embedded (FFPE) tissue is challenging due to low yields and degraded DNA. We describe a robust, cost-effective low-coverage whole genome sequencing (LC WGS) method for CNA detection using 5 ng of FFPE-derived DNA. CN profiles using 100 ng or 5 ng input DNA were highly concordant and comparable with molecular inversion probe (MIP) array profiles. LC WGS improved CN profiles of samples that performed poorly using MIP arrays. Our technique enables identification of driver and prognostic CNAs in archival patient samples previously deemed unsuitable for genomic analysis due to DNA limitations.

PMID: 27846907 [PubMed - indexed for MEDLINE]

Merkel cell polyomavirus IgG antibody levels are associated with progression to AIDS among HIV-infected individuals.

Fetched: March 16th, 2017, 4:04pm EDT

Merkel cell polyomavirus IgG antibody levels are associated with progression to AIDS among HIV-infected individuals.

Arch Virol. 2017 Apr;162(4):963-969

Authors: Vahabpour R, Nasimi M, Naderi N, Salehi-Vaziri M, Mohajel N, Sadeghi F, Keyvani H, Monavari SH

Abstract
The association of Merkel cell polyomavirus (MCPyV) with Merkel cell carcinoma (MCC) in immunocompromised individuals has been revealed in a number of surveys. The study of MCPyV specific antibody titers and viral loads in such patients has a great attraction for research groups interested in viral reactivation. In this cross-sectional study to evaluate MCPyV antibody titer, DNA prevalence and viral load in peripheral blood mononuclear cells (PBMCs), we examined 205 HIV-1 infected patients and 100 un-infected controls. The HIV-1 infected patients divided into two groups (HIV/AIDS and non-AIDS) according to their CD4 status. Total IgG antibody titer against MCPyV was analyzed by virus like particle (VLP)-based enzyme linked immunosorbent assay (ELISA). Presence of MCPyV-DNA in subject's PBMCs was examined by quantitative real-time PCR assay. Levels of anti-MCPyV IgG in HIV/AIDS patients were significantly higher than those in non-AIDS HIV-infected and control subjects (p value = <0.001). The prevalence rate of MCPyV-DNA in PBMCs of HIV/AIDS, non-AIDS HIV-infected and un-infected controls were 17%, 16%, and 14% respectively. The MCPyV viral load among the groups ranged between 0.15 to 2.9 copies/10(3)cells (median, 1.9 copies/10(3)cells), with no significant difference between the studied populations (p value = 0.3).

PMID: 28000050 [PubMed - indexed for MEDLINE]

Erratum to: Metastatic Merkel cell carcinoma response to nivolumab.

Fetched: March 15th, 2017, 1:00am EDT

Erratum to: Metastatic Merkel cell carcinoma response to nivolumab.

J Immunother Cancer. 2017;5:27

Authors: Walocko FM, Scheier BY, Harms PW, Fecher LA, Lao CD

Abstract
[This corrects the article DOI: 10.1186/s40425-016-0186-1.].

PMID: 28286652 [PubMed - in process]

Permalink for 'Detection of Merkel Cell Polyomavirus and Human Papillomavirus in Esophageal Squamous Cell Carcinomas and Non-Cancerous Esophageal Samples in Northern Iran.'

Detection of Merkel Cell Polyomavirus and Human Papillomavirus in Esophageal Squamous Cell Carcinomas and Non-Cancerous Esophageal Samples in Northern Iran.

Fetched: March 12th, 2017, 12:00am EST

Detection of Merkel Cell Polyomavirus and Human Papillomavirus in Esophageal Squamous Cell Carcinomas and Non-Cancerous Esophageal Samples in Northern Iran.

Pathol Oncol Res. 2016 Oct;22(4):667-72

Authors: Yahyapour Y, Sadeghi F, Alizadeh A, Rajabnia R, Siadati S

Abstract
Human papillomavirus (HPV) infection is one of the hypothesized causes of esophageal squamous cell carcinoma (ESCC), but the etiological association remains uncertain. It was postulated that other infectious agents together with HPV may increase the risk of ESCC. The current investigation aimed to explore the presence of a new human tumor virus, Merkel cell polyomavirus (MCPyV), together with HPV in ESCC tumors and non-cancerous esophageal samples in northern Iran. In total, 96 esophageal samples (51 with ESCC, and 45 without esophageal malignancy) were examined. HPV DNA was detected in esophageal specimens of 16 out of the 51 ESCC cases (31.4 %) and 20 out of the 45 non-cancerous samples (44.4 %). Untypable HPV genotypes were recognized in high rates in cancerous (75.0 %) and non-cancerous (55.0 %) esophageal specimens. MCPyV DNA was detected in esophageal specimens of 23 out of the 51 ESCC cases (45.1 %) and 16 out of the 45 non-cancerous samples (35.6 %). The mean MCPyV DNA copy number was 1.0 × 10(-5) ± 2.4 × 10(-5) and 6.0 × 10(-6) ± 1.3 × 10(-5) per cell in ESCC cases and non-cancerous samples, respectively. There was no statistically significant difference between cancerous and non-cancerous samples regarding mean MCPyV DNA load (P = 0.353). A bayesian logistic regression model adjusted to the location of esophageal specimen and MCPyV infection, revealed a significant association between HPV and odds of ESCC (OR, 2.45; 95 % CI: 1.01-6.16). This study provides the evidence of the detection of the MCPyV DNA at a low viral copy number in cancerous and non- cancerous esophageal samples.

PMID: 26879397 [PubMed - indexed for MEDLINE]

New developments in the biology and the treatment of metastatic Merkel cell carcinoma.

Fetched: March 12th, 2017, 12:00am EST

New developments in the biology and the treatment of metastatic Merkel cell carcinoma.

Curr Opin Oncol. 2017 Mar 09;:

Authors: Terheyden P, Becker JC

Abstract
PURPOSE OF REVIEW: Patients with stage IIIB und IV metastatic Merkel cell carcinoma (mMCC), who are not suitable candidates for surgery or radiotherapy, are unlikely to achieve lasting remission or tumor control by chemo or targeted therapy. In the majority of cases, the tumor arises from viral carcinogenesis associated with the Merkel cell polyomavirus (MCPyV). In MCPyV-negative tumors with a presumable ultraviolet carcinogenesis, a high mutational burden resulting in neoantigens was discovered. In two phase II clinical trials in either the first or second-line setting, a high response rate was observed for immunotherapies with antibodies blocking the programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) immune checkpoints.
RECENT FINDINGS: The response rate was 56% with the anti-PD-1 inhibitor pembrolizumab as a first-line and 32% with the anti-PD-L1 antibody avelumab used as second-line therapy. Both treatments were well tolerated. Treatment response was rapid and in most cases maintained during follow-up, which, however, is still rather short. Whether the MCPyV or the PD-L1 status is predictive for treatment response and progression-free survival is still ambiguous. Additionally, clinical criteria for patient selection for immunotherapy of mMCC have not yet been defined.
SUMMARY: PD-1/PD-L1 inhibition can be regarded as new first-line therapy for patients with mMCC not amendable by surgery and/or radiation.

PMID: 28282342 [PubMed - as supplied by publisher]

Reduced H3K27me3 expression in Merkel cell polyoma virus-positive tumors.

Fetched: March 12th, 2017, 12:00am EST

Reduced H3K27me3 expression in Merkel cell polyoma virus-positive tumors.

Mod Pathol. 2017 Mar 10;:

Authors: Busam KJ, Pulitzer MP, Coit DC, Arcila M, Leng D, Jungbluth AA, Wiesner T

Abstract
Merkel cell carcinoma is a primary cutaneous neuroendocrine carcinoma, which once metastatic is difficult to treat. Recent mutation analyses of Merkel cell carcinoma revealed a low number of mutations in Merkel cell polyomavirus-associated tumors, and a high number of mutations in virus-negative combined squamous cell and neuroendocrine carcinomas of chronically sun-damaged skin. We speculated that the paucity of mutations in virus-positive Merkel cell carcinoma may reflect a pathomechanism that depends on derangements of chromatin without alterations in the DNA sequence (epigenetic dysregulation). One central epigenetic regulator is the Polycomb repressive complex 2 (PRC2), which silences genomic regions by trimethylating (me3) lysine (K) 27 of histone H3, and thereby establishes the histone mark H3K27me3. Recent experimental research data demonstrated that PRC2 loss in mice skin results in the formation of Merkel cells. Prompted by these findings, we explored a possible contribution of PRC2 loss in human Merkel cell carcinoma. We examined the immunohistochemical expression of H3K27me3 in 35 Merkel cell carcinomas with pure histological features (22 primary and 13 metastatic lesions) and in 5 combined squamous and neuroendocrine carcinomas of the skin. We found a strong reduction of H3K27me3 staining in tumors with pure histologic features and virus-positive Merkel cell carcinomas. Combined neuroendocrine carcinomas had no or only minimal loss of H3K27me3 labeling. Our findings suggest that a PRC2-mediated epigenetic deregulation may play a role in the pathogenesis of virus-positive Merkel cell carcinomas and in tumors with pure histologic features.Modern Pathology advance online publication, 10 March 2017; doi:10.1038/modpathol.2017.8.

PMID: 28281550 [PubMed - as supplied by publisher]

Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.

Fetched: March 11th, 2017, 12:01am EST

Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.

Expert Opin Biol Ther. 2017 Apr;17(4):515-523

Authors: Hamilton G, Rath B

Abstract
INTRODUCTION: Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination. Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.

PMID: 28274143 [PubMed - in process]

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

Fetched: March 8th, 2017, 12:00am EST

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

Br J Dermatol. 2016 Apr;174(4):813-22

Authors: Samimi M, Molet L, Fleury M, Laude H, Carlotti A, Gardair C, Baudin M, Gouguet L, Maubec E, Avenel-Audran M, Esteve E, Wierzbicka-Hainaut E, Beneton N, Aubin F, Rozenberg F, Dupin N, Avril MF, Lorette G, Guyetant S, Coursaget P, Touzé A

Abstract
BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC.
OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease.
METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline.
RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis.
CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.

PMID: 26600395 [PubMed - indexed for MEDLINE]

Topics in histopathology of sweat gland and sebaceous neoplasms.

Fetched: March 5th, 2017, 12:00am EST

Topics in histopathology of sweat gland and sebaceous neoplasms.

J Dermatol. 2017 Mar;44(3):315-326

Authors: Ansai SI

Abstract
This article reviews several topics regarding sweat gland and sebaceous neoplasms. First, the clinicopathological characteristics of poroid neoplasms are summarized. It was recently reported that one-fourth of poroid neoplasms are composite tumors and one-fourth are apocrine type lesions. Recent progress in the immunohistochemical diagnosis of sweat gland neoplasms is also reviewed. CD117 can help to distinguish sweat gland or sebaceous tumors from other non-Merkel cell epithelial tumors of the skin. For immunohistochemical differential diagnosis between sweat gland carcinoma (SGC) other than primary cutanesous apocrine carcinoma and skin metastasis of breast carcinoma (SMBC), a panel of antibodies may be useful, including p63 (SGC(+) , SMBC(-) ), CK5/6 (SGC(+) , SMBC(-) ), podoplanin (SGC(+) , SMBC(-) ) and mammaglobin (SGC(-) , SMBC(+) ). Comparison of antibodies used for immunohistochemical diagnosis of sebaceous carcinoma (SC) suggests that adipophilin has the highest sensitivity and specificity. Some authors have found that immunostaining for survivin, androgen receptor and ZEB2/SIP1 has prognostic value for ocular SC, but not extraocular SC. In situ SC is rare, especially extraocular SC, but there have been several recent reports that actinic keratosis and Bowen's disease are the source of invasive SC. Finally, based on recent reports, classification of sebaceous neoplasms into three categories is proposed, which are sebaceoma (a benign neoplasm with well-defined architecture and no atypia), borderline sebaceous neoplasm (low-grade SC; an intermediate tumor with well-defined architecture and nuclear atypia) and SC (a malignant tumor with invasive growth and evident nuclear atypia).

PMID: 28256768 [PubMed - in process]

Ipilimumab has efficacy in metastatic Merkel Cell Carcinoma: a case series of five patients.

Fetched: March 5th, 2017, 12:00am EST

Ipilimumab has efficacy in metastatic Merkel Cell Carcinoma: a case series of five patients.

J Eur Acad Dermatol Venereol. 2017 Mar 03;:

Authors: Winkler JK, Dimitrakopoulou-Strauss A, Sachpekidis C, Enk A, Hassel JC

Abstract
Immunotherapy with immune checkpoint blockers such as the CTLA-4 antibody ipilimumab and PD-1 antibodies has revolutionized oncological treatment options(1) . MCC is an immunogenic tumor and the efficacy of PD-1 blockade has recently been demonstrated(2,3,4) . Here, we present a retrospective analysis of five patients with metastatic MCC individually treated with ipilimumab between 2012 and 2015. Administration of four cycles (3 mg/kg every three weeks) was planned. Informed consent was obtained from all patients. Patient characteristics are depicted in table 1. All patients had received previous surgical and radiation therapy before initiation of ipilimumab. This article is protected by copyright. All rights reserved.

PMID: 28256019 [PubMed - as supplied by publisher]

Intracranial pathway for dermal lymphatic drainage.

Fetched: March 4th, 2017, 12:00am EST

Intracranial pathway for dermal lymphatic drainage.

ANZ J Surg. 2016 Dec;86(12):1058-1059

Authors: Lo MF, Donahoe SR

PMID: 25060528 [PubMed - indexed for MEDLINE]

Permalink for 'Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What Is New in the 2017 WHO Blue Book for Tumors and Tumor-Like Lesions of the Neck and Lymph Nodes.'

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What Is New in the 2017 WHO Blue Book for Tumors and Tumor-Like Lesions of the Neck and Lymph Nodes.

Fetched: March 3rd, 2017, 12:00am EST

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What Is New in the 2017 WHO Blue Book for Tumors and Tumor-Like Lesions of the Neck and Lymph Nodes.

Head Neck Pathol. 2017 Feb 28;:

Authors: Katabi N, Lewis JS

Abstract
The World Health Organization (WHO) 2017 Classification of Head and Neck Tumors ("Blue Book") will now include a new chapter on tumors and tumor-like lesions of the neck and lymph nodes, which was not included in the previous edition. Tumors and tumor-like lesions, including a variety of cysts and metastases, can arise in any component in the neck, including soft tissue, lymph nodes, and developmental remnants. The pathology and clinical features of metastatic carcinoma of unknown primary in the head and neck has changed dramatically in the last several years. Many of these tumors which were previously diagnosed as unknown primary are now identified as oropharyngeal and nasopharyngeal carcinomas related to human papillomavirus (HPV), less commonly to Epstein-Barr virus (EBV) and occasionally even to Merkel cell polyomavirus. Many unusual features can arise in these metastases, such as undifferentiated morphology, extensive cystic change with central degeneration, gland formation, and even ciliated cells. Rarely, carcinoma in the neck can arise in association with a heterotopic tissue, primarily thyroid or salivary gland tissue. Tumor-like lesions include branchial cleft cysts, thyroglossal duct cyst, dermoid and teratoid cyst, and ranula. Pathologists should be familiar with the diagnostic features and clinicopathologic corrections of these neck lesions in order to correctly diagnosis them and to provide for proper clinical management. This article will briefly describe the pathologic and clinical features of these entities as they are covered in the new 2017 Blue Book.

PMID: 28247228 [PubMed - as supplied by publisher]

Permalink for 'Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?'

Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

Fetched: March 2nd, 2017, 12:00am EST

Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

J Nucl Med Technol. 2016 Jun;44(2):85-7

Authors: Basu S, Ranade R

Abstract
This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients.

PMID: 26471333 [PubMed - indexed for MEDLINE]

Molecular prevalence of Merkel cell polyomavirus in nonmelanoma skin cancer in a Brazilian population.

Fetched: February 28th, 2017, 5:13am EST

Molecular prevalence of Merkel cell polyomavirus in nonmelanoma skin cancer in a Brazilian population.

Clin Exp Dermatol. 2017 Feb 27;:

Authors: Bellott TR, Baez CF, Almeida SG, Venceslau MT, Zalis MG, Guimarães MA, Rochael MC, Luz FB, Varella RB, Almeida JR

Abstract
BACKGROUND: Merkel cell polyomavirus (MCPyV), a newly described oncogenic virus, has been found in association with tumours other than Merkel cell carcinoma (MCC). As yet, little is known about the involvement or influence of MCPyV on the development of these tumours and its prevalence in various populations.
AIM: To assess the prevalence of MCPyV DNA in cases of nonmelanoma skin cancer (NMSC).
METHODS: The prevalence of MCPyV DNA was assessed in 96 cases of NMSC in a Brazilian population comprising 76 subjects, and these results were correlated with epidemiological and demographical data.
RESULTS: MCPyV DNA was detected in 23 of 69 (33.3%) basal cell carcinomas, in 2 of 11 (18%) squamous cell carcinomas, 2 of 4 Bowen disease case, 0 of 1 MCC and 4 of 11 other skin disorders.
CONCLUSION: Despite the frequent detection of MCPyV DNA in NMSC, its possible role in the development of NMSC still needs further investigation.

PMID: 28239901 [PubMed - as supplied by publisher]

Metabolic assessment of Merkel cell carcinoma: the role of 18F-FDG PET/CT.

Fetched: February 28th, 2017, 5:13am EST

Metabolic assessment of Merkel cell carcinoma: the role of 18F-FDG PET/CT.

Nucl Med Commun. 2016 Aug;37(8):865-73

Authors: Ben-Haim S, Garkaby J, Primashvili N, Goshen E, Shapira R, Davidson T, Israel O, Epelbaum R

Abstract
OBJECTIVES: Merkel cell carcinoma (MCC) is a rare aggressive skin tumor associated with a high mortality rate. The present study evaluated the role of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in subsequent management of patients with MCC.
METHODS: A total of 101 consecutive F-FDG PET/CT studies of 46 patients with MCC (28 men, 68±15.4 years) were retrospectively evaluated and the role in clinical care was documented.
RESULTS: There were 40 positive studies (40%) in 28 patients (61%); of these, 33 studies (33%) in 27 patients (59%) showed metastatic disease. Fifty-two PET/CT studies (51%) in 23/46 (50%) patients were negative. Fifty-three studies (52%) were performed for staging or restaging in 41 patients, 29 scans (29%) were performed for routine follow-up in 10 patients, nine studies were carried out for suspected recurrent disease in eight patients, and 10 studies were carried out for assessment of response to therapy in seven patients. On the basis of PET/CT results, there was a change in disease stage in 12 studies in 12 patients (26%) and further change in the management of seven patients (15%). Overall, 2/29 routine follow-up studies were positive with further impact on management in one patient.
CONCLUSION: F-FDG PET-CT altered the stage of one of four patients and changed the management of one of seven MCC patients. In the majority of patients, a negative F-FDG PET-CT study excluded active MCC with a high degree of confidence. PET-CT contributed toward patient management when performed for staging and restaging, monitoring response to treatment, and suspected recurrent disease, but not in the routine follow-up of asymptomatic patients with MCC.

PMID: 27092665 [PubMed - indexed for MEDLINE]

Patterns of lymphatic spread and the management of eyelid carcinomas.

Fetched: February 28th, 2017, 5:13am EST

Patterns of lymphatic spread and the management of eyelid carcinomas.

Auris Nasus Larynx. 2016 Dec;43(6):666-71

Authors: Hashimoto K, Yasumatsu R, Toh S, Shiratsuchi H, Yoshida T, Nishiyama K, Yoshikawa H, Nakashima T, Nakagawa T

Abstract
OBJECTIVE: Eyelid carcinomas are rare, and the management strategy of regional lymph node metastasis linked to eyelid carcinomas has not been standardized to date. The aim of the present study was to analyze the patterns of regional metastasis and to assess the optimal extent of surgical treatment for lymph node metastasis of eyelid carcinoma.
METHODS: This study was a retrospective review of patient data from a single institution. From a series of 268 eyelid carcinomas, we selected the 21 patients with lymph node metastasis, and we analyzed the patterns of lymphatic spread, approach to treatment and outcomes.
RESULTS: The most common histological type of eyelid carcinoma with regional metastasis was sebaceous carcinoma (17/21, 81.0%). Submandibular area metastases were seen only in the patients with the primary tumor originating in the medial half of the eyelid, but parotid area metastases were seen in both the patients whose tumors had a medial-half origin and those with a lateral-half origin. Although 11 of the 16 patients with parotid-area metastases underwent a tumorectomy or superficial parotidectomy (which resulted in four cases of recurrence in the parotid area), none of the five patients who underwent a total parotidectomy developed parotid-area recurrence. The incidence of regional recurrence of the patients who received adjuvant radiotherapy (14.3%) was lower than that of the patients without adjuvant radiotherapy (57.1%).
CONCLUSION: Continued surveillance and optimal management of regional lymph node metastases are important for the control and survival of eyelid carcinomas.

PMID: 26965587 [PubMed - indexed for MEDLINE]

'Awareness Can Save a Life' - Argonaut Online

Posted: June 21st, 2017, 6:40pm EDT

Argonaut Online

'Awareness Can Save a Life'
Argonaut Online
After her 2005 neuroendocrine cancer diagnosis, classical pianist Giovanna Imbesi underwent two difficult surgeries to remove the tumors in her intestines and liver. Worse even than the pain for Imbesi was the fear. “Doctors can give you pain meds ...

DOTmed.com - Research presented at SNMMI meeting highlights ... - DOTmed.com

Posted: June 16th, 2017, 9:56am EDT

DOTmed.com - Research presented at SNMMI meeting highlights ...
DOTmed.com
Reston, Va. – More than 5,000 physicians, technologists, scientists and exhibitors gathered for the Society of Nuclear Medicine and Molecular Imaging's ...

and more »

Orphan drug improves quality of life for patients with malignant NET gut tumors - DOTmed.com

Posted: June 14th, 2017, 12:35pm EDT

DOTmed.com

Orphan drug improves quality of life for patients with malignant NET gut tumors
DOTmed.com
An expanded trial of a radiolabeled somatostatin analogs (SSA) treatment protocol has shown significant promise in improving the quality of life for people with neuroendocrine tumors (NET) most common to the intestinal tract. Study findings were ...

NTR Is the New SSTR? Perspective for Neurotensin Receptor 1 (NTR)–Directed Theranostics - Journal of Nuclear Medicine

Posted: June 1st, 2017, 7:17am EDT

NTR Is the New SSTR? Perspective for Neurotensin Receptor 1 (NTR)–Directed Theranostics
Journal of Nuclear Medicine
¹⁷⁷Lu-DOTATATE for RLT of metastatic neuroendocrine tumors proved highly efficacious, with a near 80% risk reduction for disease progression or death in a recently published prospective randomized international multicenter trial (6). ¹⁷⁷Lu-PSMA led to ...

Learning to Speak Up With Cancer - Curetoday.com

Posted: May 31st, 2017, 10:39am EDT

Curetoday.com

Learning to Speak Up With Cancer
Curetoday.com
I recently had the privilege of moderating a panel discussion about what stands in the way of patient-physician communications about neuroendocrine tumors (or NET) and carcinoid syndrome. The discussion was eye-opening. Conversations between a ...

Neuroendocrine Tumor Treatment Market to Surpass US$ 2.9 Billion ... - Digital Journal

Posted: May 29th, 2017, 11:00am EDT

Digital Journal

Neuroendocrine Tumor Treatment Market to Surpass US$ 2.9 Billion by 2025, Underpinned by Increasing Incidence of ...
Digital Journal
The Global Neuroendocrine Tumor Treatment Market was valued at US$ 1,197.3 million in 2016 and is projected to expand at a CAGR of 10.5% during the forecast period (2017–2025), as highlighted in a new report published by Coherent Market Insights.

and more »

Ross D. Handahl, 64, St. Cloud - WJON News

Posted: May 19th, 2017, 3:26pm EDT

WJON News

Ross D. Handahl, 64, St. Cloud
WJON News
Ross Handahl Memorial services will be at 11AM Monday, May 22, 2017 at Bethlehem Lutheran Church in St. Cloud for Ross Handahl, age 64, of St. Cloud who passed away peacefully on Thursday at the St. Cloud Hospital. Visitation will be Sunday May 21, ...

The Voice of the Community: News from NORD and its Member Organizations – May 2017 - Rare Disease Report

Posted: May 16th, 2017, 1:23pm EDT

Rare Disease Report

The Voice of the Community: News from NORD and its Member Organizations – May 2017
Rare Disease Report
The 2017 Neuroendocrine Tumor Research Foundation grants have been announced, infusing $4 million of new funding into neuroendocrine tumor research to drive development and application of precision therapies. This is the largest commitment NETRF ...

Netherlands Cancer Institute selects PLANET Dose for radionuclide-based therapies - DOTmed.com

Posted: May 16th, 2017, 8:57am EDT

Netherlands Cancer Institute selects PLANET Dose for radionuclide-based therapies
DOTmed.com
New radionuclide therapies, in particular for neuroendocrine tumors using 177Lu-peptide, are showing promising results. Advanced and personalized 3D dosimetry, used in planning and post-treatment stages as well as for therapy response assessment, ...

Permalink for 'The Impact of Somatostatin Receptor–Directed PET/CT on the Management of Patients with Neuroendocrine Tumor: A ... - Journal of Nuclear Medicine'

The Impact of Somatostatin Receptor–Directed PET/CT on the Management of Patients with Neuroendocrine Tumor: A ... - Journal of Nuclear Medicine

Posted: May 1st, 2017, 12:30pm EDT

The Impact of Somatostatin Receptor–Directed PET/CT on the Management of Patients with Neuroendocrine Tumor: A ...
Journal of Nuclear Medicine
Somatostatin receptor (SSTR) imaging is widely used for guiding the management of neuroendocrine tumor (NET) patients. ⁶⁸Ga-DOTATATE approval by the U.S. Food and Drug Administration has triggered widespread clinical interest in SSTR PET/CT ...

Comparison of Empiric Versus Dosimetry-Guided Radioiodine Therapy: The Devil Is in the Details - Journal of Nuclear Medicine

Posted: May 1st, 2017, 12:30pm EDT

Comparison of Empiric Versus Dosimetry-Guided Radioiodine Therapy: The Devil Is in the Details
Journal of Nuclear Medicine
An activity of 3,700 MBq, or multiples thereof, was subsequently administered for the treatment of adult and pediatric neuroendocrine tumors using ¹³¹I-metaiodobenzylguanidine, ⁹⁰Y-DOTATOC, or ¹⁷⁷Lu-DOTATATE; for the initial treatment of liver ...

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Permalink for 'Parametric Net Influx Rate Images of 68 Ga-DOTATOC and 68 Ga-DOTATATE: Quantitative Accuracy and Improved ... - Journal of Nuclear Medicine'

Parametric Net Influx Rate Images of 68 Ga-DOTATOC and 68 Ga-DOTATATE: Quantitative Accuracy and Improved ... - Journal of Nuclear Medicine

Posted: May 1st, 2017, 12:30pm EDT

Parametric Net Influx Rate Images of 68 Ga-DOTATOC and 68 Ga-DOTATATE: Quantitative Accuracy and Improved ...
Journal of Nuclear Medicine
⁶⁸Ga-DOTATOC and ⁶⁸Ga-DOTATATE are radiolabeled somatostatin analogs used for the diagnosis of somatostatin receptor–expressing neuroendocrine tumors (NETs), and SUV measurements are suggested for treatment monitoring. However, changes in ...

Dramatic Jump in Incidence of NETs Over Past 4 Decades - Medscape

Posted: April 27th, 2017, 9:08am EDT

Medscape

Dramatic Jump in Incidence of NETs Over Past 4 Decades
Medscape
During the past 4 decades, the incidence and prevalence of neuroendocrine tumors (NETs) have dramatically increased, but the researchers believe the increase is related to diagnostic advances. The new finding is published online April 27 in JAMA ...

Hepatic Lesions in a Cirrhotic Liver: Primary or Metastases? - Journal of Nuclear Medicine Technology (subscription)

Posted: March 5th, 2017, 7:15am EST

Hepatic Lesions in a Cirrhotic Liver: Primary or Metastases?
Journal of Nuclear Medicine Technology (subscription)
Medullary thyroid carcinoma is a neuroendocrine tumor of the parafollicular cells (C cells), which secrete calcitonin and also carcinoembryonic antigen. Somatostatin receptor scintigraphy is an important tool in staging of neuroendocrine tumors ...

Hepatic Lesions in a Cirrhotic Liver: Primary or Metastases? - Journal of Nuclear Medicine Technology (subscription)

Posted: March 3rd, 2017, 7:18am EST

Permalink for 'F-FDG and Multimodality Anatomic Imaging in Metastatic Neuroendocrine Tumors of Unknown Primary in a PRRT ... - Journal of Nuclear Medicine Technology (subscription)'

F-FDG and Multimodality Anatomic Imaging in Metastatic Neuroendocrine Tumors of Unknown Primary in a PRRT ... - Journal of Nuclear Medicine Technology (subscription)

Posted: March 3rd, 2017, 7:18am EST

MIB-1 Index–Stratified Assessment of Dual-Tracer PET/CT with ...
Journal of Nuclear Medicine Technology (subscription)
For correspondence or reprints contact: Sandip Basu, Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Jerbai ...

and more »

Triple Therapy Potent Approach in Aggressive Skin Cancer - Medscape

Posted: June 19th, 2017, 9:17am EDT

Medscape

Triple Therapy Potent Approach in Aggressive Skin Cancer
Medscape
CHICAGO — A novel cellular approach that recruits three separate pathways involved in the oncogenesis of Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer, is leading to unprecedented and seemingly durable objective responses in ...

Top 5 FDA Approvals Last Month - Specialty Pharmacy Times

Posted: June 4th, 2017, 9:45am EDT

Top 5 FDA Approvals Last Month
Specialty Pharmacy Times
The drug was initially approved in March 2017 for the treatment of Merkel cell carcinoma in patients aged 12 years and older. The first medication to be indicated for this purpose, Bavencio is designed prevent tumor cells from using programmed death ...

Polyomavirus Hijacks Motor Kinesin-1 To Invade Cells - ReliaWire

Posted: June 3rd, 2017, 11:09pm EDT

ReliaWire

Polyomavirus Hijacks Motor Kinesin-1 To Invade Cells
ReliaWire
The findings could aid the search for new treatments or preventive strategies against the problems that polyomaviruses can cause, including the deadly skin cancer Merkel cell carcinoma, and the fatal problems in people who are immuno-compromised ...

5 New FDA Approvals to Know from May 2017 - Pharmacy Times

Posted: June 2nd, 2017, 9:53am EDT

5 New FDA Approvals to Know from May 2017
Pharmacy Times
The drug was initially approved in March 2017 for the treatment of Merkel cell carcinoma in patients aged 12 years and older. The first medication to be indicated for this purpose, Bavencio is designed prevent tumor cells from using programmed death ...

Polyomavirus Hijacks Motor Kinesin-1 To Invade Cells - ReliaWire

Posted: June 2nd, 2017, 9:06am EDT

ReliaWire

How polyomavirus tricks our cells into helping it build its invasion route - Science Daily

Posted: May 25th, 2017, 9:24am EDT

How polyomavirus tricks our cells into helping it build its invasion route
Science Daily
The findings could aid the search for new treatments or preventive strategies against the problems that polyomaviruses can cause, including the deadly skin cancer called Merkel cell carcinoma, and fatal problems in people who have weak immune systems ...

