Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (466 unread)

Oncogenic Role of an Epigenetic Reader of m6A RNA Modification: YTHDF1 in Merkel Cell Carcinoma.

Fetched: January 19th, 2020, 5:01am GMT

Oncogenic Role of an Epigenetic Reader of m6A RNA Modification: YTHDF1 in Merkel Cell Carcinoma.

Cancers (Basel). 2020 Jan 14;12(1):

Authors: Orouji E, Peitsch WK, Orouji A, Houben R, Utikal J

Abstract
Merkel cell carcinoma is a deadly skin cancer, which in the majority of cases is caused by the Merkel cell polyomavirus (MCPyV). The viral small T antigen is regarded as the dominant oncoprotein expressed in the tumor cells. We used genomic screening of copy number aberrations along with transcriptomic analysis to investigate regions with amplification that harbor differentially expressed genes. We identified YTHDF1, a protein that is a reader of N6-methyladenosine (m6A) RNA modifications, to have high copy gains and to be highly expressed in Merkel cell carcinoma. Importantly, we identified the presence of m6A on small T antigen mRNA suggesting a relation between YTHDF1 amplification and MCPyV gene expression. Interestingly, knockdown of YTHDF1 in Merkel cell carcinoma (MCC) cell lines negatively affected the translation initiation factor eIF3 and reduced proliferation and clonogenic capacity in vitro. Furthermore, analysis of survival data revealed worse overall survival in YTHDF1high MCC patients compared to YTHDF1low patients. Our findings indicate a novel oncogenic role of YTHDF1 through m6A machinery in the tumorigenesis of MCC.

PMID: 31947544 [PubMed]

Permalink for 'Predominance of central memory T cells with high T-cell receptor repertoire diversity is associated with response to PD-1/PD-L1 inhibition in Merkel cell carcinoma.'

Predominance of central memory T cells with high T-cell receptor repertoire diversity is associated with response to PD-1/PD-L1 inhibition in Merkel cell carcinoma.

Fetched: January 16th, 2020, 5:00am GMT

Predominance of central memory T cells with high T-cell receptor repertoire diversity is associated with response to PD-1/PD-L1 inhibition in Merkel cell carcinoma.

Clin Cancer Res. 2020 Jan 13;:

Authors: Spassova I, Ugurel S, Terheyden P, Sucker A, Hassel JC, Ritter C, Kubat L, Habermann D, Farahpour F, Saeedghalati M, Peiffer L, Kumar R, Schrama D, Hoffmann D, Schadendorf D, Becker JC

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, which can be effectively controlled by immunotherapy with PD-1/PD-L1 checkpoint inhibitors. However, a significant proportion of patients are characterized by primary therapy resistance. Predictive biomarker for response to immunotherapy are lacking.
EXPERIMENTAL DESIGN: We applied Bayesian inference analyses on 41 MCC patients testing various clinical and biomolecular characteristics to predict treatment response. Further, we performed a comprehensive analysis of tumor tissue-based immunological parameters including multiplexed immunofluorescence for T-cell activation and differentiation markers, expression of immune-related genes and T-cell receptor (TCR) repertoire analyses in 18 patients, seven objective responders and eleven non-responders.
RESULTS: Bayesian inference analyses demonstrated that among currently discussed biomarkers only unimpaired overall performance status and absence of immunosuppression were associated with response to therapy. However, in responders, a predominance of central memory T cells and expression of genes associated with lymphocyte attraction and activation was evident. Additionally, TCR repertoire usage of tumor-infiltrating lymphocytes (TIL) demonstrated low T-cell clonality, but high TCR diversity in responding patients. In non-responders, terminally differentiated effector T cells with a constrained TCR repertoire prevailed. Sequential analyses of tumor tissue obtained during immunotherapy revealed a more pronounced and diverse clonal expansion of TIL in responders indicating an impaired proliferative capacity among TIL of non-responders upon checkpoint blockade.
CONCLUSIONS: Our explorative study identified new tumor tissue-based molecular characteristics associated with response to anti-PD-1/PD-L1 therapy in MCC. These observations warrant further investigations in larger patient cohorts to confirm their potential value as predictive markers.

PMID: 31932494 [PubMed - as supplied by publisher]

Merkel cell carcinoma in an immunocompetent male statin user.

Fetched: January 16th, 2020, 5:00am GMT

Merkel cell carcinoma in an immunocompetent male statin user.

An Bras Dermatol. 2019 Nov - Dec;94(6):764-765

Authors: Fasciani IA, Bandeira LG, Valente NYS, Camargo MFVC

PMID: 31789257 [PubMed - indexed for MEDLINE]

Voriconazole-photoinduced polyomavirus-negative Merkel cell carcinoma.

Fetched: January 16th, 2020, 5:00am GMT

Voriconazole-photoinduced polyomavirus-negative Merkel cell carcinoma.

J Dermatol. 2019 08;46(8):e287-e288

Authors: Miyazawa H, Shimauchi T, Hashizume H, Masuda Y, Aoshima M, Ito T, Tokura Y

PMID: 30859619 [PubMed - indexed for MEDLINE]

Unknown primary Merkel cell carcinoma responding well to first-line treatment with avelumab.

Fetched: January 16th, 2020, 5:00am GMT

Unknown primary Merkel cell carcinoma responding well to first-line treatment with avelumab.

J Dermatol. 2019 08;46(8):e273-e275

Authors: Hanai S, Shimauchi T, Kageyama R, Aoshima M, Ito T, Tokura Y

PMID: 30802319 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma. Report of a case with an atypical location and presentation.

Fetched: January 15th, 2020, 5:00am GMT

Merkel cell carcinoma. Report of a case with an atypical location and presentation.

Rev Esp Cir Ortop Traumatol. 2019 Jul - Aug;63(4):313-315

Authors: Fernández-Regueiro R, Suárez-Sánchez FJ, Morís-de la-Tassa J

Abstract
Merkel cell tumour is a rare skin tumour of high malignancy, poor prognosis and low survival. It is characterized by its tendency to lymph node and vascular invasion and by a high percentage of locoregional recurrence in the year following surgical removal. It affects adults between 60 and 80 years of age and often occurs in the head and neck. We present the case of an 85-year-old man presenting with an ulcerated gluteal mass of 4 months' evolution. Diagnosis was by histopathological and immunohistochemical study. Early diagnosis and appropriate treatment are important to improve the prognosis of these patients.

PMID: 31072794 [PubMed - indexed for MEDLINE]

[Merkel-cell carcinoma].

Fetched: January 12th, 2020, 5:01am GMT

[Merkel-cell carcinoma].

Pathologe. 2019 Dec;40(Suppl 3):350-354

Authors: Moll I

Abstract
Merkel-cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma named for its Merkel-cell-like ultrastructure. The neuroendocrine Merkel cell was previously believed to be the cell of origin. However, Merkel cells are postmitotic and thus probably not the cell of origin of MCC. It is derived from an epidermal stem cell, which also might represent the cell of origin of MCC. Further putative cells of origin are dermal stem cells and pre/pro‑B cells, the latter showing some similar markers (e.g. PAX5).About 80% of MCCs are induced by the integration of DNA of the Merkel cell polyoma virus (MCPyV) into the genome. On the other hand, about 20% of MCCs show UV-induced mutations in numerous genes (e.g. TP53, RB1). In routine histology, MCC appears monomorphic and the diagnosis is confirmed by immunohistochemistry showing CK20 arranged in typical paranuclear plaques, together with the presence of neurofilaments and chromogranin A. Virus-positive and virus-negative MCC are not different histologically.UV-induced and viral neoantigens cause the strong immunogenicity of MCC. Moreover, over the last few years, the presence of PD-1 and PD-L1 has been demonstrated within tumor and immune cells. For the checkpoint inhibitors pembrolizumab and avelumab, responses of about 50% have been shown, independent of virus state. Circulating tumor cells (CTCs) seem to be helpful in tumor tracking. Further immunological and molecular studies are necessary for future individual therapies, also concerning immunocompromised patients.

PMID: 31820040 [PubMed - indexed for MEDLINE]

Dermoscopic and reflectance microscopy features of primary and metastatic Merkel cell carcinoma: Ten cases.

Fetched: January 10th, 2020, 5:01am GMT

Dermoscopic and reflectance microscopy features of primary and metastatic Merkel cell carcinoma: Ten cases.

Skin Res Technol. 2019 May;25(3):407-409

Authors: Cinotti E, Provvidenziale L, Habougit C, Fimiani M, Tognetti L, Perrot JL, Rubegni P

PMID: 30593691 [PubMed - indexed for MEDLINE]

Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance.

Fetched: January 10th, 2020, 5:00am GMT

Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance.

Semin Cancer Biol. 2020 Jan 03;:

Authors: Olino K, Park T, Ahuja N

Abstract
Advances in immunotherapy, most notably antibodies targeting the inhibitory immune receptors cytotoxic T-lymphocyte associated protein 4 (CTLA-4/CD152), programmed death protein 1 (PD-1/CD279) and programmed death-ligand 1 (PD-L1/B7H1/CD274) have become effective standard therapies in advanced malignancies including melanoma,1-4 merkel cell carcinoma5, urological cancers6-8, non-small cell lung cancer9-11, mis-match repair (MMR) deficient tumors12, and Hodgkin lymphoma with response rates ranging from 25-60% in the first and second line settings13,14. FDA approval has also been given for treatment for hepatocellular carcinoma, gastric cancer, triple negative breast cancer, cervical and head and neck cancers with response rates closer to 15%15. Additionally, some clinical efficacy has been observed in ovarian cancer, mesothelioma, prostate cancer, diffuse large B cell lymphoma, follicular lymphoma, and both cutaneous and peripheral T-cell lymphoma. However, despite these successes, most patients will initially fail to respond to treatment and almost half of initial responders will develop secondary resistance to immunotherapy and progress. Moreover, many prevalent solid organ tumors remain resistant to immunotherapy including colorectal, pancreatic and hepatobiliary cancers. Therefore, new therapies are needed to increase both initial and durable response rates and to develop new mechanistic insights into pathways of immune resistance so that immunotherapy may become more widely available as a therapeutic option in common malignancies.

PMID: 31911188 [PubMed - as supplied by publisher]

Definitive Radiotherapy for Locally Advanced Merkel Cell Carcinoma of the Head and Neck Region: A Case Report.

Fetched: January 8th, 2020, 5:01am GMT

Definitive Radiotherapy for Locally Advanced Merkel Cell Carcinoma of the Head and Neck Region: A Case Report.

Cureus. 2019 Dec 01;11(12):e6270

Authors: Gortman A

Abstract
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine malignancy of skin origin. It is most commonly managed with upfront surgical resection which is then followed by radiotherapy as soon as possible postoperatively. Radiotherapy alone has been used in inoperable cases and in cases of patient preference to omit surgical management. MCC is a very radiosensitive disease, and an ideal location for definitive radiotherapy is the head and neck region (which represents the majority of cases), where resection often leads to reduced outcomes given the number of critical structures in the region and the inability of surgery to achieve the excision margins required for the aggressive nature of the disease without leading to severely impacted cosmesis and function. This case study looks at an elderly woman who was treated with definitive dose fractionation (to a total dose of 60 Gray in 30 fractions) radiotherapy to the head and neck region for Stage III, T1N2M0 disease, following rapid loco-regional relapse after surgical wide local excision. Two years postdefinitive radiotherapy, she has had complete loco-regional control both clinically and radiologically.

PMID: 31903306 [PubMed]

A new immunohistochemical marker, insulinoma-associated protein 1 (INSM1), for Merkel cell carcinoma: Evaluation of 24 cases.

Fetched: January 8th, 2020, 5:01am GMT

A new immunohistochemical marker, insulinoma-associated protein 1 (INSM1), for Merkel cell carcinoma: Evaluation of 24 cases.

Ann Diagn Pathol. 2019 Jun;40:53-58

Authors: Leblebici C, Yeni B, Savli TC, Aydın Ö, Güneş P, Cinel L, Şimşek BÇ, Yıldız P, Tuncel D, Kayahan S

Abstract
Merkel cell carcinoma (MCC) is an uncommon primary neuroendocrine carcinoma of the skin. Nowadays, pathologists are required to perform immunohistochemistry to demonstrate neuroendocrine and epithelial differentiation for diagnosis of MCC. Insulinoma-associated protein 1 (INSM1) is a zinc-finger transcription factor expressed in tissues undergoing terminal neuroendocrine differentiation, and INSM1 immunohistochemistry is a well-validated nuclear marker of neuroendocrine differentiation. We evaluated 24 cases of MCC for the expression of INSM1 and compared it with frequently used neuroendocrine markers, Chromogranin A, Synaptophysin, and CD56. INSM1 was positive in all cases, and its expression was stronger, more extensive, clean and homogeneous compared to other markers. As a consequence, INSM1 can be used to serve as a solitary marker for neuroendocrine differentiation due to high sensitivity and specificity in MCC cases.

PMID: 31031215 [PubMed - indexed for MEDLINE]

Prevalence and Viral Loads of Cutaneous Human Polyomaviruses in the Skin of Patients With Chronic Inflammatory Skin Diseases.

Fetched: January 8th, 2020, 5:01am GMT

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Prevalence and Viral Loads of Cutaneous Human Polyomaviruses in the Skin of Patients With Chronic Inflammatory Skin Diseases.

J Infect Dis. 2019 04 19;219(10):1564-1573

Authors: Hashida Y, Higuchi T, Tanaka M, Shibata Y, Nakajima K, Sano S, Daibata M

Abstract
BACKGROUND: Human skin microorganisms have been associated with various skin diseases. However, most studies have focused on bacterial communities, and little is known about normally resident skin viruses such as the Polyomaviridae and their association with cutaneous disorders.
METHODS: We investigated the infection levels of Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), and human polyomavirus 7 (HPyV7), using triplet skin swabs collected from lesional and nonlesional skins of 86 Japanese patients with inflammatory skin diseases and mycosis fungoides, and from 149 healthy control individuals.
RESULTS: This age-matched case-control study provides the first analyses of the loads of polyomaviruses in association with various skin diseases. The viral loads were significantly higher for HPyV6/HPyV7 and lower for MCPyV in patients with psoriasis. The viral load variation was observed not only at lesion sites, but also at clinically unaffected skin sites in most of the patients. The viral strains tested were all of the Asian/Japanese genotype.
CONCLUSIONS: Our findings suggest a covariation in the infection levels of cutaneous polyomaviruses in certain inflammatory skin conditions. Worldwide prospective longitudinal studies are warranted to understand the influence of such alterations on the pathogenesis of inflammatory skin disorders.

PMID: 30357388 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma with kidney metastasis in a 81-year-old man. A rare case report.

Fetched: January 4th, 2020, 5:01am GMT

Merkel cell carcinoma with kidney metastasis in a 81-year-old man. A rare case report.

Arch Ital Urol Androl. 2019 Jul 02;91(2):

Authors: Anastasiou A, Moulavasilis N, Leotsakos I, Nerantzis CE, Anastasiou I

Abstract
Merkel cell carcinoma (MCC) is a primary neuroendocrine carcinoma of the skin. The prognosis of the disease is considered poor. Secondary metastasis is common, however a secondary metastasis to kidney from Merkel cell is a very rare phenomenon. We report a case of a man with a MCC metastasis to the right kidney. The suggested management is surgery and afterwards a platinum-based chemotherapy.

PMID: 31266284 [PubMed - indexed for MEDLINE]

Clinical and Epidemiological Characteristics of Merkel Cell Carcinoma in a Series of 38 Patients.

Fetched: January 4th, 2020, 5:01am GMT

Clinical and Epidemiological Characteristics of Merkel Cell Carcinoma in a Series of 38 Patients.

Actas Dermosifiliogr. 2019 Jun;110(5):360-365

Authors: Dañino-García M, Domínguez-Cruz JJ, Pérez-Ruiz C, Conejo-Mir J, Pereyra-Rodríguez JJ

Abstract
BACKGROUND: Merkel cell carcinoma is a rare yet aggressive cutaneous tumor with a poor prognosis. Few studies have analyzed series of patients from the same hospital.
METHODOLOGY: We performed a retrospective, descriptive, observational study of all patients diagnosed with Merkel cell carcinoma at a tertiary care hospital between 2002 and 2017. We recorded epidemiological, clinical, and histologic data and information on treatments and survival. For analysis, the sample was divided into 2 groups from different periods: 2002-2009 and 2010-2017. We performed survival analysis using Kaplan-Meier curves and multivariate analysis using a Cox proportional hazards model.
RESULTS: Thirty-eight patients (24 men and 14 women) with a mean age of 77.76 years were included. Mean follow-up time was 30.11 months. On comparing 2010-2017 with 2002-2009, we observed a 116% increase in the number of Merkel cell carcinoma cases (26 vs. 12), an older mean age at diagnosis (80.92 vs. 70.92 years, P<.05), and an increase in lesions located on the trunk and lower limbs (0% vs. 34.62%). Eleven patients died of Merkel cell carcinoma. Overall survival was 78.2% at 12 months and 69.3% at 24 months. In the univariate analysis, age over 70 years and lymph node involvement were associated with mortality, while tumor location on the upper extremities and wide surgical excision were associated with improved survival. Only lymph node involvement retained its prognostic significance in the multivariate analysis.
CONCLUSIONS: In this series, we observed that Merkel cell carcinoma has become more common in recent years and is now diagnosed at an older age and found in new anatomic locations.

PMID: 30376954 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma of the eyelid: A review.

Fetched: January 1st, 2020, 5:01am GMT

Merkel cell carcinoma of the eyelid: A review.

Surv Ophthalmol. 2019 Sep - Oct;64(5):659-667

Authors: North VS, Habib LA, Yoon MK

Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive tumor of both epithelial and neuroendocrine origin, which carries a mortality rate of up to 40%. MCC tumors typically present as painless, expanding nodules on the sun-exposed skin areas of older, white patients. Eyelid and periocular tumors comprise approximately 2.5% of all cases of MCC and may be mistaken for chalazia or basal cell carcinomas. Immunosuppression is a significant risk factor, particularly in solid-organ-transplant recipients, patients with chronic lymphocytic leukemia, and patients with HIV. Sentinel lymph node biopsy is often used for accurate staging of head and neck MCC. Treatment includes wide local excision, commonly with the addition of radiotherapy for improved locoregional disease control. Historically, adjuvant chemotherapy had been reserved for metastatic disease, but immunotherapy and targeted chemotherapies are currently being investigated for use in primary disease. The clinical characteristics of all available published cases of eyelid MCC are summarized in this article.

PMID: 30871952 [PubMed - indexed for MEDLINE]

Patterns of distant metastases in 215 Merkel cell carcinoma patients: Implications for prognosis and surveillance.

Fetched: December 30th, 2019, 5:01am GMT

Patterns of distant metastases in 215 Merkel cell carcinoma patients: Implications for prognosis and surveillance.

Cancer Med. 2019 Dec 27;:

Authors: Lewis CW, Qazi J, Hippe DS, Lachance K, Thomas H, Cook MM, Juhlin I, Singh N, Thuesmunn Z, Takagishi SR, McEvoy A, Doolittle-Amieva C, Bhatia S, Paulson KG, O'Malley RB, Wang CL, Nghiem P

Abstract
Approximately one-third of Merkel cell carcinoma (MCC) patients eventually develop distant metastatic disease. Little is known about whether the location of the primary lesion is predictive of initial distant metastatic site, or if survival likelihood differs depending on the metastatic site. Such data could inform imaging/surveillance practices and improve prognostic accuracy. Multivariate and competing-risk analyses were performed on a cohort of 215 MCC patients with distant metastases, 31% of whom had two or more initial sites of distant metastasis. At time of initial distant metastasis in the 215 patients, metastatic sites (n = 305) included non-regional lymph nodes (present in 41% of patients), skin/body wall (25%), liver (23%), bone (21%), pancreas (8%), lung (7%), and brain (5%). Among the 194 patients who presented with MCC limited to local or regional sites (stage I-III) but who ultimately developed distant metastases, distant progression occurred in 49% by 1 year and in 80% by 2 years following initial diagnosis. Primary MCC locations differed in how likely they were to metastasize to specific organs/sites (P < .001). For example, liver metastases were far more likely from a head/neck primary (43% of 58 patients) versus a lower limb primary (5% of 39 patients; P < .0001). Skin-only distant metastasis was associated with lower MCC-specific mortality as compared to metastases in multiple organs/sites (HR 2.7; P = .003), in the liver (HR 2.1; P = .05), or in distant lymph nodes (HR 2.0; P = .045). These data reflect outcomes before PD1-pathway inhibitor availability, which may positively impact survival. In conclusion, primary MCC location is associated with a pattern of distant spread, which may assist in optimizing surveillance. Because it is linked to survival, the site of initial distant metastasis should be considered when assessing prognosis.

PMID: 31883234 [PubMed - as supplied by publisher]

The Rising Incidence of Merkel Cell Carcinoma.

Fetched: December 29th, 2019, 5:01am GMT

The Rising Incidence of Merkel Cell Carcinoma.

Actas Dermosifiliogr. 2019 Jun;110(5):337

Authors: Llombart B

PMID: 30797522 [PubMed - indexed for MEDLINE]

Definitive radiotherapy for Merkel cell carcinoma in the setting of epidermolysis bullosa simplex.

Fetched: December 29th, 2019, 5:01am GMT

Definitive radiotherapy for Merkel cell carcinoma in the setting of epidermolysis bullosa simplex.

Australas J Dermatol. 2019 May;60(2):153-154

Authors: Ong WL, Bailey E, McCormack C, Weston L, Morgan V, McDowell L

PMID: 30450568 [PubMed - indexed for MEDLINE]

Typically Atypical: Merkel Cell Carcinoma.

Fetched: December 29th, 2019, 5:01am GMT

Typically Atypical: Merkel Cell Carcinoma.

Am J Med. 2019 04;132(4):468-470

Authors: Krispinsky AJ, Massick S

PMID: 30447204 [PubMed - indexed for MEDLINE]

Merkel-Cell Carcinoma.

Fetched: December 20th, 2019, 5:01am GMT

Merkel-Cell Carcinoma.

N Engl J Med. 2019 Dec 05;381(23):e40

Authors: Gomez-Arias PJ, Salido-Vallejo R

PMID: 31800991 [PubMed - indexed for MEDLINE]

Management of Skin Cancer in the Elderly.

Fetched: December 19th, 2019, 5:01am GMT

Management of Skin Cancer in the Elderly.

Dermatol Clin. 2019 Jul;37(3):279-286

Authors: Renzi M, Schimmel J, Decker A, Lawrence N

Abstract
Over the next 30 years, dermatologists face a rising population of elderly patients, causing a marked increase in the incidence of cutaneous malignancies. For this reason, it is important to review the approach to the management of skin cancer in the elderly. In the current medical environment, there has been debate as to how cutaneous malignancy should be treated in elderly patients, especially those with multiple comorbid conditions. Clinicians should use a comprehensive approach that accounts for functional status, impact on quality of life, cost, and potential adverse outcomes when managing high- and low-morbidity skin cancers in the elderly.

PMID: 31084722 [PubMed - indexed for MEDLINE]

Permalink for 'PD-L1, RB1 and mismatch repair protein immunohistochemical expression in neuroendocrine carcinoma, small cell type, of the uterine cervix.'

PD-L1, RB1 and mismatch repair protein immunohistochemical expression in neuroendocrine carcinoma, small cell type, of the uterine cervix.

Fetched: December 19th, 2019, 5:01am GMT

PD-L1, RB1 and mismatch repair protein immunohistochemical expression in neuroendocrine carcinoma, small cell type, of the uterine cervix.

Histopathology. 2019 Jun;74(7):997-1004

Authors: Morgan S, Slodkowska E, Parra-Herran C, Mirkovic J

Abstract
AIMS: Neuroendocrine carcinoma, small cell type, of the uterine cervix (SmCC-Cx) is a rare human papilloma virus (HPV) related tumour with limited therapeutic options. Merkel cell carcinoma, another virus-associated neuroendocrine malignancy, has significant programmed death ligand 1 (PD-L1) expression rates. PD-L1 expression has been reported in other malignancies of the cervix. We aimed to determine the prevalence of PD-L1 in the context of mismatch repair protein (MMR) and RB1 expression status in SmCC-Cx.
METHODS AND RESULTS: Ten cases of SmCC-Cx were tested by immunohistochemistry for expression of PD-L1, MLH1, MSH2, MSH6, PMS2, RB1, CD3, CD20 and for HPV by in-situ hybridisation (ISH). PD-L1 expression was scored quantitatively (H-score) in tumour cells and lymphocytes (tumoral/peritumoral). PD-L1 positivity was seen in seven cases, focal in most (H-score range 3-140). Three of nine cases showed MMR deficiency. PD-L1 expression levels correlated with MMR expression status: all three MLH1/PMS2-deficient cases had a ≥5% PD-L1 staining and an H-score ≥10 (P = 0.01). RB1 was lost in four of nine cases, all PD-L1 positive, but this correlation was not statistically significant. Seven of nine tumours were positive for HPV-ISH; two of these had MLH1/PMS2 loss. Of the two HPV-ISH negative tumours, one had MLS1/PMS2 loss.
CONCLUSIONS: PD-L1 expression, predominantly focal, is seen in 70% of SmCC-Cx, while loss of MMR expression is seen in 33% of SmCC-Cx in our cohort. PD-L1 expression in more than 10% of tumour cells is seen in a subset of tumours in association with loss of MMR expression. These patients may be amenable to immune checkpoint inhibitor therapy as a promising alternative for this aggressive disease.

PMID: 30667073 [PubMed - indexed for MEDLINE]

Permalink for 'Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas.'

Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas.

Fetched: December 19th, 2019, 5:01am GMT

Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas.

Mod Pathol. 2019 04;32(4):499-510

Authors: Kervarrec T, Tallet A, Miquelestorena-Standley E, Houben R, Schrama D, Gambichler T, Berthon P, Le Corre Y, Hainaut-Wierzbicka E, Aubin F, Bens G, Tabareau-Delalande F, Beneton N, Fromont G, Arbion F, Leteurtre E, Touzé A, Samimi M, Guyétant S

Abstract
Merkel cell carcinoma is a rare neuroendocrine carcinoma of the skin mostly induced by Merkel cell polyomavirus integration. Cytokeratin 20 (CK20) positivity is currently used to distinguish Merkel cell carcinomas from other neuroendocrine carcinomas. However, this distinction may be challenging in CK20-negative cases and in cases without a primary skin tumor. The objectives of this study were first to evaluate the diagnostic accuracy of previously described markers for the diagnosis of Merkel cell carcinoma and second to validate these markers in the setting of difficult-to-diagnose Merkel cell carcinoma variants. In a preliminary set (n = 30), we assessed optimal immunohistochemical patterns (CK20, thyroid transcription factor 1 [TTF-1], atonal homolog 1 [ATOH1], neurofilament [NF], special AT-rich sequence-binding protein 2 [SATB2], paired box protein 5, terminal desoxynucleotidyl transferase, CD99, mucin 1, and Merkel cell polyomavirus-large T antigen) and Merkel cell polyomavirus load thresholds (real-time PCR). The diagnostic accuracy of each marker was then assessed in a validation set of 103 Merkel cell carcinomas (9 CK20-negative cases and 15 cases without a primary skin tumor) and 70 extracutaneous neuroendocrine carcinoma cases. The most discriminant markers for a diagnosis of Merkel cell carcinoma were SATB2, NF expression, and Merkel cell polyomavirus DNA detection (positive likelihood ratios: 36.6, 44.4, and 28.2, respectively). Regarding Merkel cell carcinoma variants, cases without a primary skin tumor retained a similar immunohistochemical profile and CK20-negative tumors displayed a different profile (decrease frequency of NF and SATB2 expression), but Merkel cell polyomavirus DNA remained detected (78% of cases by qPCR). Moreover, 8/9 (89%) CK20-negative Merkel cell carcinoma cases but only 3/61 (5%) CK20-negative extracutaneous neuroendocrine cases were positive for at least one of these markers. In conclusion, detection of SATB2 and NF expression and Merkel cell polyomavirus DNA helps distinguish between Merkel cell carcinoma classical and variant cases and extracutaneous neuroendocrine carcinomas.