Permalink for 'Merck KGaA, Darmstadt, Germany, and Pfizer to Present Data Highlighting Potential of Avelumab in Challenging ... - PharmiWeb.com (press release)'

Merck KGaA, Darmstadt, Germany, and Pfizer to Present Data Highlighting Potential of Avelumab in Challenging ... - PharmiWeb.com (press release)

Posted: May 19th, 2017, 3:33pm EDT

Merck KGaA, Darmstadt, Germany, and Pfizer to Present Data Highlighting Potential of Avelumab in Challenging ...
PharmiWeb.com (press release)
"We're particularly excited to share the latest avelumab data in both metastatic Merkel cell carcinoma in the first-line setting and previously treated metastatic urothelial carcinoma with the cancer community." "Our data at ASCO this year underscore ...

Avelumab: Another Immunotherapy for Bladder Cancer - Medscape

Posted: May 9th, 2017, 11:45am EDT

Medscape

Avelumab: Another Immunotherapy for Bladder Cancer
Medscape
Avelumab was recently approved for the first time worldwide for use in the treatment of Merkel cell carcinoma, a rare and aggressive type of skin cancer. The new drug joins three similar immunotherapies already approved for similar indications, and ...

and more »

PAF Adds Support for Merkel Cell Carcinoma Patients in Financial Aid Fund Program - Patient Advocate Foundation

Posted: April 4th, 2017, 7:33am EDT

PAF Adds Support for Merkel Cell Carcinoma Patients in Financial Aid Fund Program
Patient Advocate Foundation
Patient Advocate Foundation reaffirms its commitment to providing patients with transportation assistance by announcing a new grant for those diagnosed with a rare form of skin cancer, Merkel cell carcinoma (MCC). The fund will join PAF's existing ...

PAF Adds Support for Merkel Cell Carcinoma Patients in Financial Aid Fund Program - Patient Advocate Foundation

Posted: April 4th, 2017, 7:33am EDT

BAVENCIO® (avelumab) Approved for the Treatment of Metastatic Merkel Cell Carcinoma, Available for Order at ... - Digital Journal

Posted: March 29th, 2017, 7:02am EDT

BAVENCIO® (avelumab) Approved for the Treatment of Metastatic Merkel Cell Carcinoma, Available for Order at ...
Digital Journal
... U.S. Food and Drug Administration (FDA) on March 23, 2017, BAVENCIO is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).

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Permalink for 'FDA Grants Approval for BAVENCIO® (avelumab), the First Immunotherapy Approved for Metastatic Merkel Cell ... - PharmiWeb.com (press release)'

FDA Grants Approval for BAVENCIO® (avelumab), the First Immunotherapy Approved for Metastatic Merkel Cell ... - PharmiWeb.com (press release)

Posted: March 25th, 2017, 3:22pm EDT

FDA Grants Approval for BAVENCIO® (avelumab), the First Immunotherapy Approved for Metastatic Merkel Cell ...
PharmiWeb.com (press release)
“At the heart of this FDA approval is our drive to make a meaningful difference for patients with hard-to-treat cancers like metastatic Merkel cell carcinoma,” said Belén Garijo, CEO Healthcare and Member of the Executive Board of Merck. “BAVENCIO's ...

Avelumab Approved For Metastatic Merkel Cell Carcinoma Treatment - ReliaWire

Posted: March 25th, 2017, 11:19am EDT

ReliaWire

Avelumab Approved For Metastatic Merkel Cell Carcinoma Treatment
ReliaWire
Accelerated approval has been granted by the FDA for the checkpoint inhibitor avelumab (brand name Bavencio) for the treatment of patients with metastatic Merkel cell carcinoma (MCC), including those who have not received prior chemotherapy. Avelumab ...

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Drugs and Targets Bavencio receives accelerated approval for Merkel cell carcinoma - The Cancer Letter Publications

Posted: March 24th, 2017, 5:37pm EDT

Drugs and Targets Bavencio receives accelerated approval for Merkel cell carcinoma
The Cancer Letter Publications
FDA granted an accelerated approval to Bavencio (avelumab) for the treatment of patients 12 years and older with metastatic Merkel cell carcinoma. The agent is sponsored by EMD Serono Inc., a biopharmaceutical business of Merck KGaA and Pfizer Inc.

and more »

Tom and Karen Judd - Fred Hutch News Service

Posted: March 24th, 2017, 12:35pm EDT

Fred Hutch News Service

Tom and Karen Judd
Fred Hutch News Service
Tom Judd, now 66, entered a clinical trial at Fred Hutch in March 2015 to test an experimental drug for a rare and deadly cancer, Merkel cell carcinoma. Today the drug, avelumab, has become the first treatment for metastatic MCC to be approved by the ...

NantKwest Announces FDA Grant of Orphan Drug Designation for the Company's aNK Natural Killer Cell Therapy in ... - Digital Journal

Posted: March 20th, 2017, 5:03am EDT

NantKwest Announces FDA Grant of Orphan Drug Designation for the Company's aNK Natural Killer Cell Therapy in ...
Digital Journal
NantKwest's aNK cell therapy is currently in Phase II clinical trials at clinical sites in the United States treating subjects with metastatic or locally advanced Merkel cell carcinoma. This protocol was recently amended to include ALT-803, an IL-15 ...

and more »

Yuan Chang and Patrick Moore win prize for the discovery of two cancer viruses - EurekAlert (press release)

Posted: March 14th, 2017, 7:31am EDT

Yuan Chang and Patrick Moore win prize for the discovery of two cancer viruses
EurekAlert (press release)
MCV is responsible for causing Merkel cell carcinoma, an extremely rare, malignant skin cancer. Chang and Moore refined their strategy in the search for the virus causing Merkel cell carcinoma. Fourteen years after the discovery of HHV-8, their ...

Skin Cancer Immune Responses in Virus-Related Skin Cancer Suggest Immunotherapy Strategy - The Cancer Letter Publications

Posted: February 28th, 2017, 12:47pm EST

Skin Cancer Immune Responses in Virus-Related Skin Cancer Suggest Immunotherapy Strategy
The Cancer Letter Publications
Researchers at the Fred Hutchinson Cancer Research Center and the University of Washington say a new study suggests ways to improve immune therapy for certain cancers including a virus-associated form of Merkel cell carcinoma, a rare, aggressive skin ...

Permalink for 'FDA Accepts the Biologics License Application for Avelumab for the Treatment of Metastatic Urothelial Carcinoma for ... - PharmiWeb.com (press release)'

FDA Accepts the Biologics License Application for Avelumab for the Treatment of Metastatic Urothelial Carcinoma for ... - PharmiWeb.com (press release)

Posted: February 28th, 2017, 5:08am EST

FDA Accepts the Biologics License Application for Avelumab for the Treatment of Metastatic Urothelial Carcinoma for ...
PharmiWeb.com (press release)
"Taken together with last year's filing for metastatic Merkel cell carcinoma, this BLA acceptance confirms our rapid and continued progress in the clinical development of avelumab," said Luciano Rossetti, M.D., Executive Vice President, Global Head of ...

TSET clinical trials program offers groundbreaking cancer treatment to people across the region - NewsOK.com

Posted: February 10th, 2017, 3:20pm EST

NewsOK.com

TSET clinical trials program offers groundbreaking cancer treatment to people across the region
NewsOK.com
Stover battles a rare and aggressive form of cancer called Merkel cell carcinoma. He is a participant in the Oklahoma TSET Phase I Clinical Trials Program at the Stephenson Cancer Center in Oklahoma City. The trial provides an opportunity for cancer ...

and more »

Permalink for 'QUILT-3.045: NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After PD-L1 Therapy'

QUILT-3.045: NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After PD-L1 Therapy

Posted: May 23rd, 2017, 10:00am EDT

Condition: Merkel Cell Carcinoma
Interventions: Biological: Avelumab; Biological: Bevacizumab; Drug: Capecitabine; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: 5-fluorouracil; Drug: Leucovorin; Drug: nab-Paclitaxel; Drug: omega-3-acid ethyl esters; Radiation: Stereotactic Body Radiation Therapy; Biological: ALT-803; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-6301; Biological: haNK
Sponsor: NantCell, Inc.
Not yet recruiting - verified May 2017

Permalink for 'Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies'

Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies

Posted: April 19th, 2017, 10:00am EDT

Conditions: Advanced Malignancies; Metastatic Malignancies
Interventions: Drug: INCAGN01876; Drug: Nivolumab; Drug: Ipilimumab
Sponsor: Incyte Corporation
Recruiting - verified May 2017

Expanded Access to Avelumab for Treatment of Metastatic Merkel Cell Carcinoma (mMCC)

Posted: March 20th, 2017, 10:00am EDT

Condition: Metastatic Merkel Cell Carcinoma
Intervention: Drug: Avelumab
Sponsors: Merck KGaA; Pfizer
Available - verified March 2017

Permalink for 'A Study of the Safety, Tolerability and Pharmacokinetics of ABBV-368 as a Single Agent and Combination in Subjects With Locally Advanced or Metastatic Solid Tumors'

A Study of the Safety, Tolerability and Pharmacokinetics of ABBV-368 as a Single Agent and Combination in Subjects With Locally Advanced or Metastatic Solid Tumors

Posted: March 2nd, 2017, 10:00am EST

Condition: Advanced or Metastatic Solid Tumors
Interventions: Drug: ABBV-368; Drug: Nivolumab
Sponsor: AbbVie
Recruiting - verified May 2017

Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma

Posted: March 1st, 2017, 10:00am EST

Conditions: Merkel Cell Carcinoma; Skin Cancer
Interventions: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Bristol-Myers Squibb
Recruiting - verified March 2017

CUDC-907 Treatment in People With Metastatic and Locally Advanced Thyroid Cancer

Posted: December 22nd, 2016, 10:00am EST

Conditions: Thyroid Neoplasms; Poorly Differentiated and Undifferentiated Thyroid Cancer; Differentiated Thyroid Cancer
Intervention: Drug: CUDC-907
Sponsor: National Cancer Institute (NCI)
Recruiting - verified April 12, 2017

A Study of ABBV-181 in Participants With Advanced Solid Tumors

Posted: December 15th, 2016, 10:00am EST

Condition: Advanced Solid Tumors
Intervention: Drug: ABBV-181
Sponsor: AbbVie
Recruiting - verified May 2017

$Permalink for 'Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers'$

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

Posted: November 30th, 2016, 10:00am EST

Conditions: Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma
Interventions: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: Talimogene Laherparepvec
Sponsor: National Cancer Institute (NCI)
Not yet recruiting - verified May 2017

PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers

Posted: October 13th, 2016, 10:00am EDT

Conditions: Neuroendocrine Tumors; Carcinoma, Small Cell Lung; Carcinoma, Large Cell Lung; Merkel Cell Carcinoma; Pheochromocytoma; Paraganglioma; Thyroid Cancer, Medullary; Neuroendocrine Carcinoma
Intervention: Drug: PEN-221
Sponsor: Tarveda Therapeutics
Recruiting - verified May 2017

Permalink for 'A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers'

A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers

Posted: December 18th, 2015, 10:00am EST

Conditions: Head and Neck Squamous Cell Carcinoma; Breast Cancer; Sarcoma; Merkel Cell Carcinoma; Cutaneous T-Cell Lymphoma; Melanoma; Renal Cancer; Bladder Cancer; Prostate Cancer
Interventions: Drug: Durvalumab; Drug: Tremelimumab; Drug: Poly ICLC
Sponsors: Ludwig Institute for Cancer Research; MedImmune LLC; Cancer Research Institute, New York City
Recruiting - verified April 2017

MLN0128 in Recurrent/Metastatic Merkel Cell Carcinoma

Posted: July 28th, 2015, 10:00am EDT

Condition: Merkel Cell Carcinoma
Intervention: Drug: MLN0128
Sponsors: Dana-Farber Cancer Institute; Millennium Pharmaceuticals, Inc.
Recruiting - verified May 2017

Studies of Dermatologic Diseases Biospecimen Acquisition Protocol

Posted: June 12th, 2015, 10:00am EDT

Conditions: Dermatologic Conditions; Healthy Volunteers; Normal Volunteers; Carcinoma, Merkel Cell
Intervention:
Sponsor: National Cancer Institute (NCI)
Recruiting - verified April 20, 2017

Permalink for 'Study of Mutation-Targeted Therapy With Sunitinib or Everolimus in People With Advanced Low- or Intermediate-Grade Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas With or Without Cytoreductive Surgery'

Study of Mutation-Targeted Therapy With Sunitinib or Everolimus in People With Advanced Low- or Intermediate-Grade Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas With or Without Cytoreductive Surgery

Posted: December 11th, 2014, 10:00am EST

Condition: Neuroendocrine Tumors
Interventions: Drug: Sunitinib; Drug: Everolimus; Procedure: Surgery
Sponsor: National Cancer Institute (NCI)
Recruiting - verified April 18, 2017

Evaluation of 68Gallium-DOTATATE PET/CT for Detecting Neuroendocrine Tumors

Posted: October 18th, 2013, 10:00am EDT

Conditions: Neuroendocrine Tumors; Von Hippel-Lindau Syndrome; Hippel-Lindau Disease
Interventions: Drug: 68Gallium DOTATATE; Procedure: Radio-guided surgery
Sponsor: National Cancer Institute (NCI)
Recruiting - verified January 17, 2017

SwissNET - a Registry for Neuroendocrine Tumours in Switzerland

Posted: December 24th, 2009, 10:00am EST

Conditions: Neuroendocrine Tumors; Carcinoid Tumor
Intervention:
Sponsors: University Hospital Inselspital, Berne; Cantonal Hospital of St. Gallen; University Hospital, Basel, Switzerland; University Hospital, Geneva; University of Lausanne Hospitals; University of Zurich; Triemlispital Zurich; Spitalnetz Bern; Ente Ospedaliero Cantonale, Bellinzona; Luzerner Kantonsspital; Kantonsspital Liestal; Kantonsspital Graubuenden; Spital Limmattal Schlieren; Waid City Hospital, Zurich; Spital STS AG
Recruiting - verified April 2017

Yttrium-90 DOTA-TOC Intra-arterial (IA) Peptide Receptor Radionuclide Therapy (PRRT) for Neuroendocrine Tumor

Posted: June 20th, 2017, 10:00am EDT

Condition: Neuroendocrine Tumor
Interventions: Drug: 90Y-DOTA-TOC; Drug: 68Ga-DOTA-TOC
Sponsor: Thomas Hope
Not yet recruiting - verified June 2017

Pembrolizumab for the Treatment of Recurrent High Grade Neuroendocrine Carcinoma

Posted: June 13th, 2017, 10:00am EDT

Condition: Neuroendocrine Tumors
Intervention: Drug: Pembrolizumab Injection
Sponsors: University of Utah; Merck Sharp & Dohme Corp.
Not yet recruiting - verified June 2017

PD-L1 Inhibition as ChecKpoint Immunotherapy for NeuroEndocrine Phenotype Prostate Cancer

Posted: June 5th, 2017, 10:00am EDT

Condition: Prostate Cancer
Intervention: Drug: Avelumab
Sponsor: Andrew J. Armstrong, MD
Not yet recruiting - verified June 2017

Teaching Skin Self-Examination to First-degree Relatives of Melanoma Patients Using Mobile App Technology

Posted: June 2nd, 2017, 10:00am EDT

Condition: Melanoma
Intervention: Other: Eviderma Smart Phone Teledermatology Application (Eviderma)
Sponsors: Northwestern University; Vibrent Health; National Institutes of Health (NIH)
Not yet recruiting - verified May 2017

Tissue Predictors of Abiraterone Benefit

Posted: June 1st, 2017, 10:00am EDT

Condition: Metastatic Castration-resistant Prostate Cancer
Intervention:
Sponsors: Tianjin Medical University Second Hospital; Tianjin Medical University General Hospital; Tianjin Medical University Cancer Institute and Hospital; Beijing Chao Yang Hospital; The Second Hospital of Hebei Medical University; Affiliated Hospital of Hebei University
Recruiting - verified June 2017

Evaluation of Pathway Modulation by Raf, MEK, & Kinase Inhibitors

Posted: June 1st, 2017, 10:00am EDT

Conditions: Metastatic Cancer; Melanoma; Colon Cancer; Differentiated Thyroid Cancer; Hepatocellular Carcinoma; Renal Cell Carcinoma; Metastatic Melanoma; HCC; Metastatic Colon Cancer
Intervention: Other: Solar Simulator
Sponsor: University of Arizona
Recruiting - verified June 2017

Permalink for 'A Study Evaluating Cobimetinib (Targeted Therapy) Plus Atezolizumab (Immunotherapy) in Participants With Advanced Melanoma Whose Cancer Has Worsened During or After Treatment With Previous Immunotherapy'

A Study Evaluating Cobimetinib (Targeted Therapy) Plus Atezolizumab (Immunotherapy) in Participants With Advanced Melanoma Whose Cancer Has Worsened During or After Treatment With Previous Immunotherapy

Posted: June 1st, 2017, 10:00am EDT

Condition: Malignant Melanoma
Interventions: Drug: Atezolizumab; Drug: Cobimetinib; Drug: Atezolizumab
Sponsor: Hoffmann-La Roche
Recruiting - verified June 2017

Two Cancers, One Gene. Why Some People in Families Develop Melanoma or Pancreas Cancer, While Still Others Never Develop Cancer.

Posted: May 31st, 2017, 10:00am EDT

Conditions: Pancreas Cancer; Melanoma
Intervention:
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Recruiting - verified June 2017

Study of BEvacizumab in Combination With ATezolizumab in Patients With Untreated Melanoma Brain Metastases

Posted: May 31st, 2017, 10:00am EDT

Condition: Melanoma and Other Malignant Neoplasms of Skin
Interventions: Behavioral: Neurocognitive Exam; Behavioral: Questionnaires; Drug: Bevacizumab; Drug: Atezolizumab
Sponsors: M.D. Anderson Cancer Center; Genentech, Inc.
Recruiting - verified June 2017

Randomized Controlled Trial of Preoperative Alpha Blockade for Pheochromocytoma

Posted: May 31st, 2017, 10:00am EDT

Conditions: Pheochromocytoma; Paraganglioma
Interventions: Drug: Phenoxybenzamine; Drug: Doxazosin
Sponsor: University of California, Los Angeles
Recruiting - verified June 2017

Permalink for 'Prevention of Neovascular Glaucoma by Intravitreal Injections of Anti-VEGF in Patients Treated With Proton Therapy for a Large Choroidal Melanoma'

Prevention of Neovascular Glaucoma by Intravitreal Injections of Anti-VEGF in Patients Treated With Proton Therapy for a Large Choroidal Melanoma

Posted: May 29th, 2017, 10:00am EDT

Condition: Ocular Melanoma
Interventions: Drug: Aflibercept Injection; Drug: False injection
Sponsor: Centre Hospitalier Universitaire de Nice
Not yet recruiting - verified May 2017

The Study of JS001 Compared to High-Dose Interferon In Patients With Mucosal Melanoma That Has Been Removed by Surgery

Posted: May 27th, 2017, 10:00am EDT

Condition: Mucosal Melanoma
Interventions: Biological: humanized anti-PD-1 monoclonal antibody; Biological: high-dose recombinant interferon a-2B
Sponsor: Shanghai Junshi Bioscience Co.,Ltd.
Recruiting - verified May 2017

Exercise as a Supportive Measure for Patients Undergoing Checkpoint-inhibitor Treatment

Posted: May 24th, 2017, 10:00am EDT

Conditions: PD-1 Antibodies; Exercise; Melanoma
Intervention: Behavioral: Resistance and Endurance Exercise
Sponsors: University Hospital Heidelberg; Department of Dermatology, Heidelberg University Hospital
Not yet recruiting - verified May 2017

Permalink for 'A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer'

A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer

Posted: May 23rd, 2017, 10:00am EDT

Conditions: Paraganglioma; Gastrointestinal Stromal Tumors; Carcinoma, Renal Cell; Renal Neoplasms; Pheochromocytoma
Intervention: Drug: SGI-110 (guadecitabine)
Sponsor: National Cancer Institute (NCI)
Not yet recruiting - verified April 13, 2017

QUILT-3.045: NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After PD-L1 Therapy

Posted: May 23rd, 2017, 10:00am EDT

Permalink for 'QUILT-3.046: NANT Melanoma Vaccine: Combination Immunotherapy in Subjects With Melanoma Who Have Progressed On or After Chemotherapy and PD-1/PD-L1 Therapy'

QUILT-3.046: NANT Melanoma Vaccine: Combination Immunotherapy in Subjects With Melanoma Who Have Progressed On or After Chemotherapy and PD-1/PD-L1 Therapy

Posted: May 23rd, 2017, 10:00am EDT

Condition: Melanoma
Interventions: Biological: Avelumab; Biological: Bevacizumab; Drug: Capecitabine; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: 5-fluorouracil; Drug: Leucovorin; Drug: nab-paclitaxel; Biological: Nivolumab; Drug: omega-3-acid ethyl esters; Radiation: Stereotactic Body Radiation Therapy; Biological: ALT-803; Biological: ETBX-011; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-6207; Biological: GI-6301; Biological: haNK
Sponsor: NantCell, Inc.
Not yet recruiting - verified May 2017

Adoptive Cell Therapy Following a Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Melanoma Patients

Posted: May 21st, 2017, 10:00am EDT

Condition: Malignant Melanoma Stage IV
Interventions: Drug: Fludarabine; Radiation: Radiation; Biological: TIL; Drug: IL-2
Sponsor: Sheba Medical Center
Recruiting - verified May 2017

Pfizer PF-06688992 in Patients With Stage III or Stage IV Melanoma

Posted: May 17th, 2017, 10:00am EDT

Condition: Melanoma
Intervention: Drug: PF-06688992
Sponsors: Memorial Sloan Kettering Cancer Center; Pfizer
Recruiting - verified May 2017

Surgeon-Anesthesiologist Collaboration

Posted: May 17th, 2017, 10:00am EDT

Conditions: Pheochromocytoma; Collaboration
Intervention: Procedure: Surgery complications
Sponsor: Hospices Civils de Lyon
Not yet recruiting - verified May 2017

SX-682 Treatment in Subjects With Metastatic Melanoma Concurrently Treated With Pembrolizumab

Posted: May 16th, 2017, 10:00am EDT

Conditions: Melanoma Stage Iii; Melanoma Stage Iv
Interventions: Drug: SX-682; Biological: Pembrolizumab
Sponsors: Syntrix Biosystems, Inc.; Massachusetts General Hospital; The Wistar Institute; National Cancer Institute (NCI)
Not yet recruiting - verified May 2017

A Real-World Study of Ipilimumab Treatment After Nivolumab Treatment in Melanoma in Japan

Posted: May 16th, 2017, 10:00am EDT

Condition: Melanoma
Intervention: Other: Non-Interventional
Sponsors: Bristol-Myers Squibb; Ono Pharmaceutical
Not yet recruiting - verified May 2017

To Evaluate the Efficacy of NY-ESO-1-specific T Cell Receptor (TCR) Affinity Enhancing Specific T Cell in Solid Tumors

Posted: May 15th, 2017, 10:00am EDT

Conditions: Bone Sarcoma; Soft Tissue Sarcoma; Melanoma; Liver Cancer; Esophageal Cancer; Breast Cancer; Thyroid Cancer; Ovarian Cancer
Interventions: Drug: Cyclophosphamide; Biological: TAEST16001
Sponsors: Zhujiang Hospital; Xiangxue Life Science Research Center; Guangdong Xiangxue Precision Medical Technology Co., Ltd; Guangzhou Xiangxue Pharmaceutical Co., Ltd
Recruiting - verified May 2017

Permalink for 'Evaluation of Denosumab in Combination With Immune Checkpoint Inhibitors in Patients With Unresectable or Metastatic Melanoma'

Evaluation of Denosumab in Combination With Immune Checkpoint Inhibitors in Patients With Unresectable or Metastatic Melanoma

Posted: May 11th, 2017, 10:00am EDT

Conditions: Melanoma Stage Iv; Melanoma Stage Iii; Melanoma
Interventions: Drug: Denosumab; Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Australia and New Zealand Melanoma Trials Group; Amgen; Bristol-Myers Squibb
Not yet recruiting - verified May 2017

Study of JS001 in Patients With Advanced Neuroendocrine Tumors

Posted: May 10th, 2017, 10:00am EDT

Condition: Neuroendocrine Tumors
Intervention: Biological: humanized anti-PD-1 monoclonal antibody
Sponsors: Peking University; Shanghai Junshi Biosciencee Co.,Ltd
Recruiting - verified May 2017

Study to Evaluate the Efficiency of FOLFIRI as Seconde-line Chemotherapy in Neuroendocrine Carcinoma

Posted: May 10th, 2017, 10:00am EDT

Condition: Neuroendocrine Carcinoma
Intervention: Drug: FOLFIRI Protocol
Sponsor: Peking University
Recruiting - verified May 2017

Permalink for 'Study to Compare Irinotecan Combined With Cisplatin (IP) Versus Etoposide Combined With Cisplatin (EP) in Advanced and Metastatic Gastrointestinal Pancreatic and Esophageal Neuroendocrine Carcinoma'

Study to Compare Irinotecan Combined With Cisplatin (IP) Versus Etoposide Combined With Cisplatin (EP) in Advanced and Metastatic Gastrointestinal Pancreatic and Esophageal Neuroendocrine Carcinoma

Posted: May 10th, 2017, 10:00am EDT

Condition: Neuroendocrine Carcinoma
Interventions: Drug: irinotecan cisplatin; Drug: Etoposide cisplatin
Sponsor: Peking University
Recruiting - verified May 2017

Phase 1 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET-Fusion Lung Cancer and Medullary Thyroid Cancer

Posted: May 9th, 2017, 10:00am EDT

Conditions: Non-Small Cell Lung Cancer; Medullary Thyroid Cancer; Colon Cancer; Solid Tumor
Intervention: Drug: LOXO-292
Sponsor: Loxo Oncology, Inc.
Recruiting - verified May 2017

The ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) Trial

Posted: May 9th, 2017, 10:00am EDT

Conditions: Advanced Ovarian Cancer; Malignant Melanoma
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Pembrolizumab; Biological: Tumor-Infiltrating Lymphocytes (TILs); Biological: Interleukin-2 (IL-2)
Sponsors: University Health Network, Toronto; Merck Sharp & Dohme Corp.
Not yet recruiting - verified May 2017

Phase I Feasibility Safety Study: Laser Tissue Welding - Distal Pancreatectomy Sealing Study

Posted: May 8th, 2017, 10:00am EDT

Conditions: Pancreatic Tumor, Benign; Pancreatic Neoplasms; Pancreatic Adenocarcinoma; Pancreatic Pseudocyst; Pancreatic Neuroendocrine Tumor; Pancreas; Insulinoma; Pancreatic Cyst; Pancreatic Teratoma; Pancreatic Polypeptide Tumor; Pancreatic Vipoma; Pancreatic Cystadenoma; Pancreas Injury; Pancreatic Gastrinoma; Pancreatic Glucagonoma
Intervention: Device: Distal Pancreatectomy Sealing Using LTW
Sponsors: Laser Tissue Welding, Inc.; National Cancer Institute (NCI); CHI St. Luke's Health, Texas
Recruiting - verified May 2017

Permalink for 'Phase II Study of Avelumab in Metastatic Gastronetro-pancreatic （GEP） Neuroendocrine Carcinoma （NEC, WHO Grade 3） as Second-line Treatment After Failing to Etoposide+Cisplatin: Integration of Genomic Analysis to Identify Predictive Molecular Subt'

Phase II Study of Avelumab in Metastatic Gastronetro-pancreatic （GEP） Neuroendocrine Carcinoma （NEC, WHO Grade 3） as Second-line Treatment After Failing to Etoposide+Cisplatin: Integration of Genomic Analysis to Identify Predictive Molecular Subt

Posted: May 8th, 2017, 10:00am EDT

Condition: Neuroendocrine Carcinoma, Grade 3
Intervention: Drug: Avelumab
Sponsor: Samsung Medical Center
Not yet recruiting - verified May 2017

Abbreviated MAPK Targeted Therapy Plus Pembrolizumab in Melanoma

Posted: May 8th, 2017, 10:00am EDT

Condition: Metastatic Melanoma
Interventions: Drug: Pembrolizumab; Drug: Dabrafenib; Drug: Trametinib
Sponsors: Massachusetts General Hospital; Merck Sharp & Dohme Corp.
Not yet recruiting - verified May 2017

A Study of Combination With TBI-1401(HF10) and Ipilimumab in Japanese Patients With Unresectable or Metastatic Melanoma

Posted: May 8th, 2017, 10:00am EDT

Conditions: Melanoma Stage Iii; Melanoma Stage Iv
Interventions: Biological: TBI-1401(HF10); Drug: Ipilimumab
Sponsor: Takara Bio Inc.
Recruiting - verified May 2017

Permalink for 'A Study to Evaluate a New Way to Identify/Diagnose Tumours With Somatostatin Receptors Using [68]Ga-HA-DOTATATE and to Ensure it is Safe to Use'

A Study to Evaluate a New Way to Identify/Diagnose Tumours With Somatostatin Receptors Using [68]Ga-HA-DOTATATE and to Ensure it is Safe to Use

Posted: May 5th, 2017, 10:00am EDT

Condition: Neuroendocrine Tumors
Intervention: Drug: [68]Ga-HA-DOTATATE
Sponsor: Alexander McEwan
Not yet recruiting - verified May 2017

Tolerance of Targeted Therapy Used in Metastatic Melanoma in Patients Aged Over 65 and 75-year-old

Posted: May 5th, 2017, 10:00am EDT

Condition: Metastatic Melanoma
Intervention:
Sponsors: University Hospital, Montpellier; Saint-Louis Hospital, Paris, France
Recruiting - verified May 2017

Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions

Posted: May 5th, 2017, 10:00am EDT

Conditions: Pheochromocytoma; Paraganglioma; Inherited Cancer Syndrome; Associated Conditions; Kidney Neoplasms; Bone Cancer; Thyroid Neoplasms; Other Cancer
Intervention: Genetic: Genetic screening
Sponsor: The University of Texas Health Science Center at San Antonio
Recruiting - verified May 2017

Permalink for 'A Study of Adult Participants With BRAF V600 Mutation-Positive Advanced Melanoma Treated With Cobimetinib (Cotellic®) During the French Early Access Program (Temporary Authorization for Use [TAU])'

A Study of Adult Participants With BRAF V600 Mutation-Positive Advanced Melanoma Treated With Cobimetinib (Cotellic®) During the French Early Access Program (Temporary Authorization for Use [TAU])

Posted: May 2nd, 2017, 10:00am EDT

Condition: Melanoma
Interventions: Drug: Cobimetinib; Drug: Vemurafenib
Sponsor: Hoffmann-La Roche
Recruiting - verified June 2017

A Prospective Multi-center Observational Study in Patients With Mucosal Melanoma of Head and Neck

Posted: May 1st, 2017, 10:00am EDT

Condition: Mucosal Melanoma
Intervention:
Sponsors: Sun Yat-sen University; First Affiliated Hospital, Sun Yat-Sen University; Zhejiang Cancer Hospital
Recruiting - verified May 2017

New Tumor Models in Three Dimensions and in a Human Skin Environment for Personalized Melanoma Therapy

Posted: April 28th, 2017, 10:00am EDT

Condition: Melanoma (Skin)
Intervention: Other: Development of the most specific physiologically relevant experimental patient models
Sponsor: Centre Hospitalier Universitaire, Amiens
Recruiting - verified April 2017