PMID: 30349028 [PubMed - indexed for MEDLINE]

Merkel cell polyomavirus integration-PCR in bilateral metachronous Merkel cell carcinoma on the nose.

Fetched: December 19th, 2019, 5:01am GMT

Merkel cell polyomavirus integration-PCR in bilateral metachronous Merkel cell carcinoma on the nose.

J Eur Acad Dermatol Venereol. 2019 Jan;33(1):e16-e18

Authors: Hanner S, Wieland U, Hartschuh W, Enk A, Toberer F

PMID: 29888815 [PubMed - indexed for MEDLINE]

Recent advances in Merkel cell carcinoma.

Fetched: December 13th, 2019, 5:01am GMT

Recent advances in Merkel cell carcinoma.

F1000Res. 2019;8:

Authors: Robinson CG, Tan D, Yu SS

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that has been historically associated with limited treatment options and poor prognosis. In the past 10 years, research in MCC has progressed significantly, demonstrating improved outcomes when treating with immunotherapy, particularly PD-1/PD-L1 inhibitors, when compared with conventional chemotherapy. There is also increasing evidence of the abscopal effect, a phenomenon describing the regression of untreated, distant MCC tumors following local radiation therapy. Additionally, antibodies to Merkel cell polyomavirus oncoproteins have been found to correlate with disease burden in a subset of patients, providing a useful tool for surveillance after treatment. Guidelines for the management of MCC will likely continue to change as research on surveillance and treatment of MCC continues.

PMID: 31824653 [PubMed - in process]

Surgical management of non melanoma skin cancer of the head and neck.

Fetched: December 12th, 2019, 5:01am GMT

Surgical management of non melanoma skin cancer of the head and neck.

Oral Oncol. 2019 Dec 07;100:104485

Authors: Kansara S, Bell D, Weber R

Abstract
Non-melanoma skin cancer (NMSC) is the most common malignancy in the world and is reaching epidemic proportions. The most common types of NMSC include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The head and neck is the most common site for NMSC, and surgery remains the mainstay of treatment. We review the etiology, risk factors, pathogenesis as well as the preoperative, operative, and postoperative considerations in the management of NMSC. Multidisciplinary evaluation and attention to each of these phases is imperative for favorable oncologic and functional patient outcomes.

PMID: 31821988 [PubMed - as supplied by publisher]

Identification of Therapeutic Vulnerabilities in Small Cell Neuroendocrine Prostate Cancer.

Fetched: December 8th, 2019, 5:01am GMT

Identification of Therapeutic Vulnerabilities in Small Cell Neuroendocrine Prostate Cancer.

Clin Cancer Res. 2019 Dec 05;:

Authors: Corella AN, Cabiliza Ordonio MVA, Coleman I, Lucas JM, Kaipainen A, Nguyen HM, Sondheim D, Brown L, True LD, Lee JK, MacPherson D, Nghiem P, Gulati R, Morrissey C, Corey E, Nelson PS

Abstract
PURPOSE: Small-cell neuroendocrine prostate cancer (SCNPC) exhibits an aggressive clinical course and incidence rates appear to be increasing following resistance to potent androgen receptor (AR) antagonists. Currently, treatment options are limited and few model systems are available to identify new approaches for treatment. We sought to evaluate commonalities between SCNPC and other aggressive neuroendocrine carcinomas to identify therapeutic targets.
EXPERIMENTAL DESIGN: We generated whole transcriptome RNAseq data from AR-active prostate cancers (ARPC) and SCNPCs from tumors collected at rapid autopsy, and two other NE carcinomas, Merkel Cell Carcinoma (MCC) and small-cell lung cancer (SCLC). We performed cross-tumor comparisons to identify conserved patterns of expression of druggable targets. We tested inhibitors to highly upregulated drug targets in a panel of PC cell lines and in vivo patient-derived xenograft (PDX) models.
RESULTS: We identified BCL2 as highly upregulated in SCNPC compared to ARPC. Inhibitors targeting BCL2 induced apoptotic cell death in SCNPC cell lines at nanomolar concentrations while ARPC cell lines were resistant. Treatment with the BCL2 inhibitor Navitoclax lead to a reduction of growth of SCNPC PDX tumors in vivo, while ARPC PDX models were more resistant. We identified Wee1 as a second druggable target upregulated in SCNPC. Treatment with the combination of Navitoclax and the Wee1 inhibitor AZD-1775 repressed the growth of SCNPC PDX resistant to single agent BCL2 inhibitors.
CONCLUSIONS: The combination of BCL2 and Wee1 inhibition presents a novel therapeutic strategy for the treatment of SCNPC.

PMID: 31806643 [PubMed - as supplied by publisher]

Permalink for 'The Ubiquitin specific Protease Usp7, a novel Merkel cell polyomavirus Large T-Antigen interaction partner, modulates viral DNA replication.'

The Ubiquitin specific Protease Usp7, a novel Merkel cell polyomavirus Large T-Antigen interaction partner, modulates viral DNA replication.

Fetched: December 7th, 2019, 5:01am GMT

The Ubiquitin specific Protease Usp7, a novel Merkel cell polyomavirus Large T-Antigen interaction partner, modulates viral DNA replication.

J Virol. 2019 Dec 04;:

Authors: Czech-Sioli M, Siebels S, Radau S, Zahedi RP, Schmidt C, Dobner T, Grundhoff A, Fischer N

Abstract
Merkel Cell Polyomavirus (MCPyV) is the major cause for Merkel Cell Carcinoma (MCC), a rare but highly aggressive skin cancer predominantly found in elderly and immunosuppressed patients. The early viral gene products large T-Antigen (LT) and small T-Antigen (sT) are important for efficient viral DNA replication and both contribute to transformation processes. Mainly, these functions are executed through interactions with host factors. We here identify the cellular Ubiquitin-specific-processing protease 7 (Usp7) as a new interaction partner of the MCPyV LT.Using GST pulldown experiments, we show that MCPyV LT directly binds to Usp7, and that N- as well as the C-terminal regions of LT bind to the TRAF (tumor necrosis factor receptor-associated) domain of Usp7. We demonstrate that endogenous Usp7 co-precipitates with MCPyV T-antigens and re-localizes to viral DNA replication centers in cells actively replicating MCPyV genomes. We show that Usp7 does not alter ubiquitination levels of the T-antigens; however, Usp7 binding increases the binding affinity of LT to the origin of replication thereby negatively regulating viral DNA replication. Together, these data identify Usp7 as a restriction factor of MCPyV replication. In contrast to other DNA viruses, Usp7 does not affect MCPyV gene expression via its ubiquitination activity, but solely influences MCPyV DNA replication via novel mechanism that modulates binding of LT to viral DNA.Importance MCPyV is the only human polyomavirus that is associated with cancer; the majority of Merkel cell cancers have a viral etiology. While much emphasis was investigated to understand the transformation process by MCPyV oncoproteins and cellular factors, we have only limited knowledge on cellular factors participating in the MCPyV life cycle. We here describe Usp7, a cellular deubiquitination enzyme, as a new factor involved in MCPyV replication. Usp7 is known in the context of large DNA tumor viruses, EBV and KSHV, to restrict viral replication. Similar to EBV, where Usp7 binding to EBNA1 increases EBNA1 binding affinity to viral DNA, we find MCPyV LT binding to the origin of replication to be increased in the presence of Usp7 resulting in restriction of viral DNA replication. However, Usp7 induced restriction of MCPyV replication is independent of its enzymatic activity thereby constituting a novel mechanism of Usp7 induced restriction of viral replication.

PMID: 31801860 [PubMed - as supplied by publisher]

Merkel cell carcinoma mimicking transformed chronic lymphocytic leukemia/small lymphocytic lymphoma.

Fetched: December 5th, 2019, 5:01am GMT

Merkel cell carcinoma mimicking transformed chronic lymphocytic leukemia/small lymphocytic lymphoma.

Clin Case Rep. 2019 Nov;7(11):2256-2257

Authors: Bah I, Li S, Yin CC, Tang G, Xu J

Abstract
Although MCC has been reported in patients with CLL/SLL, it is extremely rare to observe these two within the same tumor. MCC's positivity for PAX5 and TdT may pose a diagnostic challenge by mimicking transformed CLL/SLL. A thorough workup is critical in reaching the correct diagnosis.

PMID: 31788294 [PubMed]

Concurrent Metastatic Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma in the Same Lymph Node.

Fetched: December 5th, 2019, 5:01am GMT

Concurrent Metastatic Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma in the Same Lymph Node.

Am J Dermatopathol. 2019 Jun;41(6):e61-e63

Authors: Suaiti L, Onajin O, Sangueza O

Abstract
The coexistence of Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC) in the same cutaneous lesion is well known. The pathogenesis is believed to be distinct from conventional polyomavirus-related MCC, and it has a more aggressive course. Metastasis of MCC and SCC to the same lymph node is exceedingly rare with only one previously reported case in the English literature. To the best of our knowledge, this is the second case of MCC and SCC with metastasis to the same lymph node. Our case demonstrates the aggressive nature of the combined MCC and SCC in the setting of immunosuppression.

PMID: 30461423 [PubMed - indexed for MEDLINE]

Male Sex is an Inherent Risk Factor for Basal Cell Carcinoma.

Fetched: November 29th, 2019, 5:01am GMT

Male Sex is an Inherent Risk Factor for Basal Cell Carcinoma.

J Skin Cancer. 2019;2019:8304271

Authors: Bassukas ID, Tatsioni A

Abstract
Basal cell carcinoma (BCC) is more frequent among females <40 years old; however, it affects preferentially older males (>60 years old). In order to contribute to the study of the still largely unknown mechanisms that underlie this peculiar sex-dependent shift, we compared the kinetics of the increase of the age-specific BCC incidence rates (R) as a function of age in males and females. Studies reporting sex-stratified R were found using a PubMed search and male to female age-specific incidence rate ratios (RR) were calculated for each age-class as reported in each study and assigned to the mean of the corresponding age periods. Trends in age were assessed with Kendall's τ test and relationships between two variables by inverse variance method-weighed Loess and linear regression analysis. Sixteen data sets were eligible and confirmed a significant shift in the male to female ratio (Kendall's τ = 0.530; P < 0.001). Moreover, the slope parameter b = 1.205 (SE = 0.014) of the best fit (r 2 = 0.980) regression line resulting by plotting male vs. female age-specific incidence rates predicts a statistically significant (P = 0.001), constant, about 20% faster increase of R in males of all ages. Similar relationship are also evident for cutaneous squamous cell and Merkel cell carcinoma and, even more intriguing, for sums of all cancers (excluding BCC and SCC) in many different registries. In conclusion, females are probably born with an inherently higher risk to develop BCC; however, also with a much slower increase rate of this risk as a function of age. Notably this observation seems to be not a BCC peculiarity. Because of its high incidence coupled with moderate morbidity and extremely low mortality rates, BCC may serve as a valuable, single-tumor paradigm to reproach the complex mechanisms that underline the interaction of age and sex in the pathogenesis of human malignancies.

PMID: 31772775 [PubMed]

Permalink for 'Anti-PD1 in Merkel cell carcinoma and cutaneous squamous cell carcinoma, description of five cases and recent data from the literature.'

Anti-PD1 in Merkel cell carcinoma and cutaneous squamous cell carcinoma, description of five cases and recent data from the literature.

Fetched: November 29th, 2019, 5:01am GMT

Anti-PD1 in Merkel cell carcinoma and cutaneous squamous cell carcinoma, description of five cases and recent data from the literature.

J Eur Acad Dermatol Venereol. 2019 Apr;33(4):e159-e161

Authors: Sellah D, Saint-Jean M, Peuvrel L, Khammari A, Quéreux G, Dréno B

PMID: 30451326 [PubMed - indexed for MEDLINE]

Permalink for 'Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus.'

Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus.

Fetched: November 27th, 2019, 5:01am GMT

Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus.

J Am Acad Dermatol. 2019 Jul;81(1):23-41

Authors: Mui UN, Haley CT, Vangipuram R, Tyring SK

Abstract
In 1964, the first human oncovirus, Epstein-Barr virus, was identified in Burkitt lymphoma cells. Since then, 6 other human oncoviruses have been identified: human papillomavirus, Merkel cell polyomavirus, hepatitis B and C viruses, human T-cell lymphotropic virus-1, and human herpesvirus-8. These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. In addition, oncoviruses are associated with multiple benign mucocutaneous diseases. Research regarding the pathogenic mechanisms of oncoviruses and virus-specific treatment and prevention is rapidly evolving. Preventative vaccines for human papillomavirus and hepatitis B virus are already available. This review discusses the mucocutaneous manifestations, pathogenesis, diagnosis, treatment, and prevention of oncovirus-related diseases. The first article in this continuing medical education series focuses on diseases associated with human papillomavirus and Merkel cell polyomavirus, while the second article in the series focuses on diseases associated with hepatitis B and C viruses, human T-cell lymphotropic virus-1, human herpesvirus-8, and Epstein-Barr virus.

PMID: 30502415 [PubMed - indexed for MEDLINE]

Permalink for 'Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma suggests an epithelial origin of this Merkel cell carcinoma.'

Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma suggests an epithelial origin of this Merkel cell carcinoma.

Fetched: November 26th, 2019, 5:01am GMT

Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma suggests an epithelial origin of this Merkel cell carcinoma.

J Invest Dermatol. 2019 Nov 21;:

Authors: Kervarrec T, Aljundi M, Appenzeller S, Samimi M, Maubec E, Cribier B, Deschamps L, Sarma B, Sarosi EM, Berthon P, Levy A, Bousquet G, Tallet A, Touzé A, Guyétant S, Schrama D, Houben R

Abstract
Merkel cell carcinoma (MCC), an aggressive neuroendocrine carcinoma of the skin, is to date the only human cancer known to be frequently caused by a polyomavirus. However, it is a matter of debate which cells are targeted by the Merkel cell polyomavirus (MCPyV) to give rise to the phenotypically multifaceted MCC cells. To assess the lineage of origin of MCPyV-positive MCC, genetic analysis of a very rare tumor combining benign trichoblastoma and MCPyV-positive MCC was conducted by massive parallel sequencing. Although MCPyV was found to be integrated only in the MCC part, six somatic mutations were shared by both tumor components. The mutational overlap between trichoblastoma and MCPyV-positive MCC part of the combined tumor implies that MCPyV integration occurred in an epithelial tumor cell prior to MCC development. Therefore, our report demonstrates that MCPyV-positive MCC can derive from the epithelial lineage.

PMID: 31759946 [PubMed - as supplied by publisher]

p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer.

Fetched: November 22nd, 2019, 5:01am GMT

p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer.

Int J Mol Sci. 2019 Nov 17;20(22):

Authors: Smirnov A, Anemona L, Novelli F, Piro CM, Annicchiarico-Petruzzelli M, Melino G, Candi E

Abstract
Skin cancer is the most common type of cancer worldwide. Ozone depletion and climate changes might cause a further increase in the incidence rate in the future. Although the early detection of skin cancer enables it to be treated successfully, some tumours can evolve and become more aggressive, especially in the case of melanoma. Therefore, good diagnostic and prognostic markers are needed to ensure correct detection and treatment. Transcription factor p63, a member of the p53 family of proteins, plays an essential role in the development of stratified epithelia such as skin. In this paper, we conduct a comprehensive review of p63 expression in different types of skin cancer and discuss its possible use in the diagnosis and prognosis of cutaneous tumours.

PMID: 31744230 [PubMed - in process]

Recent updates in the management of Merkel Cell Carcinoma.

Fetched: November 21st, 2019, 5:01am GMT

Recent updates in the management of Merkel Cell Carcinoma.

J Pak Med Assoc. 2019 Nov;69(11):1693-1699

Authors: Abbasi AN, Ahmed SM, Qureshi BM

Abstract
Merkel cell carcinoma is an aggressive non-melanomatous cutaneous tumour of neuroendocrine origin with an increasing incidence in the recent years. It is a tumour of the elderly and immunosuppressed, which most often appears on sun-exposed areas of the body. The clinical features of the cutaneous or subcutaneous lesions hardly contribute to the diagnosis, and, hence, histopathology and immunohistochemistry play a vital role in diagnosis. The latest staging system by the American Joint Committee on Cancer includes non-nodal invasion to adjacent structures i.e. bone, muscle, fascia, or cartilage into the criteria, in additionto size and depth of invasion. The management reliesheavily on a multidisciplinary approach due to rarity of incidence of this disease. According to the international guidelines, surgical management is still the preferred choice. The beneficial role of adjuvant radiotherapy has now been more clearly documented. Data is insufficient to assess whether chemotherapy improves disease-free or overall survival.

PMID: 31740881 [PubMed - in process]

Contemporary Topics in Radiation Medicine: Skin Cancer.

Fetched: November 21st, 2019, 5:01am GMT

Contemporary Topics in Radiation Medicine: Skin Cancer.

Hematol Oncol Clin North Am. 2020 Feb;34(1):189-203

Authors: Gao SJ, Decker RH

Abstract
Radiation plays an important role in the management of a variety of skin cancers. This article discusses the role of radiation in the treatment of cutaneous squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma, cutaneous T-cell lymphoma, and B-cell lymphomas.

PMID: 31739944 [PubMed - in process]

For Whom the Cell Tolls? Intratumoral Treatment Links Innate and Adaptive Immunity.

Fetched: November 21st, 2019, 5:01am GMT

For Whom the Cell Tolls? Intratumoral Treatment Links Innate and Adaptive Immunity.

Clin Cancer Res. 2019 02 15;25(4):1127-1129

Authors: Marquez-Rodas I, Aznar MA, Calles A, Melero I

Abstract
Intratumoral immunotherapy can potentially modulate the tumor microenvironment (TME) and potentiate the effects of concomitant or sequential systemic immunotherapies. Intratumoral administration of different Toll-like receptor agonists, including TLR4, can potentiate these effects through innate and adaptive immunity connection.See related article by Bhatia et al., p. 1185.

PMID: 30262506 [PubMed - indexed for MEDLINE]

Permalink for 'Concurrent Neuroendocrine Carcinoma of the Skin (Merkel Cell Carcinoma) and Squamous Cell Carcinoma of the Skin on the Right Ear Helix.'

Concurrent Neuroendocrine Carcinoma of the Skin (Merkel Cell Carcinoma) and Squamous Cell Carcinoma of the Skin on the Right Ear Helix.

Fetched: November 20th, 2019, 5:01am GMT

Concurrent Neuroendocrine Carcinoma of the Skin (Merkel Cell Carcinoma) and Squamous Cell Carcinoma of the Skin on the Right Ear Helix.

Int J Surg Pathol. 2019 Feb;27(1):64-66

Authors: Fischer S, Federspil PA, Kriegsmann K, Longerich T, Kriegsmann M

PMID: 29607680 [PubMed - indexed for MEDLINE]

Can dermoscopy open a new way to diagnosing Merkel cell carcinoma?

Fetched: November 17th, 2019, 5:01am GMT

Can dermoscopy open a new way to diagnosing Merkel cell carcinoma?

Int J Dermatol. 2019 Mar;58(3):e68-e71

Authors: Sadeghinia A, Ghanadan A, Ehsani A, Noormohammadpour P, Ansari MS

PMID: 30675720 [PubMed - indexed for MEDLINE]

Permalink for 'Non-specific labeling of macrophages with anti-cytokeratin 20 (SP33) in the evaluation of nodal micrometastasis from Merkel cell carcinoma: A pitfall for metastasis.'

Non-specific labeling of macrophages with anti-cytokeratin 20 (SP33) in the evaluation of nodal micrometastasis from Merkel cell carcinoma: A pitfall for metastasis.

Fetched: November 17th, 2019, 5:01am GMT

Non-specific labeling of macrophages with anti-cytokeratin 20 (SP33) in the evaluation of nodal micrometastasis from Merkel cell carcinoma: A pitfall for metastasis.

J Cutan Pathol. 2019 Jan;46(1):88-90

Authors: Venturi M, Pilloni L

PMID: 30288773 [PubMed - indexed for MEDLINE]

Incidental Finding of Benign Trichilemmal Cysts on 99mTc-Octreotide Scan.

Fetched: November 15th, 2019, 5:01am GMT

Incidental Finding of Benign Trichilemmal Cysts on 99mTc-Octreotide Scan.

Clin Nucl Med. 2019 Oct;44(10):834-835

Authors: Neshandar Asli I, Norouzi G

Abstract
A 63-year-old woman with neuroendocrine carcinoma of the colon was referred to our department for staging with Tc-octreotide scan. Two focal, highly intense, superficial lesions were detected in patient's scalp and paralumbar region, medial to the right kidney. Pathology correlation was recommended, revealing them both to be benign trichilemmal cysts. This unexpected finding strengthens the hypothesis of Merkel cell carcinoma and trichilemmal cysts originating from pluripotent stem cells of adnexal epithelium, making a neuroendocrine differentiation for the latter plausible.

PMID: 31306209 [PubMed - indexed for MEDLINE]

Merkel cell polyomavirus is uncommon in New Zealand Merkel cell carcinomas.

Fetched: November 15th, 2019, 5:01am GMT

Merkel cell polyomavirus is uncommon in New Zealand Merkel cell carcinomas.

Br J Dermatol. 2018 11;179(5):1197-1198

Authors: Woodhouse B, Robb TJ, Hearn JI, Houseman PS, Hayward G, Miller R, Restall AP, Findlay M, Lawrence B, Print CG, Parker K, Blenkiron C

PMID: 29928756 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma of the Wrist: A Case Report.

Fetched: November 15th, 2019, 5:01am GMT

Merkel Cell Carcinoma of the Wrist: A Case Report.

Ann Plast Surg. 2018 08;81(2):244-247

Authors: Min HJ, Kim JH, Kim YW, Cheon YW

Abstract
PURPOSE: Merkel cell carcinomas are a rare type of neuroendocrine tumors of the head, neck, and extremities commonly found in older patients. Merkel cell carcinomas present as red-to-purple and nontender nodules with or without surface ulceration, usually measuring 2 cm in diameter.
CASE PRESENTATIONS: An 83-year-old woman with a skin-colored nodule on the dorsal aspect of her right wrist was referred to our department for treatment. The regional lymph nodes were not palpable, and the positron emission tomography/computed tomography scan did not reveal any distant metastases. We conducted wide excision of the lesion and sentinel lymph node biopsy. The defect caused by the excision and partial bone resection was reconstructed using a radical forearm rotational flap and a split-thickness skin graft. Postoperatively, the patient received adjuvant radiation therapy. We observed wound healing and an absence of complications such as recurrence at 1-year follow-up.
CONCLUSIONS: Merkel cell carcinomas are rare but aggressive neuroendocrine skin cancers, which rarely occur in the upper extremity. Our treatment of nonamputative wide excision and sentinel lymph node dissection, followed by postoperative radiation therapy, showed no local or distant recurrence. Here, we review the current literature on Merkel cell carcinomas and describe our approach of treatment.

PMID: 29794506 [PubMed - indexed for MEDLINE]

Permalink for 'Lymph node identification in skin malignancy using indocyanine green transcutaneously study: Study protocol for a diagnostic accuracy study.'

Lymph node identification in skin malignancy using indocyanine green transcutaneously study: Study protocol for a diagnostic accuracy study.

Fetched: November 15th, 2019, 5:01am GMT

Lymph node identification in skin malignancy using indocyanine green transcutaneously study: Study protocol for a diagnostic accuracy study.

Medicine (Baltimore). 2019 Nov;98(44):e17839

Authors: Lese I, Leckenby JI, Taddeo A, Constantinescu M, Olariu R

Abstract
INTRODUCTION: The incidence of malignant melanoma has been rising steadily over the past decades and Merkel cell carcinoma is a highly aggressive neuroendocrine skin tumor with a high mortality rate. Sentinel lymph node (SLN) biopsy is a recommended prognostic tool in primary cutaneous malignant melanomas of intermediate thickness and in all clinically node-negative Merkel cell carcinomas. The gold standard method for identification of SLNs is lymphoscintigraphy, which involves radioactive tracers. Indocyanine green-based near-infrared fluorescence imaging (NIRFI) has been also used for intraoperative SLN identification. We aim to evaluate the diagnostic sensitivity of the VisionSense VS3 NIRFI device for SNL identification. This device uses stereoscopic 3D high definition for both fluorescence and visible light imaging. Our hypothesis is that SLNs may be identified transcutaneously using fluorescent dye injections and NIRFI; therefore, obviating the need for lymphoscintigraphy in the future. METHODS AND ANALYSIS:: lymph node identification in skin malignancy using indocyanine green transcutaneously is a prospective diagnostic sensitivity study conducted at the Department of Plastic and Hand Surgery at the University Hospital Berne, Inselspital, Switzerland. The study aims at recruiting 93 patients (start date September 2017) to compare the accuracy of VisionSense VS3 camera at identifying SLNs transcutaneously with the current gold standard, lymphoscintigraphy. Moreover, a secondary objective is to determine if anatomical location of the SLN and patient factors (eg, body mass index, age) have an impact on the ability of VisionSense to detect SLNs when compared with the same gold standard.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03545334.

PMID: 31689874 [PubMed - indexed for MEDLINE]

Permalink for 'Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement.'

Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement.

Fetched: November 10th, 2019, 5:01am GMT

Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement.

J Neurovirol. 2018 06;24(3):314-322

Authors: Cason C, Monasta L, Zanotta N, Campisciano G, Maestri I, Tommasino M, Pawlita M, Villani S, Comar M, Delbue S

Abstract
Human polyomaviruses (HPyVs) asymptomatically infect the human population establishing latency in the host, and their seroprevalence can reach 90% in healthy adults. Few studies have focused on the pediatric population, and there are no reports regarding the seroprevalence of all the newly isolated HPyVs among Italian children. Therefore, we investigated the frequency of serum antibodies against 12 PyVs in 182 immunocompetent children from Northeast Italy, by means of a multiplex antibody detection system. Additionally, secondary lymphoid tissues were collected to analyze the presence of HPyV DNA sequences using a specific real-time PCRs or PCRs. Almost 100% of subjects were seropositive for at least one PyV. Seropositivity ranged from 3% for antibodies against simian virus 40 (SV40) in children from 0 to 3 years, to 91% for antibodies against WU polyomavirus (WUPyV) and HPyV10 in children from 8 to 17 years. The mean number of PyV for which children were seropositive increased with the increasing of age: 4 standard deviations (SD) 1.8 in the 0-3-year group, 5 (SD 1.9) in the 4-7-year group, and 6 (SD 2.2) in the 8-17-year group. JC polyomavirus (JCPyV) DNA was detected in 1% of the adenoids, WUPyV in 12% of the tonsils, and 28% of the adenoids, and Merkel cell polyomavirus (MCPyV) was present in 6 and 2% of the tonsils and adenoids, respectively. Our study gives new insights on the serological evidence of exposure to PyVs during childhood, and on their possible respiratory route of transmission.

PMID: 29330826 [PubMed - indexed for MEDLINE]

Optimal adjuvant radiotherapy dose for stage I, II or III Merkel cell carcinoma: an analysis of the National Cancer Database.

Fetched: November 9th, 2019, 5:01am GMT

Optimal adjuvant radiotherapy dose for stage I, II or III Merkel cell carcinoma: an analysis of the National Cancer Database.