Permalink for 'Optimizing Access to Care Through New Technologies: a Randomized Study Evaluating the Impact of Telephone Contact and the Sending by the General Practitioner of Suspicious Lesions Melanoma Photographs Taken With a Smartphone, on the Time Limit to the Con'

Optimizing Access to Care Through New Technologies: a Randomized Study Evaluating the Impact of Telephone Contact and the Sending by the General Practitioner of Suspicious Lesions Melanoma Photographs Taken With a Smartphone, on the Time Limit to the Con

Posted: April 28th, 2017, 10:00am EDT

Condition: Patients at Risk for Melanoma
Intervention: Other: Taking photographs of suspicious lesions with his smartphone and sending them to the dermatologist
Sponsor: Nantes University Hospital
Recruiting - verified June 2017

Permalink for 'Study of the Selective PI3K-Beta Inhibitor GSK2636771 in Combination With Pembrolizumab in Patients With Metastatic Melanoma and PTEN Loss'

Study of the Selective PI3K-Beta Inhibitor GSK2636771 in Combination With Pembrolizumab in Patients With Metastatic Melanoma and PTEN Loss

Posted: April 24th, 2017, 10:00am EDT

Conditions: Melanoma and Other Malignant Neoplasms of Skin; Metastatic Melanoma
Interventions: Drug: GSK2636771; Drug: Pembrolizumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI); National Institutes of Health (NIH); Merck Sharp & Dohme Corp.; GlaxoSmithKline
Not yet recruiting - verified May 2017

pIL-12 and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Pembrolizumab or Nivolumab Treatment

Posted: April 24th, 2017, 10:00am EDT

Condition: Stage III/IV Melanoma
Interventions: Biological: pIL-12; Biological: Pembrolizumab; Device: Immunopulse
Sponsor: OncoSec Medical Incorporated
Not yet recruiting - verified April 2017

Skin Health Online for Melanoma: Better Risk Assessment

Posted: April 19th, 2017, 10:00am EDT

Condition: Melanoma (Skin)
Intervention: Behavioral: Web-based Module Group
Sponsors: University of New Mexico; Memorial Sloan Kettering Cancer Center
Recruiting - verified April 2017

Pembrolizumab-based Therapy in Previously Treated High Grade Neuroendocrine Carcinomas

Posted: April 18th, 2017, 10:00am EDT

Condition: High Grade Malignant Neuroendocrine Carcinoma (Diagnosis)
Interventions: Drug: Pembrolizumab; Drug: Irinotecan; Drug: Paclitaxel
Sponsors: University of California, San Francisco; Merck Sharp & Dohme Corp.
Not yet recruiting - verified June 2017

CD40 Agonistic Antibody APX005M in Combination With Nivolumab

Posted: April 17th, 2017, 10:00am EDT

Conditions: Cancer; Non Small Cell Lung Cancer Metastatic; Metastatic Melanoma; Neoplasm of Lung; Melanoma
Interventions: Drug: APX005M; Drug: Nivolumab
Sponsors: Apexigen, Inc.; Bristol-Myers Squibb
Recruiting - verified May 2017

Multi-Institutional Registry for Malignant Peripheral Nerve Sheath Tumors

Posted: April 13th, 2017, 10:00am EDT

Condition: Malignant Peripheral Nerve Sheath Tumors
Intervention:
Sponsor: Washington University School of Medicine
Recruiting - verified May 2017

Switching From Octreotide to Lanreotide - A Look Back at Patients With Neuroendocrine Tumors

Posted: April 7th, 2017, 10:00am EDT

Condition: Neuroendocrine Tumors
Intervention: Other: Data collection
Sponsor: Ipsen
Recruiting - verified April 2017

Prospective Longitudinal Biomarker Study in Pancreatic Neuroendocrine Tumours

Posted: April 6th, 2017, 10:00am EDT

Condition: Neuroendocrine Tumors
Interventions: Procedure: Core Needle Biopsy; Radiation: Computed Tomography; Radiation: 18F-FDG-PET; Procedure: Phlebotomy; Genetic: Molecular genetic analysis
Sponsor: Uppsala University
Recruiting - verified April 2017

Cobimetinib and Atezolizumab in Advanced Rare Tumors

Posted: March 31st, 2017, 10:00am EDT

Conditions: Malignant Neoplasms of Digestive Organs; Melanoma and Other Malignant Neoplasms of Skin; Appendiceal Adenocarcinoma; Cutaneous Squamous Cell Carcinoma; Small Bowel Adenocarcinoma
Interventions: Drug: Cobimetinib; Drug: Atezolizumab
Sponsors: M.D. Anderson Cancer Center; Genentech, Inc.
Recruiting - verified April 2017

A Phase I/II Study of LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma

Posted: March 30th, 2017, 10:00am EDT

Condition: Melanoma
Interventions: Drug: LY3022855; Drug: Vemurafenib; Drug: Cobimetinib
Sponsors: Dana-Farber Cancer Institute; Eli Lilly and Company
Not yet recruiting - verified April 2017

Acceptance and Commitment Therapy in Improving Well-Being in Patients With Stage III-IV Cancer and Their Partners

Posted: March 28th, 2017, 10:00am EDT

Conditions: Malignant Female Reproductive System Neoplasm; Malignant Hepatobiliary Neoplasm; Partner; Stage III Breast Cancer; Stage III Cervical Cancer; Stage III Colorectal Cancer; Stage III Lung Cancer; Stage III Prostate Cancer; Stage III Skin Melanoma; Stage III Uterine Corpus Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Lung Carcinoma; Stage IIIA Skin Melanoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Lung Carcinoma; Stage IIIB Skin Melanoma; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer; Stage IIIC Skin Melanoma; Stage IIIC Uterine Corpus Cancer; Stage IV Breast Cancer; Stage IV Cervical Cancer; Stage IV Colorectal Cancer; Stage IV Lung Cancer; Stage IV Prostate Cancer; Stage IV Skin Melanoma; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVA Colorectal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Cervical Cancer; Stage IVB Colorectal Cancer; Stage IVB Uterine Corpus Cancer
Interventions: Behavioral: Cognitive Behavior Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Other: Survey Administration
Sponsors: Rutgers, The State University of New Jersey; National Cancer Institute (NCI)
Recruiting - verified April 2017

Permalink for 'A Phase II Study of Durvalumab (MEDI4736) Plus Tremelimumab for Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin'

A Phase II Study of Durvalumab (MEDI4736) Plus Tremelimumab for Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin

Posted: March 23rd, 2017, 10:00am EDT

Conditions: Neuroendocrine Tumors; Neuroendocrine Neoplasm of Lung
Intervention: Drug: Durvalumab + Tremelimumab
Sponsor: Grupo Espanol de Tumores Neuroendocrinos
Not yet recruiting - verified March 2017

Low-dose Interleukin-2 and Pembrolizumab in Melanoma and Renal Cell Cancer

Posted: March 23rd, 2017, 10:00am EDT

Conditions: Carcinoma, Renal Cell; Melanoma
Interventions: Drug: Pembrolizumab; Drug: Interleukin-2
Sponsor: William Grosh, MD
Not yet recruiting - verified April 2017

SAbR Plus Ipilimumab Plus Nivolumab in Metastatic Melanoma Patients

Posted: March 23rd, 2017, 10:00am EDT

Conditions: Melanoma; Metastatic Melanoma
Interventions: Radiation: SAbR; Drug: Ipilimumab; Drug: Nivolumab
Sponsor: University of Texas Southwestern Medical Center
Not yet recruiting - verified April 2017

Expanded Access to Avelumab for Treatment of Metastatic Merkel Cell Carcinoma (mMCC)

Posted: March 20th, 2017, 10:00am EDT

Condition: Metastatic Merkel Cell Carcinoma
Intervention: Drug: Avelumab
Sponsors: Merck KGaA; Pfizer
Available - verified March 2017

Rh-endostatin in Combination With Dacarbazine and Cisplatin as the First Line Therapy for Metastatic Melanoma

Posted: March 20th, 2017, 10:00am EDT

Condition: Melanoma
Intervention: Drug: recombinant human endostatin
Sponsor: Beijing Cancer Hospital
Recruiting - verified March 2017

Response Prediction After GKS in Patients With Vestibular Schwannoma Using DCE MR Imaging

Posted: March 20th, 2017, 10:00am EDT

Condition: Vestibular Schwannoma
Intervention:
Sponsor: Seoul National University Hospital
Not yet recruiting - verified March 2017

A Randomized Trial to Assess the Role of Imaging During Follow up After Radical Surgery of High Risk Melanoma

Posted: March 14th, 2017, 10:00am EDT

Condition: Malignant Melanoma
Intervention: Procedure: CT or PET scans
Sponsor: Uppsala University
Not yet recruiting - verified April 2017

TEMCAP in Grade 3 and Low Ki-67 Gastroenteropancreatic Neuroendocrine Tumors

Posted: March 9th, 2017, 10:00am EST

Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma; Temozolomide; Capecitabine
Intervention: Drug: TEMCAP
Sponsor: Asan Medical Center
Not yet recruiting - verified March 2017

Tolerability and Pharmacokinetics of JS001 in Combination With Axitinib in Patients With Kidney Cancer and Melanoma

Posted: March 9th, 2017, 10:00am EST

Conditions: Kidney Cancer Stage Iv; Advanced Melanoma
Intervention: Biological: humanized anti-PD-1 monoclonal antibody
Sponsor: Shanghai Junshi Bioscience Co.,Ltd.
Recruiting - verified March 2017

Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors

Posted: March 8th, 2017, 10:00am EST

Conditions: Neurofibromatosis 2; Vestibular Schwannoma; Meningioma; Ependymoma; Glioma
Intervention: Drug: Selumetinib
Sponsors: Children's Hospital Medical Center, Cincinnati; AstraZeneca
Recruiting - verified May 2017

Investigating the Clinical Utility of the MDS

Posted: March 8th, 2017, 10:00am EST

Conditions: Skin Lesion; Melanoma; Moles
Intervention: Diagnostic Test: Melanoma Detection System -MDS
Sponsors: Orlucent, Inc; NHS Lanarkshire; NHS Tayside; NHS Greater Glasgow and Clyde; University Hospitals, Leicester; University of Dundee
Not yet recruiting - verified March 2017

Combining Talimogene Laherparepvec With BRAF and MEK Inhibitors in BRAF Mutated Advanced Melanoma

Posted: March 7th, 2017, 10:00am EST

Conditions: Melanoma; BRAF Gene Mutation
Interventions: Drug: Talimogene Laherparepvec 1 Million Pfu/Ml Inj,Susp,1Ml,Vil; Drug: Talimogene Laherparep 100 Mil Pfu/Ml 1Ml; Drug: Dabrafenib; Drug: Trametinib
Sponsors: West Cancer Center; University of Tennessee Health Science Center; Amgen
Not yet recruiting - verified March 2017

Dendritic Cell Vaccination in Patients With Advanced Melamona

Posted: March 7th, 2017, 10:00am EST

Condition: Melanoma
Interventions: Biological: Mature DC vaccine; Drug: Cyclophosphamide 300mg/m^2; Drug: Pembrolizumab
Sponsor: University of Pennsylvania
Recruiting - verified June 2017

Early Therapy Response Monitoring in Melanoma Patients Using PET/MRI

Posted: March 7th, 2017, 10:00am EST

Condition: Malignant Melanoma Stage IV
Intervention: Diagnostic Test: PET/MR (Biograph mMR)
Sponsor: University Hospital Tuebingen
Recruiting - verified April 2017

Study to Evaluate the Efficacy, Safety, and Immunological Response of OBP-301

Posted: March 7th, 2017, 10:00am EST

Conditions: Melanoma Stage III; Melanoma Stage Iv
Intervention: Drug: OBP-301
Sponsors: INC Research; Oncolys BioPharma Inc
Recruiting - verified June 2017

Study of Aspirin in Patients With Vestibular Schwannoma

Posted: March 6th, 2017, 10:00am EST

Conditions: Vestibular Schwannoma; Acoustic Neuroma; Neurofibromatosis 2
Interventions: Drug: Aspirin; Drug: Placebo
Sponsors: Massachusetts Eye and Ear Infirmary; United States Department of Defense; Massachusetts General Hospital
Not yet recruiting - verified May 2017

Asymptomatic Small Pancreatic Endocrine Neoplasms.

Posted: March 6th, 2017, 10:00am EST

Condition: Non Functioning Pancreatic Endocrine Tumor
Interventions: Diagnostic Test: Radiological imaging studies; Other: Quality of Life Assessment
Sponsor: IRCCS San Raffaele
Recruiting - verified March 2017

Permalink for 'Phase 1b Study Evaluating Alternative Routes of Administration of CMP-001 in Combination With Pembrolizumab in Subjects With Advanced Melanoma'

Phase 1b Study Evaluating Alternative Routes of Administration of CMP-001 in Combination With Pembrolizumab in Subjects With Advanced Melanoma

Posted: March 6th, 2017, 10:00am EST

Condition: Malignant Melanoma
Interventions: Drug: CMP-001; Drug: Pembrolizumab
Sponsor: Checkmate Pharmaceuticals
Recruiting - verified June 2017

Pembrolizumab in Recurrent or Metastatic Medullary Thyroid Cancer

Posted: March 3rd, 2017, 10:00am EST

Condition: Medullary Thyroid Cancer (MTC)
Intervention: Drug: Pembrolizumab
Sponsor: National Cancer Institute (NCI)
Recruiting - verified June 15, 2017

Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma

Posted: March 1st, 2017, 10:00am EST

A Study of LEE011 With Everolimus in Patients With Advanced Neuroendocrine Tumors

Posted: February 28th, 2017, 10:00am EST

Condition: Neuroendocrine Tumors
Interventions: Drug: LEE011; Drug: everolimus
Sponsors: Memorial Sloan Kettering Cancer Center; Novartis; Dana-Farber Cancer Institute; M.D. Anderson Cancer Center
Recruiting - verified May 2017

Permalink for 'A Study of Nivolumab in Combination With Ipilimumab Compared to Nivolumab or Ipilimumab Alone in Treatment of Patients After Complete Resection of Stage IIIb/c/d or Stage IV Melanoma.'

A Study of Nivolumab in Combination With Ipilimumab Compared to Nivolumab or Ipilimumab Alone in Treatment of Patients After Complete Resection of Stage IIIb/c/d or Stage IV Melanoma.

Posted: February 27th, 2017, 10:00am EST

Condition: Melanoma
Interventions: Biological: nivolumab; Biological: ipilimumab
Sponsor: Bristol-Myers Squibb
Recruiting - verified April 2017

Pembrolizumab TX-naive Distant Mets Melanoma and Use of AMT (PET) at Baseline as Imaging Biomarker

Posted: February 24th, 2017, 10:00am EST

Condition: Melanoma
Interventions: Diagnostic Test: FDG PET/CT scan; Diagnostic Test: C11-AMT PET scan; Drug: Pembrolizumab; Diagnostic Test: FDG PET/CT scan with IV contrast
Sponsors: UNC Lineberger Comprehensive Cancer Center; Merck Sharp & Dohme Corp.
Not yet recruiting - verified March 2017

$Permalink for 'Image Guided Hypofractionated Radiation Therapy, Nelfinavir Mesylate, and Nivolumab in Treating Patients With Advanced Melanoma, Lung, or Kidney Cancer'$

Image Guided Hypofractionated Radiation Therapy, Nelfinavir Mesylate, and Nivolumab in Treating Patients With Advanced Melanoma, Lung, or Kidney Cancer

Posted: February 8th, 2017, 10:00am EST

Conditions: Metastatic Renal Cell Cancer; Recurrent Melanoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma
Interventions: Radiation: Hypofractionated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Nelfinavir Mesylate; Biological: Nivolumab
Sponsors: University of Washington; National Cancer Institute (NCI)
Recruiting - verified June 2017

Phase 1B Study in Subjects With Small to Medium Primary Choroidal Melanoma

Posted: February 6th, 2017, 10:00am EST

Conditions: Uveal Melanoma; Ocular Melanoma; Choroidal Melanoma
Intervention: Drug: Light-activated AU-011
Sponsor: Aura Biosciences
Recruiting - verified March 2017

Study to Evaluate the Safety of Combining Two Radionuclide Therapies to Treat Mid-gut Neuroendocrine Tumors

Posted: February 2nd, 2017, 10:00am EST

Conditions: Neuroendocrine Tumor, Malignant; Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting
Interventions: Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG
Sponsors: David Bushnell; National Institutes of Health (NIH); National Cancer Institute (NCI); Holden Comprehensive Cancer Center
Recruiting - verified May 2017

18F-DOPA PET Imaging: an Evaluation of Biodistribution and Safety

Posted: February 1st, 2017, 10:00am EST

Conditions: Congenital Hyperinsulinism; Neuroblastoma; Neuroendocrine Tumors; Parkinson Disease; Brain Glioma
Intervention: Drug: 18F-DOPA
Sponsors: University of Alberta; Alberta Health Services
Recruiting - verified February 2017

Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors

Posted: February 1st, 2017, 10:00am EST

Condition: Gastroenteropancreatic Neuroendocrine Tumors
Interventions: Drug: Somatuline Depot; Drug: Keytruda
Sponsors: Duke University; Merck Sharp & Dohme Corp.; Ipsen
Not yet recruiting - verified May 2017

Permalink for 'Ipilimumab With or Without Nivolumab in Treating Patients With Melanoma That is Stage IV or Stage III and Cannot Be Removed by Surgery'

Ipilimumab With or Without Nivolumab in Treating Patients With Melanoma That is Stage IV or Stage III and Cannot Be Removed by Surgery

Posted: January 26th, 2017, 10:00am EST

Conditions: Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma
Interventions: Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Not yet recruiting - verified June 2017

Everolimus TDM to Predict Long Term Toxicity

Posted: January 24th, 2017, 10:00am EST

Conditions: Breast Cancer; Renal Cell Carcinoma; Pancreatic Neuroendocrine Tumour; Gastrointestinal Neuroendocrine Tumour; Neuroendocrine Neoplasm of Lung
Intervention:
Sponsor: Maastricht University Medical Center
Recruiting - verified May 2017

Study of Concurrent Intravenous and Intrathecal Nivolumab for Patients With Leptomeningeal Disease (LMD)

Posted: January 17th, 2017, 10:00am EST

Conditions: Melanoma and Other Malignant Neoplasms of Skin; Leptomeningeal Disease
Intervention: Drug: Nivolumab
Sponsors: M.D. Anderson Cancer Center; Bristol-Myers Squibb
Not yet recruiting - verified May 2017

89Zr-Df-IAB22M2C PET/CT in Patients With Melanoma Receiving Check Point Inhibitors

Posted: January 16th, 2017, 10:00am EST

Conditions: Positron-Emission Tomography; Immunomodulation; Melanoma
Intervention: Drug: 89Zr-Df-IAB22M2C Infusion
Sponsor: ImaginAb, Inc.
Recruiting - verified April 2017

Pembrolizumab and Ibrutinib in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

Posted: January 12th, 2017, 10:00am EST

Conditions: Metastatic Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma
Interventions: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Recruiting - verified January 2017

Permalink for 'Evaluation of Neuroendocrine Differentiation as a Potential Mechanism of Tumor Recurrence Following Radiotherapy in Prostate Carcinoma'

Evaluation of Neuroendocrine Differentiation as a Potential Mechanism of Tumor Recurrence Following Radiotherapy in Prostate Carcinoma

Posted: January 9th, 2017, 10:00am EST

Condition: Prostate Cancer
Intervention:
Sponsor: Mayo Clinic
Recruiting - verified May 2017

Secured Access to Pembrolizumab for Adult Patients With Selected Rare Cancer Types

Posted: January 2nd, 2017, 10:00am EST

Conditions: Sarcoma; Ovarian Neoplasm; Central Nervous System Neoplasm; Thyroid Neoplasm; Carcinoma, Neuroendocrine; Neoplasms, Germ Cell and Embryonal
Intervention: Drug: Pembrolizumab
Sponsors: UNICANCER; National Cancer Institute, France; Ligue contre le cancer, France; Merck Sharp & Dohme Corp.
Not yet recruiting - verified May 2017

Fosbretabulin With Everolimus in Neuroendocrine Tumors With Progression

Posted: December 21st, 2016, 10:00am EST

Conditions: Neuroendocrine Tumors; Everolimus
Interventions: Drug: everolimus; Drug: fosbretabulin
Sponsor: Lowell Anthony, MD
Recruiting - verified April 2017

Permalink for 'An Exploratory Tumor Biopsy-driven Study to Understand the Relationship Between Biomarkers and Clinical Response in Melanoma Patients Receiving REGN2810 (Anti-PD-1)'

An Exploratory Tumor Biopsy-driven Study to Understand the Relationship Between Biomarkers and Clinical Response in Melanoma Patients Receiving REGN2810 (Anti-PD-1)

Posted: December 20th, 2016, 10:00am EST

Condition: Melanoma
Intervention: Drug: REGN2810
Sponsors: Regeneron Pharmaceuticals; Sanofi
Recruiting - verified May 2017

An Expanded Access Imaging of Neuroendocrine Tumors Using 68Ga-DOTA-TOC

Posted: December 20th, 2016, 10:00am EST

Conditions: Malignant Neoplasms of Digestive Organs; Neuroendocrine Tumor; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System
Interventions: Drug: 68Ga-DOTATOC; Procedure: PET/CT
Sponsor: M.D. Anderson Cancer Center
Available - verified June 2017

Surgical Intervention and the NETest

Posted: December 6th, 2016, 10:00am EST

Conditions: Neuroendocrine Tumor; Gastroenteropancreatic
Intervention: Procedure: Surgery
Sponsor: Wren Laboratories LLC
Recruiting - verified May 2017

Permalink for 'Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery'

Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery

Posted: December 5th, 2016, 10:00am EST

Conditions: Metastatic Angiosarcoma; Metastatic Epithelioid Sarcoma; Metastatic Fibrosarcoma; Metastatic Leiomyosarcoma; Metastatic Liposarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Pleomorphic Rhabdomyosarcoma; Stage III Soft Tissue Sarcoma; Stage IV Soft Tissue Sarcoma; Undifferentiated (Embryonal) Sarcoma
Interventions: Drug: Doxorubicin; Drug: Ribociclib
Sponsors: OHSU Knight Cancer Institute; National Cancer Institute (NCI)
Recruiting - verified April 2017

$Permalink for 'Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers'$

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

Posted: November 30th, 2016, 10:00am EST

A Biomarker Study in Advanced Mucosal or Acral Lentiginous Melanoma Receiving Nivolumab in Combination With Ipilimumab

Posted: November 23rd, 2016, 10:00am EST

Conditions: Acral Lentiginous Melanoma; Mucosal Melanoma
Interventions: Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Georgetown University; Melanoma Research Foundation Breakthrough Consortium; Bristol-Myers Squibb; University of Colorado, Denver; University of California, San Francisco; Vanderbilt University; Columbia University; University of Pittsburgh; Yale University; M.D. Anderson Cancer Center; H. Lee Moffitt Cancer Center and Research Institute; Memorial Sloan Kettering Cancer Center; Northwestern University; Dana-Farber Cancer Institute
Recruiting - verified May 2017

Study of Imprime PGG and Pembrolizumab in Advanced Melanoma and Triple Negative Breast Cancer

Posted: November 22nd, 2016, 10:00am EST

Conditions: Advanced Melanoma; Triple-Negative Breast Cancer
Interventions: Biological: Imprime PGG; Drug: Pembrolizumab
Sponsors: Biothera; Merck Sharp & Dohme Corp.
Recruiting - verified May 2017

A Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma

Posted: November 21st, 2016, 10:00am EST

Condition: Metastatic Melanoma
Intervention: Drug: PLX3397
Sponsor: Plexxikon
Recruiting - verified April 2017

Study of CPI-0610 in Patients With Malignant Peripheral Nerve Sheath Tumors

Posted: November 21st, 2016, 10:00am EST

Condition: Peripheral Nerve Tumors
Intervention: Drug: CPI-0610
Sponsor: University of Texas Southwestern Medical Center
Not yet recruiting - verified April 2017

A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma

Posted: November 16th, 2016, 10:00am EST

Condition: Melanoma
Interventions: Biological: PDR001; Other: Placebo; Drug: Dabrafenib; Drug: Trametinib
Sponsor: Novartis Pharmaceuticals
Recruiting - verified June 2017

Talimogene Laherparepvec and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

Posted: November 16th, 2016, 10:00am EST

Conditions: Recurrent Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma
Interventions: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Talimogene Laherparepvec
Sponsor: National Cancer Institute (NCI)
Not yet recruiting - verified April 2017

Health Care Coach Support in Reducing Acute Care Use and Cost in Patients With Cancer

Posted: November 14th, 2016, 10:00am EST

Conditions: Acute Myeloid Leukemia; Brain Glioblastoma; Estrogen Receptor Negative; Extensive Stage Small Cell Lung Carcinoma; Head and Neck Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Limited Stage Small Cell Lung Carcinoma; Myelodysplastic Syndrome; Progesterone Receptor Negative; Progressive Disease; Recurrent Carcinoma; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage III Colon Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer; Stage III Non-Small Cell Lung Cancer; Stage III Ovarian Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Skin Melanoma; Stage IIIA Colon Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Colon Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Colon Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Bone Sarcoma; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IV Soft Tissue Sarcoma; Stage IVA Bone Sarcoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Bone Sarcoma; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Triple-Negative Breast Carcinoma
Interventions: Other: Best Practice; Other: Laboratory Biomarker Analysis; Procedure: Supportive Care; Other: Survey Administration
Sponsor: Stanford University
Recruiting - verified May 2017

Induction Therapy With Vemurafenib and Cobimetinib to Optimize Nivolumab and Ipilimumab Therapy

Posted: November 11th, 2016, 10:00am EST

Condition: Melanoma, Malignant, of Soft Parts
Intervention: Drug: Vemurafenib and Cobimetinib
Sponsors: Radboud University; The Netherlands Cancer Institute; Isala
Recruiting - verified May 2017

MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers

Posted: November 7th, 2016, 10:00am EST

Conditions: Urinary Bladder Cancer; Head and Neck Cancer; Melanoma
Intervention: Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Sponsor: Adaptimmune
Recruiting - verified May 2017

Cutaneous malignant melanoma and Parkinson disease: Common pathways?

Fetched: June 21st, 2017, 1:00am EDT

Cutaneous malignant melanoma and Parkinson disease: Common pathways?

Ann Neurol. 2016 Dec;80(6):811-820

Authors: Inzelberg R, Flash S, Friedman E, Azizi E

Abstract
The mechanisms underlying the high prevalence of cutaneous malignant melanoma (CMM) in Parkinson disease (PD) are unclear, but plausibly involve common pathways. 129Ser-phosphorylated α-synuclein, a pathological PD hallmark, is abundantly expressed in CMM, but not in normal skin. In inherited PD, PARK genes harbor germline mutations; the same genes are somatically mutated in CMM, or their encoded proteins are involved in melanomagenesis. Conversely, genes associated with CMM affect PD risk. PD/CMM-targeted cells share neural crest origin and melanogenesis capability. Pigmentation gene variants may underlie their susceptibility. We review putative genetic intersections that may be suggestive of shared pathways in neurodegeneration/melanomagenesis. Ann Neurol 2016;80:811-820.

PMID: 27761938 [PubMed - indexed for MEDLINE]

Ethanolic Extract of Algerian Propolis and Galangin Decreased Murine Melanoma T.

Fetched: June 21st, 2017, 1:00am EDT

Ethanolic Extract of Algerian Propolis and Galangin Decreased Murine Melanoma T.

Anticancer Agents Med Chem. 2016;16(9):1172-83

Authors: Benguedouar L, Lahouel M, Gangloff SC, Durlach A, Grange F, Bernard P, Antonicelli F

Abstract
Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated.

PMID: 26863880 [PubMed - indexed for MEDLINE]

Laryngeal Schwannoma: A Case Presentation and Review of the Mayo Clinic Experience.

Fetched: June 21st, 2017, 1:00am EDT

Laryngeal Schwannoma: A Case Presentation and Review of the Mayo Clinic Experience.

J Voice. 2017 Jan;31(1):129.e15-129.e18

Authors: Romak JJ, Neel HB, Ekbom DC

Abstract
OBJECTIVES: The aim of this study was to clarify the nature of laryngeal schwannomas through review of the experience of a single institution during a 104-year period.
STUDY DESIGN: This is a retrospective case series.
METHODS: The Mayo Clinic, Rochester, Minnesota clinical and surgical pathology database was reviewed for the years 1985-2011. Four cases of laryngeal schwannoma were identified. These cases were pooled with a previously published series of laryngeal schwannomas treated at our institution between 1907 and 1986. The characteristics of all 11 cases were studied, and relevant literature was reviewed.
RESULTS: A total of 11 cases of schwannoma of the larynx were identified. The mean age at presentation was 48 years (range 12-73 years). The most common presenting symptoms were dysphonia and dysphagia. The most frequently involved primary site was the false vocal fold (six patients), followed by the aryepiglottic fold (three), epiglottis (two), subglottis (two), ventricle (one), true vocal fold (one) and postcricoid region (one). The mean maximal tumor diameter was 2.5 cm. In all but one case, surgical excision was curative with no recurrence during recorded follow up ranging from 1 to 17 years.
CONCLUSIONS: Laryngeal schwannomas, although rare, should be considered in the differential diagnosis of laryngeal tumors. They occur most frequently in the false vocal fold and present most commonly with dysphonia and/or dysphagia. Surgical excision is the treatment of choice.

PMID: 26795969 [PubMed - indexed for MEDLINE]

A Case Report: Gastric Mixed Neuroendocrine-Nonneuroendocrine Neoplasm with Aggressive Neuroendocrine Component.

Fetched: June 21st, 2017, 1:00am EDT

A Case Report: Gastric Mixed Neuroendocrine-Nonneuroendocrine Neoplasm with Aggressive Neuroendocrine Component.

Case Rep Pathol. 2017;2017:9871687

Authors: Pham QD, Mori I, Osamura RY

Abstract
Mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN) is defined as mixed epithelial neoplasms composed of both neuroendocrine and nonneuroendocrine components with variable proportions for each component. Neuroendocrine component can show morphological features including well- or poorly differentiated neuroendocrine neoplasms and nonneuroendocrine component can present different tumor types depending on the site of origin. Recently, studies of tumors have shown that MiNENs are not as rare as our traditional belief, due to the wide application for immunohistochemistry. However, our knowledge of MiNENs is still limited. There is no universal consensus about nomenclature, classification, and guideline of treatment. Hereby, we would like to present a case report of gastric MiNEN with aggressive neuroendocrine component to contribute a small part towards common understanding of gastric MiNENs.

PMID: 28626594 [PubMed]

Permalink for 'Long-Term Efficacy of S-1 Chemotherapy plus Administration of Octreotide for a Patient with Metastatic Neuroendocrine Tumor (Gastrinoma).'

Long-Term Efficacy of S-1 Chemotherapy plus Administration of Octreotide for a Patient with Metastatic Neuroendocrine Tumor (Gastrinoma).

Fetched: June 21st, 2017, 1:00am EDT

Long-Term Efficacy of S-1 Chemotherapy plus Administration of Octreotide for a Patient with Metastatic Neuroendocrine Tumor (Gastrinoma).

Case Rep Oncol. 2017 May-Aug;10(2):420-427

Authors: Hiraide S, Ono S, Kato S

Abstract
Metastatic neuroendocrine tumors (gastrinomas) have a poor prognosis. Octreotide can reduce gastrin levels and alleviate hormonal symptoms, and possibly slow tumor growth as well. No drugs were available except streptozocin for the treatment of metastatic pancreatic neuroendocrine tumor (PNET) in 2008. We report a case of PNET in a 53-year-old woman with multiple liver tumors treated with S-1 plus octreotide. After 6 months from the initiation of the treatment, the pancreatic tumor and liver metastases regressed, and the patient achieved partial response without the development of any serious adverse event. For more than 8 years, the patient has remained asymptomatic without disease progression and is continuing treatment with octreotide and S-1. A marked suppression of gastrin levels has also been achieved. Combination therapy with octreotide and S-1 has been effective and well tolerated in patients with metastatic gastrinoma.

PMID: 28626400 [PubMed]

Small Cell Lung Cancer in a 20-year-old Non-Smoking Man with Systemic Sclerosis.

Fetched: June 21st, 2017, 1:00am EDT

Small Cell Lung Cancer in a 20-year-old Non-Smoking Man with Systemic Sclerosis.

Intern Med. 2017;56(12):1549-1552

Authors: Saito G, Jinta T, Nakaoka H, Kitamura A, Yamaguchi K, Nishimura N

Abstract
Small cell lung cancer (SCLC) is a neuroendocrine tumor, and the median age of onset is about 70 years old. A 20-year-old non-smoking man with known systemic sclerosis presented with discomfort in his left chest. Chest X-ray showed a mass shadow in the left upper zone. A transbronchial lung biopsy revealed small cell carcinoma, and imaging studies reached the diagnosis of extensive disease small cell lung cancer. He had concurrent interstitial lung disease with a non-specific interstitial pneumonia pattern and anti-Scl-70 antibodies. He died eight months after the diagnosis during fifth-line chemotherapy. We herein report the youngest case to date of SCLC with systemic sclerosis.

PMID: 28626182 [PubMed - in process]

Recurrence 30 Years after Surgical Resection of a Localized Rectal Neuroendocrine Tumor.

Fetched: June 21st, 2017, 1:00am EDT

Recurrence 30 Years after Surgical Resection of a Localized Rectal Neuroendocrine Tumor.

Intern Med. 2017;56(12):1521-1525

Authors: Shigematsu Y, Kanda H, Konishi T, Takazawa Y, Inoue Y, Muto T, Ishikawa Y, Takahashi S

Abstract
Localized small rectal neuroendocrine tumors (NETs) without any vascular involvement rarely metastasize, and their resection alone is considered curative. We herein report a case of localized rectal NET (10×8 mm) without vascular involvement. Although resected initially, it recurred as liver metastasis 30 years later. For rectal NETs smaller than 10 to 20 mm, surveillance for 12 months is considered sufficient. However, this case suggests that such tumors can recur even 30 years after curative resection. The interval of recurrence is the longest among reported cases.

PMID: 28626177 [PubMed - in process]

PD-L1 expression in neuroendocrine tumors of the lung.

Fetched: June 21st, 2017, 1:00am EDT

PD-L1 expression in neuroendocrine tumors of the lung.

Lung Cancer. 2017 Jun;108:115-120

Authors: Tsuruoka K, Horinouchi H, Goto Y, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Asakura K, Nakagawa K, Sakurai H, Watanabe SI, Tsuta K, Ohe Y

Abstract
BACKGROUND: Various tumors express programmed cell death ligand 1 (PD-L1), an immune checkpoint ligand, the expression of which correlates with certain effects of anti-programmed cell death 1 (PD-1)/PD-L1 drugs. The aim of this study was to assess the frequency of PD-L1 expression in each of the types of neuroendocrine tumors of the lung.
METHODS: The subjects enrolled in this study were patients who had been diagnosed with neuroendocrine tumors of the lung and had been treated at the National Cancer Center Hospital (Tokyo, Japan) between 1982 and 2010. We performed immunohistochemical analysis on a tissue microarray (TMA) of the surgical specimens using the validated PD-L1 antibody clone, E1L3N. Tumor PD-L1 expression scores were calculated semiquantitatively (staining intensity [0-3]×stained area [0-100%]). A score of 1 was used as a cut-off to determine the presence or absence of PD-L1 expression.
RESULTS: Among the 227 patients included in this study, the patient demographics were as follows: median age (range), 65 years (19-84); sex (male/female), 168/59; pStage (IA, IB, IIA, IIB, IIIA, IIIB, IV): 79, 36, 25, 29, 47, 6, 5, respectively; and histology was typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), small cell lung cancer (SCLC): 46, 6, 106, 69, respectively. The numbers (proportions) of PD-L1-expression tumors were as follows: TC/AC/LCNEC/SCLC, 0/0/11 (10.4%)/4 (5.8%).
CONCLUSIONS: PD-L1 expression was apparent in 10.4% of LCNEC and 5.8% of SCLC tumors, and was not observed in carcinoid tumors.

PMID: 28625622 [PubMed - in process]

A rectal neuroendocrine neoplasm.

Fetched: June 21st, 2017, 1:00am EDT

A rectal neuroendocrine neoplasm.

Rev Esp Enferm Dig. 2017 Jun 19;109:

Authors: Varas Lorenzo MJ, Muñoz Agel F

Abstract
The incidence of gastric and rectal carcinoids is increasing. This is probably due to endoscopic screening. The prognosis is primarily dependent upon tumor size, aggressiveness (pathology, Ki-67), metastatic disease and stage. However, neuroendocrine carcinoma usually behaves as an adenocarcinoma.

PMID: 28625066 [PubMed - as supplied by publisher]

New predictors of complications in carotid body tumor resection.

Fetched: June 21st, 2017, 1:00am EDT

New predictors of complications in carotid body tumor resection.

J Vasc Surg. 2017 Jun;65(6):1673-1679

Authors: Kim GY, Lawrence PF, Moridzadeh RS, Zimmerman K, Munoz A, Luna-Ortiz K, Oderich GS, de Francisco J, Ospina J, Huertas S, de Souza LR, Bower TC, Farley S, Gelabert HA, Kret MR, Harris EJ, De Caridi G, Spinelli F, Smeds MR, Liapis CD, Kakisis J, Papapetrou AP, Debus ES, Behrendt CA, Kleinspehn E, Horton JD, Mussa FF, Cheng SWK, Morasch MD, Rasheed K, Bennett ME, Bismuth J, Lumsden AB, Abularrage CJ, Farber A

Abstract
OBJECTIVE: This study examined the relationship between two new variables, tumor distance to base of skull (DTBOS) and tumor volume, with complications of carotid body tumor (CBT) resection, including bleeding and cranial nerve injury.
METHODS: Patients who underwent CBT resection between 2004 and 2014 were studied using a standardized, multi-institutional database. Demographic, perioperative, and outcomes data were collected. CBT measurements were determined from computed tomography, magnetic resonance imaging, and ultrasound examination.
RESULTS: There were 356 CBTs resected in 332 patients (mean age, 51 years; 72% female); 32% were classified as Shamblin I, 43% as Shamblin II, and 23% as Shamblin III. The mean DTBOS was 3.3 cm (standard deviation [SD], 2.1; range, 0-10), and the mean tumor volume was 209.7 cm(3) (SD, 266.7; range, 1.1-1642.0 cm(3)). The mean estimated blood loss (EBL) was 257 mL (SD, 426; range, 0-3500 mL). Twenty-four percent of patients had cranial nerve injuries. The most common cranial nerves injured were the hypoglossal (10%), vagus (11%), and superior laryngeal (5%) nerves. Both Shamblin grade and DTBOS were statistically significantly correlated with EBL of surgery and cranial nerve injuries, whereas tumor volume was statistically significantly correlated with EBL. The logistic model for predicting blood loss and cranial nerve injury with all three variables-Shamblin, DTBOS, and volume (R(2) = 0.171, 0.221, respectively)-was superior to a model with Shamblin alone (R(2) = 0.043, 0.091, respectively). After adjusting for Shamblin grade and volume, every 1-cm decrease in DTBOS was associated with 1.8 times increase in risk of >250 mL of blood loss (95% confidence interval, 1.25-2.55) and 1.5 times increased risk of cranial nerve injury (95% confidence interval, 1.19-1.92).
CONCLUSIONS: This large study of CBTs demonstrates the value of preoperatively determining tumor dimensions and how far the tumor is located from the base of the skull. DTBOS and tumor volume, when used in combination with the Shamblin grade, better predict bleeding and cranial nerve injury risk. Furthermore, surgical resection before expansion toward the base of the skull reduces complications as every 1-cm decrease in the distance to the skull base results in 1.8 times increase in >250 mL of blood loss and 1.5 times increased risk of cranial nerve injury.

PMID: 28527929 [PubMed - indexed for MEDLINE]

Avelumab: First Global Approval.

Fetched: June 21st, 2017, 1:00am EDT

Avelumab: First Global Approval.

Drugs. 2017 May;77(8):929-937

Authors: Kim ES

PMID: 28456944 [PubMed - indexed for MEDLINE]

Melanoma growth and lymph node metastasis is independent of host CD169 expression.

Fetched: June 21st, 2017, 1:00am EDT

Melanoma growth and lymph node metastasis is independent of host CD169 expression.

Biochem Biophys Res Commun. 2017 May 13;486(4):965-970

Authors: Muhsin-Sharafaldine MR, Saunderson SC, Dunn AC, McLellan AD

Abstract
Metastasis to the lymph node is a frequent and early event in tumour dissemination. Tumour soluble factors, including extracellular vesicles, condition host organs for metastatic tumour spread, thereby facilitating tumour cell migration and survival. In the peripheral lymphatics, extracellular vesicles are captured via their sialic acids by lymph node macrophages expressing the CD169 (sialoadhesin) molecule, thereby suppressing the immune response. We hypothesised that the CD169 molecule could modulate primary tumour growth and invasion into the regional lymph node by altering the immune response to tumour extracellular vesicles, or by directly interacting with invading tumour cells. No significant difference was noted in primary tumour growth between wild-type and CD169(-/-) mice, and protection against tumour challenge with tumour extracellular vesicle immunisation was similar between the strains. Subcutaneous implantation of B16 (F1 or F10) into the ventral-carpal aspect of forelimb resulted in melanoma infiltration into the axillary and brachial lymph nodes. CD169(-/-) mice displayed a lower level of metastatic lymph node lesions, however this failed to reach statistical significance. Although CD169 participates in the immune response to tumour antigen and appears to be a positive prognostic marker for human cancers, its role in modulating melanoma growth and metastasis is less clear.

PMID: 28359758 [PubMed - indexed for MEDLINE]

Permalink for 'Comparative investigation of the effects of specific antigen‑sensitized DC‑CIK and DC‑CTL cells against B16 melanoma tumor cells.'

Comparative investigation of the effects of specific antigen‑sensitized DC‑CIK and DC‑CTL cells against B16 melanoma tumor cells.

Fetched: June 21st, 2017, 1:00am EDT

Comparative investigation of the effects of specific antigen‑sensitized DC‑CIK and DC‑CTL cells against B16 melanoma tumor cells.

Mol Med Rep. 2017 Apr;15(4):1533-1538

Authors: Ren PT, Zhang Y

Abstract
The use of personalized adoptive immunotherapy as a potential novel approach is promising in the treatment of tumors resistant to conventional therapies. In the present study, dendritic cell (DC)‑cytokine‑induced killer (CIK) and DC‑cytotoxic lymphocyte (CTL) cells were cultured to examine their phenotype, proliferation and cytotoxicity against B16 melanoma tumor cells. In addition, comparative investigations of the effect of specific antigen‑sensitized DC‑CIK and DC‑CTL cells against B16 melanoma tumor cells were performed in vitro and in vivo. The results showed that the phenotypes of the co‑cultured cells were altered, and DCs promoted DC‑CIK cell and DC‑CTL cell differentiation and maturation in vitro. Lactate dehydrogenase cytotoxic analysis indicated that the cytotoxicity increased as the effector to target ratio increased between 10:1 and 40:1, and the cytotoxic effect towards B16 melanoma cells by DC‑CTL cells was significantly higher, compared with that of DC‑CIK cells. To further examine the antineoplastic efficacy of DC‑CIK and DC‑CTL cells in vivo, the present study performed tail‑intravenous injection of DC‑CIK cells and DC‑CTL cells, which attenuated B16 melanoma cell‑engrafted tumor growth, induced G0/G1 cell cycle arrest and accelerated cell apoptosis. Taken together, these results suggested that the use of DC‑CTL or DC‑CIK cell therapy as a personalized adoptive immunotherapy may regulate immune status and inhibit tumor growth in vivo. In addition, the experiments indicated that DC‑CTL cells offer superior antineoplastic activity, compared with DC‑CIK cells against B16 melanoma tumor cells.

PMID: 28260039 [PubMed - indexed for MEDLINE]

Permalink for 'Correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with malignant melanoma susceptibility and prognosis: A case-control study.'

Correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with malignant melanoma susceptibility and prognosis: A case-control study.

Fetched: June 21st, 2017, 1:00am EDT

Correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with malignant melanoma susceptibility and prognosis: A case-control study.

Gene. 2017 Jun 20;617:44-53

Authors: Wang XH, Long ZW

Abstract
This case-control study aims to investigate the correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with the susceptibility and prognosis of malignant melanoma. A total of 153 patients with multiple primary melanomas were collected as the case group and another 170 healthy individuals were selected as the control group. ELISA and PCR-RFLP were performed to test the serum level of VEGF and to analyze the genotype as well as allele frequencies of VEGF T460C, EGF G1380A, and bFGF C754G, respectively. The patients were assigned into complete remission (CR), partial remission (PR) and non-remission groups after treatment. HE and CD34 staining were conducted in tissue samples of CR and PR patients. Event-free survival (EFS) and overall survival (OS) were measured. AA genotype of EGF G1380A and GG genotype of bFGF C754G had higher frequency distribution in the case group than the control group. Patients with AA genotype of EGF G1380 and GG genotype of bFGF C754G had an elevated VEGF level in comparison to other genotypes. Patients with GA+GG genotypes of EGF G1380A and CG+CC genotypes of bFGF C754G had higher EFS and OS than those with AA genotype and those with GG genotype, respectively. According to the haplotype analysis, the case group had a notably higher frequency of TAG and CAG along with while lower frequency of TGG and CGC compared with the control group. Logistic regression analysis revealed that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma. The results indicated that EGF G1380A and bFGF C754G gene polymorphisms were associated with the susceptibility and prognosis of malignant melanoma, and that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma.

PMID: 28219779 [PubMed - indexed for MEDLINE]

Inhibition of proliferation and invasion in 2D and 3D models by 2-methoxyestradiol in human melanoma cells.

Fetched: June 21st, 2017, 1:00am EDT

Inhibition of proliferation and invasion in 2D and 3D models by 2-methoxyestradiol in human melanoma cells.

Pharmacol Res. 2017 May;119:242-250

Authors: Massaro RR, Faião-Flores F, Rebecca VW, Sandri S, Alves-Fernandes DK, Pennacchi PC, Smalley KSM, Maria-Engler SS

Abstract
Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and Cyclin B1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assay, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors. We further show that 2ME is effective against melanoma with different BRAF and NRAS mutational status. Moreover, 2ME induced the retraction of cytoplasmic projections in a 3D spheroid model and significantly decreased cell proliferation in a 3D skin reconstruct model. Together our studies bring new insights into the mechanism of action of 2ME allowing melanoma targeted therapy to be further refined. Continued progress in this area is expected to lead to improved anti-cancer treatments and the development of new and more effective clinical analogues.

PMID: 28212889 [PubMed - indexed for MEDLINE]

Expression profile of SIRT2 in human melanoma and implications for sirtuin-based chemotherapy.

Fetched: June 21st, 2017, 1:00am EDT

Expression profile of SIRT2 in human melanoma and implications for sirtuin-based chemotherapy.

Cell Cycle. 2017 Mar 19;16(6):574-577

Authors: Wilking-Busch MJ, Ndiaye MA, Huang W, Ahmad N

Abstract
Melanoma is cancer of melanin-containing melanocyte cells. This neoplasm is one of the most deadly forms of skin cancer, and currently available therapeutic options are insufficient in significantly improve outcomes for many patients. Therefore, novel targets are required to effectively manage this neoplasm. Several sirtuins have previously been found to be upregulated in melanoma, so in this study, the expression profile of SIRT2 was determined. Employing a tissue microarray containing benign nevi, primary melanomas, and lymph node metastases, we have found that the tissue from lymph node metastases appears to have a significant upregulation of SIRT2 relative to primary tumors across the nuclear, cytoplasmic, and whole cell data. Additionally, SIRT2 staining was found to be higher in the nucleus of metastatic melanomas compared to cytoplasmic staining. As SIRT2 is considered to be a predominantly cytoplasmic protein, this is a novel and very interesting finding. This, combined with previous studies that show other sirtuins are increased in melanoma and involved in cellular proliferation and survival, leads to the suggestion that exploring pan-sirtuin inhibitors may be the best target for the next iteration of melanoma chemotherapeutics.

PMID: 28166441 [PubMed - indexed for MEDLINE]

Relative Importance of Traditional Risk Factors for Malignant Melanoma in the Czech Population.

Fetched: June 21st, 2017, 1:00am EDT

Relative Importance of Traditional Risk Factors for Malignant Melanoma in the Czech Population.

Cent Eur J Public Health. 2016 Dec;24(4):268-271

Authors: Rajská L, Göpfertová D, Hercogová J, Jiráková A, Sečníková Z, Rob F, Šmerhovský Z

Abstract
AIM: The Czech Republic is one of the leading European countries in incident cases of malignant melanoma (MM), which is on the rise. The study objective was to assess the strength of associations between MM and the known generally accepted risk factors for MM in the population of the Czech Republic.
METHODS: The study was designed as a case-control study where cases were incident cases of MM detected at the Department of Dermatology and Venereology of the Bulovka Hospital. Controls were selected from cancer-free patients admitted to departments other than Dermatology and Venereology. Validated questionnaires were used to collect demographic, epidemiological, and clinical data.
RESULTS: The binary logistic model shows the main risk factors for MM: male, female (OR=0.292, 95% CI=0.175-0.486), a changed mole (OR=6.371, 95% CI=3.774-10.756), a history of skin cancer (OR=95.704, 95% CI=37.241-10.756), and sunbeds use (OR=3.594, 95% CI=1.288-10.028). Using sunscreen products was considered as a protective factor against MM (OR=0.253, 95% CI=0.137-0.466).
CONCLUSION: The primary and secondary prevention increasingly emerges as a public health priority in the effort to reverse the negative trend in cases of MM and mortality from this disease in the Czech Republic. A prerequisite for an effective secondary prevention through screening is, among others, the identification of the population groups at highest risk for MM.

PMID: 28095280 [PubMed - indexed for MEDLINE]

Permalink for 'NF-κB Signaling Activation Induced by Chloroquine Requires Autophagosome, p62 Protein, and c-Jun N-terminal Kinase (JNK) Signaling and Promotes Tumor Cell Resistance.'

NF-κB Signaling Activation Induced by Chloroquine Requires Autophagosome, p62 Protein, and c-Jun N-terminal Kinase (JNK) Signaling and Promotes Tumor Cell Resistance.

Fetched: June 21st, 2017, 1:00am EDT

NF-κB Signaling Activation Induced by Chloroquine Requires Autophagosome, p62 Protein, and c-Jun N-terminal Kinase (JNK) Signaling and Promotes Tumor Cell Resistance.

J Biol Chem. 2017 Feb 24;292(8):3379-3388

Authors: Yang S, Qiang L, Sample A, Shah P, He YY

Abstract
Macroautophagy (hereafter autophagy) is a catabolic cellular self-eating process by which unwanted organelles or proteins are delivered to lysosomes for degradation through autophagosomes. Although the role of autophagy in cancer has been shown to be context-dependent, the role of autophagy in tumor cell survival has attracted great interest in targeting autophagy for cancer therapy. One family of potential autophagy blockers is the quinoline-derived antimalarial family, including chloroquine (CQ). However, the molecular basis for tumor cell response to CQ remains poorly understood. We show here that in both squamous cell carcinoma cells and melanoma tumor cells, CQ induced NF-κB activation and the expression of its target genes HIF-1α, IL-8, BCL-2, and BCL-XL through the accumulation of autophagosomes, p62, and JNK signaling. The activation of NF-κB further increased p62 gene expression. Either genetic knockdown of p62 or inhibition of NF-κB sensitized tumor cells to CQ, resulting in increased apoptotic cell death following treatment. Our findings provide new molecular insights into the CQ response in tumor cells and CQ resistance in cancer therapy. These findings may facilitate development of improved therapeutic strategies by targeting the p62/NF-κB pathway.

PMID: 28082672 [PubMed - indexed for MEDLINE]

Oncology's Trojan Horse: Using Viruses to Battle Cancer.

Fetched: June 21st, 2017, 1:00am EDT

Oncology's Trojan Horse: Using Viruses to Battle Cancer.

Consult Pharm. 2016 Dec 01;31(12):676-684

Authors: Mavani HJ, Wick JY

Abstract
In 2016, the American health care system was faced with more than 1.6 million new cases of cancer, and individuals older than 65 years of age will be affected disproportionately. Many older individuals are poor candidates for traditional treatments (e.g., chemotherapy, radiation) because of actual or potential treatment-related adverse events. Researchers continuously look for novel therapeutic strategies, and an exciting new one is on the horizon: virotherapy. Viruses' ability to infect and kill human cells makes them promising cancer treatments. The greatest success has been seen in acute lymphocytic leukemia. To date, four genetically engineered oncolytic viruses have been approved globally by several countries' health regulatory agencies, but several challenges remain. Only one, talimogene laherparepvec (T-Vec), is available in the United States. Treatment-naive patients tend to respond better than patients receiving T-Vec as second-line therapy. Other good candidates for T-Vec include elderly patients who do not tolerate checkpoint inhibitors (the leading immunotherapy in advanced melanoma). Researchers continue to look for ways to increase oncolytic viruses' clinical potency. Once they do, these agents will become effective cancer therapy.
ABBREVIATIONS: GM-CSF = Genetically modified colony-stimulating factor, HIV = Human immunodeficiency virus, HSV-1 = Herpes simplex virus, OV = Oncolytic virus.

PMID: 28074746 [PubMed - indexed for MEDLINE]

Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma.

Fetched: June 21st, 2017, 1:00am EDT

Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma.

Drug Des Devel Ther. 2016;10:3755-3761

Authors: Yang C, Cao H, Liu N, Xu K, Ding M, Mao LJ

Abstract
Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18, and these were not affected by DTIC. ZD55-IL-18 enhanced the cytotoxicity of DTIC accompanied by increased apoptosis. Moreover, ZD55-IL-18 and DTIC synergistically inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited vascular endothelial growth factor expression and lung metastasis in xenografts of nude mice. In conclusion, this is the first study to show synergistic anticancer activity of ZD55-IL-18 and DTIC for malignant melanoma. Our results provide evidence that chemo-gene-viro therapeutic approach has greater potential for malignant cancers than conventional chemotherapy or gene therapy.

PMID: 27895465 [PubMed - indexed for MEDLINE]

Permalink for 'A comparison of enhancement patterns on dynamic enhanced CT and survival between patients with pancreatic neuroendocrine tumors with and without intratumoral fibrosis.'

A comparison of enhancement patterns on dynamic enhanced CT and survival between patients with pancreatic neuroendocrine tumors with and without intratumoral fibrosis.

Fetched: June 20th, 2017, 1:00am EDT

A comparison of enhancement patterns on dynamic enhanced CT and survival between patients with pancreatic neuroendocrine tumors with and without intratumoral fibrosis.

Abdom Radiol (NY). 2017 Jun 17;:

Authors: Kim C, Byun JH, Hong SM, An S, Kim JH, Lee SS, Kim HJ

Abstract
PURPOSE: To compare CT findings and survival between patients with pancreatic neuroendocrine tumors (pNETs) with and without fibrosis.
METHODS: Forty-five pNET patients with intratumoral fibrosis (group A) were matched for age, gender, and tumor size and grade with 45 pNET patients without (group B), and CT images were retrospectively reviewed. Hounsfield units (HUs) of tumors in unenhanced, arterial and portal phases, HU ratio (tumor to normal parenchyma) in each phase, enhancement patterns, visible enhancement pattern changes, and survival were compared.
RESULTS: Group A showed progressive enhancement patterns, while group B showed early enhancement and wash-out patterns (p < 0.05). HUs of tumors and HU ratio in the unenhanced phase were significantly higher in group A than group B (p ≤ 0.024), whereas those in the arterial phase were significantly lower in group A than group B (p ≤ 0.003). Peripheral to full or peripheral to peripheral enhancement change was more frequent in group A, while full to full enhancement change was more frequent in group B (p < 0.05). Group A showed significantly lower overall survival than group B (p = 0.029).
CONCLUSIONS: pNETs with fibrosis showed a progressive enhancement pattern and worse overall survival than pNETs without, which showed an early enhancement and wash-out pattern.

PMID: 28624923 [PubMed - as supplied by publisher]

Diffuse Enlargement of the Pancreas: An Unusual Radiologic Presentation of a Pancreatic Neuroendocrine Tumor.

Fetched: June 20th, 2017, 1:00am EDT

Diffuse Enlargement of the Pancreas: An Unusual Radiologic Presentation of a Pancreatic Neuroendocrine Tumor.

Clin Gastroenterol Hepatol. 2017 Jun 14;:

Authors: Santes O, Morales-Maza J, Domínguez-Rosado I

PMID: 28624649 [PubMed - as supplied by publisher]

Permalink for 'Hsp90 inhibitor geldanamycin attenuates the cytotoxicity of sunitinib in cardiomyocytes via inhibition of the autophagy pathway.'

Hsp90 inhibitor geldanamycin attenuates the cytotoxicity of sunitinib in cardiomyocytes via inhibition of the autophagy pathway.

Fetched: June 20th, 2017, 1:00am EDT

Hsp90 inhibitor geldanamycin attenuates the cytotoxicity of sunitinib in cardiomyocytes via inhibition of the autophagy pathway.

Toxicol Appl Pharmacol. 2017 Jun 14;:

Authors: Kimura T, Uesugi M, Takase K, Miyamoto N, Sawada K

Abstract
Sunitinib malate (sunitinib) is an orally available, multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. Although sunitinib is effective for the treatment of patients with gastrointestinal stromal tumor, advanced renal cell carcinoma, or pancreatic neuroendocrine tumor, adverse cardiac events associated with sunitinib administration have been reported. Here, we examined the effect of geldanamycin, an inhibitor of heat shock protein (Hsp) 90, on sunitinib-induced cytotoxicity in cardiomyocytes. First, we found that treatment with geldanamycin or other Hsp90 inhibitors (tanespimycin, ganetespib, or BIIB021) significantly attenuated sunitinib-induced cytotoxicity in rat H9c2 cardiomyocytes, suggesting a drug-class effect of Hsp90 inhibitors. We then examined the mechanisms underlying sunitinib-induced cytotoxicity and found that sunitinib induced autophagy in H9c2 cells and that pretreatment with geldanamycin inhibited the induction of autophagy by promoting degradation of the autophagy-related proteins Atg7, Beclin-1, and ULK1. Pharmacological assessment with autophagy inhibitors confirmed that geldanamycin attenuated the cytotoxicity of sunitinib by interfering with autophagy. In addition, we found that the molecular chaperone Hsp70, which is induced by geldanamycin, was not involved in the attenuation of sunitinib-induced cytotoxicity. Finally, to provide more clinically relevant data, we confirmed that geldanamycin attenuated sunitinib-induced cytotoxicity in human induced pluripotent stem cell-derived cardiomyocytes. Together, these data suggest that geldanamycin attenuates sunitinib-induced cytotoxicity in cardiomyocytes by inhibiting the autophagy pathway. Thus, the further investigation of combination or sequential treatment with an Hsp90 inhibitor and sunitinib is warranted as a potential strategy of attenuating the cardiotoxicity associated with sunitinib administration in the clinical setting.

PMID: 28624441 [PubMed - as supplied by publisher]

Liver transplantation in patients with liver metastases from neuroendocrine tumors: A systematic review.

Fetched: June 20th, 2017, 1:00am EDT

Liver transplantation in patients with liver metastases from neuroendocrine tumors: A systematic review.

Surgery. 2017 Jun 14;:

Authors: Moris D, Tsilimigras DI, Ntanasis-Stathopoulos I, Beal EW, Felekouras E, Vernadakis S, Fung JJ, Pawlik TM

Abstract
BACKGROUND: Liver transplantation to treat neuroendocrine tumors, especially in the setting of diffuse liver involvement not amenable to operative resection remains controversial. We sought to perform a systematic review of the current literature to summarize data on patients undergoing liver transplantation with neuroendocrine tumors liver metastases as the indication.
METHODS: A systematic review was conducted in accordance to the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Eligible studies were identified using 3 distinct databases through March 2017: Medline (PubMed), ClinicalTrials.gov, and Cochrane library, Cochrane Central Register of Controlled Trials using a search algorithm: "(neuroendocrine or NET) and transplantation and liver."
RESULTS: From the 1,216 records retrieved, 64 studies were eligible. Overall, 4 studies presented data from registries, namely the European Liver Transplant Registry and the United Network for Organ Transplantation/Organ Procurement and Transplantation Network databases, 3 were multicenter studies. The largest cohort of data on patients undergoing liver transplantation for neuroendocrine tumors liver metastasis indication were from single center studies comprising a total of 279 patients. Pancreas was the primary tumor site for most patients followed by the ileum. Several studies reported that more than half of patients presented with synchronous disease (55.9% and 57.7%); in contrast, metachronous neuroendocrine tumors liver metastasis ranged from 17.7% to 38.7%. Overall, recurrence after liver transplantation ranged from 31.3% to 56.8%. Reported 1-, 3-, and 5-year overall survival was 89%, 69%, and 63%, respectively. Several prognostic factors associated with worse long-term survival including transplantation >50% liver tumor involvement, high Ki67, as well as a pancreatic neuroendocrine tumors versus gastrointestinal neuroendocrine tumors tumor location.
CONCLUSION: Liver transplantation may provide a survival benefit among patients with diffuse neuroendocrine tumors metastases to the liver. However, due to high recurrence rates, strict selection of patients is critical. Due to the scarcity of available grafts and the lack of level 1 evidence, the recommendations to endorse liver transplantation for extensive liver neuroendocrine tumors metastases warrants ongoing deliberations.

PMID: 28624178 [PubMed - as supplied by publisher]

The role of wireless capsule endoscopy (WCE) in the detection of occult primary neuroendocrine tumors.

Fetched: June 17th, 2017, 1:00am EDT

The role of wireless capsule endoscopy (WCE) in the detection of occult primary neuroendocrine tumors.