Jpn J Clin Oncol. 2019 Nov 07;:

Authors: Yusuf M, Gaskins J, Wall W, Tennant P, Bumpous J, Dunlap N

Abstract
BACKGROUND: We performed an analysis of the National Cancer Database to determine optimal doses of conventionally-fractionated adjuvant radiotherapy for patients with stage I/II or III Merkel cell carcinoma.
METHODS: The cohort included 2735 patients with resected Merkel cell carcinoma of the head and neck, trunk or extremities receiving radiotherapy. Exclusion criteria included doses of radiotherapy <30 or >80 Gy, or dose per fraction >200 or <180 cGy. Recursive partitioning analysis and spline models were used to select dose thresholds. Multivariable Cox regression was performed to validate thresholds with respect to overall survival.
RESULTS: Recursive partitioning analysis models defined a threshold of 57 Gy for stage I/II Merkel cell carcinoma, above which 3-year overall survival rate was decreased (P < 0.0001). The 3-year overall survival rate for patients receiving 50.0-57.0 Gy (81.2%) was greater compared to doses of 30.0-49.9 Gy (75.3%) or >57.0 Gy (70%, P < 0.0001). Doses > 57.0 Gy were associated with an increased hazard of death (1.31, confidence interval 1.07-1.60) with respect to doses of 50.0-57.0 Gy. Doses < 50.0 Gy for stage III Merkel cell carcinoma were associated with worsened 3-year overall survival (P < 0.0001) and increased hazard of death (2.01, confidence interval 1.43-2.82) with respect to doses between 50.0 and 57.0 Gy.
CONCLUSIONS: Our results support doses of 50-57 Gy for most patients with stage I/II Merkel cell carcinoma receiving conventionally-fractionated adjuvant radiotherapy. In contrast to a prior National Cancer Database analysis, our results suggest doses ≥ 50 Gy should be strongly considered for patients with stage III Merkel cell carcinoma regardless of anatomic subsite.

PMID: 31697368 [PubMed - as supplied by publisher]

Permalink for 'Merkel Cell Polyomavirus downregulates N-myc downstream regulated gene-1 (NDRG1) leading to cellular proliferation and migration.'

Merkel Cell Polyomavirus downregulates N-myc downstream regulated gene-1 (NDRG1) leading to cellular proliferation and migration.

Fetched: November 8th, 2019, 5:01am GMT

Merkel Cell Polyomavirus downregulates N-myc downstream regulated gene-1 (NDRG1) leading to cellular proliferation and migration.

J Virol. 2019 Nov 06;:

Authors: Gupta P, Shahzad N, Harold A, Shuda M, Venuti A, Romero-Medina MC, Pacini L, Brault L, Robitaille A, Taverniti V, Hernandez-Vargas H, Durand G, Le Calvez-Kelm F, Gheit T, Accardi R, Tommasino M

Abstract
Merkel cell polyomavirus (MCPyV) is the first human polyomavirus etiologically associated with Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. Similar to other polyomaviruses, MCPyV encodes early T antigen genes, a viral oncogene required for MCC tumor growth. To identify the unique oncogenic properties of MCPyV, we analysed the gene expression profiles in human spontaneously immortalized keratinocytes (NIKs) expressing the early genes from six distinct human polyomaviruses (PyVs), including MCPyV. A comparison of the gene expression profiles revealed 28 genes specifically deregulated by MCPyV. In particular, the MCPyV early gene downregulated the expression of the tumor suppressor gene N-myc downstream regulated gene-1 (NDRG1) in NIKs-MCPyV and hTERT-MCPyV human keratinocytes (HK) as compared to their controls. In MCPyV-positive MCC cells, the expression of NDRG1 was downregulated by the MCPyV early gene, as T antigen knockdown rescued the level of NDRG1. In addition, NDRG1 overexpression in hTERT-MCPyV HK or MCC cells resulted in decrease of cells in S phase and cell proliferation inhibition. Moreover, a decrease in wound healing capacity in hTERT-MCPyV HK was observed. Further analysis revealed that NDRG1 exerts its biological effect in Merkel cell lines by regulating the expression of CDK2 and cyclinD1 proteins. Overall NDRG1 plays an important role in MCPyV induced cellular proliferation.Importance Merkel Cell Carcinoma was first described in 1972 as a neuroendocrine tumor of skin most of which in 2008, was reported to be caused by a PyV named Merkel Cell Polyomavirus (MCPyV), the first PyV linked to human cancer. Thereafter, numerous studies have been conducted to understand the etiology of this virus induced carcinogenesis. However, it is still a new field and much work is needed to understand the molecular pathogenesis of MCC. In the current work, we sought to identify the host genes specifically deregulated by MCPyV as opposed to other PyVs in order to better understand the relevance of the genes analyzed on the biological impact and progression of the disease. These findings open newer avenues for targeted drug therapies thereby providing hope for management of patients suffering from this highly aggressive cancer.

PMID: 31694959 [PubMed - as supplied by publisher]

Merkel cell carcinoma in Taiwan: A series of 24 cases and literature review.

Fetched: November 8th, 2019, 5:01am GMT

Merkel cell carcinoma in Taiwan: A series of 24 cases and literature review.

Medicine (Baltimore). 2019 Oct;98(42):e17538

Authors: Chang JW, Chang YY, Huang YL, Lo YF, Ho TY, Huang YT, Chen HW, Yeh CN, Wu CE

Abstract
Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin. The available reports of MCC in Asia are limited; in this study, we report the largest series of MCC in Taiwan to date.The series is composed by 24 pathologically proven MCC cases, which were retrospectively reviewed in Chang Gung Memorial Hospital in Taiwan between 2000 and 2018.The tumor occurred predominantly in men (80%) and in the elderly (median 74.8 years). Twenty-one patients had locoregional MCC and 3 had metastatic MCC at the time of diagnosis. Patients with pathologically proven negative nodes by sentinel lymph node biopsy (SLNB) showed better survival time than those without SLNB in 16 clinically node-negative MCC cases undergoing primary surgery. Salvage surgery for loco-regional recurrence lengthened the survival time and possibly cured recurrent MCC. Palliative chemotherapy with cisplatin and etoposide showed a response rate of 25%, progression-free survival of 3.6 months, and overall survival of 14.8 months in 4 metastatic/recurrent MCC. Avelumab treatment was effective in 1 patient, who achieved a durable disease control.This observational cohort of MCC patients in Taiwan suggests aggressive surgical intervention including wide excision and lymph node management, salvage operation is critical for early MCC patients, and palliative chemotherapy and immunotherapy showed their efficacy for advanced MCC patients.

PMID: 31626116 [PubMed - indexed for MEDLINE]

Permalink for 'Danger is only skin deep: aggressive epidermal carcinomas. An overview of the diagnosis, demographics, molecular-genetics, staging, prognostic biomarkers, and therapeutic advances in Merkel cell carcinoma.'

Danger is only skin deep: aggressive epidermal carcinomas. An overview of the diagnosis, demographics, molecular-genetics, staging, prognostic biomarkers, and therapeutic advances in Merkel cell carcinoma.

Fetched: November 5th, 2019, 5:01am GMT

Danger is only skin deep: aggressive epidermal carcinomas. An overview of the diagnosis, demographics, molecular-genetics, staging, prognostic biomarkers, and therapeutic advances in Merkel cell carcinoma.

Mod Pathol. 2019 Nov 01;:

Authors: Tetzlaff MT, Harms PW

Abstract
Merkel cell carcinoma (MCC) is a high grade primary cutaneous neuroendocrine carcinoma and is among the most aggressive cutaneous malignancies. The rising incidence of MCC, together with its often rapidly aggressive course, underscore a critical need to recognize the histopathologic and the immunohistochemical features that inform its accurate diagnosis. In the current review, we summarize the current state of knowledge regarding the accurate diagnosis of MCC and the exclusion of other entities in the differential diagnosis. We provide a comprehensive review of genomic studies that identified the molecular-genetic drivers of MCC as well as a summary of studies identifying prognostic biomarkers that can facilitate risk stratification. Importantly, Merkel cell polyomavirus (MCPyV) appears to be causative in most cases of MCC and represents both a diagnostic and prognostic marker. Finally, as staging of MCC has undergone critical refinements with the introduction of the 8th Edition of the American Joint Committee on Cancer staging system, we provide an update on MCC staging. In particular, the prognostic significance of the sentinel lymph node (SLN) in MCC necessitates a systematic approach to its evaluation and diagnosis to ensure accurate and consistent risk stratification for patients, and we therefore provide a comprehensive overview of SLN evaluation in MCC. Finally, the intimate relationship between MCC and the integrity of the host immune system has led to paradigm-shifting therapeutic advances with the successful application of immune checkpoint blockade to treat patients with advanced disease, and we therefore summarize those studies and the correlative studies in which predictive biomarkers have been identified.

PMID: 31676786 [PubMed - as supplied by publisher]

Pan-Tumor Pathologic Scoring of Response to PD-(L)1 Blockade.

Fetched: November 2nd, 2019, 5:01am GMT

Pan-Tumor Pathologic Scoring of Response to PD-(L)1 Blockade.

Clin Cancer Res. 2019 Oct 31;:

Authors: Stein JE, Lipson EJ, Cottrell TR, Forde PM, Anders RA, Cimino-Mathews A, Thompson ED, Allaf ME, Yarchoan M, Feliciano J, Wang H, Jaffee EM, Pardoll DM, Topalian SL, Taube JM

Abstract
PURPOSE: Pathologic response assessment of tumor specimens from patients receiving systemic treatment provide an early indication of therapeutic efficacy and predict long-term survival. Grading systems for pathologic response were first developed for chemotherapy in select tumor types. Immunotherapeutic agents have a mechanism of action distinct from chemotherapy and are being used across a broad array of tumor types. A standardized, universal scoring system for pathologic response that encompasses features characteristic for immunotherapy and spans tumor types is needed.
EXPERIMENTAL DESIGN: Hematoxylin and eosin-stained slides from neoadjuvant surgical resections and on-treatment biopsies were assessed for features of immune-related pathologic response (irPR). 258 specimens from patients with 11 tumor types as part of ongoing clinical trials for anti-PD-1 were evaluated. An additional 98 specimens from patients receiving anti-PD-(L)1 in combination with other treatments were also reviewed, including those from three additional tumor types.
RESULTS: Common irPR features (immune activation, cell death, tissue repair, regression bed) were present in all tumor types reviewed, including melanoma, non-small cell lung, head and neck squamous cell, Merkel cell, and renal cell carcinoma, amongst others. Features were consistent across primary tumors, lymph nodes, and distant metastases. Specimens from patients treated with anti-PD-(L)1 in combination with another agent also exhibited irPR features.
CONCLUSION: irPR features are consistent across tumor types and treatment settings. Standardized, pan-tumor immune-mediated pathologic response criteria (irPRC) are defined and associated specimen-handling considerations are described. Future, prospective studies are merited to validate irPRC in larger datasets and to associate pathologic features with long-term patient outcomes.

PMID: 31672770 [PubMed - as supplied by publisher]

Effectiveness of Multi-Prognostic Index in older patients with advanced malignancies treated with immunotherapy.

Fetched: November 2nd, 2019, 5:01am GMT

Effectiveness of Multi-Prognostic Index in older patients with advanced malignancies treated with immunotherapy.

J Geriatr Oncol. 2019 Oct 28;:

Authors: Sbrana A, Antognoli R, Pasqualetti G, Linsalata G, Okoye C, Calsolaro V, Paolieri F, Bloise F, Ricci S, Antonuzzo A, Monzani F

Abstract
BACKGROUND: Older adults with cancer are less likely to be offered treatment for cost-benefit concern. The Multi-Prognostic Index (MPI) has been validated in various clinical settings for survival estimation. We aimed to evaluate MPI as a screening tool for older adults with cancer eligible to receive immunotherapy.
PATIENTS AND METHODS: Older adults with advanced or metastatic cancer, admitted to the Oncology Day Hospital of the University Hospital of Pisa from January 2017 to May 2018, eligible to receive immunotherapy were prospectively enrolled. In addition to routine oncological evaluation, each patient received a comprehensive geriatric assessment with MPI calculation. Overall survival (Cox-adjusted curve) was stratified by tertiles of MPI score. Drug toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03: June 14, 2010).
RESULTS: Seventy-nine patients [26.6% women, mean age (±SD) 74.0 ± 6.1 years] were enrolled with the following diagnosis: melanoma (51.9%), non-small cell lung cancer (25.3%), renal cell cancer (12.7%), urothelial cancer (8.9%) and Merkel cell carcinoma (1.2%). Median follow-up was 7 months (range 1-35). The patients' survival rate resulted progressively longer proceeding from the first to the third MPI tertile [HR 1.76 (0.49-6.31) Vs 2nd tertile, p < 0.05; HR 5.33 (1.68-16.89) Vs 3rd tertile, p < 0.01].
CONCLUSIONS: MPI score is an effective tool for the stratification of older patients with cancer eligible for immunotherapy with checkpoint inhibitors. Further studies are required to achieve conclusive remarks on MPI usefulness in different underlying tumor types.

PMID: 31672558 [PubMed - as supplied by publisher]

Pembrolizumab-associated mucous membrane pemphigoid in a patient with Merkel cell carcinoma.

Fetched: November 1st, 2019, 5:01am GMT

Pembrolizumab-associated mucous membrane pemphigoid in a patient with Merkel cell carcinoma.

Br J Dermatol. 2018 10;179(4):993-994

Authors: Haug V, Behle V, Benoit S, Kneitz H, Schilling B, Goebeler M, Gesierich A

PMID: 29758087 [PubMed - indexed for MEDLINE]

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced MCC or cSCC

Posted: November 11th, 2019, 3:00pm GMT

Conditions: Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
Intervention: Biological: IFx-Hu2.0
Sponsors: Morphogenesis, Inc.; H. Lee Moffitt Cancer Center and Research Institute
Recruiting

Phase II Trial of Avelumab (Bavencio (R)) With IL-15 in Subjects With Clear-Cell Renal Carcinoma

Posted: November 4th, 2019, 3:00pm GMT

Condition: Clear-Cell Renal Carcinoma
Interventions: Drug: rhIL-15; Biological: Avelumab
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Permalink for 'Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers'

Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

Posted: January 25th, 2019, 3:00pm GMT

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Merkel Cell Carcinoma AJCC v8; High-Frequency Microsatellite Instability; Metastatic Basal Cell Carcinoma; Metastatic Melanoma; Metastatic Merkel Cell Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Merkel Cell Carcinoma AJCC v8; Unresectable Basal Cell Carcinoma; Unresectable Melanoma; Unresectable Merkel Cell Carcinoma
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Drug: Prednisone; Drug: Tacrolimus
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'This Study Evaluates KRT-232, a Novel Oral Small Molecule Inhibitor of MDM2, for the Treatment of Patients With (p53WT) Merkel Cell Carcinoma Who Have Failed Anti-PD-1/ PD-L1 Immunotherapy'

This Study Evaluates KRT-232, a Novel Oral Small Molecule Inhibitor of MDM2, for the Treatment of Patients With (p53WT) Merkel Cell Carcinoma Who Have Failed Anti-PD-1/ PD-L1 Immunotherapy

Posted: December 25th, 2018, 3:00pm GMT

Condition: Merkel Cell Carcinoma
Intervention: Drug: KRT-232
Sponsor: Kartos Therapeutics, Inc.
Recruiting

Gene-Modified Immune Cells (FH-MCVA2TCR) in Treating Patients With Metastatic or Unresectable Merkel Cell Cancer

Posted: November 20th, 2018, 3:00pm GMT

Condition: Other Skin
Interventions: Biological: Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR; Drug: Avelumab; Radiation: Radiation Therapy; Biological: Pembrolizumab
Sponsors: Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI); bluebird bio, Inc.
Recruiting

Permalink for 'Pembrolizumab Compared to Standard of Care Observation in Treating Patients With Completely Resected Stage I-III Merkel Cell Cancer'

Pembrolizumab Compared to Standard of Care Observation in Treating Patients With Completely Resected Stage I-III Merkel Cell Cancer

Posted: October 19th, 2018, 2:00pm GMT

Conditions: Pathologic Stage I Merkel Cell Carcinoma AJCC v8; Pathologic Stage II Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIB Merkel Cell Carcinoma AJCC v8; Pathologic Stage III Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
Interventions: Other: Best Practice; Biological: Pembrolizumab; Radiation: Radiation Therapy
Sponsor: National Cancer Institute (NCI)
Recruiting

Intratumoral AST-008 Combined With Pembrolizumab in Patients With Advanced Solid Tumors

Posted: September 26th, 2018, 2:00pm GMT

Conditions: Advanced or Metastatic Solid Tumors; Advanced or Metastatic Melanoma; Advanced or Metastatic Head and Neck Squamous Cell Carcinoma; Advanced or Metastatic Cutaneous Squamous Cell Carcinoma; Advanced or Metastatic Merkel Cell Carcinoma
Interventions: Drug: AST-008; Biological: Pembrolizumab
Sponsor: Exicure, Inc.
Recruiting

A Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies

Posted: August 14th, 2018, 2:00pm GMT

Conditions: Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Breast Cancer; Colorectal Cancer; Melanoma; Bladder Cancer; Ovarian Cancer; Endometrial Cancer; Merkel Cell Carcinoma; GastroEsophageal Cancer; Renal Cell Carcinoma; Castration-resistant Prostate Cancer
Interventions: Drug: AB928; Drug: AB122
Sponsor: Arcus Biosciences, Inc.
Recruiting

A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma (POD1UM-201)

Posted: July 25th, 2018, 2:00pm GMT

Condition: Metastatic Merkel Cell Carcinoma
Intervention: Drug: INCMGA00012
Sponsor: Incyte Corporation
Recruiting

Adjuvant Avelumab in Merkel Cell Cancer

Posted: September 5th, 2017, 2:00pm GMT

Conditions: Stage III Merkel Cell Carcinoma AJCC v7; Stage IIIB Merkel Cell Carcinoma AJCC v7
Interventions: Drug: Avelumab; Other: Laboratory Biomarker Analysis; Other: Placebo
Sponsors: University of Washington; National Cancer Institute (NCI); EMD Serono
Recruiting

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 31st, 2015, 3:00pm GMT

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

Permalink for 'An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors'

An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors

Posted: July 2nd, 2015, 2:00pm GMT

Condition: Various Advanced Cancer
Interventions: Drug: Nivolumab; Drug: Ipilimumab; Drug: Relatlimab; Drug: Daratumumab
Sponsors: Bristol-Myers Squibb; Ono Pharmaceutical Co. Ltd
Recruiting

Studies of Dermatologic Diseases Biospecimen Acquisition Protocol

Posted: June 15th, 2015, 2:00pm GMT

Conditions: Dermatologic Conditions; Healthy Volunteers; Normal Volunteers; Carcinoma, Merkel Cell
Intervention:
Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Recruiting

Patients With ES-SCLC and ECOG PS=2 Receiving Atezolizumab-Carboplatin-Etoposide

Posted: January 8th, 2020, 3:00pm GMT

Condition: SCLC, Extensive Stage
Intervention: Drug: Atezolizumab
Sponsors: AIO-Studien-gGmbH; Hoffmann-La Roche
Recruiting

Testing Treatment With Encorafenib and Binimetinib Before Surgery for Melanoma With Lymph Node Involvement

Posted: January 8th, 2020, 3:00pm GMT

Conditions: Melanoma of Unknown Primary; Metastatic Malignant Neoplasm in Lymph Node; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Recurrent Cutaneous Melanoma
Interventions: Drug: Binimetinib; Procedure: Computed Tomography; Procedure: Conventional Surgery; Drug: Encorafenib; Other: Fluorothymidine F-18; Procedure: Positron Emission Tomography
Sponsors: ECOG-ACRIN Cancer Research Group; National Cancer Institute (NCI)
Not yet recruiting

Natural History of Medullary Thyroid Cancer to Inform Advanced Disease Management

Posted: January 3rd, 2020, 3:00pm GMT

Conditions: Advanced Thyroid Gland Medullary Carcinoma; Stage III Thyroid Gland Medullary Carcinoma AJCC v8; Stage IV Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v8
Interventions: Other: Blood Pressure; Other: Questionnaire Administration
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI); Food and Drug Administration (FDA)
Not yet recruiting

Detection of PitNET Tissue During TSS Using Bevacizumab-800CW

Posted: December 30th, 2019, 3:00pm GMT

Conditions: Pituitary Tumor; Pituitary Adenoma; Pituitary Macroadenoma
Interventions: Drug: Bevacizumab-IRDye800CW; Device: Molecular Fluorescence Endoscopy platform
Sponsor: University Medical Center Groningen
Not yet recruiting

A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer

Posted: December 25th, 2019, 3:00pm GMT

Condition: Medullary Thyroid Cancer
Interventions: Drug: Selpercatinib; Drug: Cabozantinib; Drug: Vandetanib
Sponsors: Eli Lilly and Company; Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Not yet recruiting

18F-AmBF3-TATE PET/CT for Imaging NET Patients

Posted: December 23rd, 2019, 3:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Diagnostic Test: 18F-AmBF3-TATE PET/CT; Diagnostic Test: Routine blood draw
Sponsor: British Columbia Cancer Agency
Not yet recruiting

Study of VE800 and Nivolumab in Patients With Selected Types of Advanced or Metastatic Cancer

Posted: December 23rd, 2019, 3:00pm GMT

Conditions: Metastatic Cancer; Melanoma; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma; Colorectal Cancer
Interventions: Biological: VE800; Drug: Nivolumab; Drug: Vancomycin Oral Capsule
Sponsors: Vedanta Biosciences, Inc.; Bristol-Myers Squibb (BMS)
Recruiting

Permalink for 'A Study of Anlotinib and AK105 Injection in Subjects With Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors'

A Study of Anlotinib and AK105 Injection in Subjects With Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors

Posted: December 20th, 2019, 3:00pm GMT

Condition: Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors
Interventions: Drug: AK105; Drug: Anlotinib
Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Not yet recruiting

Study to Evaluate OrienX010 in Combination With JS001 in the Treatment of Stage IV (M1c) Liver Metastasis From Melanoma

Posted: December 20th, 2019, 3:00pm GMT

Condition: Melanoma
Intervention: Biological: OrienX010 combination with JS001
Sponsor: Beijing Cancer Hospital
Recruiting

Microbiotic Analysis in Digestive Endocrine Tumors

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Digestive Neuroendocrine Tumor; Fecal Microbiota; Bacterial Signature
Intervention: Biological: Biological sampling
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting

Cabozantinib and Nivolumab for Carcinoid Tumors

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Carcinoid Tumor; Carcinoid Tumor of GI System; Neuroendocrine Tumors
Interventions: Drug: Nivolumab; Drug: Cabozantinib
Sponsors: Dana-Farber Cancer Institute; Bristol-Myers Squibb; Exelixis
Recruiting

Study of INBRX-106 in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Solid Tumor; Non-Small Cell Lung Cancer; Melanoma; Head and Neck Cancer; Gastric Cancer; Renal Cell Carcinoma; Urothelial Carcinoma
Interventions: Drug: INBRX-106 - Hexavalent OX40 agonist antibody; Drug: Pembrolizumab
Sponsor: Inhibrx, Inc.
Recruiting

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HH2710 in Patient With Advanced Tumors

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Advanced Tumors; Melanoma; Non-Small-Cell Lung Cancer; Erdheim-Chester Disease; Other RAS/RAF/MEK/ERK Mutated Tumors
Intervention: Drug: HH2710
Sponsor: ShangHai HaiHe Pharmaceutical
Not yet recruiting

Clinical Study to Evaluate OrienX010 in Combination With Treprizumab Injection as Neoadjuvant Treatment in Melanoma

Posted: December 13th, 2019, 3:00pm GMT

Condition: Melanoma (Skin)
Intervention: Biological: OrienX010 Combination with Treprizumab injection
Sponsor: Beijing Cancer Hospital
Recruiting

Personalized CAPTEM Radiopeptide Therapy of Advanced, Non-resectable Neuroendocrine Cancer

Posted: December 11th, 2019, 3:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: 177Lu-DOTATOC
Sponsors: University of Warmia and Mazury; Maria Sklodowska-Curie Institute - Oncology Center; The Medical University of Warsaw; Poland; The Diagnostic and Therapeutic Center Gammed; Poland; National Center for Research and Development, Poland
Recruiting

POINTING: Clinical Cohort Study of Patients With Melanoma and NSCLC Receiving Checkpoint Inhibitors

Posted: December 11th, 2019, 3:00pm GMT

Conditions: Melanoma; Non-Small Cell Lung Cancer
Interventions: Other: Standard-of-care procedures; Other: Study procedures
Sponsor: Prof.dr. E.G.E. de Vries
Recruiting

Clinical Evaluation of 68Ga-NOTA-MAL-Cys39-exendin-4 Positron Emission Tomography in the Detection of Insulinoma

Posted: December 4th, 2019, 3:00pm GMT

Condition: Insulinoma
Intervention: Drug: 68Ga-NOTA-MAL-Cys39-exendin-4
Sponsor: Nanjing First Hospital, Nanjing Medical University
Recruiting

Safety and Efficacy of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Selected Advanced Solid Tumors

Posted: November 21st, 2019, 3:00pm GMT

Conditions: Advaced Solid Tumors; Melanoma
Intervention: Biological: AK104
Sponsors: Akeso; Akeso Pharmaceuticals, Inc.
Not yet recruiting

Granzyme B PET Imaging Drug as a Predictor of Immunotherapy Response in Melanoma or NSCLC Participants

Posted: November 19th, 2019, 3:00pm GMT

Conditions: Melanoma; Non-Small Cell Lung Cancer
Intervention: Drug: Single Arm
Sponsors: Cytosite Biopharma Inc.; Massachusetts General Hospital; University of Alabama at Birmingham
Not yet recruiting

Permalink for 'A Phase II Study on Adjuvant Vaccination With Dendritic Cells Loaded With Autologous Tumor Homogenate in Resected Stage IV Rare Cancers.'

A Phase II Study on Adjuvant Vaccination With Dendritic Cells Loaded With Autologous Tumor Homogenate in Resected Stage IV Rare Cancers.

Posted: November 18th, 2019, 3:00pm GMT

Conditions: Head Neck Tumors; Neuroendocrine Tumors; Soft Tissue Sarcoma; Rare Cancer; Vaccination
Interventions: Biological: Autologous DC vaccine; Drug: Interleukin-2
Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Not yet recruiting

Adoptive Tumor-infiltrating Lymphocyte Transfer With Nivolumab for Melanoma

Posted: November 18th, 2019, 3:00pm GMT

Condition: Advanced Melanoma
Intervention: Drug: Combination of TIL Transfer with anti-PD-1 Therapy and low dose IL-2
Sponsors: University Hospital, Basel, Switzerland; GMP network of Basel
Not yet recruiting

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced MCC or cSCC

Posted: November 11th, 2019, 3:00pm GMT

A Study of ZN-c3 in Participants With Solid Tumors

Posted: November 8th, 2019, 3:00pm GMT

Conditions: Solid Tumor; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer; Triple Negative Breast Cancer; Small Cell Lung Cancer; Metastatic Breast Cancer; Malignant Melanoma; Non Small Cell Lung Cancer; Urothelial Carcinoma
Interventions: Drug: ZN-c3; Drug: Talazoparib; Drug: Pembrolizumab
Sponsors: K-Group Beta; IQVIA Biotech
Recruiting

Developing a Method Using PET-MR to Improve Staging and Monitoring of Neuroendocrine Tumor

Posted: November 6th, 2019, 3:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Diagnostic Test: PET/MR scan
Sponsor: Tel-Aviv Sourasky Medical Center
Not yet recruiting

Applying PET/MR in Neuroendocrine Tumors - Imaging Dynamic Processes in Both Modalities

Posted: November 6th, 2019, 3:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Diagnostic Test: PET/MR scan
Sponsor: Tel-Aviv Sourasky Medical Center
Not yet recruiting

Appropriate Dosing to Optimise Personalised Cancer Treatments

Posted: November 6th, 2019, 3:00pm GMT

Conditions: Melanoma Stage III; Melanoma Stage IV; Ovarian Cancer; Renal Cancer Stage III; Renal Cancer Stage IV; Lung Cancer, Non-small Cell
Interventions: Diagnostic Test: Dried blood Spot (DBS); Diagnostic Test: Venous blood sampling
Sponsor: University of Dundee
Recruiting

Gene Modified Immune Cells (IL13Ralpha2 CAR T Cells) After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma

Posted: October 8th, 2019, 2:00pm GMT

Conditions: Clinical Stage IV Cutaneous Melanoma AJCC v8; IL13RA2 Positive; Metastatic Melanoma; Cutaneous Melanoma, Stage III; Cutaneous Melanoma, Stage IV
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells; Drug: Recombinant Interleukin-2
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting

Communicating With Patients on Cancer Resistance to Treatment: the Development of a Communication Tool. (HECTOR)

Posted: October 7th, 2019, 2:00pm GMT

Conditions: Metastatic Uveal Melanoma; Triple Negative Breast Cancer; Luminal B Breast Cancer; Pediatric Cancer
Interventions: Behavioral: Questionnaires; Behavioral: Semi-structured individual interviews; Other: Focus Group; Other: DELPHI Consensus Method
Sponsor: Institut Curie
Not yet recruiting

Clinico-biological Database in Patients Treated With Metabolic Radiotherapy in the Nuclear Medicine Department

Posted: September 26th, 2019, 2:00pm GMT

Conditions: Thyroid Cancer; Prostate Cancer; Neuroendocrine Tumors
Intervention: Other: Biological collection
Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Recruiting

$Permalink for 'Polarized Dendritic Cell (aDC1) Vaccine, Interferon Alpha-2, Rintalolimid, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma'$

Polarized Dendritic Cell (aDC1) Vaccine, Interferon Alpha-2, Rintalolimid, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma

Posted: September 18th, 2019, 2:00pm GMT

Conditions: HLA-A2 Positive Cells Present; Refractory Melanoma
Interventions: Biological: Alpha-type-1 Polarized Dendritic Cells; Drug: Celecoxib; Drug: PD-1 Ligand Inhibitor; Drug: PD1 Inhibitor; Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI)
Not yet recruiting

Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)

Posted: September 11th, 2019, 2:00pm GMT

Conditions: Gastroenteropancreatico Tumors; Neuroendocrine Tumors; Neuroendocrine Neoplasms
Interventions: Drug: Lu-177-DOTATATE; Drug: Olaparib; Diagnostic Test: Ga dotatate scanning; Diagnostic Test: FDG-PET scanning
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Testing the Combination of XL184 (Cabozantinib), Nivolumab, and Ipilimumab for Poorly Differentiated Neuroendocrine Tumors

Posted: September 5th, 2019, 2:00pm GMT

Conditions: Metastatic Large Cell Neuroendocrine Carcinoma; Metastatic Neuroendocrine Carcinoma; Metastatic Neuroendocrine Neoplasm; Metastatic Small Cell Carcinoma
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors

Posted: August 29th, 2019, 2:00pm GMT

Conditions: VHL Pancreatic Neuroendocrine Tumors; Von Hippel-Lindau Disease; Neuroendocrine Tumors
Intervention:
Sponsor: National Cancer Institute (NCI)
Recruiting

Use of 68Ga-dotatate PET Scan in Neuroendocrine Carcinoma of the GI Tract

Posted: August 26th, 2019, 2:00pm GMT

Condition: Neuroendocrine Carcinoma
Interventions: Drug: 68Ga-DOTATATE; Diagnostic Test: Positron Emission Tomography (PET) Scan
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Advanced Accelerator Applications
Recruiting

Predicting Responsiveness in Oncology Patients Based on Host Response Evaluation During Anti Cancer Treatments

Posted: August 14th, 2019, 2:00pm GMT

Conditions: Stage IV Non-small Cell Lung Cancer; Stage IV Malignant Melanoma
Intervention: Other: Plasma sample collection
Sponsor: OncoHost Ltd.
Recruiting

A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors

Posted: August 6th, 2019, 2:00pm GMT

Condition: Advanced Solid Tumors
Intervention: Drug: FF-10850 Topotecan Liposome Injection
Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
Recruiting

Surpass: ADP-A2M4CD8 in HLA-A2+ Subjects With MAGE-A4 Positive Tumors

Posted: August 5th, 2019, 2:00pm GMT

Conditions: Synovial Sarcoma; Myxoid/Round Cell Liposarcoma (MRCLS); Melanoma; Urothelial Carcinoma; Head and Neck; Ovarian; Gastric Cancer; Esophagogastric Junction Disorder; Nonsmall Cell Lung Cancer; Esophageal Cancer
Intervention: Genetic: Autologous genetically modified ADP-A2M4CD8 cells
Sponsor: Adaptimmune
Recruiting

TAS-102 in Extrapulmonary Neuroendocrine Carcinoma

Posted: August 2nd, 2019, 2:00pm GMT

Condition: High-grade Extra Pulmonary Neuroendocrine Cancer
Intervention: Drug: All patients- TAS-102
Sponsors: Baylor Research Institute; Taiho Oncology, Inc.
Recruiting

An Investigational Scan (68Ga-DOTATATE PET/CT) in Diagnosing Pediatric Metastatic Neuroendocrine Tumors

Posted: July 31st, 2019, 2:00pm GMT

Conditions: Ganglioneuroblastoma; Ganglioneuroma; Metastatic Neuroblastoma
Interventions: Procedure: Computed Tomography; Drug: Gallium Ga 68-DOTATATE; Procedure: Positron Emission Tomography
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Not yet recruiting

Sonidegib and Pembrolizumab in Treating Patients With Advanced Solid Tumors

Posted: July 3rd, 2019, 2:00pm GMT

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Gastric Cancer AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastric Cancer AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastric Cancer AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; High-Frequency Microsatellite Instability; Locally Advanced Urothelial Carcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Pancreatic Adenocarcinoma; Metastatic Urothelial Carcinoma; Mismatch Repair Deficiency; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Gastric Cancer AJCC v8; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastric Cancer AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastric Cancer AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIC Gastric Cancer AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Gastric Cancer AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; PD-L1 Positive; Progressive Disease; Recurrent Head and Neck Squamous Cell Carcinoma; Refractory Lung Non-Small Cell Carcinoma; Refractory Pancreatic Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage IIA Pancreatic Cancer AJCC v8; Stage IIB Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Unresectable Malignant Solid Neoplasm; Unresectable Melanoma; Unresectable Pancreatic Adenocarcinoma
Interventions: Biological: Pembrolizumab; Drug: Sonidegib
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Not yet recruiting

3TMPO (Triple-Tracer Strategy Against Metastatic Prostate Cancer

Posted: June 27th, 2019, 2:00pm GMT

Condition: Metastatic Castration-resistant Prostate Cancer
Interventions: Diagnostic Test: FDG Positron emission tomography (PET) scan; Diagnostic Test: PSMA Positron emission tomography (PET) scan; Diagnostic Test: OCTREOTATE Positron emission tomography (PET) scan; Other: Optional Bone or soft-tissue biopsies
Sponsors: Université de Sherbrooke; Fonds de la Recherche en Santé du Québec; Oncopole; Canadian Cancer Society Research Institute (CCSRI); Merck Canada Inc.
Recruiting

Permalink for 'Binimetinib and Palbociclib or TAS-102 in Treating Patients With KRAS and NRAS Mutant Metastatic or Unresectable Colorectal Cancer'

Binimetinib and Palbociclib or TAS-102 in Treating Patients With KRAS and NRAS Mutant Metastatic or Unresectable Colorectal Cancer

Posted: June 11th, 2019, 2:00pm GMT

Conditions: KRAS Gene Mutation; Metastatic Colorectal Carcinoma; NRAS Gene Mutation; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Neuroendocrine Tumor AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Unresectable Carcinoma
Interventions: Drug: Binimetinib; Drug: Palbociclib; Drug: Trifluridine and Tipiracil Hydrochloride
Sponsors: Academic and Community Cancer Research United; National Cancer Institute (NCI)
Recruiting

Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET

Posted: June 3rd, 2019, 2:00pm GMT

Condition: Gastro-enteropancreatic Neuroendocrine Tumor
Interventions: Drug: Lutathera; Drug: long-acting octreotide; Drug: high dose long-acting octreotide
Sponsor: Advanced Accelerator Applications
Not yet recruiting

Phase II Study in the Treatment of Patients With Advanced Mucinous Melanoma

Posted: May 8th, 2019, 2:00pm GMT

Condition: Advanced Mucosal Melanoma
Interventions: Biological: JS001(Toripalimab Injection); Drug: Axitinib 1 MG [Inlyta]; Other: JS001 and Axitinib
Sponsor: Beijing Cancer Hospital
Recruiting

A Trial of BXCL701 and Pembrolizumab in Patients With Small Cell Neuroendocrine Prostate Cancer

Posted: April 10th, 2019, 2:00pm GMT

Conditions: Prostate Cancer; Neuroendocrine Tumors; Small Cell Carcinoma
Intervention: Drug: Talabostat Mesylate plus Pembrolizumab
Sponsor: BioXcel Therapeutics Inc
Recruiting

Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors

Posted: March 19th, 2019, 2:00pm GMT

Conditions: Lung Atypical Carcinoid Tumor; Lung Typical Carcinoid Tumor; Metastatic Pancreatic Neuroendocrine Tumor
Interventions: Biological: Incomplete Freund's Adjuvant; Drug: Octreotide Acetate; Biological: Sargramostim; Biological: SVN53-67/M57-KLH Peptide Vaccine
Sponsors: Roswell Park Cancer Institute; NeuroEndocrine Tumor Research Foundation (NETRF); National Cancer Institute (NCI)
Recruiting

Permalink for 'Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors'

Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors

Posted: March 7th, 2019, 3:00pm GMT

Conditions: Bladder Adenocarcinoma; Bladder Mixed Adenocarcinoma; Bladder Small Cell Carcinoma; Bladder Squamous Cell Carcinoma; Chromophobe Renal Cell Carcinoma; Infiltrating Bladder Lymphoepithelioma-Like Carcinoma; Infiltrating Bladder Urothelial Carcinoma; Infiltrating Bladder Urothelial Carcinoma With Giant Cells; Infiltrating Bladder Urothelial Carcinoma, Nested Variant; Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant; Infiltrating Bladder Urothelial Carcinoma, Sarcomatoid Variant; Kidney Medullary Carcinoma; Large Cell Neuroendocrine Carcinoma; Metastatic Bladder Carcinoma; Metastatic Bladder Large Cell Neuroendocrine Carcinoma; Metastatic Bladder Small Cell Carcinoma; Metastatic Bladder Squamous Cell Carcinoma; Metastatic Infiltrating Bladder Urothelial Carcinoma, Clear Cell Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Lipid-Rich Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Micropapillary Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Sarcomatoid Variant; Metastatic Kidney Medullary Carcinoma; Metastatic Malignant Genitourinary System Neoplasm; Metastatic Penile Carcinoma; Metastatic Prostate Small Cell Carcinoma; Metastatic Sarcomatoid Renal Cell Carcinoma; Papillary Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage IV Bladder Cancer AJCC v8; Stage IV Penile Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Testicular Leydig Cell Tumor; Testicular Sertoli Cell Tumor
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors'

Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors

Posted: March 6th, 2019, 3:00pm GMT

Conditions: Advanced Solid Tumors; Metastatic Melanoma
Interventions: Drug: losartan; Drug: dextromethorphan; Drug: caffeine; Drug: omeprazole; Drug: midazolam; Drug: rosuvastatin; Drug: bupropion immediate release (IR); Drug: encorafenib; Drug: binimetinib; Drug: modafinil
Sponsors: Array BioPharma; Pierre Fabre Laboratories
Recruiting

A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

Posted: February 21st, 2019, 3:00pm GMT

Conditions: Melanoma; Cervical Carcinoma; Pancreatic Carcinoma; Triple Negative Breast Cancer; Hepatocellular Carcinoma; Urothelial Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Nasopharyngeal Carcinoma; Renal Cell Carcinoma; Non-small Cell Lung Carcinoma; Small Cell Lung Carcinoma; Gastric or Gastroesophageal Junction Adenocarcinoma; Advanced or Metastatic Solid Tumors; Prostate Carcinoma; MSI-H; Mismatch Repair Deficiency; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma; Intrahepatic Cholangiocarcinoma
Interventions: Biological: XmAb®22841; Biological: Pembrolizumab (Keytruda®)
Sponsors: Xencor, Inc.; ICON Clinical Research
Recruiting

Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

Posted: January 25th, 2019, 3:00pm GMT

Study of INBRX-105 in Patients With Solid Tumors, Hodgkin or Non-Hodgkin Lymphoma

Posted: January 18th, 2019, 3:00pm GMT

Conditions: Metastatic Solid Tumors; Hodgkin Lymphoma; Non Hodgkin Lymphoma; Non-small Cell Lung Cancer; Melanoma; Head and Neck Squamous Cell Carcinoma; Gastric Adenocarcinoma; Renal Cell Carcinoma; Urothelial Carcinoma; Esophageal Adenocarcinoma
Intervention: Drug: INBRX-105 - PDL1x41BB antibody
Sponsor: Inhibrx, Inc.
Recruiting

Permalink for 'This Study is a Phase II Study of AZD6738 in Combination With Durvalumab in Patients With Solid Tumor (Cohort A (N=30): GC Who Have Failed Secondary Chemotherapy Treatments Regimen; Cohort B (B=30): Melanoma Patients Who Have Failed to IO)'

This Study is a Phase II Study of AZD6738 in Combination With Durvalumab in Patients With Solid Tumor (Cohort A (N=30): GC Who Have Failed Secondary Chemotherapy Treatments Regimen; Cohort B (B=30): Melanoma Patients Who Have Failed to IO)

Posted: December 19th, 2018, 3:00pm GMT

Conditions: Gastric Adenocarcinoma; Malignant Melanoma
Interventions: Drug: AZD6738; Drug: Durvalumab
Sponsor: Samsung Medical Center
Recruiting

Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

Posted: December 6th, 2018, 3:00pm GMT

Conditions: Cancer; Melanoma (Skin); Melanoma, Uveal; Melanoma, Ocular; Bladder Cancer; Mismatch Repair Deficiency; Microsatellite Instability; Non-melanoma Skin Cancer
Interventions: Biological: RP1; Biological: nivolumab
Sponsor: Replimune Inc.
Recruiting

Personalized Neo-antigen Vaccine in Advanced Solid Tumors (NeoPepVac)

Posted: October 23rd, 2018, 2:00pm GMT

Conditions: Malignant Melanoma, Metastatic; Non Small Cell Lung Cancer Metastatic; Kidney Cancer Metastatic
Intervention: Drug: EVAX-01-CAF09b
Sponsor: Herlev Hospital
Recruiting

Permalink for 'Study to Evaluate the Safety of Pembrolizumab in Participants With Unresectable or Metastatic Melanoma or Non-small Cell Lung Cancer in India (MK-3475-593/KEYNOTE-593)'

Study to Evaluate the Safety of Pembrolizumab in Participants With Unresectable or Metastatic Melanoma or Non-small Cell Lung Cancer in India (MK-3475-593/KEYNOTE-593)

Posted: October 23rd, 2018, 2:00pm GMT

Conditions: Carcinoma, Non-Small-Cell Lung; Melanoma
Intervention: Drug: Pembrolizumab
Sponsor: Merck Sharp & Dohme Corp.
Recruiting

Pembrolizumab Compared to Standard of Care Observation in Treating Patients With Completely Resected Stage I-III Merkel Cell Cancer

Posted: October 19th, 2018, 2:00pm GMT

A Study of IMMray™ PanCan-d Test for Early Detection of Pancreatic Cancer in High-risk Groups

Posted: October 3rd, 2018, 2:00pm GMT

Conditions: Pancreatic Ductal Adenocarcinoma; Familial Pancreatic Cancer; FAMMM - Familial Atypical Mole Malignant Melanoma Syndrome
Intervention:
Sponsor: Immunovia, Inc.
Recruiting

Intratumoral AST-008 Combined With Pembrolizumab in Patients With Advanced Solid Tumors

Posted: September 26th, 2018, 2:00pm GMT

$Permalink for 'C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N)'$

C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N)

Posted: August 17th, 2018, 2:00pm GMT

Conditions: Relapsed Neuroblastoma; Refractory Neuroblastoma; Relapsed Osteosarcoma; Relapsed Ewing Sarcoma; Relapsed Rhabdomyosarcoma; Uveal Melanoma; Phyllodes Breast Tumor
Interventions: Genetic: C7R-GD2.CART cells; Drug: Cyclophosphamide; Drug: Fludarabine
Sponsors: Baylor College of Medicine; Texas Children's Hospital; Center for Cell and Gene Therapy, Baylor College of Medicine; The Methodist Hospital System; Cancer Prevention Research Institute of Texas
Recruiting

A Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies

Posted: August 14th, 2018, 2:00pm GMT

Ixazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

Posted: July 16th, 2018, 2:00pm GMT

Conditions: Metastatic Kidney Medullary Carcinoma; Metastatic Renal Cell Carcinoma; SMARCB1 Negative; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8
Interventions: Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Drug: Ixazomib; Drug: Ixazomib Citrate
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Perception of Information and Quality of Life in Neuroendocrine Tumour on Lanreotide Autogel

Posted: June 19th, 2018, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Other: Data collection
Sponsor: Ipsen
Recruiting

Permalink for 'A Study of Cetrelimab (JNJ-63723283), a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, Administered in Combination With Apalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer'

A Study of Cetrelimab (JNJ-63723283), a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, Administered in Combination With Apalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer

Posted: June 11th, 2018, 2:00pm GMT

Condition: Castration-Resistant Prostatic Neoplasms
Interventions: Drug: Cetrelimab 480 mg; Drug: Apalutamide 240 mg
Sponsor: Janssen Research & Development, LLC
Recruiting

A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors

Posted: May 7th, 2018, 2:00pm GMT

Conditions: Melanoma; Breast Carcinoma; Hepatocellular Carcinoma; Urothelial Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Renal Cell Carcinoma; Colorectal Carcinoma; Non-small Cell Lung Carcinoma; Gastric or Gastroesophageal Junction Adenocarcinoma; Endometrial Carcinoma; Mesothelioma; Neuroendocrine Carcinoma; Cervical Cancer; Small Cell Lung Carcinoma; Squamous Cell Carcinoma of the Anus
Intervention: Biological: XmAb20717
Sponsors: Xencor, Inc.; ICON plc
Recruiting

Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET

Posted: March 15th, 2018, 2:00pm GMT

Condition: Neuroendocrine Tumor
Intervention: Drug: AlphaMedix
Sponsors: Radiomedix, Inc.; Orano Med LLC
Recruiting

Anti-SEMA4D Monoclonal Antibody VX15/2503 With Nivolumab or Ipilimumab in Treating Patients With Stage III or IV Melanoma

Posted: February 7th, 2018, 3:00pm GMT

Conditions: Metastatic Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
Interventions: Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Pharmacological Study
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting

Nivolumab With Ipilimumab in Subjects With Neuroendocrine Tumors

Posted: February 2nd, 2018, 3:00pm GMT

Conditions: Neuroendocrine Tumors; Carcinoid Tumor
Interventions: Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Bristol-Myers Squibb
Recruiting

Treating Patients With Melanoma and ALK Alterations With Ensartinib

Posted: February 2nd, 2018, 3:00pm GMT

Condition: Melanoma
Interventions: Drug: Ensartinib; Diagnostic Test: ALKATI by Customized Nanostring Assay
Sponsors: Memorial Sloan Kettering Cancer Center; Xcovery Holding Company, LLC
Recruiting

A Study of XmAb®18087 in Subjects With NET and GIST

Posted: January 26th, 2018, 3:00pm GMT

Conditions: Neuroendocrine Tumor; Gastrointestinal Neoplasm
Intervention: Biological: XmAb18087
Sponsors: Xencor, Inc.; ICON plc
Recruiting

Permalink for 'Cabozantinib S-malate in Treating Patients With Neuroendocrine Tumors Previously Treated With Everolimus That Are Locally Advanced, Metastatic, or Cannot Be Removed by Surgery'

Cabozantinib S-malate in Treating Patients With Neuroendocrine Tumors Previously Treated With Everolimus That Are Locally Advanced, Metastatic, or Cannot Be Removed by Surgery

Posted: December 18th, 2017, 3:00pm GMT

Conditions: Atypical Carcinoid Tumor; Carcinoid Tumor; Digestive System Neuroendocrine Neoplasm; Functioning Pancreatic Neuroendocrine Tumor; Intermediate Grade Lung Neuroendocrine Neoplasm; Low Grade Lung Neuroendocrine Neoplasm; Lung Atypical Carcinoid Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Neuroendocrine Neoplasm; Non-Functioning Pancreatic Neuroendocrine Tumor; Pancreatic Neuroendocrine Tumor; Serotonin-Producing Pancreatic Neuroendocrine Tumor; Stage IIIA Digestive System Neuroendocrine Tumor AJCC v7; Stage IIIB Digestive System Neuroendocrine Tumor AJCC v7; Stage IV Digestive System Neuroendocrine Tumor AJCC v7
Interventions: Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Other: Quality-of-Life Assessment
Sponsor: National Cancer Institute (NCI)
Recruiting

Two Chemotherapy Regimens Plus or Minus Bevacizumab

Posted: November 22nd, 2017, 3:00pm GMT

Condition: Pancreatic Cancer
Interventions: Drug: LV5FU2; Drug: Streptozocin; Drug: Capecitabine; Drug: Temozolomide; Drug: Bevacizumab
Sponsors: Gustave Roussy, Cancer Campus, Grand Paris; National Cancer Institute, France
Recruiting

TNF in Melanoma Patients Treated With Immunotherapy

Posted: November 21st, 2017, 3:00pm GMT

Condition: Melanoma
Intervention: Other: Tumor biopsy specimens and blood samples
Sponsor: Institut Claudius Regaud
Recruiting

Permalink for 'Viewpoints on the Social Representations and Rationale Concerning the Choices of Patients, Doctors and Caregivers With Regard to the Management of Patients With Non-resectable Metastatic Cancer of the Colon, Stomach, Bile Ducts, Rectum or Lung, or Gastro'

Viewpoints on the Social Representations and Rationale Concerning the Choices of Patients, Doctors and Caregivers With Regard to the Management of Patients With Non-resectable Metastatic Cancer of the Colon, Stomach, Bile Ducts, Rectum or Lung, or Gastro

Posted: November 1st, 2017, 2:00pm GMT

Conditions: Non-resectable Metastatic Cancer of the Lung; Non-resectable Metastatic Cancer of the Colon; Non-resectable Metastatic Cancer of the Rectosigmoid Junction; Non-resectable Metastatic Cancer of the Stomach; Non-resectable Metastatic Cancer of the Bile Duct; Non-resectable Metastatic Cancer of the Rectum; Non-resectable Metastatic Cancer of Gastrointestinal Neuroendocrine Tumour
Interventions: Other: Interviews; Other: Questionnaires
Sponsor: Centre Hospitalier Universitaire Dijon
Recruiting

A Study of PLX2853 in Advanced Malignancies.

Posted: September 29th, 2017, 2:00pm GMT

Conditions: Small Cell Lung Cancer; Uveal Melanoma; Ovarian Clear Cell Carcinoma; Non-Hodgkin Lymphoma; Advanced Malignancies; Solid Tumor; Diffuse Large B Cell Lymphoma; Follicular Lymphoma
Intervention: Drug: PLX2853
Sponsor: Plexxikon
Recruiting

Adjuvant Avelumab in Merkel Cell Cancer

Posted: September 5th, 2017, 2:00pm GMT

Permalink for 'MGMT-NET: O6-methylguanine-DNA Methyltransferase (MGMT) Status in Neuroendocrine Tumors: Predictive Factor of Response to Alkylating Agents'

MGMT-NET: O6-methylguanine-DNA Methyltransferase (MGMT) Status in Neuroendocrine Tumors: Predictive Factor of Response to Alkylating Agents

Posted: July 13th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: Oxaliplatin-based chemotherapy; Drug: Alkylating-based chemotherapy
Sponsor: Hospices Civils de Lyon
Recruiting

Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma

Posted: July 2nd, 2017, 2:00pm GMT

Conditions: Pheochromocytoma; Paraganglioma; Neuroendocrine Tumors; Neuroendocrine Neoplasms
Interventions: Drug: Lu-177-DOTATATE; Drug: Ga-68-DOTATATE; Drug: F-18-FDG; Drug: Amino Acid solution
Sponsor: National Cancer Institute (NCI)
Recruiting

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 24th, 2017, 2:00pm GMT

Conditions: Paraganglioma; Gastrointestinal Stromal Tumors; Carcinoma, Renal Cell; Renal Neoplasms; Pheochromocytoma
Intervention: Drug: SGI-110 (guadecitabine)
Sponsor: National Cancer Institute (NCI)
Recruiting

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 22nd, 2017, 2:00pm GMT

Conditions: Melanoma Stage Iv; Melanoma Stage Iii; Melanoma
Interventions: Drug: Denosumab; Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Melanoma and Skin Cancer Trials Limited; Peter MacCallum Cancer Centre, Australia; Amgen; Bristol-Myers Squibb
Recruiting

Phase 1/2 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer

Posted: May 17th, 2017, 2:00pm GMT

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

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 27th, 2017, 2:00pm GMT

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
Recruiting

A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

Posted: March 28th, 2017, 2:00pm GMT

Conditions: Locally Advanced Solid Tumors; Metastatic Solid Tumors
Intervention: Drug: Oral repotrectinib (TPX-0005)
Sponsor: Turning Point Therapeutics, Inc.
Recruiting

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

Posted: March 3rd, 2017, 3:00pm GMT

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

Uveal Melanoma T Cel Therapy

Posted: March 3rd, 2017, 3:00pm GMT

Conditions: Metastatic Uveal Melanoma; Uveal Melanoma Metastatic in the Liver
Interventions: Biological: Aldesleukin; Biological: Autologous CD8+ SLC45A2-specific T Lymphocytes; Drug: Cyclophosphamide; Biological: Ipilimumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Permalink for 'Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutation With Advanced Breast Cancer Who Have Progressed on or After Prior Treatments'

Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutation With Advanced Breast Cancer Who Have Progressed on or After Prior Treatments

Posted: February 17th, 2017, 3:00pm GMT

Condition: Breast Cancer
Interventions: Drug: alpelisib; Drug: fulvestrant; Drug: letrozole; Drug: Goserelin; Drug: Leuprolide
Sponsor: Novartis Pharmaceuticals
Recruiting

Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients

Posted: February 9th, 2017, 3:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: 177Lu-edotreotide PRRT; Drug: Everolimus; Other: Amino-Acid Solution
Sponsors: ITM Solucin GmbH; ABX CRO
Recruiting

Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors

Posted: February 6th, 2017, 3:00pm GMT

Condition: Gastroenteropancreatic Neuroendocrine Tumors
Interventions: Drug: Somatuline Depot; Drug: Keytruda
Sponsors: Duke University; Merck Sharp & Dohme Corp.; Ipsen
Recruiting

Permalink for 'Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors'

Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

Posted: January 31st, 2017, 3:00pm GMT

Conditions: RET-altered Non Small Cell Lung Cancer; Medullary Thyroid Cancer; RET-altered Papillary Thyroid Cancer; RET-altered Colon Cancer; RET-altered Solid Tumors; Lung Neoplasm; Carcinoma, Non-Small-Cell Lung; Thyroid Diseases; Thyroid Neoplasm; Thyroid Cancer, Papillary; Carcinoma, Neuroendocrine; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Disease; Carcinoma, Bronchogenic; Bronchial Neoplasms; Endocrine System Diseases; Endocrine Gland Neoplasm; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Colonic Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasm; Digestive System Disease; Gastrointestinal Disease; Colonic Diseases; Intestinal Disease
Intervention: Drug: pralsetinib (BLU-667)
Sponsor: Blueprint Medicines Corporation
Recruiting

Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease

Posted: January 19th, 2017, 3:00pm GMT

Conditions: Acral Lentiginous Melanoma; Central Nervous System Melanoma; Clinical Stage IV Cutaneous Melanoma AJCC v8; Leptomeningeal Neoplasm; Melanocytoma; Metastatic Melanoma; Metastatic Uveal Melanoma; Mucosal Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8
Intervention: Biological: Nivolumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Pembrolizumab and Ibrutinib in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

Posted: January 16th, 2017, 3:00pm GMT

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

Permalink for 'Nivolumab and Trametinib With or Without Dabrafenib in Treating Patients With BRAF Mutated or Wild Type Metastatic Stage III-IV Melanoma That Cannot Be Removed by Surgery'

Nivolumab and Trametinib With or Without Dabrafenib in Treating Patients With BRAF Mutated or Wild Type Metastatic Stage III-IV Melanoma That Cannot Be Removed by Surgery