J Gastrointestin Liver Dis. 2017 Jun;26(2):151-156

Authors: Furnari M, Buda A, Delconte G, Citterio D, Voiosu T, Ballardini G, Cavallaro F, Savarino E, Mazzaferro V, Meroni E

Abstract
BACKGROUND AND AIMS: Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with unclear etiology that may show functioning or non-functioning features. Primary tumor localization often requires integrated imaging. The European Neuroendocrine Tumors Society (ENETS) guidelines proposed wireless-capsule endoscopy (WCE) as a possible diagnostic tool for NETs, if intestinal origin is suspected. However, its impact on therapeutic management is debated. We aimed to evaluate the yield of WCE in detecting intestinal primary tumors in patients showing liver NET metastases when first-line investigations are inconclusive.
METHOD: Twenty-four patients with a histological diagnosis of metastatic NET from liver biopsy and no evidence of primary lesions at first-line investigations were prospectively studied in an ENETS-certified tertiary care center. Wireless-capsule endoscopy was requested before explorative laparotomy and intra-operative ultrasound. The diagnostic yield of WCE was compared to the surgical exploration.
RESULTS: Sixteen subjects underwent surgery; 11/16 had positive WCE identifying 16 bulging lesions. Mini-laparotomy found 13 NETs in 11/16 patients (9 small bowel, 3 pancreas, 1 bile ducts). Agreement between WCE and laparotomy was recorded in 9 patients (Sensitivity=75%; Specificity=37.5%; PPV=55%; NPV=60%). Correspondence assessed per-lesions produced similar results (Sensitivity=70%; Specificity=25%; PPV=44%; NPV=50%). No capsule retentions were recorded.
CONCLUSIONS: Wireless-capsule endoscopy is not indicated as second-line investigation for patients with gastro-entero-pancreatic NETs. In the setting of a referral center, it might provide additional information when conventional investigations are inconclusive about the primary site.

PMID: 28617885 [PubMed - in process]

Usefulness of NKX2.2 Immunohistochemistry for Distinguishing Ewing Sarcoma from Other Sinonasal Small Round Blue Cell Tumors.

Fetched: June 17th, 2017, 1:00am EDT

Usefulness of NKX2.2 Immunohistochemistry for Distinguishing Ewing Sarcoma from Other Sinonasal Small Round Blue Cell Tumors.

Head Neck Pathol. 2017 Jun 14;:

Authors: McCuiston A, Bishop JA

Abstract
NKX2.2 is a new immunohistochemical marker that has been reported to be sensitive and specific for Ewing sarcoma (ES). It has not, however, been investigated specifically in the sinonasal small round blue cell tumor (SRBCT) differential diagnosis which includes many tumors specific to that site. It has also not been investigated in the newly recognized "adamantinoma-like" variant of ES. Immunohistochemistry for NKX2.2 was performed on 170 poorly differentiated sinonasal neoplasms: 73 squamous cell carcinomas (67 poorly differentiated, non-keratinizing, or basaloid types and 6 nasopharyngeal carcinomas), 46 olfactory neuroblastomas, 8 sinonasal undifferentiated carcinomas (SNUCs), 6 melanomas, 7 Ewing sarcomas, 6 SMARCB1-deficient carcinomas, 6 teratocarcinosarcomas, 5 alveolar rhabdomyosarcomas, 4 solid adenoid cystic carcinomas, 4 NK/T cell lymphomas, 3 NUT carcinomas, and 2 small cell carcinomas. NKX2.2 was positive in 7 of 7 (100%) Ewing sarcomas, including 3 adamantinoma-like variant (all diffuse, 5 strong and 2 weak). It was also positive in 5 of 6 (83%) teratocarcinosarcomas (strong, but focal), 12 of 46 (26%) olfactory neuroblastomas (diffuse, 2 strong and 10 weak), 4 of 6 melanomas (2 diffuse, 2 focal, all weak), and 1 of 2 small cell carcinomas (diffuse and strong). All squamous cell carcinomas, NUT carcinomas, SMARCB1-deficient carcinomas, SNUCs, solid adenoid cystic carcinomas, NK/T cell lymphomas, and alveolar rhabdomyosarcomas were negative. In the sinonasal SRBCT differential diagnosis, NKX2.2 is a useful and very sensitive marker for Ewing sarcoma, including the treacherous adamantinoma-like variant. At the same time, it is not entirely specific, as it will be positive in a subset of other neuroendocrine/neuroectodermal tumors. As a result, NKX2.2 must be utilized as part of an immunohistochemical panel with other markers, especially cytokeratins, melanoma markers, and CD99.

PMID: 28616785 [PubMed - as supplied by publisher]

17β-Estradiol and progesterone decrease MDP induced NOD2 expression in bovine mammary epithelial cells.

Fetched: June 17th, 2017, 1:00am EDT

17β-Estradiol and progesterone decrease MDP induced NOD2 expression in bovine mammary epithelial cells.

Vet Immunol Immunopathol. 2017 Jun;188:59-64

Authors: Xu DD, Wang G, He XJ, Wang JF, Yang B, Sun ZP, Sun DB, He QY, Zhang X, Wu R

Abstract
During the periparturient period, many neuroendocrine changes develop in cows. Periparturient hormone fluxes may adversely affect mammary gland immunity and mastitis susceptibility. 17β-Estradiol (E2) and progesterone (P4) have been reported to function on immune regulation, and their concentration fluctuates dramatically during the perinatal period. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) mediate numerous aspects of innate immunity in humans and experimental animals. This study aimed to explore the effects of E2 and P4 on NOD2 expression in bovine mammary epithelial cells (BMECs). BMECs were isolated and purified from bovine mammary tissue and treated with E2/P4 and muramyl dipeptide (MDP). After these treatments, the mRNA levels of NOD2, receptor-interacting protein kinase (RIP) 2, interleukin (IL) 1β, IL-6, IL-8 and tumor necrosis factor (TNF) α were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) respectively, and the protein levels of NOD2 were analyzed by western blotting. The results showed that E2 and P4 decreased MDP-induced transcriptional expression of NOD2 and the downstream molecules. Moreover, E2 reduced MDP-induced NOD2 protein expression levels. Our study suggests that down-regulation of NOD2 by E2 and P4 may be one of the reasons for mastitis susceptibility in periparturient dairy cows.

PMID: 28615128 [PubMed - in process]

Recurrent promoter mutations in melanoma are defined by an extended context-specific mutational signature.

Fetched: June 17th, 2017, 1:00am EDT

Recurrent promoter mutations in melanoma are defined by an extended context-specific mutational signature.

PLoS Genet. 2017 May;13(5):e1006773

Authors: Fredriksson NJ, Elliott K, Filges S, Van den Eynden J, Ståhlberg A, Larsson E

Abstract
Sequencing of whole tumor genomes holds the promise of revealing functional somatic regulatory mutations, such as those described in the TERT promoter. Recurrent promoter mutations have been identified in many additional genes and appear to be particularly common in melanoma, but convincing functional data such as influence on gene expression has been more elusive. Here, we show that frequently recurring promoter mutations in melanoma occur almost exclusively at cytosines flanked by a distinct sequence signature, TTCCG, with TERT as a notable exception. In active, but not inactive, promoters, mutation frequencies for cytosines at the 5' end of this ETS-like motif were considerably higher than expected based on a UV trinucleotide mutational signature. Additional analyses solidify this pattern as an extended context-specific mutational signature that mediates an exceptional position-specific vulnerability to UV mutagenesis, arguing against positive selection. We further use ultra-sensitive amplicon sequencing to demonstrate that cell cultures exposed to UV light quickly develop subclonal mutations specifically in affected positions. Our findings have implications for the interpretation of somatic mutations in regulatory regions, and underscore the importance of genomic context and extended sequence patterns to accurately describe mutational signatures in cancer.

PMID: 28489852 [PubMed - indexed for MEDLINE]

Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma.

Fetched: June 17th, 2017, 1:00am EDT

Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma.

J Natl Compr Canc Netw. 2017 Apr;15(4):473-482

Authors: Strom T, Torres-Roca JF, Parekh A, Naghavi AO, Caudell JJ, Oliver DE, Messina JL, Khushalani NI, Zager JS, Sarnaik A, Mulé JJ, Trotti AM, Eschrich SA, Sondak VK, Harrison LB

Abstract
Background: Regional radiation therapy (RT) has been shown to reduce the risk of regional recurrence with node-positive cutaneous melanoma. However, risk factors for regional recurrence, especially in the era of sentinel lymph node biopsy (SLNB), are less clear. Our goals were to identify risk factors associated with regional recurrence and to determine whether a radiosensitivity index (RSI) gene expression signature (GES) could identify patients who experience a survival benefit with regional RT. Methods: A single-institution, Institutional Review Board-approved study was performed including 410 patients treated with either SLNB with or without completion lymph node dissection (LND; n=270) or therapeutic LND (n=91). Postoperative regional RT was delivered to the involved nodal basin in 83 cases (20.2%), to a median dose of 54 Gy (range, 30-60 Gy) in 27 fractions (range, 5-30). Primary outcomes were regional control and overall survival by RSI GES status. Results: Median follow-up was 69 months (range, 13-180). Postoperative regional RT was associated with a reduced risk of regional recurrence among all patients on univariate (5-year estimate: 95.0% vs 83.3%; P=.036) and multivariate analysis (hazard ratio[HR], 0.15; 95% CI, 0.05-0.43; P<.001). Among higher-risk subgroups, regional RT was associated with a lower risk of regional recurrence among patients with clinically detected lymph nodes (n=175; 5-year regional control: 94.1% vs 69.5%; P=.003) and extracapsular extension (ECE) present (n=138; 5-year regional control: 96.7% vs 62.2%; P<.001). Among a subset of radiated patients with gene expression data available, a low RSI GES (radiosensitive) tumor status was associated with improved survival compared with a high RSI GES (5-year: 75% vs 0%; HR, 10.68; 95% CI, 1.24-92.14). Conclusions: Regional RT was associated with a reduced risk of regional recurrence among patients with ECE and clinically detected nodal disease. Gene expression data show promise for better predicting radiocurable patients in the future. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance.

PMID: 28404758 [PubMed - indexed for MEDLINE]

Surgical management of lung metastases.

Fetched: June 17th, 2017, 1:00am EDT

Surgical management of lung metastases.

Br J Hosp Med (Lond). 2017 Apr 02;78(4):192-198

Authors: Patrini D, Panagiotopoulos N, Lawrence D, Scarci M

Abstract
Management of pulmonary metastases has evolved considerably over the last few decades but is still controversial. The surgical management of lung metastases is outlined, discussing the preoperative management, indications for surgery, the surgical approach and outcomes according to the primary histology.

PMID: 28398890 [PubMed - indexed for MEDLINE]

CDKN2A and MC1R variants found in Cypriot patients diagnosed with cutaneous melanoma.

Fetched: June 17th, 2017, 1:00am EDT

CDKN2A and MC1R variants found in Cypriot patients diagnosed with cutaneous melanoma.

J Genet. 2017 Mar;96(1):155-160

Authors: Koulermou G, Shammas C, Vassiliou A, Kyriakides TC, Costi C, Neocleous V, Phylactou LA, Pantelidou M

Abstract
The prevalence of genetic variants associated to cutaneous melanoma (CM) has never been determined within Cypriot melanomas. This study evaluates the frequency of variants in cyclin-dependent kinase inhibitor 2A (CDKN2A) and melanocortin-1 receptor (MC1R) in 32 patients diagnosed with CM. Other characteristics and risk factors were also assessed. CDKN2A p.Ala148Thr was detected in three of 32 patients, while the control group revealed no variations within CDKN2A. MC1R screening in 32 patients revealed the following variations: p.Val60Leu in 11 patients, p.Arg142His in four patients, p.Thr314Thr in one patient, p.Arg160Trp in one patient, p.Val92Met/p.Thr314Thr in one patient and p.Val92Met/p.Arg142His/p.Thr314Thr in one patient. The control group revealed only p.Val60Leu (in 10 of 45 individuals), which is frequently found in general populations. Two unrelated patients carried CDKN2A p.Ala148Thr in combination with MC1R p.Arg142His, suggesting digenic inheritance that may provide evidence of different gene variants acting synergistically to contribute for CM development. This study confirms the presence of CDKN2A and MC1R variants among Cypriot melanomas and supports existing evidence of a role for these variants in susceptibility to melanoma.

PMID: 28360400 [PubMed - indexed for MEDLINE]

Permalink for 'Induction of Chemokine Secretion and Monocyte Migration by Human Choroidal Melanocytes in Response to Proinflammatory Cytokines.'

Induction of Chemokine Secretion and Monocyte Migration by Human Choroidal Melanocytes in Response to Proinflammatory Cytokines.

Fetched: June 17th, 2017, 1:00am EDT

Induction of Chemokine Secretion and Monocyte Migration by Human Choroidal Melanocytes in Response to Proinflammatory Cytokines.

Invest Ophthalmol Vis Sci. 2016 Dec 01;57(15):6568-6579

Authors: Jehs T, Faber C, Udsen MS, Jager MJ, Clark SJ, Nissen MH

Abstract
Purpose: To determine to which extent inflammatory cytokines affect chemokine secretion by primary human choroidal melanocytes (HCMs), their capacity to attract monocytes, and whether HCMs are able to influence the proliferation of activated T cells.
Methods: Primary cultures of HCMs were established from eyes of 13 donors. Human choroidal melanocytes were stimulated with IFN-γ and TNF-α or with supernatant from activated T cells (T-cell-conditioned media [TCM]). Gene expression analysis was performed by using microarrays. Protein levels were quantified with ELISA or cytometric bead array. Supernatants of HCMs were assessed for the capability to attract monocytes in a transwell plate. Proliferation of activated T cells was assessed in a direct coculture with HCMs by a [3H]-thymidine incorporation assay.
Results: Stimulation of HCMs with TCM or IFN-γ and TNF-α resulted in increased expression and secretion of CXCL8, CXCL9, CXCL10, CXCL11, CCL2, CCL5 and intercellular adhesion molecule 1. Vascular endothelial growth factor and monocyte migration inhibitory factor were constitutively expressed without changes in response to proinflammatory cytokines. Supernatants derived from unstimulated cultures of 10 HCM donors induced a high initial level of monocyte migration, which decreased upon stimulation with either TCM or IFN-γ and TNF-α. The supernatants from three HCM donors initially showed a low level of monocyte attraction, which increased after exposure to proinflammatory cytokines. Direct coculture of HCMs with T cells resulted in inhibition of T-cell proliferation.
Conclusions: These results showed that normal and activated HCMs are immunologically active by secreting chemokines, and that HCMs are able to attract monocytes in addition to inhibiting T-cell proliferation.

PMID: 27918831 [PubMed - indexed for MEDLINE]

Permalink for 'The BRAF Inhibitor Vemurafenib Activates Mitochondrial Metabolism and Inhibits Hyperpolarized Pyruvate-Lactate Exchange in BRAF-Mutant Human Melanoma Cells.'

The BRAF Inhibitor Vemurafenib Activates Mitochondrial Metabolism and Inhibits Hyperpolarized Pyruvate-Lactate Exchange in BRAF-Mutant Human Melanoma Cells.

Fetched: June 17th, 2017, 1:00am EDT

The BRAF Inhibitor Vemurafenib Activates Mitochondrial Metabolism and Inhibits Hyperpolarized Pyruvate-Lactate Exchange in BRAF-Mutant Human Melanoma Cells.

Mol Cancer Ther. 2016 Dec;15(12):2987-2999

Authors: Delgado-Goni T, Miniotis MF, Wantuch S, Parkes HG, Marais R, Workman P, Leach MO, Beloueche-Babari M

Abstract
Understanding the impact of BRAF signaling inhibition in human melanoma on key disease mechanisms is important for developing biomarkers of therapeutic response and combination strategies to improve long-term disease control. This work investigates the downstream metabolic consequences of BRAF inhibition with vemurafenib, the molecular and biochemical processes that underpin them, their significance for antineoplastic activity, and potential as noninvasive imaging response biomarkers. (1)H NMR spectroscopy showed that vemurafenib decreases the glycolytic activity of BRAF-mutant (WM266.4 and SKMEL28) but not BRAF(WT) (CHL-1 and D04) human melanoma cells. In WM266.4 cells, this was associated with increased acetate, glycine, and myo-inositol levels and decreased fatty acyl signals, while the bioenergetic status was maintained. (13)C NMR metabolic flux analysis of treated WM266.4 cells revealed inhibition of de novo lactate synthesis and glucose utilization, associated with increased oxidative and anaplerotic pyruvate carboxylase mitochondrial metabolism and decreased lipid synthesis. This metabolic shift was associated with depletion of hexokinase 2, acyl-CoA dehydrogenase 9, 3-phosphoglycerate dehydrogenase, and monocarboxylate transporters (MCT) 1 and 4 in BRAF-mutant but not BRAF(WT) cells and, interestingly, decreased BRAF-mutant cell dependency on glucose and glutamine for growth. Further, the reduction in MCT1 expression observed led to inhibition of hyperpolarized (13)C-pyruvate-lactate exchange, a parameter that is translatable to in vivo imaging studies, in live WM266.4 cells. In conclusion, our data provide new insights into the molecular and metabolic consequences of BRAF inhibition in BRAF-driven human melanoma cells that may have potential for combinatorial therapeutic targeting as well as noninvasive imaging of response. Mol Cancer Ther; 15(12); 2987-99. ©2016 AACR.

PMID: 27765851 [PubMed - indexed for MEDLINE]

In Vivo Antitumor Activity of a Recombinant IL7/IL15 Hybrid Cytokine in Mice.

Fetched: June 17th, 2017, 1:00am EDT

In Vivo Antitumor Activity of a Recombinant IL7/IL15 Hybrid Cytokine in Mice.

Mol Cancer Ther. 2016 Oct;15(10):2413-2421

Authors: Song Y, Liu Y, Hu R, Su M, Rood D, Lai L

Abstract
Both IL7 and IL15 have become important candidate immunomodulators for cancer treatment. However, IL7 or IL15 used alone suffers from shortcomings, such as short serum half-life and limited antitumor effect. We have cloned and expressed a recombinant (r) IL7/IL15 fusion protein in which IL7 and IL15 are linked by a flexible linker. We then compared the antitumor effect of rIL7/IL15 with the individual factors rIL7 and/or rIL15. We show here that rIL7/IL15 has a higher antitumor activity than the combination of the individual factors in both murine B16F10 melanoma and CT-26 colon cancer models. This was associated with a significant increase in tumor infiltration of T cells, DCs, and NK cells and a decrease in regulatory T cells (Tregs). In addition, rIL7/IL15-treated DCs had higher expression of costimulatory molecules CD80 and CD86. The higher antitumor activity of rIL7/IL15 is likely due to its longer in vivo half-life and different effects on immune cells. Our results suggest that rIL7/IL15 may offer a new tool to enhance antitumor immunity and treat cancer. Mol Cancer Ther; 15(10); 2413-21. ©2016 AACR.

PMID: 27474151 [PubMed - indexed for MEDLINE]

Hypoxia-Driven Mechanism of Vemurafenib Resistance in Melanoma.

Fetched: June 17th, 2017, 1:00am EDT

Hypoxia-Driven Mechanism of Vemurafenib Resistance in Melanoma.

Mol Cancer Ther. 2016 Oct;15(10):2442-2454

Authors: Qin Y, Roszik J, Chattopadhyay C, Hashimoto Y, Liu C, Cooper ZA, Wargo JA, Hwu P, Ekmekcioglu S, Grimm EA

Abstract
Melanoma is molecularly and structurally heterogeneous, with some tumor cells existing under hypoxic conditions. Our cell growth assays showed that under controlled hypoxic conditions, BRAF(V600E) melanoma cells rapidly became resistant to vemurafenib. By employing both a three-dimensional (3D) spheroid model and a two-dimensional (2D) hypoxic culture system to model hypoxia in vivo, we identified upregulation of HGF/MET signaling as a major mechanism associated with vemurafenib resistance as compared with 2D standard tissue culture in ambient air. We further confirmed that the upregulation of HGF/MET signaling was evident in drug-resistant melanoma patient tissues and mouse xenografts. Pharmacologic inhibition of the c-Met/Akt pathway restored the sensitivity of melanoma spheroids or 2D hypoxic cultures to vemurafenib. Mol Cancer Ther; 15(10); 2442-54. ©2016 AACR.

PMID: 27458138 [PubMed - indexed for MEDLINE]

Spectral-Domain Optical Coherence Tomography Findings in Neurofibromatosis Type 2.

Fetched: June 17th, 2017, 1:00am EDT

Spectral-Domain Optical Coherence Tomography Findings in Neurofibromatosis Type 2.

Invest Ophthalmol Vis Sci. 2016 Jul 01;57(9):OCT262-7

Authors: Waisberg V, Rodrigues LO, Nehemy MB, Frasson M, de Miranda DM

Abstract
PURPOSE: Neurofibromatosis type 2 (NF2) is an autosomal-dominant disease, characterized by bilateral vestibular schwannomas, multiple central nervous system (CNS) tumors, skin tumors, and juvenile cataract. The present study assessed retinal abnormalities using spectral-domain optical coherence tomography (SD-OCT) in a case series of NF2 patients.
METHODS: Nine NF2 patients from the neurofibromatosis outpatient reference center of the Federal University of Minas Gerais, in Brazil, were submitted to a complete anamnesis and a detailed ophthalmic evaluation, including SD-OCT, to detect retinal lesions.
RESULTS: Of the nine NF2 patients evaluated, five had an early onset (<20 years) of NF2, and four patients had a late onset (>20 years) of symptoms. SD-OCT scans revealed retinal abnormalities in every patient with early onset (EOS) and in two patients with late onset (LOS) of the disease. In the EOS group, SD-OCT scans revealed flame-shaped epiretinal membranes (ERM) with peculiar characteristics in four eyes of three patients. Two patients had fine undulations of the inner retinal surface with a subtle ERM. Retinal hamartomas were present in four eyes of three patients with EOS; in two eyes, they were subclinical and were detected only by SD-OCT scans. In two patients with LOS and one patient with EOS, SD-OCT scans revealed retinal tufts of a nerve fiber layer.
CONCLUSIONS: SD-OCT revealed ERM in most patients with NF2, therefore it may be a valuable exam for evaluating NF2 patients. Epiretinal membranes in NF2 has unique features, distinguishing it from idiopathic ERM or membranes associated with other diseases. We suggest that flame-shaped ERM seems to be specific for NF2 and that ERM can be considered as an important diagnostic sign of NF2.

PMID: 27409481 [PubMed - indexed for MEDLINE]

Microsatellite instability as a predictive factor for immunotherapy in malignant melanoma.

Fetched: June 17th, 2017, 1:00am EDT

Microsatellite instability as a predictive factor for immunotherapy in malignant melanoma.

Med Hypotheses. 2016 Aug;93:74-6

Authors: Kubecek O, Trojanova P, Molnarova V, Kopecky J

Abstract
Immunotherapy has attracted attention as a novel treatment modality for malignant melanoma. Although the use of immunotherapy in metastatic melanoma has shown promising results, there remains a lack of predictive biomarkers indicating treatment benefit from immunotherapy. There is growing evidence suggesting that microsatellite instability (MSI) as a product of DNA mismatch repair deficiency, may be one of possible predictive markers in malignant melanoma. It has been proposed that the immunogenicity of some tumors might be determined by mutational heterogeneity and could be the key to the success of immune therapies. This is also supported by the fact that tumors with the highest amount of somatic mutations, such as malignant melanoma have showed positive results with immune checkpoint inhibitors. There are promising data regarding the association between MSI status and immunogenicity from studies with colorectal cancer, where MSI is linked to improved prognosis compared to microsatellite stable cancers. MSI in colon cancer is linked to a significant increase of immunocompetent cells responsible for the antitumor activity - CD3(+), CD8(+), CD45RO(+), and T-bet(+) lymphocytes and decrease of inhibition factors such as Foxp3, IL-6, IL-17, and TGF-β. On the other hand, taking into account the progression-dependent accumulation of somatic mutations in MSI tumors and consequent high levels of neo-antigens, the possible drug resistance of MSI tumors to traditional treatment, and the presence of inhibition checkpoints within the MSI tumors, there is a solid rationale for the use of novel therapeutic strategies such as immunotherapy in MSI melanomas. We presume that the MSI phenotype in malignant melanoma might be helpful to identify patients, who would be more likely to profit from immunotherapy than from conventional therapy.

PMID: 27372860 [PubMed - indexed for MEDLINE]

Cancer treatment and survivorship statistics, 2016.

Fetched: June 17th, 2017, 1:00am EDT

Cancer treatment and survivorship statistics, 2016.

CA Cancer J Clin. 2016 Jul;66(4):271-89

Authors: Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A

Abstract
The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care. CA Cancer J Clin 2016;66:271-289. © 2016 American Cancer Society.

PMID: 27253694 [PubMed - indexed for MEDLINE]

Primary melanoma of the stomach treated by BRAF inhibitor and immunotherapy.

Fetched: June 17th, 2017, 1:00am EDT

Primary melanoma of the stomach treated by BRAF inhibitor and immunotherapy.

Dig Liver Dis. 2016 Aug;48(8):974

Authors: Bolzacchini E, Marcon I, Bernasconi G, Pinotti G

PMID: 27158123 [PubMed - indexed for MEDLINE]

Growth and Metastasis of Intraocular Tumors in Aged Mice.

Fetched: June 17th, 2017, 1:00am EDT

Growth and Metastasis of Intraocular Tumors in Aged Mice.

Invest Ophthalmol Vis Sci. 2016 May 01;57(6):2366-76

Authors: Han Z, Brown JR, Niederkorn JY

Abstract
PURPOSE: Since deterioration of the immune apparatus is closely associated with cancer, we examined the effect of aging on the growth and metastasis of intraocular melanomas in mice.
METHODS: Murine B16LS9 melanoma cells were transplanted into the posterior compartment of the eye (vitreous chamber) and intraocular tumor growth and development of liver metastases were evaluated in young (8-10 weeks of age) and old (>18 months of age) mice. Liver metastases were also induced by intrasplenic injection of melanoma cells. Natural killer (NK) cells from the livers of mice harboring liver metastases were evaluated in vitro for their cytolytic activity.
RESULTS: Tumors grew more rapidly in the eyes of young mice than old mice, yet old mice developed significantly more liver metastases. Increased liver metastasis in old mice was evident even when melanoma cells were injected intrasplenically as a means of bypassing the influence of the ocular immunosuppressive environment. Increased liver metastases in old mice correlated with reduced cytolytic activity of liver NK cells. Lethally irradiated young mice reconstituted with bone marrow from old donors developed significantly more liver metastases than young mice reconstituted with bone marrow from young donors, indicating that bone marrow-derived cells were the root cause of the heightened development of metastases in old mice.
CONCLUSIONS: Aging affects the growth and metastasis of intraocular melanomas. Even though intraocular melanomas grow slower in old mice, the development of liver metastases is exacerbated and correlates with a reduction in liver NK cell activity in the old mouse.

PMID: 27138736 [PubMed - indexed for MEDLINE]

Permalink for 'The surgical treatment of a melanoma patient with macroscopic metastasis in peri and retrocaval lymph nodes and with a positive sentinel lymph node in the groin.'

The surgical treatment of a melanoma patient with macroscopic metastasis in peri and retrocaval lymph nodes and with a positive sentinel lymph node in the groin.

Fetched: June 17th, 2017, 1:00am EDT

The surgical treatment of a melanoma patient with macroscopic metastasis in peri and retrocaval lymph nodes and with a positive sentinel lymph node in the groin.

Ann Ital Chir. 2016 Feb 04;87(ePub):

Authors: Giudice G, Robusto F, Nacchiero E

Abstract
BACKGROUND: The extension of iliac-obturator dissection in melanoma patient with metastatic sentinel node of the groin is very debated. More recent studies - in accord with guidelines for urogenital cancers - suggest the extension to pelvic lymph nodes. At present, however, anatomical limits and indications to pelvic dissection are not defined in melanoma patients with metastatic lymph nodes of groin.
CASE REPORT: A 46-year-old man affected by nodular cutaneous melanoma (Breslow-thickness 10 mm, Clark-level V) on the anterior-medial surface of the right leg underwent sentinel node biopsy of groin. Three macro-metastatic sentinel lymph nodes were removed in right inguinal field and, after 2 weeks, an ipsi-lateral inguinal lymphadenectomy with an extended pelvic dissection was performed. During the surgery, we reported the presence of macrometastases also in retro/peri caval lymph nodes. As a result of these findings, we decided to perform the super-extended pelvic lymphadenectomy. Overall we removed 56 lymph nodes with 9 peri-caval and 2 retro-caval macro metastatic lymph nodes. After a period of 49 months, the patients came to our attention with multiple scrotal metastases. The imagining restaging of the patient was already negative for other melanoma localizations.
DISCUSSION: Currently there are no guidelines about indications and anatomical limits of iliac-obturator extension in melanoma patients. The extended pelvic dissection is the gold-standard procedure used in urogenital carcinomas. In case of finding of macro-metastases during the surgical procedure, the approach to follow is even more uncertain. We perform a super-extended pelvic dissection with a good prognosis for the patient.
KEY WORDS: Caval-metastasis, Extended-pelvic-lymphadenectomy, Metastatic-melanoma.

PMID: 26903177 [PubMed - indexed for MEDLINE]

Intrapancreatic accessory spleen.

Fetched: June 16th, 2017, 1:00am EDT

Intrapancreatic accessory spleen.

Einstein (Sao Paulo). 2017 Jun 12;:0

Authors: Santos MPD, Rezende AP, Santos PVD, Gonçalves JE, Beraldo FB, Sampaio AP

Abstract
An asymptomatic 79-year-old woman, with incidental finding on abdominal ultrasound of a solid nodule in the tail of the pancreas. Magnetic resonance imaging showed a 12mm solid tumor. The suggested diagnosis was pancreatic neuroendocrine tumor. The pathological examination showed an intrapancreatic splenic tissue. This is a rare ectopic location of spleen tissue and it should be considered in the differential diagnosis of pancreatic solid tumors. RESUMO Mulher de 79 anos, com achado incidental em ultrassonografia de abdome de lesão sólida em cauda de pâncreas. Em ressonância magnética, foi confirmada lesão de 12mm. Foi aventada a hipótese diagnóstica de tumor neuroendócrino não secretor, sendo realizada pancreatectomia distal laparoscópica. Em estudo anatomopatológico, diagnosticou-se tecido esplênico, configurando baço acessório intrapancreático. Este tipo de manifestação topográfica de baço é rara, mas deve fazer parte dos diagnósticos diferenciais em tumores sólidos do pâncreas.

PMID: 28614428 [PubMed - as supplied by publisher]

AN INDIVIDUALIZED APPROACH TO THE EVALUATION OF CUSHING SYNDROME.

Fetched: June 16th, 2017, 1:00am EDT

AN INDIVIDUALIZED APPROACH TO THE EVALUATION OF CUSHING SYNDROME.

Endocr Pract. 2017 Jun;23(6):726-737

Authors: Sharma ST, AACE Adrenal Scientific Committee

Abstract
Cushing syndrome (CS) is caused by chronic exposure to excess glucocorticoids. Early recognition and treatment of hypercortisolemia can lead to decreased morbidity and mortality. The diagnosis of CS and thereafter, establishing the cause can often be difficult, especially in patients with mild and cyclic hypercortisolism. Surgical excision of the cause of excess glucocorticoids is the optimal treatment for CS. Medical therapy (steroidogenesis inhibitors, medications that decrease adrenocorticotropic hormone [ACTH] levels or glucocorticoid antagonists) and pituitary radiotherapy may be needed as adjunctive treatment modalities in patients with residual, recurrent or metastatic disease, in preparation for surgery, or when surgery is contraindicated. A multidisciplinary team approach, individualized treatment plan and long-term follow-up are important for optimal management of hypercortisolemia and the comorbidities associated with CS.
ABBREVIATIONS: ACTH = adrenocorticotropic hormone; BIPSS = bilateral inferior petrosal sinus sampling; CBG = corticosteroid-binding globulin; CD = Cushing disease; CRH = corticotropin-releasing hormone; CS = Cushing syndrome; Dex = dexamethasone; DST = dexamethasone suppression test; EAS = ectopic ACTH syndrome; FDA = U.S. Food & Drug Administration; HDDST = high-dose DST; IPS/P = inferior petrosal sinus to peripheral; MRI = magnetic resonance imaging; NET = neuroendocrine tumor; PET = positron emission tomography; UFC = urinary free cortisol.