Posted: September 22nd, 2016, 2:00pm GMT

Conditions: BRAF Gene Mutation; BRAF wt Allele; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
Interventions: Drug: Dabrafenib; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Pharmacological Study; Drug: Trametinib
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

$Permalink for 'Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors'$

Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors

Posted: August 16th, 2016, 2:00pm GMT

Conditions: Adrenal Cortex Carcinoma; Alveolar Soft Part Sarcoma; Central Nervous System Neoplasm; Childhood Clear Cell Sarcoma of Soft Parts; Clear Cell Sarcoma of Soft Tissue; Ewing Sarcoma; Hepatoblastoma; Hepatocellular Carcinoma; Osteosarcoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Alveolar Soft Part Sarcoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Hepatocellular Carcinoma; Recurrent Malignant Central Nervous System Neoplasm; Recurrent Malignant Solid Neoplasm; Recurrent Osteosarcoma; Recurrent Renal Cell Carcinoma; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Medullary Carcinoma; Refractory Ewing Sarcoma; Refractory Malignant Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Osteosarcoma; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Renal Cell Carcinoma; Rhabdomyosarcoma; Solid Neoplasm; Thyroid Gland Medullary Carcinoma; Wilms Tumor
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Other: Pharmacological Study
Sponsor: National Cancer Institute (NCI)
Recruiting

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

Posted: July 15th, 2016, 2:00pm GMT

Conditions: Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Angiosarcoma; Apocrine Neoplasm; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Basal Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cervical Clear Cell Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Extramammary Paget Disease; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gallbladder Carcinoma; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastric Undifferentiated Carcinoma; Gastrointestinal Stromal Tumor; Gestational Trophoblastic Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; PEComa; Peritoneal Mesothelioma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Rare Disorder; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous Cell Carcinoma; Solid Neoplasm; Spindle Cell Neoplasm; Squamous Cell Carcinoma of the Penis; Teratoma With Somatic-Type Malignancy; Testicular Non-Seminomatous Germ Cell Tumor; Thyroid Gland Carcinoma; Tracheal Carcinoma; Transitional Cell Carcinoma; Ureter Adenocarcinoma; Ureter Squamous Cell Carcinoma; Urethral Adenocarcinoma; Urethral Squamous Cell Carcinoma; Vaginal Adenocarcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified; Vulvar Carcinoma
Interventions: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Diagnostic Performances of Urine and Plasma 5-hydroxyindolacetic Acid (5HIAA) Values in Patients With Small-intestine Neuroendocrine Tumors'

Diagnostic Performances of Urine and Plasma 5-hydroxyindolacetic Acid (5HIAA) Values in Patients With Small-intestine Neuroendocrine Tumors

Posted: July 11th, 2016, 2:00pm GMT

Condition: Small-intestine Neuroendocrine Tumors (Carcinoid Tumors)
Intervention: Biological: blood sample withdrawn
Sponsor: CHU de Reims
Recruiting

Permalink for 'Assessment of the Efficacy of Bevacizumab in Combination With Folfiri as Second-line Treatment in Patients Suffering From an Advanced Inoperable Poorly Differentiated Neuroendocrine Carcinoma of an Unknown or Gastroentero-pancreatic Primary Cancer'

Assessment of the Efficacy of Bevacizumab in Combination With Folfiri as Second-line Treatment in Patients Suffering From an Advanced Inoperable Poorly Differentiated Neuroendocrine Carcinoma of an Unknown or Gastroentero-pancreatic Primary Cancer

Posted: July 1st, 2016, 2:00pm GMT

Condition: Neuroendocrine Carcinomas
Interventions: Drug: Folfiri-bevacizumab; Drug: Folfiri
Sponsor: Hospices Civils de Lyon
Recruiting

Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery

Posted: May 18th, 2016, 2:00pm GMT

Condition: Desmoplastic Melanoma
Interventions: Biological: Pembrolizumab; Procedure: Therapeutic Conventional Surgery
Sponsor: National Cancer Institute (NCI)
Recruiting

SRS and Nivolumab in Treating Patients With Newly Diagnosed Melanoma Metastases in the Brain or Spine

Posted: March 23rd, 2016, 2:00pm GMT

Conditions: Metastatic Malignant Neoplasm in the Brain; Metastatic Malignant Neoplasm in the Spine; Stage IV Skin Melanoma
Interventions: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Radiation: Stereotactic Radiosurgery
Sponsors: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Accuray Incorporated
Recruiting

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 31st, 2015, 3:00pm GMT

Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)

Posted: December 11th, 2015, 3:00pm GMT

Condition: Advanced Cancer
Intervention: Biological: pembrolizumab
Sponsor: Merck Sharp & Dohme Corp.
Recruiting

Permalink for 'A Prospective Randomized and Phase 2 Trial for Metastatic Melanoma Using Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes Plus IL-2 Either Alone or Following the Administration of Pembrolizumab'

A Prospective Randomized and Phase 2 Trial for Metastatic Melanoma Using Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes Plus IL-2 Either Alone or Following the Administration of Pembrolizumab

Posted: December 3rd, 2015, 3:00pm GMT

Condition: Melanoma
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldeslaukin; Drug: Pembrolizumab; Biological: young TIL
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Novel Scoring System for Recurrence Risk Classification of Surgically Resected G1/2 Pancreatic Neuroendocrine Tumors - Retrospective Cohort Study.'

Novel Scoring System for Recurrence Risk Classification of Surgically Resected G1/2 Pancreatic Neuroendocrine Tumors - Retrospective Cohort Study.

Fetched: January 13th, 2020, 5:01am GMT

Novel Scoring System for Recurrence Risk Classification of Surgically Resected G1/2 Pancreatic Neuroendocrine Tumors - Retrospective Cohort Study.

Int J Surg. 2020 Jan 08;:

Authors: Siyi Z, Yu J, Weishen W, Qian Z, Xiaxing D, Baiyong S

Abstract
BACKGROUND: Existing staging systems for pancreatic neuroendocrine neoplasms only provide accuracy in stratifying disease severity without enough sensitivity in prognosis predicting. Previously presented models mainly set overall survival as endpoint but ignore the importance of recurrence.
METHODS: Univariate and multivariate analyses were retrospectively conducted on the potential prognostic factors of 245 patients who underwent curable surgery of G1/2 pancreatic neuroendocrine tumors from December 2002 to May 2018 in our institute. Proposed model based on statistically significant factors were tested for recurrence risk classification estimation validity as measured by discrimination (receiver operator characteristic [ROC] curve and Harrell's c-index [HCI]) and calibration.
RESULTS: Multivariate analyses found lymph node metastasis, larger tumor size and grade 2 independent risk factors of disease-free survival (DFS). The novel scoring system for recurrence risk classification sorted patients into three groups: score<15.4 for low risk (79.0%, 3- and 5-year recurrence risk 0.8% and 4.3%, median DFS not reached), score>15.4, <24.5 for intermediate risk (20.8%, 3- and 5-year recurrence risk 11.6% and 21.4%, median DFS 70 months,) and score >24.5 for high risk (10.2%, 3- and 5-year recurrence risk 37.3% and 68.7%, median DFS 49 months).The area under curve (AUC) and HCI of our system were 0.871 and 0.929, superior to those of European Neuroendocrine Tumor Society (AUC 0.833, HCI 0.806).
CONCLUSION: The presented system can be utilized to identify G1/2 pancreatic neuroendocrine tumors patients with high recurrence risk, which might be appropriate for peri-operative adjuvant therapy.

PMID: 31926324 [PubMed - as supplied by publisher]

Permalink for 'Antidepressant use limits serotonin as a marker for neuroendocrine tumor disease activity by lowering of circulating serotonin concentrations.'

Antidepressant use limits serotonin as a marker for neuroendocrine tumor disease activity by lowering of circulating serotonin concentrations.

Fetched: January 13th, 2020, 5:01am GMT

Antidepressant use limits serotonin as a marker for neuroendocrine tumor disease activity by lowering of circulating serotonin concentrations.

Clin Chem Lab Med. 2020 Jan 11;:

Authors: van Rossum HH, Spruit J, Korse CM, de Vries FE, Tesselaar MET

PMID: 31926073 [PubMed - as supplied by publisher]

Theranostics: Leveraging Molecular Imaging and Therapy to Impact Patient Management and Secure the Future of Nuclear Medicine.

Fetched: January 13th, 2020, 5:01am GMT

Theranostics: Leveraging Molecular Imaging and Therapy to Impact Patient Management and Secure the Future of Nuclear Medicine.

J Nucl Med. 2020 Jan 10;:

Authors: Solnes L, Werner R, Jones KM, Sadaghiani MS, Bailey CR, Lapa C, Pomper MG, Rowe SP

Abstract
Nuclear medicine is experiencing a renaissance with recent FDA approval of theranostics and a wide variety of such agents soon to impact patient care significantly in the era of precision medicine. The NETTER-1 trial demonstrated the therapeutic effect of a theranostic agent in markedly improving progression free survival in patients with metastatic gastroenteropancreatic neuroendocrine tumors. Retrospective studies have demonstrated a significant response to 177Lu-labeled agents targeting PSMA in patients with prostate cancer. At least two prospective clinical trials involving Lu-PSMA agents are under way that will likely pave the way for FDA approval in the United States. A significant upside to theranostics is that patients tend to tolerate those agents better than chemotherapy. Theranostic compounds are likely to impact many cancers in the near future, not only through improvements in quality of life but also in terms of survival. This manuscript provides an overview of already approved agents as well as those on the horizon. It is important that as these agents are clinically onboarded that nuclear medicine, in which they were discovered and first implemented, be at the helm. Nuclear medicine physicians have the expertise to deploy theranostics safely and efficiently, ensuring that these agents attain and maintain their rightful positions as leading lines of therapy in managing patients with cancer.

PMID: 31924727 [PubMed - as supplied by publisher]

Permalink for '64Cu-DOTATATE PET/CT for Imaging Patients with Known or Suspected Somatostatin Receptor-Positive Neuroendocrine Tumors: Results of the First US Prospective, Reader-Blinded Clinical Trial.'

64Cu-DOTATATE PET/CT for Imaging Patients with Known or Suspected Somatostatin Receptor-Positive Neuroendocrine Tumors: Results of the First US Prospective, Reader-Blinded Clinical Trial.

Fetched: January 13th, 2020, 5:01am GMT

64Cu-DOTATATE PET/CT for Imaging Patients with Known or Suspected Somatostatin Receptor-Positive Neuroendocrine Tumors: Results of the First US Prospective, Reader-Blinded Clinical Trial.

J Nucl Med. 2020 Jan 10;:

Authors: Delpassand ES, Ranganathan D, Wagh N, Shafie A, Gaber A, Abbasi A, Kjaer A, Tworowska I, Nunez R

Abstract
Studies demonstrate that the investigational 64Cu-DOTATATE radiopharmaceutical may provide diagnostic and logistical benefits over available imaging agents for patients with somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs). Accordingly, we aimed to prospectively determine the lowest dose of 64Cu-DOTATATE that facilitates diagnostic quality scans and evaluated the diagnostic performance and safety in a phase III study of patients with SSTR-expressing NETs. Methods: A dose-ranging study was conducted in 12 patients divided into 3 dose groups (111 MBq [3.0 mCi], 148 MBq [4.0 mCi], and 185 MBq [5.0 mCi] ± 10%) to determine the lowest dose of 64Cu-DOTATATE that produced diagnostic quality PET/CT images. Using the 64Cu-DOTATATE dose identified in the dose-ranging study, 3 independent nuclear medicine physicians who were blinded to all clinical information read PET/CT scans from 21 healthy volunteers and 42 NET-positive patients to determine those with "Disease" and "No Disease," as well as "Localized" versus "Metastatic" status. Blinded-reader evaluations were compared to a patient-specific standard of truth (SOT), which was established by an independent oncologist who used all previously available pathology, clinical, and conventional imaging data. Diagnostic performance calculated for 64Cu-DOTATATE included sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. Inter- and intra-reader reliability, as well as ability to differentiate between localized and metastatic disease, was also determined. Adverse events (AEs) were recorded from 64Cu-DOTATATE injection through 48 hours post-injection. Results: The dose-ranging study identified 148 MBq (4.0 mCi) as the optimal dose to obtain diagnostic quality PET/CT images. Following database lock, diagnostic performance from an initial majority read of the 3 independent readers showed a significant 90.9% sensitivity (P = 0.0042) and 96.6% specificity (P < 0.0001) for detecting NETs, which translated to a 100.0% sensitivity and 96.8% specificity after correcting for an initial SOT misread. Excellent inter- and intra-reader reliability, as well as ability to distinguish between localized and metastatic disease, was also noted. No AEs were related to 64Cu-DOTATATE, and no serious AEs were observed. Conclusion: 64Cu-DOTATATE PET/CT is a safe imaging technique that provides high-quality and accurate images at a dose of 148 MBq (4.0 mCi) for the detection of somatostatin-expressing NETs.

PMID: 31924723 [PubMed - as supplied by publisher]

Permalink for 'P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms.'

P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms.

Fetched: January 13th, 2020, 5:01am GMT

P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms.

BMC Cancer. 2020 Jan 10;20(1):27

Authors: Nielsen K, Binderup T, Langer SW, Kjaer A, Knigge P, Grøndahl V, Melchior L, Federspiel B, Knigge U

Abstract
BACKGROUND: High grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) with a Ki67 proliferation index > 20%, include well-differentiated tumours grade 3 (NET G3) and poorly differentiated (PD) neuroendocrine carcinomas (NEC). Abnormal p53-expression is a feature of PD tumours, while expression of chromogranin A (CgA) and somatostatin-receptor 2a (SSTR-2a) may be a feature of well-differentiated tumours. The aim of this study was to elucidate the expression and prognostic value of these three markers in 163 GEP-NEN patients with a Ki67-index > 20%.
METHOD: Clinical data, histopathology and overall survival were analysed according to Kaplan-Meier's method and Cox regression. The expression of SSTR-2a, CgA and synaptophysin was analysed in tumour specimens by immunohistochemistry, and semi-quantitatively scored as negative (< 5%), heterogeneously positive (5-30%) or strongly positive (> 30%). P53 was defined as normal when scored as heterogeneously positive (1-30%), and abnormal when negative (0%) or strongly positive (> 30%).
RESULTS: In multivariate analysis, better survival was observed among patients with heterogeneously positive p53 compared to strongly positive (p < 0.001). When dichotomised, tumours with a heterogeneously positive p53 vs. negative and strongly positive p53 also showed a significantly better survival (p = 0.002). Survival was significantly worse for negative CgA compared to heterogeneously positive CgA (p = 0.02). Strongly positive SSTR-2a expression was found in 26% of the 163 included patients. Well-differentiated morphology correlated with strong expression of SSTR-2a and CgA, and heterogeneously positive p53-staining, and was more frequent in pancreatic primaries. In pancreatic primaries, strongly positive SSTR-2a was associated with longer survival (univariate analysis, p = 0.02). A significantly lower Ki67 proliferation index was found in patients with a heterogeneously positive p53, a positive SSTR-2a and CgA expression.
CONCLUSION: Our results suggest that abnormal p53-expression is an independent negative prognostic marker in GEP-NEN with a Ki67-index > 20%. Patients with heterogeneously positive p53 had the best prognosis. SSTR-2a was a positive prognostic marker in pancreatic NEN. Negative CgA was associated with a significantly worse OS compared to heterogeneously positive CgA-expression in a multivariate sub-analysis. Lower Ki67 index correlated significantly with heterogeneously positive p53, positive SSTR-2a and CgA expression.

PMID: 31924180 [PubMed - in process]

Permalink for 'Can we differentiate histologic subtypes of neuroendocrine tumor liver metastases at a single phase contrast enhanced CT- correlation with Ga-68 DOTATATE PET/CT findings.'

Can we differentiate histologic subtypes of neuroendocrine tumor liver metastases at a single phase contrast enhanced CT- correlation with Ga-68 DOTATATE PET/CT findings.

Fetched: January 12th, 2020, 5:01am GMT

Can we differentiate histologic subtypes of neuroendocrine tumor liver metastases at a single phase contrast enhanced CT- correlation with Ga-68 DOTATATE PET/CT findings.

Br J Radiol. 2020 Jan 10;:20190735

Authors: Gulpinar B, Peker E, Soydal C, Araz M, Elhan AH

Abstract
OBJECTIVES: To assess the usefulness of a single-phase contrast enhanced CT to differentiate subtypes of NET liver metastases and to evaluate the correlation between CT features and Ga-68 DOTATATE PET/CT findings.
METHODS: Between December 2017 and April 2019 patients with liver metastases of neuroendocrine tumours who underwent CT and Ga-68 DOTATATE PET/CT were enrolled in the study.All patients involved in the study had undergone a standardized single-phase contrast-enhanced CT.Whole body PET/CT images were obtained with a combined PET/CT scanner.All CT images were retrospectively analysed by two radiologists.Enhancement patterns of lesions were assessed.For quantitative examination;CT attenuation values of metastatic lesions,liver parenchyma and aorta were measured using a freehand ROI and tumour-to-liver ratio [T-L = (Tumour - Liver) / Liver] and tumour-to-aorta ratio [T-A = (Tumour - Aorta) / Aorta] were calculated. The lesion with the highest Ga-68 DOTATATE uptake in the liver was used for calculations.The metabolic tumour volume (MTV), SUV max and SUV mean were calculated for the target liver lesion.
RESULTS: A total of 137 NET liver metastases divided into in three groups:49 (35.7%) pancreatic,60 (44.5%) gastroenteric and 26 (18.9%) lung NET liver metastases were analysed.Gastroenteric NET metastases often showed heterogeneous enhancement which was significantly higher than in the pancreas and lung NET liver metastases (p < 0.001).96.72% (n = 59) of the gastroenteric NET liver metastases were hypoattenuating whereas the most frequent presentation for the pancreatic group was hyperattenuation (63.26%,n = 31).The difference in enhancement patterns of the liver metastases was statistically significant (p < 0.001) with respect to the location of the primary tumour.For quantitative analysis;tumour CT values were significantly different between the groups (p < 0.001).The T-L ratio was statistically different between gastroenteric and pancreatic NET liver metastases and pancreatic and lung NETgroups (p < 0.001).The T-A ratio was significantly higher in the pancreatic NET metastases (p < 0.001).SUVmax,SUVmean and MTV values however were not significantly different between the subgroups.There was a weak positive correlation between T-L ratio and SUV meanvalues.
CONCLUSION: We noticed statistically significant differences in both qualitative and quantitative CT features between histologic subgroups of neuroendocrine tumour liver metastases at a single Phase contrast enhanced CT.
ADVANCES IN KNOWLEDGE: Our study will be the first in the literature which extensively focus on assessing the CT features of liver metastases of NETs at a single Phase CT and Ga-68DOTATATE PET/CT. As the different histological subtypes of NET liver metastases exhibit different clinical outcomes these features might help to identify the primary tumour to provide optimal treatment.

PMID: 31922897 [PubMed - as supplied by publisher]

A rare case of perivascular epithelioid cell tumor (PEComa) of the pancreas diagnosed by endoscopic ultrasound.

Fetched: January 12th, 2020, 5:01am GMT

A rare case of perivascular epithelioid cell tumor (PEComa) of the pancreas diagnosed by endoscopic ultrasound.

Endosc Int Open. 2020 Jan;8(1):E25-E28

Authors: Ulrich JD, Specht K, Schlitter AM, Ceyhan GO, Quante M, Schmid RM, Schlag C

Abstract
A 49-year-old woman consulted her general practitioner (GP) regarding epigastric pain that she had experienced for 2 months. Physical examination and laboratory results were unremarkable. An abdominal ultrasound indicated a solid pancreatic tumor, which was confirmed on subsequent CT and MRI. Endoscopic ultrasound (EUS) showed a well-defined heterogeneous, predominantly hypoechoic mass in the pancreatic body, so a neuroendocrine tumor (NET) was suspected. However, EUS-guided fine-needle aspiration (EUS-FNA) was performed and based on (immuno-)histochemical findings, the extremely rare diagnosis of a perivascular epithelioid cell tumor (PEComa) of the pancreas was made. Due to the malignant potential of pancreatic PEComas, laparoscopic left-sided pancreatectomy was performed. We present a case diagnosed by preoperative EUS-FNA highlighting the clinical and endosonographic features which help to distinguish it from its most important differential diagnosis, neuroendocrine tumors (NETs) of the pancreas.

PMID: 31921981 [PubMed]

Permalink for 'Application of Somatostatin, Chemotherapy Combined with TAE in Heterogeneous Glucagonoma Presented with Necrolytic Migratory Erythema.'

Application of Somatostatin, Chemotherapy Combined with TAE in Heterogeneous Glucagonoma Presented with Necrolytic Migratory Erythema.

Fetched: January 12th, 2020, 5:01am GMT

Application of Somatostatin, Chemotherapy Combined with TAE in Heterogeneous Glucagonoma Presented with Necrolytic Migratory Erythema.

Onco Targets Ther. 2019;12:11339-11344

Authors: Shen C, He J, Le X, Zheng L, Cao D

Abstract
Glucagonoma, a rare neuroendocrine tumor of the pancreas, which is often misdiagnosed because of non-characteristic clinical manifestations. In addition, the treatment has not been well established for this disease so far. We here report a case of glucagonoma previous misdiagnosed as recurrent erythema. In this case, necrolytic migratory erythema was the main clinical manifestation, and he received surgical resection after admission although with liver metastasis. Postoperative pathological results showed that the heterogeneity of proliferative index in primary (Ki-67: 5~10%) and metastatic (Ki-67: 25~30%) tumors were obviously observed. One month postoperatively, abdominal CT and MRI showed multiple liver metastasis (type III) again. Interestingly, the skin rash was obviously improved after treatment with somatostatin combined with chemotherapy (octreotide, temozolomide and capecitabine). Subsequently, the patient received transarterial embolization (TAE). Up to now, no progression was noted for liver metastasis. Due to its rarity, clinical diagnosis is challenging; thus, further understanding of the disease by clinicians is helpful for early diagnosis and treatment, so as to improve the prognosis of patients.

PMID: 31920326 [PubMed]

Synchronous NET and colorectal cancer development: a case report.

Fetched: January 12th, 2020, 5:01am GMT

Synchronous NET and colorectal cancer development: a case report.

Surg Case Rep. 2020 Jan 09;6(1):10

Authors: Yumoto S, Miyamoto Y, Akiyama T, Kiyozumi Y, Eto K, Hiyoshi Y, Nagai Y, Iwatsuki M, Baba Y, Iwagami S, Yoshida N, Baba H

Abstract
BACKGROUND: The incidence of synchronous gastrointestinal neuroendocrine tumors (GI-NETs) and colorectal cancer is very low.
CASE PRESENTATION: We present a 72-year-old man diagnosed with a rectal neuroendocrine tumor (NET) with multiple organ metastases and simultaneous sigmoid colon cancer. Although the NET was his prognostic factor, he underwent a laparoscopic sigmoidectomy at first because it was expected that the colon cancer would cause obstruction or bleeding during NET treatment. Subsequently, he started taking everolimus.
CONCLUSIONS: We should consider surgical resection of the synchronous cancer before systemic therapy for a GI-NET regardless of the difference in prognosis between synchronous tumors, if the cancer may impair the continuation of systemic therapy.

PMID: 31919616 [PubMed]

[A case of ectopic adrenocorticotropic hormone syndrome caused by thymoma].

Fetched: January 12th, 2020, 5:01am GMT

[A case of ectopic adrenocorticotropic hormone syndrome caused by thymoma].

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2019 Nov 28;44(11):1316-1320

Authors: Liu J, Zhong B, Zhang D

Abstract
Cushing's syndrome is a clinically common type of clinical syndrome caused by excessive glucocorticoids. It can be divided into adrenocorticotropic-dependent and independent types according to its etiology. A female patient with Cushing's syndrome is reported to have a clinical manifestation of mild full moon face, masculinization of androgen increase, deeper skin color, elevated blood pressure, and pulmonary infection. The cause is unknown. Radiographic examination indicated that pituitary tumor and adrenal tumors did not exist. Chest enhancement CT examination revealed that the lesion was in the thymus. Thoracoscopy was performed to remove the tumor. Since wound infection occurred after operation, a variety of antibiotics were used for anti-infective treatment, and the wound gradually healed. After 21 months of follow-up, the above symptoms disappeared completely and the prognosis was good in the near future. Postoperative pathological diagnosis was thymic neuroendocrine carcinoma. This is a typical case that the thymoma ectopically secrets adrenocorticotropic hormone, which leads to Cushing's syndrome, referring to ectopic adrenocorticotropic hormone syndrome.

PMID: 31919330 [PubMed - in process]

Transient Sox9 Expression Facilitates Progression to Castrate Resistant Prostate Cancer.

Fetched: January 12th, 2020, 5:01am GMT

Transient Sox9 Expression Facilitates Progression to Castrate Resistant Prostate Cancer.

Clin Cancer Res. 2020 Jan 09;:

Authors: Nouri M, Massah S, Caradec J, Lubik AA, Li N, Truong S, Lee AR, Fazli L, Ramnarine VR, Lovnicki JM, Moore J, Wang M, Foo J, Gleave ME, Hollier BG, Nelson CC, Dong X, Collins CC, Buttyan R

Abstract
PURPOSE: Metastatic prostate cancer (PCa) patients are increasingly presenting with treatment-resistant, androgen receptor-Negative/Low (AR-/Low) tumors, with or without neuroendocrine characteristics, in processes attributed to tumor cell plasticity. This plasticity has been modeled by Rb1/p53 knockdown/knockout and is accompanied by overexpression of the pluripotency factor, Sox2. Here we explore the role of the developmental transcription factor Sox9 in the process of PCa therapy response and tumor progression.
EXPERIMENTAL DESIGN: Unique PCa cell models that capture AR-/Low stem cell-like intermediates were analyzed for features of plasticity and the functional role of Sox9. Human PCa xenografts and tissue microarrays were evaluated for temporal alterations in Sox9 expression. The role of NF-κB pathway activity in Sox9 overexpression was explored.
RESULTS: PCa stem cell-like intermediates have reduced Rb1 and p53 protein expression and overexpress Sox2 as well as Sox9. Sox9 was required for spheroid growth, and overexpression increased invasiveness and neural features of PCa cells. Sox9 was transiently upregulated in castration-induced progression of PCa xenografts and was specifically overexpressed in neoadjuvant hormone therapy (NHT) treated patient tumors. High Sox9 expression in NHT-treated patients predicts biochemical recurrence. Finally, we link Sox9 induction to NF-κB dimer activation in PCa cells.
CONCLUSIONS: Developmentally reprogrammed PCa cell models recapitulate features of clinically-advanced prostate tumors including downregulated Rb1/p53 and overexpression of Sox2 with Sox9. Sox9 is a marker of a transitional state that identifies PCa cells under the stress of therapeutic assault and facilitates progression to therapy resistance. Its expression may index the relative activity of the NF-κB pathway.

PMID: 31919137 [PubMed - as supplied by publisher]

National Analysis of Patients With External Ear Melanoma in the United States.

Fetched: January 12th, 2020, 5:01am GMT

National Analysis of Patients With External Ear Melanoma in the United States.

J Craniofac Surg. 2019 Nov-Dec;30(8):e787-e790

Authors: Oliver JD, Boczar D, Sisti A, Huayllani MT, Restrepo DJ, Spaulding AC, Gabriel E, Bagaria S, Rinker BD, Forte AJ

Abstract
BACKGROUND: External ear melanoma (EEM) is a rare condition with controversies in the literature. We analyzed patients with EEM in the United States compared to other head and neck melanomas (OHNMs).
METHODS: The National Cancer Database (NCDB) was used to select patients with head and neck melanoma from January 1, 2004 to December 31, 2015. Mann-Whitney and χ tests were used to estimate statistical significance, and multivariate logistic regression to identify independent associations adjusted for confounders.
RESULTS: A total of 137,233 patients met the study criteria. Among them, 16,991 (12.4%) had EEM and 120,242 (87.6%) had OHNM. For patients with EEM, the mean (standard deviation) age was 66.26 (15.798) years. Most of the patients with EEM were men (85.5%), insured by Medicare (52.4%), and treated in Academic/Research Programs (47.7%) or Comprehensive Community Cancer Programs (32.3%). Most of the EEM tumors had invasive behavior (68.0%) were Stages 0 (30.3%) or I (40.3%), and were without ulceration (76.9%). Mean time to receive any treatment was 14.1 days for EEM compared with 14.6 days for OHNM (P < 0.001). We noticed a greater proportion of EEM in men (14.8%; adjusted odds ratio [aOR] 2.72 [2.605-2.852]; P < 0.001) compared to women (6.22%; reference). EEM was an independent factor for tumor Stage I (14.47%; aOR 1.61 [1.101-1.224], P < 0.001) and invasive behavior (13.86%; aOR 1.268 [1.15-1.389]; P < 0.001) compared to OHNM.
CONCLUSION: EEM was associated with higher odds of invasive behavior compared to OHNM. Furthermore, men were found to have a higher likelihood to develop EEM compared to women.

PMID: 31369498 [PubMed - indexed for MEDLINE]

The Application of Deep Learning in the Risk Grading of Skin Tumors for Patients Using Clinical Images.

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The Application of Deep Learning in the Risk Grading of Skin Tumors for Patients Using Clinical Images.

J Med Syst. 2019 Jul 13;43(8):283

Authors: Zhao XY, Wu X, Li FF, Li Y, Huang WH, Huang K, He XY, Fan W, Wu Z, Chen ML, Li J, Luo ZL, Su J, Xie B, Zhao S

Abstract
According to diagnostic criteria, skin tumors can be divided into three categories: benign, low degree and high degree malignancy. For high degree malignant skin tumors, if not detected in time, they can do serious harm to patients' health. However, in clinical practice, identifying malignant degree requires biopsy and pathological examination which is time costly. Furthermore, in many areas, due to the severe shortage of dermatologists, it's inconvenient for patients to go to hospital for examination. Therefore, an easy to access screening method of malignant skin tumors is needed urgently. Firstly, we spend 5 years to build a dataset which includes 4,500 images of 10 kinds of skin tumors. All instances are verified pathologically thus trustworthy; Secondly, we label each instance to be either low-risk, high-risk or dangerous in which Junctional nevus, Intradermal nevus, Dermatofibroma, Lipoma and Seborrheic keratosis are low-risk, Basal cell carcinoma, Bowen's disease and Actinic keratosis are high-risk, Squamous cell carcinoma and Malignant melanoma are dangerous; Thirdly, we apply the Xception architecture to build the risk degree classifier. The area under the curve (AUC) for three risk degrees reach 0.959, 0.919 and 0.947 respectively. To further evaluate the validity of the proposed risk degree classifier, we conduct a competition with 20 professional dermatologists. The results showed the proposed classifier outperforms dermatologists. Our system is helpful to patients in preliminary screening. It can identify the patients who are at risk and alert them to go to hospital for further examination.

PMID: 31300897 [PubMed - indexed for MEDLINE]

Phenotypic characterisation of immune cells associated with histological regression in cutaneous melanoma.

Fetched: January 12th, 2020, 5:01am GMT

Phenotypic characterisation of immune cells associated with histological regression in cutaneous melanoma.

Pathology. 2019 Aug;51(5):487-493

Authors: Osella-Abate S, Conti L, Annaratone L, Senetta R, Bertero L, Licciardello M, Caliendo V, Picciotto F, Quaglino P, Cassoni P, Ribero S

Abstract
Histological regression and tumour infiltrating lymphocytes represent an early sign of activation of the immune system against primary melanoma. The first phenomenon has been especially discussed in the literature because of its prognostic role, but no clear agreement on its evaluation has been reached. Immunotherapy of advanced stage melanoma has recently shown promising results; an improved understanding of the initial interplay between melanoma cells and the immune system would potentially help tailor treatment for patients. Seventy consecutive melanomas with regression were analysed to identify a prognostic cut-off value of regression extension. Then, we compared the immune infiltrate between regressed and not regressed areas of these regressed melanomas, assessing CD3, CD4, CD8, CD20, CD123, PD1 and FOXP3/CD25 expression. The immune infiltrate of these cases was further compared with 28 control melanomas without regression. A regression extension of 10% represented a reliable cut-off to distinguish two different risk categories in regressed melanomas. Regressed areas were less infiltrated by CD4/CD25, FOXP3/CD4 or PD1/CD4 compared to not regressed areas of each sample. These lymphocyte subsets are associated with anergy and hamper the immune CD8+ response towards the cancer cells. Moreover, the relevance of these findings was further supported by the observation that not regressed controls were significantly more infiltrated by these anergic immune cell subsets compared to the regressed cases. These results help understand the real meaning of regression in melanoma. Moreover, the association here identified between specific immunomodulatory immune cell subsets and regression could help in developing new therapeutic strategies.

PMID: 31266597 [PubMed - indexed for MEDLINE]

Prognostic value of cyclin A2 and B1 expression in lung carcinoids.

Fetched: January 12th, 2020, 5:01am GMT

Prognostic value of cyclin A2 and B1 expression in lung carcinoids.

Pathology. 2019 Aug;51(5):481-486

Authors: Brcic L, Heidinger M, Sever AZ, Zacharias M, Jakopovic M, Fediuk M, Maier A, Quehenberger F, Seiwerth S, Popper H

Abstract
Carcinoid classification in the lung is still based on morphological criteria. Although there are many studies investigating the role of Ki-67 proliferation index in the classification of lung neuroendocrine tumours, it is still not used in routine diagnostics. Interestingly, cyclins, which have a crucial role in controlling the cell cycle, have not been thoroughly studied in lung neuroendocrine tumours. The aim of our study was to investigate the correlation of cyclin A2 and B1 expression with prognosis, Ki-67 proliferation index, and carcinoid morphology. A cohort of 134 resected typical and atypical carcinoids was stained with antibodies against Ki-67, cyclin A2 and B1. The positive nuclear reaction was assessed in hot spot areas and expressed as the percentage of tumour cells. Univariate analyses found the highest relative hazard between low and high cyclin A2 expression both with respect to overall survival [hazard ratio (HR)=16; 95% confidence interval (CI) 4.8-51; p=0.0000054], and relapse (HR=8; 95% CI 3.1-21; p=0.00002). In multivariate analysis for overall survival cyclin A2 (HR=10; 95% CI 2.5->100; p=0.0082) and B1 (HR=6.5; 95% CI 1.5-35; p=0.02) remained significant when adjusted for other risk factors, whereas Ki-67 was no longer significant (HR=0.64; 95% CI 0.003-5.5; p=0.65). This suggests that Ki-67 is closer to conventional risk factors for survival than cyclin A2 and B1. Furthermore, the analysis revealed 4 mitoses per 2 mm2 as a more powerful prognostic cut-off than currently accepted 2 mitoses. We have clearly demonstrated that application of cyclin A2 and cyclin B1 might bring additional value regarding the overall and progression-free survival of patients with carcinoids of the lung.

PMID: 31230818 [PubMed - indexed for MEDLINE]

Association Between Urinary Catecholamine Excretion and Urine Volume.

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Association Between Urinary Catecholamine Excretion and Urine Volume.

Horm Metab Res. 2019 Aug;51(8):531-538

Authors: Haap M, Blaschka F, Lehmann R, Hoyer A, Müssig K

Abstract
Several confounders must be considered in the evaluation of urinary catecholamine excretion. However, literature is contradictory about potential confounders. The aim of the present study was to assess correlations between catecholamine excretion and anthropometric or clinical parameters with special attention to urine volume. A total of 967 24-h urinary catecholamine measurements were performed in 593 patients for diagnostic purposes. The indication for urine examination was suspicion of secondary hypertension, phaeochromocytoma, or paraganglioma. From the patients examined, 57% were females and 43% were males. The patients' age ranged between 15 and 87 years with a median [Q1; Q3] of 51 [39; 62] years. Seventy-eight percent of the patients suffered from hypertension. Seventy percent of patients took one or more antihypertensive drugs. The most commonly used drugs were ACE inhibitors (43%), while α-blockers (15%) were the least used drugs. Urinary excretion was between 500 and 11 950 ml/24 h with a median of 2200 [1600; 2685] ml/24 h. The median body mass index (BMI) was 26.7 [24.0; 30.4] kg/m2. The excretion of all catecholamines was greater in men than in women (all p<0.0001). Epinephrine (p=0.0026), dopamine (p<0.0001), and metanephrine (p=0.0106) excretion decreased with age. BMI was associated with urinary excretion of dopamine (p<0.0001), norepinephrine (p=0.0026), normetanephrine (p<0.0001), and homovanillylmandelic acid (HVMA; p=0.0251). Urine volume correlated with urinary dopamine (p=0.0127), metanephrine (p<0.0001), normetanephrine (p=0.0070), and HVMA (p<0.0028) excretion. In addition to the established associations between urinary catecholamine excretion and age, gender, and BMI in the present study, urinary catecholamine excretion correlated also with urine volume.

PMID: 31174227 [PubMed - indexed for MEDLINE]

Class 2 Gene Expression Profile of a Hemorrhagic Pigment Epithelial Detachment Misdiagnosed as Melanoma.

Fetched: January 12th, 2020, 5:01am GMT

Class 2 Gene Expression Profile of a Hemorrhagic Pigment Epithelial Detachment Misdiagnosed as Melanoma.

Ophthalmol Retina. 2019 05;3(5):453-455

Authors: Bellerive C, Binkley E, Singh AD

PMID: 31044741 [PubMed - indexed for MEDLINE]

Cure and survival of sporadic medullary thyroid carcinoma following systematic preoperative calcitonin screening.

Fetched: January 12th, 2020, 5:01am GMT

Cure and survival of sporadic medullary thyroid carcinoma following systematic preoperative calcitonin screening.

Langenbecks Arch Surg. 2019 Jun;404(4):411-419

Authors: Torresan F, Mian C, Cavedon E, Iacobone M

Abstract
BACKGROUND: The improvement in outcome of sporadic medullary thyroid carcinoma (MTC) during the last decades remains controversial, even if a trend toward a better prognosis has been recently proposed. This study was aimed to determine the time trend cure and survival rates in sporadic MTC according to the use of systematic preoperative calcitonin screening.
METHODS: Retrospective analysis of 178 sporadic MTC patients operated between 1980 and 2017 was performed. The impact of prognostic factors on cure and survival following the introduction of routine preoperative calcitonin screening in 2001 was evaluated according to the year of surgery.
RESULTS: Since 2001, a significant decline of node-positive tumors (from 56.1 to 34.7%) and advanced stage at diagnosis (stage III/IV from 56.1 to 34.7%) occurred, with a concomitant significant increase in cure rate (64.5% vs 38.6%; p = 0.0012) and survival (p < 0.05). At univariate analysis, the cure was achieved more frequently in more recently operated patients (64.5% vs 38.6%; p = 0.0012), in disease staging I/II (86.5% vs 13.5%; p < 0.0001), in patients undergoing preoperative calcitonin screening (63.8% vs 23.5%; p < 0.0001) and in the absence of lymph node metastases (86.5% vs 13.5%; p < 0.0001). At multivariate analysis, only preoperative calcitonin screening and stage at diagnosis turned out to be significant independent prognostic factors for cure and survival.
CONCLUSION: The outcome of sporadic MTC improved in the new millennium; diagnosis was achieved earlier, at a less advanced stage. Routine preoperative calcitonin screening may have contributed to improve cure and survival rates.

PMID: 30903267 [PubMed - indexed for MEDLINE]

Gamma Knife Radiosurgery for the Management of More Than 15 Cerebral Metastases.

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Gamma Knife Radiosurgery for the Management of More Than 15 Cerebral Metastases.

World Neurosurg. 2019 Jun;126:e989-e997

Authors: Bowden G, Faramand A, Niranjan A, Lunsford LD, Monaco E

Abstract
BACKGROUND: The number of metastases that can be treated safely and effectively with Gamma Knife stereotactic radiosurgery (SRS) remains controversial despite continuing evidence to support its expanded utilization. We endeavored to elucidate the survival outcomes for patients who presented with ≥15 brain metastases at the time of initial SRS.
METHODS: This retrospective analysis reviewed patients treated for ≥15 brain metastases originating from breast cancer, lung cancer, or melanoma. Ninety-three patients met the inclusion criteria. In this study, 3016 tumors were treated. The median number of tumors at the first SRS procedure was 23 (range, 15-67) for breast cancer, 21 (range, 15-48) for lung cancer, and 21 (range, 15-67) for melanoma. The mean aggregate metastases volume was 8.75 cm3 for breast, 6.89 cm3 for lung, and 9.98 cm3 for melanoma.
RESULTS: Patients with breast cancer, lung cancer, and melanoma had a median survival after diagnosis of brain metastases of 18.0, 9.4, and 6.3 months, respectively. The survival after SRS was 16 months for breast cancer, 4.6 months for lung cancer, and 3.1 months for melanoma. Patients with breast cancer had significantly longer survival than patients with lung cancer and melanoma after SRS (P = 0.001). A higher Karnofsky Performance Status score was associated with an increase in survival across all tumor types. Repeat SRS for local or distant progression was performed in 56% of patients with breast cancer, 35% of patients with lung cancer, and 24% of patients with melanoma.
CONCLUSIONS: SRS is an effective means of managing extensive brain metastases, particularly in patients with breast cancer. The primary tumor type, systemic disease, and performance status heavily influence survival outcomes.

PMID: 30876993 [PubMed - indexed for MEDLINE]

[Brachial plexus schwannoma as a reason for severest chronic shoulder pain, surgical management and follow up].

Fetched: January 12th, 2020, 5:01am GMT

[Brachial plexus schwannoma as a reason for severest chronic shoulder pain, surgical management and follow up].

Handchir Mikrochir Plast Chir. 2019 08;51(4):334-335

Authors: Wechselberger G, Koeninger F, Neureiter J, Heinrich K, Schwaiger K

PMID: 30703804 [PubMed - indexed for MEDLINE]

Permalink for 'Temporal Dynamics of Pseudoprogression After Gamma Knife Radiosurgery for Vestibular Schwannomas-A Retrospective Volumetric Study.'

Temporal Dynamics of Pseudoprogression After Gamma Knife Radiosurgery for Vestibular Schwannomas-A Retrospective Volumetric Study.

Fetched: January 12th, 2020, 5:01am GMT

Temporal Dynamics of Pseudoprogression After Gamma Knife Radiosurgery for Vestibular Schwannomas-A Retrospective Volumetric Study.

Neurosurgery. 2019 01 01;84(1):123-131

Authors: Breshears JD, Chang J, Molinaro AM, Sneed PK, McDermott MW, Tward A, Theodosopoulos PV

Abstract
BACKGROUND: The optimal observation interval after the radiosurgical treatment of a sporadic vestibular schwannoma, prior to salvage intervention, is unknown.
OBJECTIVE: To determine an optimal postradiosurgical treatment interval for differentiating between pseudoprogression and true tumor growth by analyzing serial volumetric data.
METHODS: This single-institution retrospective study included all sporadic vestibular schwannomas treated with Gamma Knife radiosurgery (Eketa AB, Stockholm, Sweden; 12-13 Gy) from 2002 to 2014. Volumetric analysis was performed on all available pre- and posttreatment magnetic resonance imaging scans. Tumors were classified as "stable/decreasing," "transient enlargement", or "persistent growth" after treatment, based on incrementally increasing follow-up durations.
RESULTS: A total of 118 patients included in the study had a median treatment tumor volume of 0.74 cm3 (interquartile range [IQR] = 0.34-1.77 cm3) and a median follow-up of 4.1 yr (IQR = 2.6-6.0 yr). Transient tumor enlargement was observed in 44% of patients, beginning at a median of 1 yr (IQR = 0.6-1.4 yr) posttreatment, with 90% reaching peak volume within 3.5 yr, posttreatment. Volumetric enlargement resolved at a median of 2.4 yr (IQR 1.9-3.6 yr), with 90% of cases resolved at 6.9 yr. Increasing follow-up revealed that many of the tumors initially enlarging 1 to 3 yr after stereotactic radiosurgery ultimately begin to shrink on longer follow-up (45% by 4 yr, 77% by 6 yr).
CONCLUSION: Tumor enlargement within ∼3.5 yr of treatment should not be used as a sole criterion for salvage treatment. Patient symptoms and tumor size must be considered, and giving tumors a chance to regress before opting for salvage treatment may be worthwhile.

PMID: 29518221 [PubMed - indexed for MEDLINE]

Sunbeds and Melanoma Risk: Many Open Questions, Not Yet Time to Close the Debate.

Fetched: January 11th, 2020, 5:01am GMT

Sunbeds and Melanoma Risk: Many Open Questions, Not Yet Time to Close the Debate.

Anticancer Res. 2020 Jan;40(1):501-509

Authors: Reichrath J, Lindqvist PG, Pilz S, März W, Grant WB, Holick MF, DE Gruijl FR

Abstract
BACKGROUND: Intensive scientific debate is ongoing about whether moderate solarium use increases melanoma risk. The authors of some recent publications demand the debate be closed and propose "actions against solarium use for skin cancer prevention" because new studies have convincingly demonstrated causality. This minireview aims to investigate whether those demands are sufficiently supported by present scientific knowledge and comply with the principles of evidence-based medicine.
MATERIALS AND METHODS: We performed a systematic literature search (through June 2019; PubMed, ISI Web of Science) to identify publications investigating how solarium use affects melanoma risk.
RESULTS: We found no studies that demonstrate a causal relationship between moderate solarium use and melanoma risk. Results of cohort and case-control studies published to date, including recent investigations, do not prove causality, and randomized controlled trials providing unequivocal proof are still lacking. Moreover, the overall quality of observational studies is low as a result of severe limitations (including unobserved or unrecorded confounding), possibly leading to bias. We also disagree with recent claims that Hill's criteria for the epidemiological evidence of a causal relationship between a potential causal factor and an observed effect are fulfilled in regard to the conclusion that moderate solarium use per se would increase melanoma risk Conclusion: Current scientific knowledge does not demonstrate a causal relationship between moderate solarium use and melanoma risk. Therefore, the debate is not closed.

PMID: 31892605 [PubMed - indexed for MEDLINE]

Relevance of Vitamin D in Melanoma Development, Progression and Therapy.

Fetched: January 11th, 2020, 5:01am GMT

Relevance of Vitamin D in Melanoma Development, Progression and Therapy.

Anticancer Res. 2020 Jan;40(1):473-489

Authors: Brożyna AA, Hoffman RM, Slominski AT

Abstract
Melanoma is one of the most lethal types of skin cancer, with a poor prognosis once the disease enters metastasis. The efficacy of currently available treatment schemes for advanced melanomas is low, expensive, and burdened by significant side-effects. Therefore, there is a need to develop new treatment options. Skin cells are able to activate vitamin D via classical and non-classical pathways. Vitamin D derivatives have anticancer properties which promote differentiation and inhibit proliferation. The role of systemic vitamin D in patients with melanoma is unclear as epidemiological studies are not definitive. In contrast, experimental data have clearly shown that vitamin D and its derivatives have anti-melanoma properties. Furthermore, molecular and clinicopathological studies have demonstrated a correlation between defects in vitamin D signaling and progression of melanoma and disease outcome. Therefore, adequate vitamin D signaling can play a role in the treatment of melanoma.

PMID: 31892603 [PubMed - indexed for MEDLINE]

Permalink for 'Tumor-specific design of PEGylated gadolinium-based nanoscale particles: Facile synthesis, characterization, and improved magnetic resonance imaging of metastasis lung cancer.'

Tumor-specific design of PEGylated gadolinium-based nanoscale particles: Facile synthesis, characterization, and improved magnetic resonance imaging of metastasis lung cancer.

Fetched: January 11th, 2020, 5:01am GMT

Tumor-specific design of PEGylated gadolinium-based nanoscale particles: Facile synthesis, characterization, and improved magnetic resonance imaging of metastasis lung cancer.

J Photochem Photobiol B. 2020 Jan;202:111669

Authors: Sui Y, Li Y, Li Y, Jin H, Zheng Y, Huang W, Chen S

Abstract
Herein we report the synthesis and characterization of the antifouling Gadolinium oxide (Gd2O3) nanoparticles (NPs) modified with PEG with improved biocompatibility for MR imaging purposes. In this report, using the solvothermal decomposition of Gadolinium (III) in the presence of Na3cit, monitored by surface modification with PEG and L-Cys. The synthesized nanoparticles were confirmed by the TEM, DLS and UV-Visible spectroscopy. The morphological results show normal distance across of the flawless Gd2O3-PEG-Cys-NPs show 7.9 ± 0.4 nm, discretely, with a thin size exchange. This infers the surface adjustment does not obviously alteration the center size of the Gd2O3-NPs when contrasted with the perfect sodium citrate-balanced out Gd2O3-NPs. The Gd2O3-PEG-L-Cys-NPs are highly stable at room temperature, water dispersible and importantly less cytotoxic at high concentration of the NPs. The T1-weighted MR phantasm readings evidentially displayed that the formed PEG coated Gd2O3-PEG and Gd2O3-PEG-Cys-NPs with and without Cys may be performed as the promising T1-weighted MR imaging. The NPs displays no signs of toxicity against the human blood, which represents the biocompatibility for the human medicine applications. The Gd2O3-PEG-Cys-NPs shows relatively, high r1 acceptable cytocompatibility, target specific cancer cells and activate the dual mode MR imaging of lung metastasis cancer model in vitro. The development of versatile zwitterion functionalized Gd2O3 may be promising as an active nanoparticle probe for improved multi-model of MR imaging agents for various cancer diseases.

PMID: 31739258 [PubMed - indexed for MEDLINE]

Anti-TNF, a magic bullet in cancer immunotherapy?

Fetched: January 11th, 2020, 5:01am GMT

Anti-TNF, a magic bullet in cancer immunotherapy?

J Immunother Cancer. 2019 11 14;7(1):303

Authors: Montfort A, Dufau C, Colacios C, Andrieu-Abadie N, Levade T, Filleron T, Delord JP, Ayyoub M, Meyer N, Ségui B

Abstract
Immune checkpoint blockers (ICB) have revolutionized cancer therapy. However, complete response is observed in a minority of patients and most patients develop immune-related adverse events (irAEs). These include colitis, which can be treated with anti-tumor necrosis factor (TNF) antibodies such as Infliximab. In a recent issue of the Journal for ImmunoTherapy of Cancer, Badran et al. reported that co-administering Infliximab together with ICB to five cancer patients prevents colitis recurrence, with four of them exhibiting overall disease stability. The basis for this treatment strategy stemmed from our pre-clinical demonstration that TNF contributes to resistance to anti-PD-1 therapy. In agreement with this concept, we have shown that TNF blockers improve the anti-tumor therapeutic activity of ICB in mice and based on these findings we are currently evaluating the combination in melanoma patients enrolled in the TICIMEL clinical trial. Herein, (i) we discuss the scientific rationale for combining anti-TNF and ICB in cancer patients, (ii) comment on the paper published by Badran et al. and (iii) provide the TICIMEL clinical trial design.

PMID: 31727152 [PubMed - indexed for MEDLINE]

Diagnostic Accuracy of Computed Tomography to Exclude Pheochromocytoma: A Systematic Review, Meta-analysis, and Cost Analysis.

Fetched: January 11th, 2020, 5:01am GMT

Diagnostic Accuracy of Computed Tomography to Exclude Pheochromocytoma: A Systematic Review, Meta-analysis, and Cost Analysis.

Mayo Clin Proc. 2019 10;94(10):2040-2052

Authors: Buitenwerf E, Berends AMA, van Asselt ADI, Korteweg T, Greuter MJW, Veeger NJM, Links TP, Dullaart RPF, Kerstens MN

Abstract
OBJECTIVES: To assess the diagnostic accuracy of unenhanced computed tomography (CT) attenuation values to exclude a pheochromocytoma in the diagnostic work-up of patients with an adrenal incidentaloma and to model the associated difference in diagnostic costs.
METHODS: The MEDLINE and Embase databases were searched from indexing to September 27, 2018, and studies reporting the proportion of pheochromocytomas on either side of the 10-Hounsfield unit (HU) threshold on unenhanced CT were included. The pooled proportion of pheochromocytomas with an attenuation value greater than 10 HU was determined, as were the modeled financial costs of the current and alternative diagnostic approaches.
RESULTS: Of 2957 studies identified, 31 were included (N=1167 pheochromocytomas). Overall risk of bias was low. Heterogeneity was not observed between studies (Q=11.5, P=.99, I2=0%). The pooled proportion of patients with attenuation values greater than 10 HU was 0.990 (95% CI, 0.984-0.995). The modeled financial costs using the new diagnostic approach were €55 (∼$63) lower per patient.
CONCLUSION: Pheochromocytomas can be reliably ruled out in the case of an adrenal lesion with an unenhanced CT attenuation value of 10 HU or less. Therefore, determination of metanephrine levels can be restricted to adrenal tumors with an unenhanced CT attenuation value greater than 10 HU. Implementing this novel diagnostic strategy is cost-saving.

PMID: 31515105 [PubMed - indexed for MEDLINE]

DNA Methylation Module Network-Based Prognosis and Molecular Typing of Cancer.

Fetched: January 11th, 2020, 5:01am GMT

DNA Methylation Module Network-Based Prognosis and Molecular Typing of Cancer.

Genes (Basel). 2019 07 28;10(8):

Authors: Cui ZJ, Zhou XH, Zhang HY

Abstract
Achieving cancer prognosis and molecular typing is critical for cancer treatment. Previous studies have identified some gene signatures for the prognosis and typing of cancer based on gene expression data. Some studies have shown that DNA methylation is associated with cancer development, progression, and metastasis. In addition, DNA methylation data are more stable than gene expression data in cancer prognosis. Therefore, in this work, we focused on DNA methylation data. Some prior researches have shown that gene modules are more reliable in cancer prognosis than are gene signatures and that gene modules are not isolated. However, few studies have considered cross-talk among the gene modules, which may allow some important gene modules for cancer to be overlooked. Therefore, we constructed a gene co-methylation network based on the DNA methylation data of cancer patients, and detected the gene modules in the co-methylation network. Then, by permutation testing, cross-talk between every two modules was identified; thus, the module network was generated. Next, the core gene modules in the module network of cancer were identified using the K-shell method, and these core gene modules were used as features to study the prognosis and molecular typing of cancer. Our method was applied in three types of cancer (breast invasive carcinoma, skin cutaneous melanoma, and uterine corpus endometrial carcinoma). Based on the core gene modules identified by the constructed DNA methylation module networks, we can distinguish not only the prognosis of cancer patients but also use them for molecular typing of cancer. These results indicated that our method has important application value for the diagnosis of cancer and may reveal potential carcinogenic mechanisms.

PMID: 31357729 [PubMed - indexed for MEDLINE]

Immune Checkpoint Inhibitor Toxicities.

Fetched: January 11th, 2020, 5:01am GMT

Immune Checkpoint Inhibitor Toxicities.

Mayo Clin Proc. 2019 07;94(7):1321-1329

Authors: Marin-Acevedo JA, Chirila RM, Dronca RS

Abstract
Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.

PMID: 31272574 [PubMed - indexed for MEDLINE]

TNF-Alpha Inhibition and Other Immunosuppressants in the Development of Uveal and Cutaneous Melanoma.

Fetched: January 11th, 2020, 5:01am GMT

TNF-Alpha Inhibition and Other Immunosuppressants in the Development of Uveal and Cutaneous Melanoma.