PMID: 28614036 [PubMed - in process]

ECTOPIC CUSHING'S SYNDROME: A TEN YEAR EXPERIENCE FROM A TERTIARY CARE CENTRE IN SOUTHERN INDIA.

Fetched: June 16th, 2017, 1:00am EDT

ECTOPIC CUSHING'S SYNDROME: A TEN YEAR EXPERIENCE FROM A TERTIARY CARE CENTRE IN SOUTHERN INDIA.

Endocr Pract. 2017 Jun 14;:

Authors: Sathyakumar S, Paul TV, Asha HS, Gnanamuthu BR, Paul MJ, Abraham DT, Rajaratnam S, Thomas N

Abstract
OBJECTIVE: Ectopic ACTH secretion is a less common cause of Cushing's syndrome, and is seen in 5 to 10% of cases with endogenous hypercortisolemia. We hereby describe our experience of patients with ectopic ACTH syndrome, who have been managed over the past 10 years at a tertiary care centre in Southern India.
METHODS: The inpatient and outpatient records of patients from 2006 to 2015 were retrospectively reviewed. The clinical features, clinical history, biochemical values, imaging features which included radiological findings and PET scans, management, details of follow-up and outcomes were documented. We compared the biochemical findings in these patients with 20 consecutive patients with Cushing's disease (Cushing's syndrome of pituitary origin).
RESULTS: A total of 21 patients were studied. The median age at presentation was 34 (19-55) years. Seven patients had thymic carcinoid, 7 had bronchial carcinoid, 3 had lung malignancies, 2 had medullary carcinoma thyroid, 1 patient had a pancreatic neuroendocrine tumor and one patient had an occult source of ACTH. The most common clinical features at presentation were muscle weakness (95%), hyperpigmentation (90%), facial puffiness (76%), easy bruisability (61%), edema (57%), striae (52%). Extensive acne was seen in a large number of patients (43%). Only three patients (14%) had central obesity. The median 8 am cortisol was 55.5mcg/dl (13.8 - 131), median 8am ACTH was 207pg/ml (31.1 to 703) and the median 24 hour urinary free cortisol was 2484 mcg(248 - 25,438). Basal cortisol and ACTH, as well as midnight cortisol and ACTH level were markedly higher in patients with ectopic Cushing's syndrome as compared to patients with Cushing's disease. Twelve of twenty one patients had developed life threatening infections during follow up. Nine patients had undergone surgical intervention to address the primary tumour. However, only one patient sustained a complete cure on follow up.
CONCLUSION: In our series, ectopic Cushing's syndrome(ECS) was most commonly seen in association with intrathoracic tumors such as bronchial or thymic carcinoid. Hyperpigmentation and proximal myopathy were frequent, while central obesity was uncommon. Early and rapid control of hypercortisolemia was important in order to prevent life threatening infections and metabolic complications.

PMID: 28614007 [PubMed - as supplied by publisher]

Activation of DRD5 (Dopamine Receptor D5) Inhibits Tumor Growth by Autophagic Cell Death.

Fetched: June 16th, 2017, 1:00am EDT

Activation of DRD5 (Dopamine Receptor D5) Inhibits Tumor Growth by Autophagic Cell Death.

Autophagy. 2017 Jun 14;:0

Authors: Leng ZG, Lin SJ, Wu ZR, Guo YH, Cai L, Shang HB, Tang H, Xue YJ, Lou MQ, Zhao W, Le WD, Zhao WG, Zhang X, Wu ZB

Abstract
Dopamine agonists such as bromocriptine and cabergoline have been successfully used in the treatment of pituitary prolactinomas and other neuroendocrine tumors. However, their therapeutic mechanisms are not fully understood. In this study we demonstrated that DRD5 (dopamine receptor D5) agonists were potent inhibitors of pituitary tumor growth. We further found that DRD5 activation increased production of reactive oxygen species (ROS), inhibited the MTOR pathway, induced macroautophagy/autophagy, and led to autophagic cell death (ACD) in vitro and in vivo. In addition, DRD5 protein was highly expressed in the majority of human pituitary adenomas, and treatment of different human pituitary tumor cell cultures with the DRD5 agonist SKF83959 resulted in growth suppression, and the efficacy was correlated with the expression levels of DRD5 in the tumors. Furthermore, we found that DRD5 was expressed in other human cancer cells such as glioblastomas, colon cancer, and gastric cancer. DRD5 activation in these cell lines suppressed their growth, inhibited MTOR activity, and induced autophagy. Finally, in vivo SKF83959 also inhibited human gastric cancer cell growth in nude mice. Our studies revealed novel mechanisms for the tumor suppressive effects of DRD5 agonists, and suggested a potential use of DRD5 agonists as a novel therapeutic approach in the treatment of different human tumors and cancers.

PMID: 28613975 [PubMed - as supplied by publisher]

Two Cases of Primary Hepatic Neuroendocrine Tumors and a Review of the Current Literature.

Fetched: June 16th, 2017, 1:00am EDT

Two Cases of Primary Hepatic Neuroendocrine Tumors and a Review of the Current Literature.

Ann Hepatol. 2017 Aug 01;16(4):621-629

Authors: R DeLuzio M, L Barbieri A, Israel G, Emre S

Abstract
Neuroendocrine tumors comprise approximately 1-2% of all gastrointestinal tumors, and while the liver is the most common site for metastasis of these tumors, primary hepatic neuroendocrine tumors are very rare entities. Since first being reported in 1958, there have been less than 150 cases reported in the literature. Because of the infrequent occurrence of these tumors, the pool of data available for analysis regarding these tumors is small. As such, the medical community must rely on the publication of case report data to further enlarge this data pool, with the hopes of eventually having enough data to draw meaningful, statistically significant conclusions with regard to diagnosis and management of these rare tumors. We have encountered two patients at our institution within the last year with primary hepatic neuroendocrine tumors. We present their cases in this manuscript in an effort to contribute to the available data on the disease. We also provide a concise review of the literature available to date regarding primary hepatic neuroendocrine tumors.

PMID: 28611270 [PubMed - in process]

Revised nodal stage for pancreatic neuroendocrine tumors.

Fetched: June 16th, 2017, 1:00am EDT

Revised nodal stage for pancreatic neuroendocrine tumors.

Pancreatology. 2017 Jun 10;:

Authors: Luo G, Jin K, Cheng H, Guo M, Lu Y, Wang Z, Yang C, Xu J, Gao H, Zhang S, Zhang B, Long J, Xu J, Ni Q, Liu C, Yu X

Abstract
BACKGROUND: Previously we have proposed a modified European Neuroendocrine Tumor Society (mENETS) staging system for pNETs, which is more suitable than either the American Joint Committee on Cancer (AJCC) or the European Neuroendocrine Tumor Society (ENETS) systems. However, it is necessary to revise the nodal stage of the mENETS system for the under representation of stage III diseases.
METHODS: Nodal substages of the upper gastrointestinal organs (N0: 0 node, N1: 1-2 nodes; N2: ≥3 nodes) or the lower gastrointestinal organs (0: 0 node, N1: 1-3 nodes, and N2:≥ 4 nodes) were incorporated into the mENETS system and evaluated using the Surveillance, Epidemiology, and End Results (SEER) registry series.
RESULTS: The mENETS classification with the upper gastrointestinal N-stage revision (stage III, 17.1%) had better proportional distribution than the mENETS classification (stage III, 8.7%) or the lower gastrointestinal N-stage revision (stage III, 14.5%). N-stage revision (N0: 0 node, N1: 1-2 nodes; N2: ≥3 nodes) was incorporated in the mENETS staging definition for further analysis. Survival curves were well separated by nodal substages. HRs of stage IIA (T3N0M0) and IIB (T1-3N1M0) of the mENETS classification with N-stage revision were similar, indicating these two substages should be attributed to stage II. Survival curves were well separated by stage using the mENETS classification with N-stage revision.
CONCLUSIONS: The mENETS classification with N-stage revision (N0: 0 node, N1: 1-2 nodes; N2: ≥3 nodes) had better prognostic value and proportional distribution than the mENETS classification for pNETs and can be used in clinical practice.

PMID: 28610828 [PubMed - as supplied by publisher]

[Intramedullary spinal cord tumors and neurofibromatosis].

Fetched: June 16th, 2017, 1:00am EDT

[Intramedullary spinal cord tumors and neurofibromatosis].

Zh Vopr Neirokhir Im N N Burdenko. 2017;81(1):70-73

Authors: Kushel' YV, Belova YD, Tekoev AR

Abstract
The article addresses the issue of a combination and relationship between intramedullary spinal cord tumors (IMSCTs) and neurofibromatosis (NF).
AIM: To study, based on large clinical material, features of the prevalence and biological nature of intramedullary spinal cord tumors in neurofibromatosis patients in different age groups.
MATERIAL AND METHODS: We analyzed the data of the largest series of patients from all age groups who underwent surgery for spinal cord intramedullary tumors (541 patients; 586 surgeries; age, 2 months to 72 years).
RESULTS: Our findings support a potential pathogenetic relationship between intramedullary tumors and neurofibromatosis. Astrocytoma was a predominant intramedullary tumor in patients with NF-1, while ependymoma predominated in patients with NF-2. IMSCTs combined with NF-1 occur predominantly in children and adolescents, while a combination with NF-2 is typical of young adults. Our findings confirm the fact that IMSCT surgery is required for a small number of NF patients.

PMID: 28291216 [PubMed - indexed for MEDLINE]

Lactoferrin inhibits melanogenesis by down-regulating MITF in melanoma cells and normal melanocytes.

Fetched: June 16th, 2017, 1:00am EDT

Lactoferrin inhibits melanogenesis by down-regulating MITF in melanoma cells and normal melanocytes.

Biochem Cell Biol. 2017 Feb;95(1):119-125

Authors: Ishii N, Ryu M, Suzuki YA

Abstract
The aim of this study was to evaluate the effect of bovine lactoferrin (bLf) on melanin-producing cells and to elucidate its mechanism of action. We tested the anti-melanogenic effect of bLf on a 3-dimensional cultured pigmentation skin model and confirmed a 20% reduction in pigmentation, suggesting that bLf was transdermally absorbed and it suppressed melanin production. Treatment of human melanoma cells with bLf resulted in a significant, dose-dependent suppression of melanin production. Apo-bLf and holo-bLf suppressed melanogenesis to the same degree as bLf. The key feature behind this anti-melanogenic effect of bLf was the down-regulation of the microphthalmia-associated transcription factor (MITF), leading to the suppression of tyrosinase activity. Treatment with bLf resulted in both decreased expression of MITF mRNA and enhanced degradation of MITF protein. However, the primary effector was enhanced phosphorylation of extracellular signal-regulated kinase (ERK), leading to the phosphorylation and degradation of MITF. Our finding that bLf suppresses melanin production in melanocytes indicates that bLf is a possible candidate for application as a skin-whitening agent.

PMID: 28165285 [PubMed - indexed for MEDLINE]

Pigmentation and Pregnancy: Knowing What Is Normal.

Fetched: June 16th, 2017, 1:00am EDT

Pigmentation and Pregnancy: Knowing What Is Normal.

Obstet Gynecol. 2017 Jan;129(1):168-173

Authors: Bieber AK, Martires KJ, Stein JA, Grant-Kels JM, Driscoll MS, Pomeranz MK

Abstract
Changes in melanocytic nevi during pregnancy are frequently attributed to the new hormonal milieu and are dismissed without concern for malignancy. Recent studies suggest that pregnancy itself does not induce significant change in nevi, and delays in the assessment of changing moles may contribute to the often more advanced nature of melanomas diagnosed during or soon after pregnancy. Nevi on the breasts and abdomen can grow as a result of skin expansion, but studies have found no significant changes in nevi located in more stable areas such as the back or lower extremities. There is also insufficient evidence to support the notion that nevi darken during pregnancy. As such, any changing nevus that would raise concern for malignancy in a nonpregnant patient should do so in a pregnant patient as well. Pregnancy can, however, induce physiologic pigmentary changes that are often worrisome to both patients and physicians. These benign changes include melasma, pigmentary demarcation lines, secondary areola, and linea nigra as well as other less common findings. It is important for physicians to recognize these changes as physiologic to provide adequate reassurance to their patients and avoid unnecessary stress.

PMID: 27926637 [PubMed - indexed for MEDLINE]

[The role of reflectance confocal microscopy in the diagnosis of cutaneous melanoma metastasis].

Fetched: June 16th, 2017, 1:00am EDT

[The role of reflectance confocal microscopy in the diagnosis of cutaneous melanoma metastasis].

Ann Dermatol Venereol. 2016 Dec;143(12):863-865

Authors: Perrot JL, Labeille B, Habougit C, Douchet C, Tognetti L, Cambazard F, Cinotti E, groupe d’imagerie cutanée non invasive (ICNI) de la Société française de dermatologie

PMID: 27418007 [PubMed - indexed for MEDLINE]

Colonic small cell neuroendocrine carcinoma in a patient with long-standing ulcerative colitis treated with azathioprine.

Fetched: June 16th, 2017, 1:00am EDT

Colonic small cell neuroendocrine carcinoma in a patient with long-standing ulcerative colitis treated with azathioprine.

Dig Liver Dis. 2016 Jul;48(7):822-3

Authors: Zerboni G, Capurso G, Pilozzi E, Papi C

PMID: 27103360 [PubMed - indexed for MEDLINE]

Efficacy of Peptide Receptor Radionuclide Therapy (PRRT) for Functional Metastatic Paraganglioma and Phaeochromocytoma.

Fetched: June 14th, 2017, 1:00am EDT

Efficacy of Peptide Receptor Radionuclide Therapy (PRRT) for Functional Metastatic Paraganglioma and Phaeochromocytoma.

J Clin Endocrinol Metab. 2017 Jun 09;:

Authors: Kong G, Grozinsky-Glasberg S, Hofman MS, Callahan J, Meirovitz A, Maimon O, Pattison DA, Gross DJ, Hicks RJ

Abstract
Purpose: Treatment options for unresectable Paraganglioma (PGL)/Phaeochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN) are limited. Preliminary studies with PRRT suggest efficacy but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from 2 referral centres.
Methods: 20 consecutive patients (M:F=13:7; 21-77y.o.) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, 9 with radiosensitising chemotherapy, were retrospectively reviewed. Median cumulative activity was 22 GBq (1-4 cycles, median 4). Fourteen patients were treated for uncontrolled HTN, and 6 for progressive or symptomatic metastatic disease or local recurrence.
Results: Three months post-PRRT, 8/14 patients treated for HTN required reduced medication doses, 5 patients had no change in anti-HTN doses, and 1 patient was lost to follow-up. 86% had serum chromogranin-A reduction. For the entire cohort, 36% had disease regression (29% partial, 7% minor response) on CT, with stable findings in 50%. Three other patients had bony disease evaluable only on SSTR imaging (2 partial response, 1 stable). Median progression-free survival was 39 months, median overall survival was not reached (5 deaths, median follow-up 28 months). Four patients had Grade 3 lymphopenia, 2 Grade 3 thrombocytopenia. Renal impairment in 2 patients was attributed to underlying disease processes.
Conclusions: Our results indicate that PRRT achieves worthwhile clinical and biochemical responses with low toxicity as well as controlling secondary HTN in most patients with PCC/PGL and encouraging survival. PRRT also has potential logistic and radiation-safety advantages over conventional 131I-MIBG therapy and warrants prospective evaluation in this clinically heterogeneous disease.

PMID: 28605448 [PubMed - as supplied by publisher]

Cytological features of adenocarcinoma admixed with small cell neuroendocrine carcinoma of the uterine cervix.

Fetched: June 14th, 2017, 1:00am EDT

Cytological features of adenocarcinoma admixed with small cell neuroendocrine carcinoma of the uterine cervix.

Cytojournal. 2017;14:12

Authors: Shimojo N, Hirokawa YS, Kanayama K, Yoneda M, Hashizume R, Hayashi A, Uchida K, Imai H, Kozuka Y, Shiraishi T

Abstract
Adenocarcinoma admixed with neuroendocrine carcinoma of the uterine cervix is a rare malignancy with a poor prognosis, and few reports have described the cytological features of this carcinoma. To characterize the cytological features of this malignancy in cervical smears, we report a case of a 52-year-old Japanese woman with cervical adenocarcinoma admixed with small cell neuroendocrine carcinoma (SCNEC). Cytologically, there were two types of cells with different sizes. The smaller cells formed clusters, which showed a partially Indian file pattern, a high nuclear/cytoplasmic ratio, and hyperchromatic nuclei. In contrast, the larger cells showed cytological features of adenocarcinoma, indicating a glandular-like pattern. Histological examination of biopsy specimens revealed that the tumors were composed of almost equal areas of SCNEC and adenocarcinoma. Neuroendocrine differentiation was confirmed by immunohistochemistry for synaptophysin and CD56. Thus, when adenocarcinoma cells are detected in smears, attempts to search for SCNEC cells should be made by combined cytological and histological analyses in order to reach an accurate diagnosis of the carcinoma in the uterine cervix.

PMID: 28603541 [PubMed - in process]

Permalink for 'Suppression of Akt1- β-catenin pathway in advanced prostate cancer promotes TGFβ1-mediated epithelial to mesenchymal transition and metastasis.'

Suppression of Akt1- β-catenin pathway in advanced prostate cancer promotes TGFβ1-mediated epithelial to mesenchymal transition and metastasis.

Fetched: June 14th, 2017, 1:00am EDT

Suppression of Akt1- β-catenin pathway in advanced prostate cancer promotes TGFβ1-mediated epithelial to mesenchymal transition and metastasis.

Cancer Lett. 2017 Jun 07;:

Authors: Gao F, Alwhaibi A, Sabbineni H, Verma A, Eldahshan W, Somanath PR

Abstract
Akt1 is essential for the oncogenic transformation and tumor growth in various cancers. However, the precise role of Akt1 in advanced cancers is conflicting. Using a neuroendocrine TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, we first show that the genetic ablation or pharmacological inhibition of Akt1 in mice blunts oncogenic transformation and prostate cancer (PCa) growth. Intriguingly, triciribine (TCBN)-mediated Akt inhibition in 25-week old, tumor-bearing TRAMP mice and Akt1 gene silencing in aggressive PCa cells enhanced epithelial to mesenchymal transition (EMT) and promoted metastasis to the lungs. Mechanistically, Akt1 suppression leads to increased expression of EMT markers such as Snail1 and N-cadherin and decreased expression of epithelial marker E-cadherin in TRAMP prostate, and in PC3 and DU145 cells. Next, we identified that Akt1 knockdown in PCa cells results in increased production of TGFβ1 and its receptor TGFβ RII, associated with a decreased expression of β-catenin. Furthermore, treatment of PCa cells with ICG001 that blocks nuclear translocation of β-catenin promoted EMT and N-cadherin expression. Together, our study demonstrates a novel role of the Akt1-β-catenin-TGFβ1 pathway in advanced PCa.

PMID: 28602980 [PubMed - as supplied by publisher]

Thymic large cell neuroendocrine carcinoma - a rare and aggressive tumor: a case report.

Fetched: June 14th, 2017, 1:00am EDT

Thymic large cell neuroendocrine carcinoma - a rare and aggressive tumor: a case report.

J Med Case Rep. 2017 Jun 12;11(1):155

Authors: Boubacar E, Atsame-Ebang G, Rabiou S, Fatimazahra A, Mazti A, Sidibé IS, Tahiri L, Hammas N, Yassine O, Mohamed S, Laila C, Hinde EF

Abstract
BACKGROUND: Neuroendocrine tumors are a large group of tumors with a wide spectrum of behavior, affecting mainly the digestive system and the lung. The thymus is very rarely affected.
CASE PRESENTATION: A 28-year-old Arab woman presented with chronic chest pain and dyspnea. A computed tomography scan showed a huge anterior mediastinal mass invading neighboring structures. A mediastinotomy was performed with biopsies of the mass. Pathological findings were consistent with a thymic large cell neuroendocrine carcinoma.
CONCLUSIONS: The occurrence of a large cell neuroendocrine carcinoma in the thymus, especially in young people, is extremely rare. In this current report, we discuss the clinicopathological issues of this rare tumor according to recent literature data.

PMID: 28602157 [PubMed - in process]

Permalink for 'Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service.'

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service.

Fetched: June 14th, 2017, 1:00am EDT

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service.

PLoS Med. 2017 Feb;14(2):e1002230

Authors: Hamblin A, Wordsworth S, Fermont JM, Page S, Kaur K, Camps C, Kaisaki P, Gupta A, Talbot D, Middleton M, Henderson S, Cutts A, Vavoulis DV, Housby N, Tomlinson I, Taylor JC, Schuh A

Abstract
BACKGROUND: Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing.
METHODS AND FINDINGS: We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of "real world" data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds.
CONCLUSIONS: This study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers.

PMID: 28196074 [PubMed - indexed for MEDLINE]

ATF4 Targets RET for Degradation and Is a Candidate Tumor Suppressor Gene in Medullary Thyroid Cancer.

Fetched: June 14th, 2017, 1:00am EDT

ATF4 Targets RET for Degradation and Is a Candidate Tumor Suppressor Gene in Medullary Thyroid Cancer.

J Clin Endocrinol Metab. 2017 Mar 01;102(3):933-941

Authors: Bagheri-Yarmand R, Williams MD, Grubbs EG, Gagel RF

Abstract
Context: Medullary thyroid cancer (MTC) is an aggressive tumor that harbors activating mutations of the RET proto-oncogene. We previously reported that RET inhibits transcriptional activity of ATF4, the master regulator of the stress response pathway, to prevent cell death.
Objective: We hypothesized that loss of function of ATF4 plays a role in initiation of MTC.
Design: Targeted deletion of Atf4 in mice was used to assess ATF4 function in the thyroid gland. ATF4 overexpression was achieved by adenoviral and lentiviral vectors. We used immunohistochemical analysis and western blotting of MTC tumors to determine protein levels of RET and ATF4 and the Kaplan-Meier method to determine their association with clinical outcome.
Results: Targeted deletion of Atf4 in mice causes C-cell hyperplasia, a precancerous lesion for MTC. Forced ATF4 expression decreased survival of MTC cells and blocked the activation of RET downstream signaling pathways (phosphorylated ERK, phosphorylated AKT, and p70S6K). ATF4 knockdown decreased sensitivity to tyrosine kinase inhibitor-induced apoptosis. Moreover, ATF4 expression decreased RET protein levels by promoting RET ubiquitination. We found decreased or loss of ATF4 in 52% of MTC tumors (n = 39) compared with normal thyroid follicle cells. A negative correlation was observed between RET and ATF4 protein levels in MTC tumors, and low ATF4 expression was associated with poor overall survival in patients with MTC.
Conclusions: ATF4 was identified as a negative regulator of RET, a candidate tumor suppressor gene, and may be a molecular marker that distinguishes patients at high risk of MTC from those with a longer survival prognosis.

PMID: 27935748 [PubMed - indexed for MEDLINE]

PLGA-loaded nanomedicines in melanoma treatment: Future prospect for efficient drug delivery.

Fetched: June 14th, 2017, 1:00am EDT

PLGA-loaded nanomedicines in melanoma treatment: Future prospect for efficient drug delivery.

Indian J Med Res. 2016 Aug;144(2):181-193

Authors: Das S, Khuda-Bukhsh AR

Abstract
Current treatment methods for melanoma have some limitations such as less target-specific action, severe side effects and resistance to drugs. Significant progress has been made in exploring novel drug delivery systems based on suitable biochemical mechanisms using nanoparticles ranging from 10 to 400 nm for drug delivery and imaging, utilizing their enhanced penetration and retention properties. Poly-lactide-co-glycolide (PLGA), a copolymer of poly-lactic acid and poly-glycolic acid, provides an ideally suited performance-based design for better penetration into skin cells, thereby having a greater potential for the treatment of melanoma. Moreover, encapsulation protects the drug from deactivation by biological reactions and interactions with biomolecules, ensuring successful delivery and bioavailability for effective treatment. Controlled and sustained delivery of drugs across the skin barrier that otherwise prohibits entry of larger molecules can be successfully made with adequately stable biocompatible nanocarriers such as PLGA for taking drugs through the small cutaneous pores permitting targeted deposition and prolonged drug action. PLGA is now being extensively used in photodynamic therapy and targeted therapy through modulation of signal proteins and drug-DNA interactions. Recent advances made on these nanomedicines and their advantages in the treatment of skin melanoma are highlighted and discussed in this review.

PMID: 27934796 [PubMed - indexed for MEDLINE]

Permalink for 'Discovery and Optimization of N-(4-(3-Aminophenyl)thiazol-2-yl)acetamide as a Novel Scaffold Active against Sensitive and Resistant Cancer Cells.'

Discovery and Optimization of N-(4-(3-Aminophenyl)thiazol-2-yl)acetamide as a Novel Scaffold Active against Sensitive and Resistant Cancer Cells.

Fetched: June 14th, 2017, 1:00am EDT

Discovery and Optimization of N-(4-(3-Aminophenyl)thiazol-2-yl)acetamide as a Novel Scaffold Active against Sensitive and Resistant Cancer Cells.

J Med Chem. 2016 Sep 22;59(18):8276-92

Authors: Millet A, Plaisant M, Ronco C, Cerezo M, Abbe P, Jaune E, Cavazza E, Rocchi S, Benhida R

Abstract
Cancer is the second cause of deaths worldwide and is forecasted to affect more that 22 million people in 2020. Despite dramatic improvement in its care over the last two decades, the treatment of resistant forms of cancer is still an unmet challenge. Thus, innovative and efficient treatments are still needed. In this context, we report herein the synthesis and the evaluation of a new class of bioactive molecules belonging to the N-(4-(3-aminophenyl(thiazol-2-yl)acetamide family. Structure-activity relationships could be driven and resulted in the discovery of lead compound 6b. The latter display high in vitro potency against both sensitive and resistant cancer cell lines on three models: melanoma, pancreatic cancer, and chronic myeloid leukemia (CML). 6b leads to cell death by concomitant induction of apoptosis and autophagy, shows good pharmacokinetic properties, and demonstrates a significant reduction of tumor growth in vivo on A375 xenograft model in mice.

PMID: 27575313 [PubMed - indexed for MEDLINE]

Synergistic effects of eIF4A and MEK inhibitors on proliferation of NRAS-mutant melanoma cell lines.

Fetched: June 14th, 2017, 1:00am EDT

Synergistic effects of eIF4A and MEK inhibitors on proliferation of NRAS-mutant melanoma cell lines.

Cell Cycle. 2016 Sep 16;15(18):2405-9

Authors: Malka-Mahieu H, Girault I, Rubington M, Leriche M, Welsch C, Kamsu-Kom N, Zhao Q, Desaubry L, Vagner S, Robert C

Abstract
Activating mutations of the NRAS (neuroblastoma rat sarcoma viral oncogene) protein kinase, present in many cancers, induce a constitutive activation of both the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway and the PI(3)K-AKT-mTOR, pathway. This in turn regulates the formation of the eIF4F eukaryotic translation initiation complex, comprising the eIF4E cap-binding protein, the eIF4G scaffolding protein and the eIF4A RNA helicase, which binds to the 7-methylguanylate cap (m(7)G) at the 5' end of messenger RNAs. Small molecules targeting MEK (MEKi: MEK inhibitors) have demonstrated activity in NRAS-mutant cell lines and tumors, but resistance sets in most cases within months of treatment. Using proximity ligation assays, that allows visualization of the binding of eIF4E to the scaffold protein eIF4G, generating the active eIF4F complex, we have found that resistance to MEKi is associated with the persistent formation of the eIF4F complex in MEKi-treated NRAS-mutant cell lines. Furthermore, inhibiting the eIF4A component of the eIF4F complex, with a small molecule of the flavagline/rocaglate family, synergizes with inhibiting MEK to kill NRAS-mutant cancer cell lines.

PMID: 27533468 [PubMed - indexed for MEDLINE]

The changing incidence of thyroid cancer.

Fetched: June 14th, 2017, 1:00am EDT

The changing incidence of thyroid cancer.

Nat Rev Endocrinol. 2016 Nov;12(11):646-653

Authors: Kitahara CM, Sosa JA

Abstract
During the past few decades, the incidence of thyroid cancer has increased substantially in many countries, including the USA. The rise in incidence seems to be attributable both to the growing use of diagnostic imaging and fine-needle aspiration biopsy, which has led to enhanced detection and diagnosis of subclinical thyroid cancers, and environmental factors. The latest American Thyroid Association (ATA) practice guidelines for the management of adult patients with thyroid nodules and differentiated thyroid cancer differ substantially from the previous ATA guidelines published in 2009. Specifically, the problems of overdiagnosis and overtreatment of a disease that is typically indolent, where treatment-related morbidity might not be justified by a survival benefit, now seem to be acknowledged. As few modifiable risk factors for thyroid cancer have been established, the specific environmental factors that have contributed to the rising incidence of thyroid cancer remain speculative. However, the findings of several large, well-designed epidemiological studies have provided new information about exposures (such as obesity) that might influence the development of thyroid cancer. In this Review, we describe the changing incidence of thyroid cancer, suggest potential explanations for these trends, emphasize the implications for patients and highlight ongoing and potential strategies to combat this growing clinical and public health issue.

PMID: 27418023 [PubMed - indexed for MEDLINE]

Permalink for 'Clinical evaluation of ultra-high-field MRI for three-dimensional visualisation of tumour size in uveal melanoma patients, with direct relevance to treatment planning.'

Clinical evaluation of ultra-high-field MRI for three-dimensional visualisation of tumour size in uveal melanoma patients, with direct relevance to treatment planning.

Fetched: June 14th, 2017, 1:00am EDT

Clinical evaluation of ultra-high-field MRI for three-dimensional visualisation of tumour size in uveal melanoma patients, with direct relevance to treatment planning.

MAGMA. 2016 Jun;29(3):571-7

Authors: Beenakker JW, Ferreira TA, Soemarwoto KP, Genders SW, Teeuwisse WM, Webb AG, Luyten GP

Abstract
OBJECTIVES: To assess the tumour dimensions in uveal melanoma patients using 7-T ocular MRI and compare these values with conventional ultrasound imaging to provide improved information for treatment options.
MATERIALS AND METHODS: Ten uveal melanoma patients were examined on a 7-T MRI system using a custom-built eye coil and dedicated 3D scan sequences to minimise eye-motion-induced image artefacts. The maximum tumour prominence was estimated from the three-dimensional images and compared with the standard clinical evaluation from 2D ultrasound images.
RESULTS: The MRI protocols resulted in high-resolution motion-free images of the eye in which the tumour and surrounding tissues could clearly be discriminated. For eight of the ten patients the MR images showed a slightly different value of tumour prominence (average 1.0 mm difference) compared to the ultrasound measurements, which can be attributed to the oblique cuts through the tumour made by the ultrasound. For two of these patients the more accurate results from the MR images changed the treatment plan, with the smaller tumour dimensions making them eligible for eye-preserving therapy.
CONCLUSION: High-field ocular MRI can yield a more accurate measurement of the tumour dimensions than conventional ultrasound, which can result in significant changes in the prescribed treatment.