Mayo Clin Proc. 2019 07;94(7):1287-1295

Authors: Damento GM, Pulido JS, Abbott BA, Hodge DO, Dalvin LA

Abstract
OBJECTIVE: To investigate an association between tumor necrosis factors-alpha (TNFα) inhibitors or other immunosuppressants and the development of uveal and cutaneous melanoma.
PATIENTS AND METHODS: We performed a retrospective incidence and case-control analysis of patients in Olmsted County, MN, who were diagnosed with uveal or cutaneous melanoma from January 1, 2000, to December 31, 2014. Incidence was adjusted by age and gender to the 2010 US white population. Controls were matched by sex and age to cases at time of diagnosis of melanoma.
RESULTS: There were 1221 cases of melanoma (33 uveal, 1188 cutaneous). Combined incidence of uveal and cutaneous melanoma per 100,000 person-years varied by gender (male > female), age (older > younger), and time period: 2010 to 2014 (77.9, 95% confidence interval [CI], 71.1-84.7) ≈ 2005 to 2009 (78.0, 95% CI, 70.9-85.0) > 2000 to 2004 (42.5, 95% CI, 36.9-48.1, P<.001). TNFa inhibitor prescription was not associated with significantly increased risk of melanoma vs controls (1.06% vs 0.41%, P=.06). Immunosuppressive agents, high-dose corticosteroids, and topical immunosuppressants were associated with melanoma (odds ratio [OR] 1.42 CI, 1.03-1.95, 3.30 CI, 2.44-4.48, and 1.87 CI, 1.06-3.28, respectively). An increased number of patients with uveal melanoma received immune modulating agents vs controls, but this was not statistically significant (P=.36). Autoimmune disease itself was not correlated with melanoma (P=.73).
CONCLUSION: Exposure to immunosuppressive agents is associated with melanoma. TNFa inhibition and autoimmune disease alone do not significantly increase risk of melanoma. In patients receiving immunosuppressive treatments, physicians should consider monitoring with dilated ophthalmic and full-body skin examinations. Further studies are needed to assess the impact of TNFa inhibitors on development of melanoma, particularly in uveal melanoma.

PMID: 31272570 [PubMed - indexed for MEDLINE]

The Patient Speaks: Importance of Patient Perspectives in Clinical Decision-Making.

Fetched: January 11th, 2020, 5:01am GMT

The Patient Speaks: Importance of Patient Perspectives in Clinical Decision-Making.

Ann Surg Oncol. 2019 Sep;26(9):2665-2666

Authors: McKinley SK, Boland GM

PMID: 31250344 [PubMed - indexed for MEDLINE]

Permalink for 'Emodin, as a mitochondrial uncoupler, induces strong decreases in adenosine triphosphate (ATP) levels and proliferation of B16F10 cells, owing to their poor glycolytic reserve.'

Emodin, as a mitochondrial uncoupler, induces strong decreases in adenosine triphosphate (ATP) levels and proliferation of B16F10 cells, owing to their poor glycolytic reserve.

Fetched: January 11th, 2020, 5:01am GMT

Emodin, as a mitochondrial uncoupler, induces strong decreases in adenosine triphosphate (ATP) levels and proliferation of B16F10 cells, owing to their poor glycolytic reserve.

Genes Cells. 2019 Aug;24(8):569-584

Authors: Sugiyama Y, Shudo T, Hosokawa S, Watanabe A, Nakano M, Kakizuka A

Abstract
Many types of cancer cells show a characteristic increase in glycolysis, which is called the "Warburg effect." By screening plant extracts, we identified one that decreases cellular adenosine triphosphate (ATP) levels and suppresses proliferation of malignant melanoma B16F10 cells, but not of noncancerous MEF cells. We showed that its active ingredient is emodin, which showed strong antiproliferative effects on B16F10 cells both in vitro and in vivo. Moreover, we also found that emodin can function as a mitochondrial uncoupler. Consistently, three known mitochondrial uncouplers also displayed potent antiproliferative effects and preferential cellular ATP reduction in B16F10 cells, but not in MEF cells. These uncouplers provoked comparable mitochondrial uncoupling in both cell types, but they manifested dramatically different cellular effects. Namely in MEF cells, these uncouplers induced three to fivefold increases in glycolysis from the basal state, and this compensatory activation appeared to be responsible for the maintenance of cellular ATP levels. In contrast, B16F10 cells treated with the uncouplers showed less than a twofold enhancement of glycolysis, which was not sufficient to compensate for the decrease of ATP production. Together, these results raise the possibility that uncouplers could be effective therapeutic agents specifically for cancer cells with prominent "Warburg effect."

PMID: 31234244 [PubMed - indexed for MEDLINE]

The personal touch: does the communication method affect response to melanoma genetic risk?

Fetched: January 11th, 2020, 5:01am GMT

The personal touch: does the communication method affect response to melanoma genetic risk?

Br J Dermatol. 2019 06;180(6):1288-1289

Authors: McInerney-Leo AM, Finnane A

PMID: 31157440 [PubMed - indexed for MEDLINE]

[Usefulness of endoscopic ultrasound guided elastography in the assessment of solid pancreatic lesions].

Fetched: January 11th, 2020, 5:01am GMT

[Usefulness of endoscopic ultrasound guided elastography in the assessment of solid pancreatic lesions].

Rev Gastroenterol Peru. 2019 Jan-Mar;39(1):38-44

Authors: Chacaltana Mendoza A, Jerez Lanza VF, Llatas Perez J, Li Salvatierra B, Vera Calderon A

Abstract
INTRODUCTION: endoscopic ultrasonography (EUS) elastography is considered a useful tool for the evaluation of solid pancreatic lesions (SPL).
OBJECTIVE: The aim of our study was to evaluate the diagnostic performance of elastography in patients with SPL.
MATERIAL AND METHODS: A prospective, cross-sectional study was performed at the Rebagliati Hospital between July 2017 and June 2018. Patients with a diagnosis of SPL and echoendoscopic study, elastography and FNA were included. Qualitative and quantitative elastography: strain ratio (SR) and strain histogram, were performed and analyzed with histopathological results. The diagnostic accuracy of EUS elastography in detecting malignancy was calculated using receiver operating curve analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for the detection of malignancy were calculated.
RESULTS: Out of 832 EUS examinations performed, 46 patients with SPL (mean age, 64.6 years; 29 women) were included in the study. Pancreatic adenocarcinoma was diagnosed in 36 cases. In qualitative elastography, score 3 was most frequent (n = 39, 84.8%) with sensitivity, specificity and accuracy of 88.9%, 30% and 76.1%, respectively, for predict adenocarcinoma. A strain ratio of 15 or higher (100% sensitivity, 66.7% specificity and 97.8% accuracy) and a histogram of less than 49 (66.7% sensitivity, 97.6% specificity and 95.6% accuracy) predicts malignancy in SPL, with area under a ROC curve of 0.941 (95% CI, 0.82 - 1.0).
CONCLUSIONS: EUS elastography provides information to predict the malignant nature of the pancreatic lesion. In our study, the elastographic detection of a score 3, SR≥15 or a histogram <49 predicts the presence of malignancy in LSP.

PMID: 31042235 [PubMed - indexed for MEDLINE]

Permalink for 'Germline large deletion of BAP1 and decreased expression in non-tumor choroid in uveal melanoma patients with high risk for inherited cancer.'

Germline large deletion of BAP1 and decreased expression in non-tumor choroid in uveal melanoma patients with high risk for inherited cancer.

Fetched: January 11th, 2020, 5:01am GMT

Germline large deletion of BAP1 and decreased expression in non-tumor choroid in uveal melanoma patients with high risk for inherited cancer.

Genes Chromosomes Cancer. 2019 09;58(9):650-656

Authors: Boru G, Grosel TW, Pilarski R, Stautberg M, Massengill JB, Jeter J, Singh A, Marino MJ, McElroy JP, Davidorf FH, Cebulla CM, Abdel-Rahman MH

Abstract
Uveal melanoma (UM) is the most common phenotype in patients with germline BAP1 mutation. This study aimed to identify selection criteria for BAP1 germline testing and assessed the role of large deletion/duplication and epigenetic inactivation. One hundred seventy-two UM patients with high risk of hereditary cancer were included. Germline variants in BAP1 were assessed by direct sequencing and large deletion/duplication by multiplex ligation-dependent probe amplification. BAP1 expression in unaffected choroid tissue from a patient with UM was assessed by quantitative RT-PCR and methylation by pyrosequencing. Twenty-eight patients had one or more germline sequence variants in BAP1; seven of these were pathogenic. One hundred forty patients were assessed for large deletion/duplication and in one BAP1 whole gene deletion was detected. In total, eight patients (4.7%) had pathogenic alterations in BAP1 with the highest frequencies of in patients with a personal/family history of ≥2 BAP1-related cancers 6/16 (38%), age of onset <35 years 4/21 (19%) and familial UM 6/34 (18%). One of 19 non-tumor choroid tissues tested showed uncharacteristically low expression as compared to the controls decrease in BAP1 RNA expression but no evidence of constitutional promotor hypermethylation was detected. UM patients with a strong personal or family history of cancers associated with BAP1, early age of onset and familial UM should be assessed for germline variants in BAP1, including large deletions.

PMID: 30883995 [PubMed - indexed for MEDLINE]

Renal Cell Carcinoma with Primary Presentation via Metastasis to the Trigeminal Ganglion.

Fetched: January 11th, 2020, 5:01am GMT

Renal Cell Carcinoma with Primary Presentation via Metastasis to the Trigeminal Ganglion.

World Neurosurg. 2019 06;126:30-36

Authors: Casabella AM, Kiyofuji S, Perry A, Graffeo CS, Eschbacher KL, Link MJ

Abstract
BACKGROUND: Renal cell carcinoma (RCC) accounts for ∼8% of all brain metastatic disease; however, spread to the cranial nerves and their ganglia is uncommon. To the best of our knowledge, we report the first case of RCC metastatic to Meckel's cave, which was diagnosed secondary to new trigeminal sensory loss.
METHODS: A 45-year-old man had presented with acute-onset right V3 numbness. Magnetic resonance imaging demonstrated contrast enhancement of the ipsilateral V3, extending from its root at the Gasserian ganglion to the foramen ovale.
RESULTS: He elected for observation, and his symptoms resolved over several weeks. At the scheduled, routine 3-month follow-up examination, he reported symptomatic relapse with new concomitant hyperesthetic/neuropathic pain. Magnetic resonance imaging demonstrated interval enlargement of the enhancing lesion in an atypical pattern, potentially consistent with trigeminal schwannoma versus meningioma, and operative resection was recommended.
CONCLUSION: We have reported a case of RCC presenting with numbness via metastatic spread to Meckel's cave. Although uncommon, metastasis is an important diagnostic consideration for enhancing cranial nerve lesions. Our case has demonstrated that, although a history of malignancy, multiple lesions, or systemic/constitutional symptoms are typical, rare cases can demonstrate isolated central nervous system findings. Thus, short-term radiographic surveillance is indicated if the diagnosis of an intracranial or cranial nerve mass lesion is equivocal.

PMID: 30844522 [PubMed - indexed for MEDLINE]

Effects of Oncogenic Gαq and Gα11 Inhibition by FR900359 in Uveal Melanoma.

Fetched: January 11th, 2020, 5:01am GMT

Effects of Oncogenic Gαq and Gα11 Inhibition by FR900359 in Uveal Melanoma.

Mol Cancer Res. 2019 04;17(4):963-973

Authors: Lapadula D, Farias E, Randolph CE, Purwin TJ, McGrath D, Charpentier TH, Zhang L, Wu S, Terai M, Sato T, Tall GG, Zhou N, Wedegaertner PB, Aplin AE, Aguirre-Ghiso J, Benovic JL

Abstract
Uveal melanoma is the most common intraocular tumor in adults and often metastasizes to the liver, leaving patients with few options. Recurrent activating mutations in the G proteins, Gαq and Gα11, are observed in approximately 93% of all uveal melanomas. Although therapeutic intervention of downstream Gαq/11 targets has been unsuccessful in treating uveal melanoma, we have found that the Gαq/11 inhibitor, FR900359 (FR), effectively inhibits oncogenic Gαq/11 signaling in uveal melanoma cells expressing either mutant Gαq or Gα11. Inhibition of oncogenic Gαq/11 by FR results in cell-cycle arrest and induction of apoptosis. Furthermore, colony formation is prevented by FR treatment of uveal melanoma cells in 3D-cell culture, providing promise for future in vivo studies. This suggests direct inhibition of activating Gαq/11 mutants may be a potential means of treating uveal melanoma. IMPLICATIONS: Oncogenic Gαq/11 inhibition by FR900359 may be a potential treatment option for those with uveal melanoma.

PMID: 30567972 [PubMed - indexed for MEDLINE]

Permalink for 'Molecular Profiling of Pheochromocytoma and Abdominal Paraganglioma Stratified by the PASS Algorithm Reveals Chromogranin B as Associated With Histologic Prediction of Malignant Behavior.'

Molecular Profiling of Pheochromocytoma and Abdominal Paraganglioma Stratified by the PASS Algorithm Reveals Chromogranin B as Associated With Histologic Prediction of Malignant Behavior.

Fetched: January 11th, 2020, 5:01am GMT

Molecular Profiling of Pheochromocytoma and Abdominal Paraganglioma Stratified by the PASS Algorithm Reveals Chromogranin B as Associated With Histologic Prediction of Malignant Behavior.

Am J Surg Pathol. 2019 03;43(3):409-421

Authors: Stenman A, Svahn F, Hojjat-Farsangi M, Zedenius J, Söderkvist P, Gimm O, Larsson C, Juhlin CC

Abstract
Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGL, are believed to exhibit malignant potential-but only subsets of cases will display full-blown malignant properties. The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) algorithm is a proposed histologic system to detect potential for aggressive behavior, but little is known regarding the coupling to underlying molecular genetics. In this study, a total of 92 PPGLs, previously characterized for susceptibility gene status and mRNA expressional profiles, were histologically assessed using the PASS criteria. A total of 32/92 PPGLs (35%) exhibited a PASS score ≥4, including all 8 cases with malignant behavior (7 with known metastases and 1 with extensively infiltrative local recurrence). Statistical analyzes between expressional data and clinical parameters as well as individual PASS criteria yielded significant associations to Chromogranin B (CHGB), BRCA2, HIST1H3B, BUB1B, and RET to name a few, and CHGB had the strongest correlation to both PASS and metastasis/local recurrence of all analyzed genes. Evident CHGB downregulation was observed in PPGLs with high PASS and overtly malignant behavior, and was also associated with shorter disease-related survival. This finding was validated using quantitative real-time polymerase chain reaction, in which CHGB expression correlated with both PASS and metastasis/local recurrence with consistent findings obtained in the TCGA cohort. Moreover, immunohistochemical analyses of subsets of tumors showed a correlation between high PASS scores and negative or weak CHGB protein expression. Patients with PPGLs obtaining high PASS scores postoperatively, also exhibited low preoperative plasma levels of CHGB. These data collectively point out CHGB as a possible preoperative and postoperative marker for PPGLs with potential for aggressive behavior.

PMID: 30451732 [PubMed - indexed for MEDLINE]

Permalink for 'Gastroenteropancreatic neuroendocrine neoplasms and inflammation: A complex cross-talk with relevant clinical implications.'

Gastroenteropancreatic neuroendocrine neoplasms and inflammation: A complex cross-talk with relevant clinical implications.

Fetched: January 11th, 2020, 5:01am GMT

Gastroenteropancreatic neuroendocrine neoplasms and inflammation: A complex cross-talk with relevant clinical implications.

Crit Rev Oncol Hematol. 2019 Dec 23;146:102840

Authors: Vitale G, Carra S, Ferraù F, Guadagno E, Faggiano A, Colao A, NIKE

Abstract
Neuroendocrine neoplasms (NENs) are a group of tumors originating from the neuroendocrine system. They mainly occur in the digestive system and the respiratory tract. It is well-know a strict interaction between neuroendocrine system and inflammation, which can play an important role in NEN carcinogenesis. Inflammatory mediators, which are produced by the tumor microenvironment, can favor cancer induction and progression, and can promote immune editing. On the other hand, a balanced immune system represents a relevant step in cancer prevention through the elimination of dysplastic and cancer cells. Therefore, an inflammatory response may be both pro- and anti-tumorigenic. In this review, we provide an overview concerning the complex interplay between inflammation and gastroenteropancreatic NENs, focusing on the tumorigenesis and clinical implications in these tumors.

PMID: 31918344 [PubMed - as supplied by publisher]

Permalink for 'Mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after trastuzumab-based chemotherapy for HER2-positive gastric cancer: a case report.'

Mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after trastuzumab-based chemotherapy for HER2-positive gastric cancer: a case report.

Fetched: January 11th, 2020, 5:01am GMT

Mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after trastuzumab-based chemotherapy for HER2-positive gastric cancer: a case report.

Surg Case Rep. 2020 Jan 08;6(1):5

Authors: Nagata H, Tsujimoto H, Yaguchi Y, Kouzu K, Itazaki Y, Ishibashi Y, Tsuchiya S, Sugihara T, Ito N, Harada M, Nomura S, Utsumi Y, Shimazaki H, Kishi Y, Ueno H

Abstract
BACKGROUND: Trastuzumab (T-mab)-based chemotherapy is a standard regimen for human epithelial growth factor 2 (HER2)-positive gastric cancer. However, some patients have demonstrated a change in HER2 status after T-mab-based treatment of breast cancer. We report a rare case of mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after T-mab-based chemotherapy for HER2-positive gastric cancer.
CASE PRESENTATION: A 60-year-old man presented with a mass of the upper abdomen, which was diagnosed as adenocarcinoma with a HER2 score of 3+ by endoscopic biopsy. He received seven cycles of combination chemotherapy with capecitabine, cisplatin, and T-mab. Subsequently, he underwent open total gastrectomy, distal pancreatosplenectomy, and extended left hepatic lobectomy as a conversion surgery. The surgically resected specimen demonstrated both adenocarcinoma and neuroendocrine components; therefore, it was diagnosed as HER2-negative mixed adenoneuroendocrine carcinoma. Although the patient received additional chemotherapy, multiple liver metastases appeared at 3 months postoperatively and he died at 6 months postoperatively because of the rapidly progressing metastatic tumor.
CONCLUSIONS: We encountered a rare case of rapidly progressive mixed adenoneuroendocrine carcinoma that was negative for HER2 expression after T-mab treatment combined with chemotherapy.

PMID: 31916037 [PubMed]

[Gastrointestinal glomus tumors: a clinicopathological analysis of fifteen cases].

Fetched: January 11th, 2020, 5:01am GMT

[Gastrointestinal glomus tumors: a clinicopathological analysis of fifteen cases].

Zhonghua Bing Li Xue Za Zhi. 2020 Jan 08;49(1):22-27

Authors: Ma YH, Li P, Jiang GZ, Jin RJ, Li WC

Abstract
Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of gastrointestinal glomus tumors (GIGT). Methods: Totally 15 cases of GIGT were collected at the First Affiliated Hospital, Zhengzhou University, from January 2011 to June 2018. The clinicopathological features, immunophenotype, BRAF V600E mutation and prognosis were retrospectively analyzed. Results: The 15 patients' age ranged from 37 to 59 years(median 49 years, mean 50 years). Eleven patients presented with intermittent abdominal pain and distention, three showed antral space-occupying lesions at physical examination, and one had abdominal pain accompanied by fecal blood. Fourteen tumors were located in the stomach, and one was in the ileum. Imaging showed the gastric glomus tumors were located in the submucosal layer with obvious enhancement in the arterial phase, and the ileum glomus tumor involved the whole layer of intestinal wall causing luminal obstruction. The maximum diameters of the tumors ranged from 1.5 to 3.0 cm (mean 2.3 cm). Grossly, the gastric glomus tumors were solid. Microscopically, the gastric glomus tumors were mostly located in the muscularispropria layer and were vascular. The tumor boundary was distinct but without capsule formation. The tumor cells were round or oval, and showed perivascular hemangiopericytoma-like or solid nest-like structures. The tumor cells were mildly pleomorphic, with rare mitosis and no necrosis. Two tumors had focal calcification, two showed mucosal invasion, two showed vascular invasion and five showed perineural invasion. The ileum glomus tumor was cellular, with prominent cellular atypia, and the mitotic count in hot spots was about 5-6/HPF. Immunohistochemistry showed that SMA and collage Ⅳ were strongly expressed in all the tumor cells; caldesmon and calponin were moderately expressed in some regions, and syn was weakly expressed in 12 cases. The Ki-67 proliferation index in the gastric glomus tumors ranged from 1% to 30% (mean 6%); and that in the ileum glomus tumor was about 70%. BRAF V600E mutations were not detected in any of 15 GIGTs. All patients did not receive radiotherapy or chemotherapy post operatively. Thirteen patients were followed up by telephone for 18-90 months (mean 42 months). Twelve patients with gastric glomus tumors survived without recurrence and metastasis, and the patient with ileum glomus tumor had liver metastasis 15 months after operation. Conclusions: Glomus tumors is a rare mesenchymal tumor of the gastrointestinal tract. It should be differentiated from gastrointestinal stromal tumors, neuroendocrine tumor, leiomyoma, solitary fibrous tumor and paraganglioma. Most GIGTs are benign and have good prognosis. More experience is needed to understand the biologic behavior and prognostication of GIGTs.

PMID: 31914530 [PubMed - in process]

Permalink for '[Clinicopathological features and outcome of gastroenteropancreatic high-grade (WHO G3) neuroendocrine tumors: a study of 60 cases].'

[Clinicopathological features and outcome of gastroenteropancreatic high-grade (WHO G3) neuroendocrine tumors: a study of 60 cases].

Fetched: January 11th, 2020, 5:01am GMT

[Clinicopathological features and outcome of gastroenteropancreatic high-grade (WHO G3) neuroendocrine tumors: a study of 60 cases].

Zhonghua Bing Li Xue Za Zhi. 2020 Jan 08;49(1):12-16

Authors: Huang D, Tan C, Weng WW, Ni SJ, Wang L, Sheng WQ

Abstract
Objective: To investigate the clinicopathological features and outcome of gastroenteropancreatic high-grade neuroendocrine tumors. Methods: A total of 60 gastroenteropancreatic high-grade neuroendocrine tumors were collected from January 1st, 2013 to December 31th, 2018 at Fudan University Shanghai Cancer Center, with available pathology databases and clinic follow-up information. At the same time, 157 cases of gastrointestinal pancreatic neuroendocrine neoplasm (NEN) diagnosed at the hospital in 2018 were collected and the incidence of NEN at all grades was compared. Results: There were 32 males and 28 females, aged 13-80 years (mean 54 years). Pancreas primary was the most common (48%, 29/60). Nodal metastatic rate was 9/16 and distant metastatic rate was 41%(18/44). Liver was the most common site of metastasis. Among all the gastroenteropancreatic neuroendocrine neoplasms diagnosed in the hospital in 2018, the incidence of high-grade neuroendocrine tumors was the lowest (7%, 11/157). High-grade neuroendocrine tumors had typical pathologic features of well-differentiated/moderate neuroendocrine tumors, but with significant differences in mitotic rates. By immunohistochemical staining, most of the tumors expressed neuroendocrine markers and somatostatin receptor 2 was positive in 60% (12/20) of the cases. The average Ki-67 index was 30%-40%, and there was significant difference between cases (18%-80%). The overall survival of high-grade neuroendocrine tumors was 43 months, and the disease-free survival was 12 months. Conclusions: High-grade neuroendocrine tumor is a rare group of neuroendocrine tumors, with unique clinicopathological features and good prognosis. Pathological classification and grading of gastroenteropancreatic neuroendocrine neoplasms can help clinicians to select appropriate treatment and accurately evaluate prognosis.

PMID: 31914528 [PubMed - in process]

[Spectrum analysis of pathological classification in 463 cases with nasal and paranasal sinuses malignant tumors].

Fetched: January 10th, 2020, 5:01am GMT

[Spectrum analysis of pathological classification in 463 cases with nasal and paranasal sinuses malignant tumors].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 Dec;33(12):1176-1180

Authors: Li J, Yuan H, Li Y, Zhao XQ, Chen L, Han MK, Liu CQ, Liu Q, Wang HT, Zhong Q, Feng B

Abstract
Objective:The characteristics of pathological histological classification of nasal and paranasal sinuses malignant tumors in the past 10 years were analyzed, so as to provide possible basis, direction and ideas for the development of relevant effective treatment measures for nasal and paranasal sinuses malignant tumors in clinical practice. Method:The clinical data of patients with nasal and paranasal sinuses malignant tumors admitted to PLA general hospital from January 2009 to December 2018 were collected. Pathological types were retrospectively analyzed, and disease spectrum distribution, composition ratio and variation tendency of these patients were calculated. Result:Among the 463 patients, the overall pathological types in the top 5 were as follows: squamous cell carcinoma, adenoid cystadenocarcinoma, olfactory neuroblastoma, melanoma, adenocarcinoma. As for male patients, the pathological types in the top 5 were squamous cell carcinoma, adenoid cystic carcinoma, olfactory neuroblastoma, adenocarcinoma, neuroendocrine carcinoma and rhabdomyosarcoma were tied for fifth; the top 5 most common pathological types in female patients were squamous cell carcinoma, adenoid cystic carcinoma, melanoma, rhabdomyosarcoma, and adenocarcinoma. From 2009 to 2013, there were 183 patients with nasal and paranasal sinuses malignant tumors, the top 5 pathological types were squamous cell carcinoma, adenoid cystadenocarcinoma, olfactory neuroblastoma, melanoma, neuroendocrine carcinoma and rhabdomyosarcoma were tied for fifth; From 2014 to 2018, 280 patients with nasal and paranasal sinuses malignant tumors were diagnosed, the top 5 pathological types were squamous cell carcinoma, adenoid cystadenocarcinoma, melanoma, adenocarcinoma, and rhabdomyosarcoma. The ratio of the number of patients from 2009 to 2013 and 2014 to 2018 was about 0.65â¶1. Malignant tumors of the nasal and paranasal sinuses tend to occur between the ages of 41 and 60, and the pathological types in the top 5 were squamous cell carcinoma,adenoid cystic carcinoma, adenocarcinoma, melanoma, neuroendocrine carcinoma. Conclusion:Malignant tumors of nasal cavity and sinus were more common in male, and the pathological types such as squamous cell carcinoma, adenoid cystic carcinoma, olfactory neuroblastoma were more common. All age groups have the disease, but the age group of 41-60 years old is the high-risk group of nasal and nasal sinus malignant tumors. However, the incidence rate of melanoma has gradually increased in the past five years, which needs to be paid more attention to.

PMID: 31914269 [PubMed - in process]

Molecular Characterization and Treatment of Pancreatic Neuroendocrine Tumors.

Fetched: January 10th, 2020, 5:01am GMT

Molecular Characterization and Treatment of Pancreatic Neuroendocrine Tumors.

Oncology (Williston Park). 2019 Dec 12;33(12):

Authors: De Jesus-Acosta AMC

PMID: 31914198 [PubMed - in process]

Permalink for 'Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers: A Comprehensive Study and Review of the Literature.'

Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers: A Comprehensive Study and Review of the Literature.

Fetched: January 10th, 2020, 5:01am GMT

Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers: A Comprehensive Study and Review of the Literature.

Arch Pathol Lab Med. 2020 Jan 08;:

Authors: Staaf J, Tran L, SÃ¶derlund L, Nodin B, JirstrÃ¶m K, Vidarsdottir H, Planck M, Mattsson JSM, Botling J, Micke P, BrunnstrÃ¶m H

Abstract
CONTEXT.—: The diagnostic distinction of pulmonary neuroendocrine (NE) tumors from non-small cell lung carcinomas (NSCLCs) is clinically relevant for prognostication and treatment. Diagnosis is based on morphology and immunohistochemical staining.
OBJECTIVE.—: To determine the diagnostic value of insulinoma-associated protein 1 (INSM1), in comparison with established NE markers, in pulmonary tumors.
DESIGN.—: Fifty-four pulmonary NE tumors and 632 NSCLCs were stained for INSM1, CD56, chromogranin A, and synaptophysin. In a subset, gene expression data were available for analysis. Also, 419 metastases to the lungs were stained for INSM1. A literature search identified 39 additional studies with data on NE markers in lung cancers from the last 15 years. Seven of these included data on INSM1.
RESULTS.—: A positive INSM1 staining was seen in 39 of 54 NE tumors (72%) and 6 of 623 NSCLCs (1%). The corresponding numbers were 47 of 54 (87%) and 14 of 626 (2%) for CD56, 30 of 54 (56%) and 6 of 629 (1%) for chromogranin A, and 46 of 54 (85%) and 49 of 630 (8%) for synaptophysin, respectively. Analysis of literature data revealed that CD56 and INSM1 were the best markers for identification of high-grade NE pulmonary tumors when considering both sensitivity and specificity, while synaptophysin also showed good sensitivity. INSM1 gene expression was clearly associated with NE histology.
CONCLUSIONS.—: The solid data of both our and previous studies confirm the diagnostic value of INSM1 as a NE marker in pulmonary pathology. The combination of CD56 with INSM1 and/or synaptophysin should be the first-hand choice to confirm pulmonary high-grade NE tumors. INSM1 gene expression could be used to predict NE tumor histology.