PMID: 26915081 [PubMed - indexed for MEDLINE]

An Elderly Man With Pancreatic Neuroendocrine Tumor and a Cavitary Right Upper Lobe Lung Mass.

Fetched: June 12th, 2017, 1:01am EDT

An Elderly Man With Pancreatic Neuroendocrine Tumor and a Cavitary Right Upper Lobe Lung Mass.

Chest. 2017 Jun;151(6):e135-e139

Authors: DeSilva P, Selvachandra A, Kanaan J, Datta D

Abstract
CASE PRESENTATION: An elderly man presented to the ED from a nursing care facility after transient loss of consciousness. Three weeks previously, the patient had been diagnosed with a high-grade pancreatic neuroendocrine tumor (NET) with metastases to the liver after being hospitalized for weakness. A chest radiograph at that time had revealed a right upper lobe mass that was presumed to represent a metastatic lesion (Fig 1); CT of the chest demonstrated similar findings (Fig 2). The patient had recovered consciousness on arrival to the ED and was diagnosed clinically as having had a syncopal episode from dehydration due to poor intake. On review of systems, the patient reported shortness of breath and a cough productive of scant mucoid sputum of 1 week's duration. He had no complaints of fever but complained of weakness and poor appetite. In addition, his medical history was significant for hypertension, diabetes mellitus, and congestive heart failure with systolic dysfunction. He was a former smoker. Prior to his recent illness and hospitalization, he lived at home with his family and was independent in his activities of daily living.

PMID: 28599947 [PubMed - in process]

Post-obstructive cyst formation in pancreas and cystic acinar transformation: Are they same?

Fetched: June 12th, 2017, 1:01am EDT

Post-obstructive cyst formation in pancreas and cystic acinar transformation: Are they same?

Pathol Res Pract. 2017 Apr 01;:

Authors: Zhang X, Zhu H, Yang X, Adsay VN, Jain D

Abstract
Pancreatic "acinar cell cystadenoma" (PACA) is a rare benign pancreatic cystic lesion showing acinar cell differentiation. The neoplastic nature of PACA has been questioned and its exact pathogenesis remains unclear. To investigate that acinar cell differentiation is a non-specific metaplastic phenomenon that can occur in pancreatic ductal system, especially when chronically inflamed and dilated, and doesn't necessarily imply an acinar cell neoplasm, we retrospectively analyzed cases diagnosed as PACA and cases with post-obstructive cystic dilatation of pancreatic ducts for acinar cell differentiation using immunohistochemistry for trypsin. The etiology of obstruction was microscopic periductal pancreatic neuroendocrine tumors (PanNET) and pancreatic ductal adenocarcinomas (PDAC). All cases of post-obstructive cystic dilatation showed multiple varying sized cysts distal to the obstruction with histologic findings virtually identical to PACAs. The cysts in both conditions were lined by a single layer of non-dysplastic flattened to columnar ductal-type epithelium with areas of acinar cell differentiation. Trypsin immunohistochemistry confirmed presence of acinar cell differentiation in all cases of post-obstructive cysts and PACAs. Our results suggest that acinar cell differentiation is common in post-obstructive cyst formation, and changes are identical to PACAs. These findings further support the notion that PACA is a benign non-neoplastic cystic lesion with acinar cell differentiation. The findings also suggest that in cases with histology resembling "PACA" or showing diffuse ductal cystic dilation, careful gross examination should be carried out for a proximal obstructive lesion, which can be subtle and easily be missed on initial examination.

PMID: 28599853 [PubMed - as supplied by publisher]

Permalink for 'Value of diffusion-weighted magnetic resonance imaging in predicting World Health Organization grade in G1/G2 pancreatic neuroendocrine tumors.'

Value of diffusion-weighted magnetic resonance imaging in predicting World Health Organization grade in G1/G2 pancreatic neuroendocrine tumors.

Fetched: June 12th, 2017, 1:01am EDT

Value of diffusion-weighted magnetic resonance imaging in predicting World Health Organization grade in G1/G2 pancreatic neuroendocrine tumors.

Oncol Lett. 2017 Jun;13(6):4141-4146

Authors: Guo C, Zhuge X, Chen X, Wang Z, Xiao W, Wang Q

Abstract
The present study aimed to investigate the value of diffusion-weighted magnetic resonance imaging (DWI) in the grading of well-differentiated pancreatic neuroendocrine tumors (PanNETs). A total of 44 patients with histologically proven well-differentiated PanNET [grade 1 (G1) and grade 2 (G2) according to the World Health Organization (WHO) criteria] underwent pretreatment magnetic resonance imaging (MRI), which was retrospectively analyzed. The location, size, cystic or solid appearance, boundary, presence or absence of tumor contrast enhancement, and MRI signal of the tumor were assessed. Apparent diffusion coefficients (ADCs) within the primary tumor were measured on ADC maps. Receiver operating characteristic curves were used to determine ADC cut-off values and the sensitivity and specificity of the grade prediction. Spearman's rank correlation was utilized to probe the association between ADC value and PanNET grade or pathological parameters. G1 tumors exhibited a well-circumscribed border more often than G2 tumors. No marked differences were observed between PanNET G1 and PanNET G2 for cystic or solid appearance, enhancement, and T1- and T2-weighted imaging signals. Marked hyperintensities were more common in PanNET G2 tumors than in PanNET G1 tumors (P<0.01). The mean ADC values were statistically different between the normal pancreas and G1 and G2 tumors (P<0.01), and between PanNET G1 and PanNET G2 (P<0.05). Correlation analysis showed that ADC value was negatively correlated with PanNET grade, mitotic count and Ki-67 proliferation index (P<0.05). The cut-off ADC value was 0.930×10(-3) mm(2)/sec, which identified G2 tumors with 82.4% sensitivity and 79.5% selectivity. ADC value therefore represents a non-invasive and valuable imaging parameter in predicting the WHO grade of tumors in well-differentiated PanNET.

PMID: 28599415 [PubMed - in process]

Permalink for 'The impact of pathologic differentiation (well/poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.'

The impact of pathologic differentiation (well/poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.

Fetched: June 11th, 2017, 1:01am EDT

The impact of pathologic differentiation (well/poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.

Oncotarget. 2017 May 25;:

Authors: Kim HK, Ha SY, Lee J, Park SH, Park JO, Lim HY, Kang WK, Park YS, Kim ST

Abstract
We investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum (EP)-based therapy, and evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from EP-based therapy. A total of 31 patients with metastatic grade 3 GEP-NECs receiving EP-based therapy were included in this study. Primary sites included 13 foregut-derived GEP-NECs [stomach (n = 4), duodenum (n = 4), and pancreas (n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. 14 patients had well differentiated (WD) and 17 had poorly differentiated (PD). Between WD and PD grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between WD and PD grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67 ≤ 60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). Among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between WD and PD NECs. Higher levels (> 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs.

PMID: 28598818 [PubMed - as supplied by publisher]

Neoplasms of the Appendix: Pictorial Review with Clinical and Pathologic Correlation.

Fetched: June 11th, 2017, 1:01am EDT

Neoplasms of the Appendix: Pictorial Review with Clinical and Pathologic Correlation.

Radiographics. 2017 Jun 09;:160150

Authors: Leonards LM, Pahwa A, Patel MK, Petersen J, Nguyen MJ, Jude CM

Abstract
Appendiceal neoplasms are uncommon tumors of the gastrointestinal tract that may manifest with symptoms of appendicitis, right lower quadrant pain, or palpable mass, leading to imaging or surgical intervention. The majority of appendiceal masses consist of primary epithelial neoplasms and neuroendocrine tumors (NETs). Epithelial neoplasms-mucinous and nonmucinous types-are more often detected at imaging than NETs due to their larger size and propensity for peritoneal spread and metastatic disease. Epithelial mucinous neoplasms are defined by the presence of mucin, detected at radiologic and pathologic examination. A mucocele or pseudomyxoma peritonei from epithelial mucinous tumors are the two most common cross-sectional imaging findings of appendiceal mucinous neoplasms. Nonmucinous epithelial tumors are less common and manifest as masses similar to colonic-type malignancies. NETs are often discovered incidentally at appendectomy due to their small size and nonaggressive behavior. Imaging findings of primary appendiceal tumors may overlap with those of acute appendicitis. Additionally, an appendiceal mass may cause acute appendicitis, obscuring the underlying mass. Other neoplasms including lymphoma, sarcoma, mesenchymal and nerve sheath tumors, or secondary malignant involvement of the appendix are rare. Treatment depends on the histologic subtype and extent of disease. Detailed description of organ, nodal, and peritoneal involvement informs surgical management with the goal of complete cytoreduction. Novel treatments such as hyperthermic intraperitoneal chemotherapy have increased survival for patients with mucinous tumors. (©)RSNA, 2017.

PMID: 28598731 [PubMed - as supplied by publisher]

Permalink for 'Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).'

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

Fetched: June 11th, 2017, 1:01am EDT

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

Endokrynol Pol. 2017;68(2):79-110

Authors: Kos-Kudła B, Blicharz-Dorniak J, Strzelczyk J, Bałdys-Waligórska A, Bednarczuk T, Bolanowski M, Boratyn-Nowicka A, Borowska M, Cichocki A, Ćwikła JB, Falconi M, Foltyn W, Handkiewicz-Junak D, Hubalewska-Dydejczyk A, Jarząb B, Junik R, Kajdaniuk D, Kamiński G, Kolasińska-Ćwikła A, Kowalska A, Król R, Królicki L, Krzakowski M, Kunikowska J, Kuśnierz K, Lampe P, Lange D, Lewczuk-Myślicka A, Lewiński A, Lipiński M, Londzin-Olesik M, Marek B, Nasierowska-Guttmejer A, Nawrocki S, Nowakowska-Duława E, Pilch-Kowalczyk J, Rosiek V, Ruchała M, Siemińska L, Sowa-Staszczak A, Starzyńska T, Steinhof-Radwańska K, Sworczak K, Syrenicz A, Szawłowski A, Szczepkowski M, Wachuła E, Zajęcki W, Zemczak A, Zgliczyński W, Zieniewicz K

Abstract
Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Żelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.

PMID: 28597909 [PubMed - in process]

Permalink for 'Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients.'

Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients.

Fetched: June 11th, 2017, 1:01am EDT

Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients.

J Pathol Transl Med. 2017 Jun 08;:

Authors: Kim SJ, An S, Lee JH, Kim JY, Song KB, Hwang DW, Kim SC, Yu E, Hong SM

Abstract
Background: Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients.
Materials and Methods: To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival.
Results: PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p<.001). PanNETs with loss of PR expression were associated with increased tumor size (p<.001), World Health Organization grade (p=.001), pT classification (p<.001), perineural invasion (p=.03), lymph node metastasis (p=.004), activation of alternative lengthening of telomeres (p=.005), other peptide hormonal expression (p<.001) and ATRX/DAXX expression (p=.02). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p=.01) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p=.02) but not multivariate analyses.
Conclusion: Loss of PR expression is noted in neuroendocrine microadenomas and is observed in the majority of PanNETs. This associated with increased grade, tumor size, and advanced pT and pN classification; and correlates with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

PMID: 28597868 [PubMed - as supplied by publisher]

Long-term treatment of Cushing's disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial.

Fetched: June 11th, 2017, 1:01am EDT

Long-term treatment of Cushing's disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial.

Endocrine. 2017 Jun 09;:

Authors: Petersenn S, Salgado LR, Schopohl J, Portocarrero-Ortiz L, Arnaldi G, Lacroix A, Scaroni C, Ravichandran S, Kandra A, Biller BMK

Abstract
BACKGROUND: Treating hypercortisolism in patients with Cushing's disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles.
METHODS: In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing's disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein.
RESULTS: Sixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was -82.6% (-89.0, -41.9) and -81.8% (-89.8, -67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time.
CONCLUSIONS: This represents the longest prospective trial of a medical therapy for Cushing's disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing's disease.

PMID: 28597198 [PubMed - as supplied by publisher]

Calcified Liver Metastases from a Neuroendocrine Tumor of the Lung (Atypical Carcinoid) - A Case Report.

Fetched: June 11th, 2017, 1:01am EDT

Calcified Liver Metastases from a Neuroendocrine Tumor of the Lung (Atypical Carcinoid) - A Case Report.

Ultrasound Int Open. 2017 Apr;3(2):E89-E90

Authors: Reiter R, Maul J, Preis JC, Blaeker H, Grozdanovic Z

Abstract
Pulmonary neuroendocrine tumors (NETs) are rare tumors with an incidence rate of 0.2-2/100 000 population/year in Western countries (M. E. Caplin et al. Ann Oncol 2015; 26:1604-20). They account for 1-2% of all neoplasms of the lung and constitute one-fourth to one-third of all NETs. Atypical carcinoids are far less common than typical carcinoids and predominantly occur in male smokers aged 50 -70 years. Most pulmonary NETs are asymptomatic due to their peripheral location. Surgical resection is the treatment of choice. Medical management should take hormone-related symptoms into account.

PMID: 28597001 [PubMed - in process]

Primary extrahepatic bile duct neuroendocrine tumor with obstructive jaundice masquerading as a Klatskin tumor.

Fetched: June 11th, 2017, 1:01am EDT

Primary extrahepatic bile duct neuroendocrine tumor with obstructive jaundice masquerading as a Klatskin tumor.

J Surg Case Rep. 2017 Jun;2017(6):rjx104

Authors: Hoepfner L, White JA

Abstract
Neuroendocrine tumors (NETs) of the extrahepatic bile duct are extremely rare and reported infrequently in the literature. These tumors are difficult to diagnose preoperatively, and the prognosis is variable, often determined by extent of disease, tumor grade and resectability. This case report presents a 45-year-old male with history of biliary obstruction relieved by endobiliary stents with common hepatic duct stricture just above the cystic duct, thought to be a Klatskin's cholangiocarcinoma. Final pathological examination was consistent with primary extrahepatic NET.

PMID: 28596824 [PubMed - in process]

The Enigma of Regional Lymph Nodes in Melanoma.

Fetched: June 11th, 2017, 1:01am EDT

The Enigma of Regional Lymph Nodes in Melanoma.

N Engl J Med. 2017 06 08;376(23):2280-2281

Authors: Coit D

PMID: 28591534 [PubMed - indexed for MEDLINE]

Primary intranasal melanoma with brain invasion in a dog.

Fetched: June 11th, 2017, 1:01am EDT

Primary intranasal melanoma with brain invasion in a dog.

Can Vet J. 2017 Apr;58(4):391-396

Authors: Lemetayer J, Al-Dissi A, Tryon K, MacDonald-Dickinson V

Abstract
A 6-year-old castrated male boxer dog with right-sided dark purulent nasal discharge and acute bilateral blindness was diagnosed on magnetic resonance imaging (MRI) and then on necropsy with primary nasal malignant melanoma that extended into the brain, as well as concurrent ocular melanosis. There was no evidence of metastasis in other organs.

PMID: 28373733 [PubMed - indexed for MEDLINE]

Long-term Outcomes of Submucosal Tunneling Endoscopic Resection for Upper Gastrointestinal Submucosal Tumors.

Fetched: June 11th, 2017, 1:01am EDT

Long-term Outcomes of Submucosal Tunneling Endoscopic Resection for Upper Gastrointestinal Submucosal Tumors.

Ann Surg. 2017 Feb;265(2):363-369

Authors: Chen T, Zhou PH, Chu Y, Zhang YQ, Chen WF, Ji Y, Yao LQ, Xu MD

Abstract
OBJECTIVE: The aim of this study is to evaluate the long-term outcomes of a large series of patients treated with submucosal tunneling endoscopic resection (STER).
BACKGROUND: STER is a newly developed treatment for upper gastrointestinal submucosal tumors originating from the muscularis propria layer. Recently, reports about STER are increasing, but a large study with long-term follow-up is little known.
METHODS: In a retrospective study, a total of 180 patients with upper gastrointestinal submucosal tumors undergoing STER were included from June 2011 to May 2013. Clinicopathological, endoscopic, and follow-up data were collected and analyzed.
RESULTS: The en bloc resection was achieved in 90.6% of patients and the complications rate was 8.3%. Based on statistical analysis, tumors with irregular shape and greater size were the significant contributors to piecemeal resection and long operative times. Besides tumor shape and size, tumor in deep muscularis propria and long operative time were also risk factors of complications. The median hospitalization time was 3.2 days. All of the complications were cured by conservative treatment. A median follow-up of 36 months was available and all patients were free from local recurrence or distant metastasis during the study period.
CONCLUSIONS: STER is an effective and safe methodology for the resection of upper gastrointestinal submucosal tumors. Tumor size and shape impact on the piecemeal resection rate and procedural difficulty. STER for large tumors with irregular shape in the deep muscularis propria is also feasible but associated with relatively high risks of piecemeal resection and complications.

PMID: 28059965 [PubMed - indexed for MEDLINE]

Schwannoma in the hepatoduodenal ligament: A case report and literature review.

Fetched: June 11th, 2017, 1:01am EDT

Schwannoma in the hepatoduodenal ligament: A case report and literature review.

World J Gastroenterol. 2016 Dec 14;22(46):10260-10266

Authors: Xu SY, Sun K, Xie HY, Zhou L, Zheng SS, Wang WL

Abstract
Schwannomas are mesenchymal neoplasms with low malignant potential that arise from Schwann cells. They can occur almost anywhere, although the most common locations are the head, neck and extremities. Primary benign schwannoma of the hepatoduodenal ligament is rare. To date, only three cases have been reported in the English literature. In the present study, we report a case of hepatoduodenal ligament schwannoma in a 43-year-old male, who was admitted to our hospital because of a abdominal mass found by physical examination. It was hard to determine the definitive location and diagnosis of the mass using ultrasound, computed tomography and magnetic resonance cholangiopancreatography. During laparotomy, the mass was found in the hepatoduodenal ligament and close to the cholecystic duct, so we resected the gallbladder and cholecystic duct along with the mass. The gross specimen revealed an 8.5 cm × 5.5 cm × 3.0 cm localized tumor. Microscopic examination showed that the tumor was mainly composed of spindle-shaped cells. Immunohistochemical staining showed a strong positive S-100 protein reaction. Finally, the lesion was diagnosed as a benign schwannoma in the hepatoduodenal ligament. However, one month later, the patient was readmitted to our hospital because of skin and sclera jaundice caused by common bile duct stenosis without common bile duct stone or tumor. The patient recovered well after implantation of a common bile duct stent under endoscopic retrograde cholangiopancreatography. He was followed up for a period of 17 mo, during which he was well with no complications.

PMID: 28028376 [PubMed - indexed for MEDLINE]

Permalink for 'Safety and Feasibility of Minimally Invasive Inguinal Lymph Node Dissection in Patients With Melanoma (SAFE-MILND): Report of a Prospective Multi-institutional Trial.'

Safety and Feasibility of Minimally Invasive Inguinal Lymph Node Dissection in Patients With Melanoma (SAFE-MILND): Report of a Prospective Multi-institutional Trial.

Fetched: June 11th, 2017, 1:01am EDT

Safety and Feasibility of Minimally Invasive Inguinal Lymph Node Dissection in Patients With Melanoma (SAFE-MILND): Report of a Prospective Multi-institutional Trial.

Ann Surg. 2017 Jan;265(1):192-196

Authors: Jakub JW, Terando AM, Sarnaik A, Ariyan CE, Faries MB, Zani S, Neuman HB, Wasif N, Farma JM, Averbook BJ, Bilimoria KY, Grotz TE, Allred JB, Suman VJ, Brady MS, Tyler D, Wayne JD, Nelson H

Abstract
BACKGROUND: Minimally invasive inguinal lymph node dissection (MILND) is a novel approach to inguinal lymphadenectomy. SAFE-MILND (NCT01500304) is a multicenter, phase I/II clinical trial evaluating the safety and feasibility of MILND for patients with melanoma in a group of surgeons newly adopting the procedure.
METHODS: Twelve melanoma surgeons from 10 institutions without any previous MILND experience, enrolled patients into a prospective study after completing specialized training including didactic lectures, participating in a hands-on cadaveric laboratory, and being provided an instructional DVD of the procedure. Complications and adverse postoperative events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.0.
RESULTS: Eighty-seven patients underwent a MILND. Seventy-seven cases (88.5%) were completed via a minimally invasive approach. The median total inguinal lymph nodes pathologically examined (SLN + MILND) was 12.0 (interquartile range 8.0, 14.0). Overall, 71% of patients suffered an adverse event (AE); the majority of these were grades 1 and 2, with 26% of patients experiencing a grade 3 AE. No grade 4 or 5 AEs were observed.
CONCLUSIONS: After a structured training program, high-volume melanoma surgeons adopted a novel surgical technique with a lymph node retrieval rate that met or exceeded current oncologic guidelines and published benchmarks, and a favorable morbidity profile.

PMID: 28009745 [PubMed - indexed for MEDLINE]

Curcumin: A new candidate for melanoma therapy?

Fetched: June 11th, 2017, 1:01am EDT

Curcumin: A new candidate for melanoma therapy?

Int J Cancer. 2016 Oct 15;139(8):1683-95

Authors: Mirzaei H, Naseri G, Rezaee R, Mohammadi M, Banikazemi Z, Mirzaei HR, Salehi H, Peyvandi M, Pawelek JM, Sahebkar A

Abstract
Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g., BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin.

PMID: 27280688 [PubMed - indexed for MEDLINE]

Health Disparities Influence Childhood Melanoma Stage at Diagnosis and Outcome.

Fetched: June 11th, 2017, 1:01am EDT

Health Disparities Influence Childhood Melanoma Stage at Diagnosis and Outcome.

J Pediatr. 2016 Aug;175:182-7

Authors: Hamilton EC, Nguyen HT, Chang YC, Eberth JM, Cormier J, Elting LS, Austin MT

Abstract
OBJECTIVE: To identify health disparities in pediatric patients with melanoma that affect disease presentation and outcome.
STUDY DESIGN: This was a retrospective cohort study of all persons aged ≤18 years diagnosed with melanoma and enrolled in the Texas Cancer Registry between 1995 and 2009. Socioeconomic status (SES) and driving distance to the nearest pediatric cancer treatment center were calculated for each patient. Logistic regression was used to determine factors associated with advanced-stage disease. Life table methods and Cox regression were used to estimate survival probability and hazard ratios.
RESULTS: A total of 185 adolescents (age >10 years) and 50 young children (age ≤10 years) were identified. Hispanics (n = 27; 12%) were 3 times more likely than non-Hispanic whites (n = 177; 75%) to present with advanced disease (OR, 3.8; 95% CI, 1.7-8.8). Young children were twice as likely as adolescents to present with advanced disease (OR, 2.2; 95% CI, 1.1-4.3). Distance to treatment center and SES did not affect stage of disease at presentation. Hispanics and those in the lowest SES quartile had a significantly higher mortality risk (hazard ratios, 3.0 [95% CI, 1.2-7.8] and 4.3 [95% CI, 1.4-13.9], respectively). In the adjusted survival model, only advanced disease was predictive of mortality (P < .001).
CONCLUSION: Hispanics and young children with melanoma are more likely to present with advanced disease, and advanced disease is the single most important predictor of survival. Heightened awareness among physicians is needed to facilitate early detection of melanoma within these groups.

PMID: 27233520 [PubMed - indexed for MEDLINE]

Permalink for 'Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.'

Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.

Fetched: June 11th, 2017, 1:01am EDT

Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.

Environ Mol Mutagen. 2016 Jun;57(5):372-81

Authors: Weitzel DH, Tovmasyan A, Ashcraft KA, Boico A, Birer SR, Roy Choudhury K, Herndon J, Rodriguiz RM, Wetsel WC, Peters KB, Spasojevic I, Batinic-Haberle I, Dewhirst MW

Abstract
Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have recently shown that MnTnBuOE-2-PyP(5+) (Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium -2-yl)porphyrin) rescued RT-induced white matter damage in cranially-irradiated mice. Radiotherapy is not used in isolation for treatment of brain tumors; temozolomide is the standard-of-care for adult glioblastoma, whereas cisplatin is often used for treatment of pediatric brain tumors. Therefore, we evaluated the brain radiation mitigation ability of MnTnBuOE-2-PyP(5+) after either temozolomide or cisplatin was used singly or in combination with 10 Gy RT. MnTnBuOE-2-PyP(5+) accumulated in brains at low nanomolar levels. Histological and neurobehavioral testing showed a drastic decrease (1) of axon density in the corpus callosum and (2) rotorod and running wheel performance in the RT only treatment group, respectively. MnTnBuOE-2-PyP(5+) completely rescued this phenotype in irradiated animals. In the temozolomide groups, temozolomide/ RT treatment resulted in further decreased rotorod responses over RT alone. Again, MnTnBuOE-2-PyP(5+) treatment rescued the negative effects of both temozolomide ± RT on rotorod performance. While the cisplatin-treated groups did not give similar results as the temozolomide groups, inclusion of MnTnBuOE-2-PyP(5+) did not negatively affect rotorod performance. Additionally, MnTnBuOE-2-PyP(5+) sensitized glioblastomas to either RT ± temozolomide in flank tumor models. Mice treated with both MnTnBuOE-2-PyP(5+) and radio-/chemo-therapy herein demonstrated brain radiation mitigation. MnTnBuOE-2-PyP(5+) may well serve as a normal tissue radio-/chemo-mitigator adjuvant therapy to standard brain cancer treatment regimens. Environ. Mol. Mutagen. 57:372-381, 2016. © 2016 Wiley Periodicals, Inc.

PMID: 27224425 [PubMed - indexed for MEDLINE]

Permalink for 'Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells.'

Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells.

Fetched: June 11th, 2017, 1:01am EDT

Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells.

Bioconjug Chem. 2016 May 18;27(5):1227-35

Authors: Wen AM, Lee KL, Cao P, Pangilinan K, Carpenter BL, Lam P, Veliz FA, Ghiladi RA, Advincula RC, Steinmetz NF

Abstract
Photodynamic therapy (PDT) is a promising avenue for greater treatment efficacy of highly resistant and aggressive melanoma. Through photosensitizer attachment to nanoparticles, specificity of delivery can be conferred to further reduce potential side effects. While the main focus of PDT is the destruction of cancer cells, additional targeting of tumor-associated macrophages also present in the tumor microenvironment could further enhance treatment by eliminating their role in processes such as invasion, metastasis, and immunosuppression. In this study, we investigated PDT of macrophages and tumor cells through delivery using the natural noninfectious nanoparticle cowpea mosaic virus (CPMV), which has been shown to have specificity for the immunosuppressive subpopulation of macrophages and also targets cancer cells. We further explored conjugation of CPMV/dendron hybrids in order to improve the drug loading capacity of the nanocarrier. Overall, we demonstrated effective elimination of both macrophage and tumor cells at low micromolar concentrations of the photosensitizer when delivered with the CPMV bioconjugate, thereby potentially improving melanoma treatment.

PMID: 27077475 [PubMed - indexed for MEDLINE]

Permalink for 'Small-cell Neuroendocrine Carcinoma Associated with Non Adenoma-like Raised Lesion in a Patient with Long-standing Ulcerative Colitis.'

Small-cell Neuroendocrine Carcinoma Associated with Non Adenoma-like Raised Lesion in a Patient with Long-standing Ulcerative Colitis.

Fetched: June 11th, 2017, 1:01am EDT

Small-cell Neuroendocrine Carcinoma Associated with Non Adenoma-like Raised Lesion in a Patient with Long-standing Ulcerative Colitis.

J Crohns Colitis. 2016 Sep;10(9):1125-6

Authors: Lacerda-Filho A, da Mota FF, Lacerda GC, de Castro AF

PMID: 26912579 [PubMed - indexed for MEDLINE]

Mesenteric Lymphadenectomy in Well-Differentiated Appendiceal Neuroendocrine Tumors.

Fetched: June 10th, 2017, 1:00am EDT

Mesenteric Lymphadenectomy in Well-Differentiated Appendiceal Neuroendocrine Tumors.

Dis Colon Rectum. 2017 Jul;60(7):674-681

Authors: Raoof M, Dumitra S, O'Leary MP, Singh G, Fong Y, Lee B

Abstract
BACKGROUND: Surgical resection is the primary therapy for local and locally advanced appendiceal neuroendocrine tumors. The role of mesenteric lymphadenectomy in these patients is undefined.
OBJECTIVE: The purpose of this study was to define the role and prognostic significance of mesenteric lymphadenectomy.
DESIGN: This was a retrospective, observational study.
SETTINGS: A population-based cohort from the National Cancer Institute Surveillance, Epidemiology, and End Results registry (January 1988 to November 2013) was used.
PATIENTS: Patients with well-differentiated neuroendocrine tumors and nonmixed histologies undergoing surgical resection were included.
MAIN OUTCOME MEASURES: The risk of lymph node metastases as a function of tumor size and overall survival with respect to lymph node count and tumor size was measured. Lymph node cut-point was determined using the Contal and O'Quigely method.
RESULTS: Of the 573 patients who met the inclusion criteria, 64% were women, 79% were white, and 76% were <60 years of age. Seventy percent of the tumors were ≤2 cm, and 77% were lymph node negative. Median lymph nodes retrieved were 0 (interquartile range, 0-14). The probability of nodal metastases was 2.7% in tumors ≤1.0 cm, 31.0% in tumors 1.1 to 2.0 cm, and 64.0% in tumors >2.0 cm. The probability of a positive lymph node increased with increasing lymph node count up to 26 lymph nodes. An ideal cut-point of 12 lymph nodes was identified by statistical modeling. After adjustment in the multivariable model, the group with 12 or fewer lymph nodes examined had significantly worse overall survival (HR = 4.33 (95% CI, 1.54-12.15); p = 0.005; 5-year survival, 88% versus 96%) than the group with more than 12 lymph nodes examined.
LIMITATIONS: Analysis was limited by the variables available in the database.
CONCLUSIONS: This is the largest study to date that looks at prognostic significance of lymph node count for well-differentiated appendiceal neuroendocrine tumors. Overall survival was worse where 12 or fewer lymph nodes were identified for tumors >1 cm. See Video Abstract at [links.lww.com]

PMID: 28594716 [PubMed - in process]

A New Scoring System to Predict Recurrent Disease in Grade 1 and 2 Nonfunctional Pancreatic Neuroendocrine Tumors.

Fetched: June 10th, 2017, 1:00am EDT

A New Scoring System to Predict Recurrent Disease in Grade 1 and 2 Nonfunctional Pancreatic Neuroendocrine Tumors.

Ann Surg. 2017 Jan 03;:

Authors: Genç CG, Jilesen AP, Partelli S, Falconi M, Muffatti F, van Kemenade FJ, van Eeden S, Verheij J, van Dieren S, van Eijck CHJ, Nieveen van Dijkum EJM

Abstract
OBJECTIVE: The aim of this study was to predict recurrence in patients with grade 1 or 2 nonfunctioning pancreatic neuroendocrine tumors (NF-pNET) after curative resection.
BACKGROUND: Surgical resection is the preferred treatment for NF-pNET; however, recurrence occurs frequently after curative surgery, worsening prognosis of patients.
METHODS: Retrospectively, patients with NF-pNET of 3 institutions were included. Patients with distant metastases, hereditary syndromes, or grade 3 tumors were excluded. Local or distant tumor recurrence was scored. Independent predictors for survival and recurrence were identified using Cox-regression analysis. The recurrence score was developed to predict recurrence within 5 years after curative resection of grade 1 to 2 NF-pNET.
RESULTS: With a median follow-up of 51 months, 211 patients with grade 1 to 2 NF-pNET were included. Thirty-five patients (17%) developed recurrence. The 5- and 10-year disease-specific/overall survival was 98%/91% and 84%/68%, respectively. Predictors for recurrence were tumor grade 2, lymph node metastasis, and perineural invasion. On the basis of these predictors, the recurrence score was made. Discrimination [c-statistic 0.81, 95% confidence interval (95% CI) 0.75-0.87] and calibration (Hosmer Lemeshow Chi-square 11.25, P = 0.258) indicated that the ability of the recurrence score to identify patients at risk for recurrence is good.
CONCLUSIONS: This new scoring system could predict recurrence after curative resection of grade 1 and 2 NF-pNET. With the use of the recurrence score, less extensive follow-up could be proposed for patients with low recurrence risk. For high-risk patients, clinical trials should be initiated to investigate whether adjuvant therapy might be beneficial. External validation is ongoing due to limited availability of adequate cohorts.

PMID: 28594340 [PubMed - as supplied by publisher]

Permalink for 'Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature.'

Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature.

Fetched: June 10th, 2017, 1:00am EDT

Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature.

Int J Surg Oncol. 2017;2017:6424812

Authors: Neychev V, Kebebew E

Abstract
Our understanding of the biology, genetics, and natural history of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas has improved considerably in the last several decades and the spectrum of available therapeutic options is rapidly expanding. The management of patients with metastatic low or intermediate grade NETs has been revolutionized by the development of new treatment strategies such as molecular targeting therapies with everolimus and sunitinib, somatostatin analogs, tryptophan hydroxylase inhibitors, and peptide receptor radionuclide therapy that can be used alone or as a multimodal approach with or without surgery. To further define and clarify the utility, appropriateness, and the sequence of the growing list of available therapies for this patient population will require more high level evidence; however, data from well-designed randomized phase III clinical trials is rapidly accumulating that will further stimulate development of new management strategies. It is therefore important to thoroughly review emerging evidence and report major findings in frequent updates, which will expand our knowledge and contribute to a better understanding, characterization, and management of advanced NETs.

PMID: 28593056 [PubMed - in process]

Permalink for '[Accurate grading of pancreatic neuroendocrine tumors with Ki-67 index in fine-needle aspiration specimens: a comparative cytologic and histologic study].'

[Accurate grading of pancreatic neuroendocrine tumors with Ki-67 index in fine-needle aspiration specimens: a comparative cytologic and histologic study].

Fetched: June 10th, 2017, 1:00am EDT

[Accurate grading of pancreatic neuroendocrine tumors with Ki-67 index in fine-needle aspiration specimens: a comparative cytologic and histologic study].

Zhonghua Bing Li Xue Za Zhi. 2017 Jun 08;46(6):393-399

Authors: He SR, Cui D, Gong H, Zhu YP, Chen L, Hu ST, Liu DG

Abstract
Objective: To study the cytomorphologic features and determine whether pancreatic neuroendocrine tumors (PanNET) sampled by fine-needle aspiration (FNA) can be accurately graded based on the Ki-67 index when compared to surgical samples. Methods: Corresponding intraoperative (19 cases) or endoscopic ultrasound-guided (3 cases) FNA cytology and surgical tissue specimens were obtained from 22 tumors, which were reviewed and stained for Ki-67 proliferation marker. The cytological samples included more than 200 tumor cells. Samples were graded by scoring the Ki-67 positive index in accordance with the 2010 WHO criteria. The grading scores assigned to the FNA cytology samples were compared with the scores assigned to the corresponding histological samples. Concordance was achieved by using 5% (instead of 2%) as a cut-off value for defining G2 tumors. One cytological sample included less than 500 tumor cells was excluded in the concordance calculation. Results: The cytological smears consisted of uniform, monotonous and isolated cells, loose cellular aggregates and rosette-like formations. Some tumor cells clustered around segments of capillaries. The cells demonstrated distinct cytoplasmic and nuclear features. Mitoses and necrosis were rarely seen. When traditional 2% Ki-67 index cut-off value were used to classify G2 tumors, the majority (86.4%, κ=0.812, P<0.01) of FNA cytology samples and corresponding surgical tissue specimens demonstrated concordance. When a 5% cut-off value was adopted, the concordance rate was 95.5% (21/22, κ=1.000, P<0.01). Similar concordance rates between the cytological and histological grades were achieved with threshold value of cytological assessment material set at more than 500 or 200 cells. Conclusions: The cytological Ki-67 index in adequate material (>200 tumor cells) is useful in grading pancreatic neuroendocrine tumors, and a cut-off value of 5% showed better predictive value compared with that of 2%. Accurate grading of PanNET is critical for predicting tumor biology, patient prognosis, and making informed decisions regarding patient management and treatment.

PMID: 28591986 [PubMed - in process]

Effect of SOCS1 silencing on proliferation and apoptosis of melanoma cells: An in vivo and in vitro study.

Fetched: June 10th, 2017, 1:00am EDT

Effect of SOCS1 silencing on proliferation and apoptosis of melanoma cells: An in vivo and in vitro study.

Tumour Biol. 2017 May;39(5):1010428317694315

Authors: Yu SJ, Long ZW

Abstract
This study aimed to investigate the effect of SOCS1 silencing on the proliferation and apoptosis of melanoma cells by in vivo and in vitro studies. Immunohistochemical staining was used to detect SOCS1 expression in melanoma tissues and pigmented nevi. Quantitative real-time polymerase chain reaction and western blotting were applied to detect the messenger RNA and protein expressions of SOCS1 in primary human melanocytes and malignant melanoma cell lines (A375, SK-MEL-5, M14, and MV3). Melanoma cells were assigned into mock, negative small interfering RNA, and SOCS1-small interfering RNA groups. The proliferation, cell cycle and apoptosis, and messenger RNA expression of SOCS1 in MV3 and A375 cells were detected using MTT assay, flow cytometry, and quantitative real-time polymerase chain reaction, respectively. The expressions of SOCS1 protein, extracellular signal-regulated kinase, and janus kinase signal transduction and activators of transcription signaling pathways-related proteins were detected using western blotting. After the establishment of subcutaneous xenograft tumor models in nude mice, the latent period, size, volume and growth speed of xenograft tumors in the mock, negative small interfering RNA, and SOCS1-small interfering RNA groups were examined and compared. The results indicated that positive expression rate of SOCS1 was higher in malignant melanoma tissues than in pigmented nevi. MV3 cells had the highest messenger RNA and protein expressions of SOCS1, followed by A357 cells. Compared with the mock and negative small interfering RNA groups, SOCS1-small interfering RNA group showed lower cell viability, elevated cell apoptosis, more cells in G0/G1 phase and less cells in S and G2/M phases, and decreased messenger RNA and protein expressions of SOCS1, p-ERK1/2, p-JAK2, p-STAT1, and p-STAT3. Compared with the mock and negative small interfering RNA groups, the SOCS1-small interfering RNA group showed longer latent period of tumor, smaller tumor size and volume, and smoother tumor growth curve. To conclude, SOCS1 silencing can inhibit proliferation and induce apoptosis of MV3 and A357 melanoma cells in vivo and in vitro by inhibiting extracellular signal-regulated kinase and janus kinase signal transduction and activators of transcription signaling pathways.

PMID: 28466787 [PubMed - indexed for MEDLINE]

Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma.

Fetched: June 10th, 2017, 1:00am EDT

Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma.

Tumour Biol. 2017 May;39(5):1010428317701646

Authors: Fogli S, Polini B, Carpi S, Pardini B, Naccarati A, Dubbini N, Lanza M, Breschi MC, Romanini A, Nieri P

Abstract
Melanoma is a devastating disease with few therapeutic options in the advanced stage and with the urgent need of reliable biomarkers for early detection. In this context, circulating microRNAs are raising great interest as diagnostic biomarkers. We analyzed the expression profiles of 21 selected microRNAs in plasma samples from melanoma patients and healthy donors to identify potential diagnostic biomarkers. Data analysis was performed using global mean normalization and NormFinder algorithm. Linear regression followed by receiver operating characteristic analyses was carried out to evaluate whether selected plasma miRNAs were able to discriminate between cases and controls. We found five microRNAs that were differently expressed among cases and controls after Bonferroni correction for multiple testing. Specifically, miR-15b-5p, miR-149-3p, and miR-150-5p were up-regulated in plasma of melanoma patients compared with healthy controls, while miR-193a-3p and miR-524-5p were down-regulated. Receiver operating characteristic analyses of these selected microRNAs provided area under the receiver operating characteristic curve values ranging from 0.80 to 0.95. Diagnostic value of microRNAs is improved when considering the combination of miR-149-3p, miR-150-5p, and miR-193a-3p. The triple classifier had a high capacity to discriminate between melanoma patients and healthy controls, making it suitable to be used in early melanoma diagnosis.

PMID: 28466785 [PubMed - indexed for MEDLINE]

Permalink for 'Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial.'

Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial.

Fetched: June 10th, 2017, 1:00am EDT

Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial.

Lancet Oncol. 2017 Apr;18(4):435-445

Authors: Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K

Abstract
BACKGROUND: There are no established therapies specific for NRAS-mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS-mutant melanoma.
METHODS: NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS-mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m(2) intravenously every 3 weeks. Randomisation was stratified by stage, performance status, and previous immunotherapy. The primary endpoint was progression-free survival assessed by blinded central review in the intention-to-treat population. Safety analyses were done in the safety population, consisting of all patients who received at least one study drug dose and one post-baseline safety assessment. This study is registered with ClinicalTrials.gov, number NCT01763164 and with EudraCT, number 2012-003593-51.
FINDINGS: Between Aug 19, 2013, and April 28, 2015, 402 patients were enrolled and randomly assigned, 269 to binimetinib and 133 to dacarbazine. Median follow-up was 1·7 months (IQR 1·4-4·1). Median progression-free survival was 2·8 months (95% CI 2·8-3·6) in the binimetinib group and 1·5 months (1·5-1·7) in the dacarbazine group (hazard ratio 0·62 [95% CI 0·47-0·80]; one-sided p<0·001). Grade 3-4 adverse events seen in at least 5% of patients the safety population in either group were increased creatine phosphokinase (52 [19%] of 269 patients in the binimetinib group vs none of 114 in the dacarbazine group), hypertension (20 [7%] vs two [2%]), anaemia (five [2%] vs six [5%]), and neutropenia (two [1%] vs ten [9%]). Serious adverse events (all grades) occurred in 91 (34%) patients in the binimetinib group and 25 (22%) patients in the dacarbazine group.
INTERPRETATION: Binimetinib improved progression-free survival compared with dacarbazine and was tolerable. Binimetinib might represent a new treatment option for patients with NRAS-mutant melanoma after failure of immunotherapy.
FUNDING: Array BioPharma and Novartis Pharmaceuticals Corporation.

PMID: 28284557 [PubMed - indexed for MEDLINE]

Permalink for 'Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF(V600)-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial.'

Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF(V600)-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial.

Fetched: June 10th, 2017, 1:00am EDT

Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF(V600)-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial.

Lancet Oncol. 2017 Apr;18(4):464-472

Authors: Schreuer M, Jansen Y, Planken S, Chevolet I, Seremet T, Kruse V, Neyns B

Abstract
BACKGROUND: Patients with BRAF(V600)-mutant melanoma benefit from treatment with the combination of BRAF and MEK inhibitors, but resistance and disease progression develops in most patients. Preclinical studies and case studies have indicated that acquired resistance to BRAF inhibition can be reversible. We aimed to assess the anti-tumour activity of rechallenge with BRAF plus MEK inhibition in a prospective clinical trial.
METHODS: In this open-label, single arm, dual-centre, phase 2 academic study in Belgium, patients aged 18 years or older with BRAF(V600)-mutant melanoma who had previously progressed on BRAF inhibitors (with or without MEK inhibitors) and were off-treatment for at least 12 weeks, were treated with dabrafenib 150 mg orally twice per day plus trametinib 2 mg orally once per day. The primary endpoint was the proportion of patients with investigator-assessed overall response at any time (defined as complete response or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed on two occasions, at least 28 days after the first response was recorded). Analyses were done in the intention-to-treat population. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT02296996.
FINDINGS: Between April 5, 2014, and Feb 2, 2016, 25 patients were enrolled and initiated treatment in our study. A partial response was documented in eight (32%) of 25 patients (95% CI 15-54; six patients had progressed on previous treatment with dabrafenib plus trametinib and two patients had progressed on previous BRAF inhibitor monotherapy). Stable disease was noted in ten patients (40%; 95% CI 21-61). Rechallenge with dabrafenib plus trametinib was well tolerated. There were no unexpected or grade 4 or 5 treatment-related adverse events. Grade 3 adverse events occurred in two patients (8%; panniculitis [n=1] and pyrexia [n=1]). Serious adverse events which occurred on study were one patient with an Addison crisis triggered by grade 2 pyrexia symptoms that resolved after discontinuation of dabrafenib and trametinib. No patients died as a result of study treatment.
INTERPRETATION: Rechallenge with dabrafenib plus trametinib showed anti-tumour activity in patients who had previously progressed on BRAF inhibitors and as such, rechallenge represents a potential new treatment option for these patients.
FUNDING: Vlaamse Liga Tegen Kanker, Novartis.

PMID: 28268064 [PubMed - indexed for MEDLINE]

UV-Radiation: From Physics to Impacts.

Fetched: June 10th, 2017, 1:00am EDT

UV-Radiation: From Physics to Impacts.

Int J Environ Res Public Health. 2017 Feb 17;14(2):

Authors: Moshammer H, Simic S, Haluza D

Abstract
Ultraviolet (UV) radiation has affected life at least since the first life forms moved out of the seas and crawled onto the land. Therefore, one might assume that evolution has adapted to natural UV radiation. However, evolution is mostly concerned with the propagation of the genetic code, not with a long, happy, and fulfilling life. Because rickets is bad for a woman giving birth, the beneficial effects of UV-radiation outweigh the adverse effects like aged skin and skin tumors of various grades of malignancy that usually only afflict us at older age. Anthropogenic damage to the stratospheric ozone layer and frighteningly high rates of melanoma skin cancer in the light-skinned descendants of British settlers in Australia piqued interest in the health impacts of UV radiation. A changing cultural perception of the beauty of tanned versus light skin and commercial interests in selling UV-emitting devices such as tanning booths caught public health experts off-guard. Counseling and health communication are extremely difficult when dealing with a "natural" risk factor, especially when this risk factor cannot (and should not) be completely avoided. How much is too much for whom or for which skin type? How even measure "much"? Is it the (cumulative) dose or the dose rate that matters most? Or should we even construct a more complex metric such as the cumulative dose above a certain dose rate threshold? We find there are still many open questions, and we are glad that this special issue offered us the opportunity to present many interesting aspects of this important topic.

PMID: 28218687 [PubMed - indexed for MEDLINE]

Permalink for 'Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial.'

Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial.

Fetched: June 10th, 2017, 1:00am EDT

Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial.

Lancet Oncol. 2017 Mar;18(3):393-403

Authors: Coens C, Suciu S, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbé C, Ferraresi V, Smylie M, Weber JS, Maio M, Bottomley A, Kotapati S, de Pril V, Testori A, Eggermont AM

Abstract
BACKGROUND: The EORTC 18071 phase 3 trial compared adjuvant ipilimumab with placebo in patients with stage III melanoma. The primary endpoint, recurrence-free survival, was significantly longer in the ipilimumab group than in the placebo group. Investigator-reported toxic effects of ipilimumab consisted mainly of skin, gastrointestinal, endocrine, and hepatic immune-related adverse events. Adjuvant treatment with ipilimumab in this setting was approved in October, 2014, by the US Food and Drug Administration based on the results of the primary outcome of this trial. Here, we report the results of the secondary endpoint, health-related quality of life (HRQoL), of this trial.
METHODS: EORTC 18071 was a multinational, double-blind, randomised, phase 3 trial in patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) in 19 countries worldwide. Participants were randomly assigned (1:1) centrally by an interactive voice response system, to receive either ipilimumab 10 mg/kg or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. Using a minimisation technique, randomisation was stratified by disease stage and geographical region. HRQoL was assessed with the EORTC QLQ-C30 quality-of-life instrument at baseline, weeks 4, 7, 10, and 24, and every 12 weeks thereafter up to 2 years, irrespective of disease progression. Results were summarised by timepoint and in a longitudinal manner in the intention-to-treat population. Two summary scores were calculated for each HRQoL scale: the average score reported during induction (ipilimumab or placebo at a dose of 10 mg/kg, administered as one single dose at the start of days 1, 22, 43, and 64-ie, four doses in 3 weeks), and the average score reported after induction. A predefined threshold of a 10 point difference between arms was considered clinically relevant. The primary HRQoL endpoint was the global health scale, with the predefined hypothesis of no clinically relevant differences after induction between groups. This trial is registered with EudraCT, number 2007-001974-10, and ClinicalTrials.gov, number NCT00636168.
FINDINGS: Between July 10, 2008, and Aug 1, 2011, 951 patients were randomly assigned to treatment: 475 in the ipilimumab group and 476 in the placebo group. Compliance with completing the HRQoL questionnaire was 893 (94%) of 951 patients at baseline, 693 (75%) of 924 at week 24, and 354 (51%) of 697 at week 108. Patient mean global health scores during (77·32 [SD 17·36] vs 72·96 [17·82]; p=0·00011) and after induction (76·48 [17·52] vs 72·32 [18·60]; p=0·00067) were statistically significantly different between groups but were not clinically relevant. Mean global health scores differed most between the groups at week 7 (77 [SD 19] in the placebo group vs 72 [22] in the ipilimumab group) and week 10 (77 [20] vs 70 [23]). Mean HRQoL scores differed by more than 10 points at week 10 between treatment groups for diarrhoea (7·67 [SD 17·05] for placebo vs 18·17 [28·35] for ipilimumab) and insomnia (15·17 [22·53] vs 25·60 [29·19]).
INTERPRETATION: Despite increased toxicity, which led to treatment discontinuation for most patients during the induction phase of ipilimumab administration, overall HRQoL, as measured by the EORTC QLQ-C30, was similar between groups, as no clinically relevant differences (10 points or more) in global health status scores were observed during or after induction. Clinically relevant deterioration for some symptoms was observed at week 10, but after induction, no clinically relevant differences remained. Together with the primary analysis, results from this trial show that treatment with ipilimumab results in longer recurrence-free survival compared with that for treatment with placebo, with little impairment in HRQoL despite grade 3-4 investigator-reported adverse events.
FUNDING: Bristol-Myers Squibb.

PMID: 28162999 [PubMed - indexed for MEDLINE]

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.

Fetched: June 10th, 2017, 1:00am EDT

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.

Cancer Cell. 2017 Feb 13;31(2):181-193

Authors: Fishbein L, Leshchiner I, Walter V, Danilova L, Robertson AG, Johnson AR, Lichtenberg TM, Murray BA, Ghayee HK, Else T, Ling S, Jefferys SR, de Cubas AA, Wenz B, Korpershoek E, Amelio AL, Makowski L, Rathmell WK, Gimenez-Roqueplo AP, Giordano TJ, Asa SL, Tischler AS, Cancer Genome Atlas Research Network, Pacak K, Nathanson KL, Wilkerson MD

Abstract
We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

PMID: 28162975 [PubMed - indexed for MEDLINE]

The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma.

Fetched: June 10th, 2017, 1:00am EDT

The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma.

Br J Cancer. 2017 Jan;116(3):310-317

Authors: Daly LE, Power DG, O'Reilly Á, Donnellan P, Cushen SJ, O'Sullivan K, Twomey M, Woodlock DP, Redmond HP, Ryan AM

Abstract
BACKGROUND: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established.
METHODS: Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Event V.4.0).
RESULTS: Eighty-four patients were included in this study (62% male, median age 54 years). At baseline, 24% were sarcopenic and 33% had low MA. On multivariate analysis, sarcopenia and low MA were significantly associated with high-grade AEs (OR=5.34, 95% CI: 1.15-24.88, P=0.033; OR=5.23, 95% CI: 1.41-19.30, P=0.013, respectively), and low MA was associated with high-grade irAEs (OR=3.57, 95% CI: 1.09-11.77, P=0.036). Longitudinal analysis (n=59) revealed significant reductions in skeletal muscle area (SMA), total body fat-free mass, fat mass (all P<0.001) and MA (P=0.030). Mean reduction in SMA was 3.3%/100 days (95% CI: -4.48 to -1.79%, P<0.001). A loss of SMA ⩾7.5%/100 days (highest quartile) was a significant predictor of overall survival in multivariable Cox regression analysis (HR: 2.1, 95% CI: 1.02-4.56, P=0.046).
CONCLUSIONS: Patients with sarcopenia and low MA are more likely to experience severe treatment-related toxicity to Ipi. Loss of muscle during treatment was predictive of worse survival. Treatments to increase muscle mass and influence outcome warrant further investigation.

PMID: 28072766 [PubMed - indexed for MEDLINE]

Simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness.

Fetched: June 10th, 2017, 1:00am EDT

Simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness.

Histochem Cell Biol. 2016 Aug;146(2):205-17

Authors: Jobe NP, Rösel D, Dvořánková B, Kodet O, Lacina L, Mateu R, Smetana K, Brábek J

Abstract
Tumour microenvironment plays a critical role in cell invasion and metastasis. To investigate the role of cancer-associated fibroblasts (CAFs) in melanoma cell invasiveness, we used 3D spheroid invasion assay. The effect of conditioned media from normal fibroblasts and CAFs cultivated alone or co-cultivated with melanoma cells on BLM or A2058 melanoma spheroid invasion was analysed. We found that conditioned media from CAFs and CAFs co-cultured with melanoma cells, especially, promote invasion and migration, without significant effect on melanoma cell proliferation. We further analysed the expression of pro-invasive cytokines IL-8 and IL-6 in media and found that melanoma cells are dominant producers of IL-8 and fibroblasts are dominant producers of IL-6 in 2D monocultures, while co-cultivation of CAFs with melanoma cells induces production/secretion of IL-6 and IL-8 into the media. The analyses of IL-6 levels in 3D cultures and human melanoma samples, however, revealed that at least in some cases IL-6 is also produced directly by melanoma cells. Analysis of the role of IL-6 and IL-8 in CAF-induced melanoma invasion, using neutralising antibodies, revealed that simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness. In summary, these experiments indicate the important role of CAFs and IL-8 and IL-6 cytokines in melanoma cell invasiveness.

PMID: 27102177 [PubMed - indexed for MEDLINE]

Permalink for 'A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma.'

A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma.

Fetched: June 10th, 2017, 1:00am EDT

A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma.

J Vet Med Sci. 2016 Jun 01;78(5):845-50

Authors: Treggiari E, Grant JP, North SM

Abstract
A xenogeneic DNA vaccination has been licensed for use in dogs with locally controlled stage II and III oral malignant melanoma (OMM). At present, there are limited outcome data for dogs with OMM treated with surgery and immunotherapy. The aim of this study is to retrospectively review the outcome and survival of 32 dogs affected by OMM that were treated with a combination of surgery and the xenogeneic DNA vaccination (with the addition of radiotherapy in some cases) and to determine the influence of surgical margins and delay in receiving vaccination. The overall median survival time (MST) was 335 days (95% CI: 301-540 days), and the overall median progression-free survival (PFS) was 160 days (mean 182 days, 95% CI: 132-232 days). Stage, completeness of surgical margins and delay in administration of the vaccine did not appear to statistically influence survival or PFS, although these results may reflect the low statistical power of the study due to small numbers. Further studies are required to assess whether the addition of any adjuvant treatment to surgery, including immunotherapy, is able to significantly prolong survival in cases of canine oral melanoma.

PMID: 26781703 [PubMed - indexed for MEDLINE]

Efficacy of radiotherapy for primary tumor in patients with unresectable pancreatic neuroendocrine tumors.

Fetched: June 9th, 2017, 1:00am EDT

Efficacy of radiotherapy for primary tumor in patients with unresectable pancreatic neuroendocrine tumors.

Jpn J Clin Oncol. 2017 Jun 07;:1-6

Authors: Iwata T, Ueno H, Itami J, Ito Y, Inaba K, Morizane C, Kondo S, Sakamoto Y, Shiba S, Sasaki M, Koga F, Okusaka T

Abstract
Background: Detailed information regarding the clinical efficacy of radiotherapy (RT) for primary tumor in patients with unresectable pancreatic neuroendocrine tumors (pNETs) is unknown. We therefore performed a retrospective study to evaluate the efficacy and safety of RT for primary pancreatic tumors in patients with pNETs.
Methods: We investigated 11 patients with pNETs who received RT to the primary site between January 1997 and June 2015. Seven patients had Grade 2 neuroendocrine tumors (NET-G2) and four had neuroendocrine carcinoma (NEC) according to the 2010 WHO histopathological classification.
Results: The tumor response and control rates were 27.2% and 100%, respectively (3: partial response, 8: stable disease). Among patients with NET-G2 tumors, the response rate was 28.5% (2/7 patients) and symptomatic improvement was noted in 33.3% of the patients (1/3 patients). The response rate for patients with NEC were 25% (1/4), one NEC patients with symptoms exhibited symptomatic improvement. The median overall survival and median progression-free survival were 35.9 months and 5.5 months, respectively. Grade 3 diarrhea as an acute toxicity and Grade 3 gastrointestinal hemorrhage as a late toxicity were observed.
Conclusions: RT to the primary cancer site in patients with pNETs was an effective modality for local disease control and the treated patients had good outcomes. If metastatic tumors are under control, RT to the primary site may be beneficial for patients with pNETs.

PMID: 28591817 [PubMed - as supplied by publisher]

DAXX/ATRX and MEN1 genes are strong prognostic markers in pancreatic neuroendocrine tumors.

Fetched: June 9th, 2017, 1:00am EDT

DAXX/ATRX and MEN1 genes are strong prognostic markers in pancreatic neuroendocrine tumors.

Oncotarget. 2017 May 18;:

Authors: Park JK, Paik WH, Lee K, Ryu JK, Lee SH, Kim YT

Abstract
BACKGROUND: PanNETs shows heterogeneous biological behaviors. The aim was to investigate prognostic markers based on most frequently mutated genes in PanNETs.
RESULTS: There was a total of 76 patients (M: 39, F: 37) with pathologically proven PanNETs. ATRX/DAXX and MEN1 protein expression was detected in 16 (21%) and 31 (41%) patients, respectively. The mean OS of the total study patients was 16 years, and DFS was 17 years among the 68 patients with curative resections. PanNETs presented with distant metastasis or loss of ATRX/DAXX protein expression was the independent prognostic factors associated with poor OS. In curative resected PanNETs, there was no significant difference in the mean DFS according to ATRX/DAXX or MEN1 protein. However, there was statistically significant difference in survival after the recurrence according to the expression of ATRX/DAXX protein; Y/N: 10 vs. 15 years, p < 0.001. In metastatic PanNETs, we could find out OS was significantly longer in negative protein expression of ATRX/DAXX and MEN1 groups; 7 vs. 1 years, p < 0.001, 6 vs. 2 years, p = 0.02, respectively.
MATERIALS AND METHODS: The histologically proven PanNETs were enrolled and the clinicopathologic and genetic alterations were evaluated.
CONCLUSIONS: Protein expression of MEN1 and DAXX/ATRX can be prognostic markers for PanNETs. Further investigation in genetic alterations of PanNETs may give us insights understanding the behavior of PanNETs.

PMID: 28591701 [PubMed - as supplied by publisher]

Permalink for 'Laparoscopic total pancreatectomy for multiple endocrine neoplasia type 1 syndrome-associated multifocal, non-functioning pancreatic neuroendocrine tumor: A case report.'

Laparoscopic total pancreatectomy for multiple endocrine neoplasia type 1 syndrome-associated multifocal, non-functioning pancreatic neuroendocrine tumor: A case report.

Fetched: June 9th, 2017, 1:00am EDT

Laparoscopic total pancreatectomy for multiple endocrine neoplasia type 1 syndrome-associated multifocal, non-functioning pancreatic neuroendocrine tumor: A case report.

Asian J Endosc Surg. 2017 Jun 06;:

Authors: Senthinathan P, Jankar SV, Sabnis SC, Kaje V, Srivatsan Gurumurthy S, Anand Vijai N, Nalankilli VP, Praveen Raj P, Parthasarathi R, Rajapandian S, Palanivelu C

Abstract
Pancreatic neuroendocrine tumors are rare, accounting for less than 3% of all pancreatic tumors. Although laparoscopic pancreas-preserving surgery for managing sporadic pancreatic neuroendocrine tumors has been described in the literature, laparoscopic total pancreatectomy has rarely been reported. We present a 30-year-old man who was incidentally diagnosed with multiple endocrine neoplasia type 1 syndrome with parathyroid hyperplasia and a non-functioning pancreatic neuroendocrine tumor. He underwent laparoscopic total pancreatectomy with splenectomy. This report highlights the technical details of laparoscopic total pancreatectomy, which appears to be a feasible and safe option in select cases.

PMID: 28589571 [PubMed - as supplied by publisher]

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Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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Endocrine/Neuroendocrine (338 unread)

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Fetched: May 3rd, 2017, 1:00am EDT

Fetched: May 1st, 2017, 1:00am EDT

Fetched: April 29th, 2017, 1:00am EDT

Fetched: April 29th, 2017, 1:00am EDT

Fetched: April 28th, 2017, 1:00am EDT

Fetched: April 27th, 2017, 1:00am EDT

Fetched: April 26th, 2017, 1:00am EDT

Fetched: April 26th, 2017, 1:00am EDT

Fetched: April 26th, 2017, 1:00am EDT

Fetched: April 26th, 2017, 1:00am EDT

Fetched: April 22nd, 2017, 1:00am EDT

Fetched: April 19th, 2017, 12:13am EDT

Fetched: April 19th, 2017, 12:13am EDT

Fetched: April 15th, 2017, 1:00am EDT

Fetched: April 15th, 2017, 1:00am EDT

Fetched: April 13th, 2017, 1:00am EDT

Fetched: April 12th, 2017, 1:00am EDT

Fetched: April 9th, 2017, 1:00am EDT

Fetched: April 8th, 2017, 1:00am EDT

Fetched: April 8th, 2017, 1:00am EDT

Fetched: April 7th, 2017, 1:00am EDT

Fetched: April 6th, 2017, 1:00am EDT

Fetched: April 5th, 2017, 1:00am EDT

Fetched: April 5th, 2017, 1:00am EDT

Fetched: April 5th, 2017, 1:00am EDT

Fetched: April 2nd, 2017, 1:00am EDT

Fetched: April 1st, 2017, 1:00am EDT

Fetched: March 31st, 2017, 1:00am EDT

Fetched: March 31st, 2017, 1:00am EDT

Fetched: March 29th, 2017, 1:00am EDT

Fetched: March 29th, 2017, 1:00am EDT

Fetched: March 25th, 2017, 1:00am EDT

Fetched: March 25th, 2017, 1:00am EDT

Fetched: March 24th, 2017, 1:00am EDT

Fetched: March 24th, 2017, 1:00am EDT

Fetched: March 22nd, 2017, 1:00am EDT

Fetched: March 16th, 2017, 4:04pm EDT