PMID: 31913660 [PubMed - as supplied by publisher]

Hemangioblastoma-like Clear Cell Stromal Tumor of the Lung: A Clinicopathologic and Immunohistochemical Study of 5 Cases.

Fetched: January 10th, 2020, 5:01am GMT

Hemangioblastoma-like Clear Cell Stromal Tumor of the Lung: A Clinicopathologic and Immunohistochemical Study of 5 Cases.

Am J Surg Pathol. 2020 Jan 06;:

Authors: Lindholm KE, Moran CA

Abstract
Five cases of an unusual primary benign stromal tumor designated as hemangioblastoma-like clear cell stromal tumor of the lung are presented. The patients are 4 women and 1 man between the ages of 39 and 52 years of age (average: 45.5ây). The patients presented with nonspecific symptoms of cough, chest pain, or dyspnea. None of the patients had any prior history of malignancy or tumor elsewhere. Diagnostic imaging showed the presence of an intrapulmonary tumor. Lobectomy was performed in all 5 patients. Grossly, the tumors were well-demarcated but not encapsulated with focal areas of hemorrhage without necrosis. Histologically, low power examination showed a cellular proliferation alternating with discrete dilated vessels reminiscent of a vascular neoplasm. Higher magnification showed medium-sized cells with clear cytoplasm arranged in sheets and cords. Mitotic activity and marked cellular atypia were not present. A wide panel of immunohistochemical studies was performed including epithelial, neural, muscle, vascular, and neuroendocrine markers, all of which showed negative staining. Tumor cells showed positive staining for vimentin. In 2 cases, fluorescence in situ hybridization for the solitary fibrous tumor was performed and was negative. Clinical follow-up in 3 patients showed no evidence of recurrence. The cases herein presented highlight an unusual benign stromal tumor of the lung, which needs to be considered in the differential diagnosis of tumors with a clear cell and vascular appearance.

PMID: 31913155 [PubMed - as supplied by publisher]

Permalink for 'Do You Know the Details of Your PAX8 Antibody? Monoclonal PAX8 (MRQ-50) Is Not Expressed in a Series of 45 Medullary Thyroid Carcinomas.'

Do You Know the Details of Your PAX8 Antibody? Monoclonal PAX8 (MRQ-50) Is Not Expressed in a Series of 45 Medullary Thyroid Carcinomas.

Fetched: January 10th, 2020, 5:01am GMT

Do You Know the Details of Your PAX8 Antibody? Monoclonal PAX8 (MRQ-50) Is Not Expressed in a Series of 45 Medullary Thyroid Carcinomas.

Endocr Pathol. 2020 Jan 07;:

Authors: Gucer H, Caliskan S, Kefeli M, Mete O

Abstract
Medullary thyroid carcinomas display cytologic and architectural features that can simulate various primary and metastatic neoplasms. PAX8 immunoexpression in neuroendocrine neoplasms yielded antibody-dependent findings. Since the data regarding the expression profile of monoclonal PAX8 (MRQ-50) antibody is limited in large series of medullary thyroid carcinomas, this study investigated the expression profile of PAX8 (MRQ-50) in a series of 45 medullary thyroid carcinomas. PAX8 (MRQ-50) expression was noted in the thyroid follicular epithelial cells surrounding the tumor and was negative in all medullary thyroid carcinomas. In addition, twenty medullary thyroid carcinomas showed scattered entrapped thyroid follicular epithelial cells at the periphery of the tumor. Entrapped follicular epithelial cells were positive for PAX8 and thyroglobulin, and were negative for monoclonal CEA and calcitonin. A panel approach combining monoclonal antibodies to transcription factors, hormones and cell-specific peptides often assist diagnosticians in the workup of the cellular origin of a neuroendocrine neoplasm. Since PAX8 immunostaining is dependent on the antibody characteristics in neuroendocrine neoplasms, pathologists should be aware of the details of the PAX8 antibody used in a particular case.

PMID: 31912298 [PubMed - as supplied by publisher]

Permalink for 'The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts.'

The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts.

Fetched: January 10th, 2020, 5:01am GMT

The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts.

Eur J Nucl Med Mol Imaging. 2020 Jan 07;:

Authors: Lundsten S, Spiegelberg D, Raval NR, Nestor M

Abstract
PURPOSE: 177Lu-DOTATATE targeting the somatostatin receptor (SSTR) is utilized for treatment of neuroendocrine tumors (NETs). Onalespib, a heat shock protein 90 (HSP90) inhibitor, has demonstrated radiosensitizing properties and may thus enhance the effect of 177Lu-DOTATATE. Consequently, the aim of this study was to assess the potential of Onalespib in combination with 177Lu-DOTATATE in vivo and to examine the toxicity profiles of the treatments.
METHODS: 177Lu-DOTATATE selectivity and distribution in NET xenografts were studied using biodistribution and autoradiography. Therapeutic effects of Onalespib in combination with 177Lu-DOTATATE were studied in NET xenografts. Histological analyses were used to assess molecular effects from treatment and to establish toxicity profiles.
RESULTS: Biodistribution and autoradiography confirmed the SSTR-selective tumor uptake of 177Lu-DOTATATE, which was unaffected by Onalespib treatment. Immunohistochemistry verified molecular responses to Onalespib therapy in the tumors. While Onalespib and 177Lu-DOTATATE monotherapies resulted in a 10% and 33% delay in tumor doubling time compared with control, the combination treatment resulted in a 73% delayed tumor doubling time. Moreover, combination treatment increased complete remissions threefold from 177Lu-DOTATATE monotherapy, resulting in 29% complete remissions. In addition, histological analyses demonstrated radiation-induced glomerular injury in the 177Lu-DOTATATE monotherapy group. The damage was decreased tenfold in the combination group, potentially due to Onalespib-induced HSP70 upregulation in the kidneys.
CONCLUSION: Treatment with Onalespib potentiated 177Lu-DOTATATE therapy of NET xenografts with a favorable toxicity profile. Utilizing Onalespib's radiosensitizing properties with 177Lu-DOTATATE may lead to better therapeutic results in the future and may reduce unwanted side effects in dose-limiting organs.

PMID: 31912256 [PubMed - as supplied by publisher]

Renal Neuroendocrine Neoplasms: A Single-center Experience.

Fetched: January 10th, 2020, 5:01am GMT

Renal Neuroendocrine Neoplasms: A Single-center Experience.

Clin Genitourin Cancer. 2019 Dec 05;:

Authors: McGarrah PW, Westin GFM, Hobday TJ, Scales JA, Ingimarsson JP, Leibovich BC, Halfdanarson TR

Abstract
BACKGROUND: Primary neuroendocrine neoplasms (NENs) of the kidney are exceedingly rare malignancies and the available data are very limited. The natural history and response to treatments have not been well characterized. We have described the presenting features, demographic data, tumor characteristics, and treatment outcomes of patients with renal NENs.
PATIENTS AND METHODS: We performed a retrospective analysis of the data from all Mayo Clinic patients with a tissue diagnosis of a primary renal NEN. The baseline patient and surgical pathologic features and treatment modalities were collected. The time to recurrence after resection and overall survival (OS) were estimated using survival analysis. The Surveillance, Epidemiology, and End Results data were used to estimate the population-wide incidence and OS.
RESULTS: A total of 17 patients were included in the present study, with a median follow-up of 62.8 months. Distant metastasis was present in 29% at diagnosis, with 76% experiencing distant metastasis at any point; 24% had a horseshoe kidney. Of the 17 patients, 14 had undergone surgical resection with no evidence of disease postoperatively. Ten of these patients had documented recurrence. The median time to recurrence was 18 months (95% confidence interval, 9-46 months). Only 1 of the 10 patients showed a radiographic response to systemic therapy. Of 9 patients, 4 had had stable disease with somatostatin analogs. The median OS was 143 months (95% confidence interval, 50-143 months).
CONCLUSIONS: Renal NENs are rare malignancies affecting mostly middle-age patients, with distant metastasis common. Approximately one half of patients will experience stable disease with somatostatin analogs. The OS will usually be > 5 years.

PMID: 31911122 [PubMed - as supplied by publisher]

An agonistic anti-Toll-like receptor 4 monoclonal antibody as an effective adjuvant for cancer immunotherapy.

Fetched: January 10th, 2020, 5:01am GMT

An agonistic anti-Toll-like receptor 4 monoclonal antibody as an effective adjuvant for cancer immunotherapy.

Immunology. 2019 10;158(2):136-149

Authors: Tsukamoto H, Kubota K, Shichiku A, Maekawa M, Mano N, Yagita H, Ohta S, Tomioka Y

Abstract
Immune-checkpoint blockade antibodies have been approved for the treatment of cancer. However, poorly immunogenic tumours are less responsive to such therapies. Agonistic anti-Toll-like receptor 4 (TLR4) monoclonal antibodies (mAbs) activate only cell-surface TLR4; in contrast, lipopolysaccharide (LPS) activates both TLR4 and intracellular inflammatory caspases. In this study, we investigated the adjuvant activity of an anti-TLR4 mAb in T-cell-mediated antitumour immunity. The anti-TLR4 mAb induced the activation of antigen-specific T-cells in adoptive transfer studies. The growth of ovalbumin (OVA)-expressing tumours was significantly suppressed by administration of OVA and the anti-TLR4 mAb in combination, but not individually. The antitumour effect of anti-PD-1 mAb was enhanced in mice administered with OVA plus the anti-TLR4 mAb. The OVA-specific IFN-Î³-producing CD8 T-cells were induced by administration of OVA and the anti-TLR4 mAb. The suppression of tumour growth was diminished by depletion of CD8, but not CD4, T-cells. The inflammatory response to the anti-TLR4 mAb was of significantly lesser magnitude than that to LPS, as assessed by NF-ÎºB activation and production of TNF-Î±, IL-6 and IL-1Î². Administration of LPS (at a dose that elicited levels of proinflammatory cytokines comparable to those by the anti-TLR4 mAb) plus OVA induced no or less-marked activation of OVA-specific T-cells and failed to suppress tumour growth in mice. In conclusion, the agonistic anti-TLR4 mAb induces potent CD8 T-cell-dependent antitumour immunity and an inflammatory response of lesser magnitude than does LPS. The agonistic anti-TLR4 mAb has potential as an adjuvant for use in vaccines against cancer.

PMID: 31515801 [PubMed - indexed for MEDLINE]

Comprehensive molecular and clinical characterization of Asian melanoma patients treated with anti-PD-1 antibody.

Fetched: January 10th, 2020, 5:01am GMT

Comprehensive molecular and clinical characterization of Asian melanoma patients treated with anti-PD-1 antibody.

BMC Cancer. 2019 Aug 14;19(1):805

Authors: Lee J, Lee SJ, Kim K, Kim ST, Jang KT, Lee J

Abstract
BACKGROUND: Clinical features of Asian melanoma patients are distinct from those of Western patients. This study was designed to determine the molecular and clinical characteristics of Asian melanoma patients treated with anti-PD-1 antibody.
METHODS: Patients with recurrent or metastatic melanoma who began anti-PD-1 antibody therapy between January 2015 and April 2018 were retrospectively reviewed. Patients who underwent next-generation sequencing were also analyzed.
RESULTS: A total of 152 patients were included. The median age was 61âyears, and 53% of patients were female. A total of 56 patients (37%) received immunotherapy as second-line or greater chemotherapy. Primary sites were acral (38%), mucosal (31%), cutaneous (24%), uveal (2%), and unknown (5%). The overall response rate was 17% (95% CI, 11-22%), and disease control rate was 60% (95% CI, 52-68%). The median progression-free survival (PFS) was 4.2âmonths (95% CI, 1.8-6.6âmonths), and median overall survival (OS) was 32.9âmonths (95% CI, 20.0-45.7âmonths). However, BRAFV600 and KIT mutational statuses were not associated with response or survival. High neutrophil-lymphocyte ratio (NLR) was associated with poor PFS (median PFS 6.9 vs. 2.4âmonths, pâ=â0.015) and OS (median OS NR vs. 10.4âmonths, pâ<â0.001). In multivariate analysis, high NLR independently predicted poor survival.
CONCLUSION: This study includes the largest set of integrated genomic data analyzing Asian patients with melanoma treated with immunotherapy. BRAF V600 and KIT mutational statuses were not associated with response or survival, and high NLR was a strong predictor of poor response to and survival with anti-PD-1 therapy.

PMID: 31412814 [PubMed - indexed for MEDLINE]

Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK/P38 MAPK signaling activation.

Fetched: January 10th, 2020, 5:01am GMT

Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK/P38 MAPK signaling activation.

Eur J Pharmacol. 2019 Oct 05;860:172568

Authors: Kim SH, Yoo ES, Woo JS, Han SH, Lee JH, Jung SH, Kim HJ, Jung JY

Abstract
In this study, we investigated whether Quercetin has anti-cancer effects on A375SM and A375P human melanoma cells. Cell viability was assessed using an MTT assay. The proliferation of melanoma cells was measured by a wound-healing assay. Quercetin significantly decreased viability and proliferation of A375SM cells in a concentration-dependent manner. However, quercetin had no effect on A375P cells. DAPI staining showed increased chromatin condensation in a concentration-dependent manner, indicating apoptosis. Flow cytometric analysis indicated that quercetin suppressed the viability of A375SM cells by inducing apoptosis. Expression of quercetin-induced apoptosis proteins was investigated by Western blot analysis. Quercetin increased the expression of Bax, phospho-JNK, phospho-p38 and phospho-ERK1/2, cleaved poly-ADP ribose polymerase and decreased Bcl-2 in a concentration-dependent manner. We also investigated the in vivo tumor-growth inhibitory effect of quercetin. Quercetin (at 50 and 100â¯mg/kg) significantly decreased the A375SM tumor volume compared to the control group and increased apoptosis as assessed by the TUNEL assay. Immunohistochemistry staining revealed that the level of phosphor-JNK and phosphor-p38 increased in the quercetin-treated mice. These results indicate that quercetin inhibited the growth of A375SM melanoma cells through apoptosis and thus can be regarded as a new and effective chemo-preventive or therapeutic agent.

PMID: 31348906 [PubMed - indexed for MEDLINE]

Management and outcome of an appendiceal collision tumour composed of neuroendocrine and mucinous neoplasms.

Fetched: January 10th, 2020, 5:01am GMT

Management and outcome of an appendiceal collision tumour composed of neuroendocrine and mucinous neoplasms.

BMJ Case Rep. 2019 Jul 10;12(7):

Authors: Sholi AN, Gray KD, Pomp A

Abstract
We report an appendiceal collision tumour in a 23-year-old woman who presented with constipation and abdominal fullness. Imaging revealed a right lower quadrant abdominal mass that was laparoscopically resected. Histology revealed an appendiceal collision tumour composed of a low-grade mucinous neoplasm and well-differentiated neuroendocrine neoplasm. A right hemicolectomy for complete oncological control was performed revealing metastatic spread of the neuroendocrine component to the lymph nodes. No further treatment was recommended and the patient was followed with expectant management. At 2-year follow-up, no evidence of disease was found on surveillance imaging. Appendiceal collision tumours can arise in young adults; treatment should be guided by oncological principles of the component tumours.

PMID: 31296638 [PubMed - indexed for MEDLINE]

Incidental Detection of Adrenal Pheochromocytoma on 99mTc-DTPA Renal Dynamic Scintigraphy.

Fetched: January 10th, 2020, 5:01am GMT

Incidental Detection of Adrenal Pheochromocytoma on 99mTc-DTPA Renal Dynamic Scintigraphy.

Clin Nucl Med. 2019 Dec;44(12):964-965

Authors: Mi Y, Huang J, Ren Y, Xie P

Abstract
A 53-year-old man with a history of primary hypertension for over 8 years underwent Tc-DTPA renal dynamic scintigraphy to evaluate the renal function. The images revealed an unexpected focus of abnormally increased DTPA activity in the region superior to the upper pole of the right kidney. Subsequent MRIs confirmed an adrenal mass. The results of pathological examination and immunohistochemistry after the resection of the lesion were consistent with adrenal pheochromocytoma.

PMID: 31283611 [PubMed - indexed for MEDLINE]

Furan inhibitory activity against tyrosinase and impact on B16F10 cell toxicity.

Fetched: January 10th, 2020, 5:01am GMT

Furan inhibitory activity against tyrosinase and impact on B16F10 cell toxicity.

Int J Biol Macromol. 2019 Sep 01;136:1034-1041

Authors: Barros MR, Menezes TM, da Silva LP, Pires DS, Princival JL, Seabra G, Neves JL

Abstract
Many skin disorders and diseases are related to tyrosinase activity, in particular, due to the vital role played by this enzyme in the melanogenic process. Although numerous natural and synthetic tyrosinase inhibitors have been published, substantial efforts have been made to understand the influence of tyrosinase inhibition on the viability of melanoma cells. Here, we assess the impact of two keto-derivatives: 2-acetyl-furan (F1), furfural-acetone (F2), and two carboxyl-derivatives: 2-furan-acrylic acid (F3), 5-methyl-2-furan-acrylic acid (F4), on the mushroom tyrosinase (mTYR) activity, by applying spectroscopic, kinetic and theoretical techniques. From an exploratory and theoretical point of view, results indicated that albeit all furans bind tightly to and inhibit mTYR very efficient, carboxyl-furan derivatives presented best inhibitory activities than keto- derivatives and performed the inhibition competitively and reversible. Moreover, we examined the influence of carboxyl derivative on the viability of melanoma cells. Results expose differential toxicity of these furan derivatives, which indicates a piece of evidence that furan inhibition activity may be related to its toxicity against B16F10 cells.

PMID: 31233796 [PubMed - indexed for MEDLINE]

Diosmetin inhibits tumor development and block tumor angiogenesis in skin cancer.

Fetched: January 10th, 2020, 5:01am GMT

Diosmetin inhibits tumor development and block tumor angiogenesis in skin cancer.

Biomed Pharmacother. 2019 Sep;117:109091

Authors: Choi J, Lee DH, Park SY, Seol JW

Abstract
Diosmetin is a natural flavonoid obtained from citrus fruits and some medicinal herbs. Previous studies have reported the anti-cancer activity of diosmetin in some types of tumors. However, it is still unclear whether diosmetin exerts anti-cancer effects, particularly anti-angiogenic effects, in skin cancer. In this study, we used B16F10 melanoma cells and human umbilical vein endothelial cells to investigate the inhibitory effect of diosmetin on cell proliferation, migration and tube formation in vitro. Rat aorta ring assays were performed to determine the effect of diosmetin on ECs sprouting ex vivo. Furthermore, a B16F10 mouse melanoma model was used to observe the effect of diosmetin on tumor growth, angiogenesis, and metastasis in vivo. Our results showed that diosmetin not only suppressed tumor cell proliferation and migration but also induced cell apoptosis via the caspase pathway in B16F10 cells, and potently inhibited tube formation and cell migration in HUVECs. Rat aorta ring assays showed that diosmetin attenuated the ECs sprouting. Moreover, the mouse melanoma model showed that diosmetin significantly delayed tumor growth by inhibiting tumor vessels sprouting and expansion during tumor progression. Notably, diosmetin induced the normalization of tumor vasculature through the downregulation of angiopoietin-2 and the improvement of pericyte coverage, leading to suppression of metastasis formation in lungs and lymph nodes. In conclusion, our results demonstrate that diosmetin suppresses tumor progression and metastasis by inducing tumor cell death and inhibiting tumor angiogenesis as well as normalizing the defective tumor vasculature, suggesting that diosmetin is a potential adjuvant chemotherapy agent.

PMID: 31228803 [PubMed - indexed for MEDLINE]

Comparison of quality of life between melanoma and non-melanoma skin cancer patients.

Fetched: January 10th, 2020, 5:01am GMT

Comparison of quality of life between melanoma and non-melanoma skin cancer patients.

Eur J Dermatol. 2019 Apr 01;29(2):185-191

Authors: Sampogna F, Paradisi A, Iemboli ML, Ricci F, Sonego G, Abeni D

Abstract
The impact of skin cancers on patients' health-related quality of life (HRQoL) is often overlooked, and direct comparisons between melanoma and non-melanoma skin cancer (NMSC) are rare. Objectives: The aim of this study was to compare HRQoL in patients with melanoma and NMSC. Participants were unselected, consecutive adult patients with a diagnosis of melanoma at the time of wide excision, or NMSC at the time of surgery. HRQoL was measured using the two scales of Skindex-17. The 12-item General Health Questionnaire (GHQ-12) was used to identify patients with possible anxiety or depression. The study population included 433 patients: 65 with melanoma and 368 with NMSC. Skindex-17 symptom mean scores were higher in NMSC than in melanoma patients. Melanoma patients had significantly higher scores for the item "feeling depressed". The percentage of GHQ-12 cases (with possible non-psychotic, minor psychiatric disorders) was significantly higher in patients with melanoma (32.8%) compared to NMSC patients (8.7%). NMSC places a greater burden of symptoms on patients than melanoma, while the psychological impact of melanoma is higher.

PMID: 31106760 [PubMed - indexed for MEDLINE]

BRAF immunohistochemistry predicts sentinel lymph node involvement in intermediate thickness melanomas.

Fetched: January 10th, 2020, 5:01am GMT

BRAF immunohistochemistry predicts sentinel lymph node involvement in intermediate thickness melanomas.

PLoS One. 2019;14(4):e0216043

Abstract
BACKGROUND: Sentinel node biopsy (SNB) is an important step in melanoma staging and prognostication. It is commonly performed for patients with intermediate thickness melanomas, based on clinicopathological features. However, only 20-25% of patients eventually demonstrate nodal involvement. The aim of this study was to evaluate whether tissue biomarkers with links to melanoma biology, together with clinicopathological parameters, could aid in the prediction of sentinel node involvement and improve selection of patients for SNB. In addition, we examined the role of these clinical or biological markers in disease outcome.
METHODS: We collected a case-control cohort of 140 intermediate thickness (Breslow 0,9-4,0mm) melanoma patients with or without SNB involvement matched for age, gender, Breslow thickness and location. From this cohort, we tested the predictive value of common clinicopathological parameters (ulceration, mitotic count and tumor regression) and FMNL-2, ezrin and BRAF V600E immunoreactivity, for sentinel node involvement and survival. We further analyzed the correlations in the superficial spreading melanoma subtype.
RESULTS: Based on our case control analysis, of the markers, BRAF V600E status (p = 0.010) and mitotic count (p = 0.036) correlated with SNB involvement. SNB status was a strong independent prognosticator for recurrence free survival (RFS p<0.001), melanoma specific survival (MSS p = 0.000) and overall survival (OS p = 0.029). In the superficially spreading melanoma subgroup, BRAF V600E positivity indicated poorer RFS (p = 0.039) and OS (p = 0.012). By combining the Breslow thickness, mitotic count and BRAF immunohistochemistry, we identified a group of superficially spreading melanomas with an excellent survival probability independent of SNB status.
CONCLUSIONS: These results demonstrate that BRAF immunohistochemistry could serve as a useful addition to a marker panel for selecting intermediate thickness melanoma patients for SNB.

PMID: 31039200 [PubMed - indexed for MEDLINE]

Higher risk of phaeochromocytoma/paraganglioma (Phaeo-Pgl) in SDHD than SDHB carriers: an Australian cohort study.

Fetched: January 10th, 2020, 5:01am GMT

Higher risk of phaeochromocytoma/paraganglioma (Phaeo-Pgl) in SDHD than SDHB carriers: an Australian cohort study.

Intern Med J. 2019 04;49(4):529-532

Authors: Hong A, Shanahan M, Schenberg T, Inder W, MacIsaac R, James P, Sachithanandan N

Abstract
Carriers of succinate dehydrogenase (SDHx) mutations are at risk of developing phaeochromocytomas, catecholamine secreting extra-adrenal paragangliomas and non-secretory head and neck paragangliomas and require lifelong surveillance. There is no current consensus on the optimal surveillance strategy. This study describes the outcomes of a cohort of 50 SDHx mutation carriers followed at a tertiary Australian hospital using a surveillance protocol involving annual clinical review with plasma/urine metanephrines and biennial magnetic resonance imaging from skull base to pelvis.

PMID: 30957378 [PubMed - indexed for MEDLINE]

Dermoscopic and reflectance microscopy features of primary and metastatic Merkel cell carcinoma: Ten cases.

Fetched: January 10th, 2020, 5:01am GMT

Dermoscopic and reflectance microscopy features of primary and metastatic Merkel cell carcinoma: Ten cases.

Skin Res Technol. 2019 May;25(3):407-409

Authors: Cinotti E, Provvidenziale L, Habougit C, Fimiani M, Tognetti L, Perrot JL, Rubegni P

PMID: 30593691 [PubMed - indexed for MEDLINE]

Preoperative 18F-FDG PET/CT in Pheochromocytomas and Paragangliomas Allows for Precision Surgery.

Fetched: January 10th, 2020, 5:01am GMT

Preoperative 18F-FDG PET/CT in Pheochromocytomas and Paragangliomas Allows for Precision Surgery.

Ann Surg. 2019 04;269(4):741-747

Authors: Nockel P, El Lakis M, Gaitanidis A, Merkel R, Patel D, Nilubol N, Prodanov T, Pacak K, Kebebew E

Abstract
BACKGROUND: Fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) imaging is recommended in patients with metastatic pheochromocytoma (PC) and paraganglioma (PGL). There are no data on whether routine preoperative F-FDG PET/CT in all patients with PC/PGL impacts surgical management.
OBJECTIVE: The aim of this study was to determine whether routine preoperative F-FDG PET/CT imaging affects the surgical management of patients with PC/PGLs.
METHODS: We analyzed clinical, biochemical, genetic, and anatomic imaging data in 93 consecutive patients with PC/PGL who collectively underwent a total of 100 operations and who had preoperative F-FDG PET/CT imaging.
RESULTS: Of 100 operations, preoperative F-FDG PET/CT showed additional lesions compared to anatomic imaging in 15 cases. These patients were more likely to undergo an open surgical approach (P < 0.05). Presence of genetic mutation, redo operations, sex, age, or tumor size had no significant association with finding additional lesions on F-FDG PET/CT.
CONCLUSIONS: Additional lesions detected on preoperative F-FDG-PET/CT imaging have an impact on the surgical approach in patients with PC/PGLs. Therefore, surgeons should routinely obtain F-FDG-PET/CT imaging in patients with PC/PGL to allow for a more precise surgical intervention.

PMID: 29334561 [PubMed - indexed for MEDLINE]

Primary epithelial-myoepithelial carcinoma of the pituitary gland.

Fetched: January 6th, 2020, 5:00am GMT

Primary epithelial-myoepithelial carcinoma of the pituitary gland.

Neuropathology. 2020 Jan 03;:

Authors: Lavin V, Callipo F, Donofrio CA, Ellwood-Thompson R, Metcalf R, Djoukhadar I, Higham CE, Kearney T, Colaco R, Gnanalingham K, Roncaroli F

Abstract
Primary salivary gland-like tumors of the sella are rare and often challenging to diagnose. They reportedly derive from serous and mucinous glands that remain trapped in the infundibulum during embryogenesis. We report a 68-year-old man who presented with partial left third cranial nerve palsy, visual loss in the left eye without visual field defects, headache, weight loss and reduced muscle bulk. Neuroimaging studies demonstrated a solid and cystic, avidly enhancing lesion expanding the pituitary fossa and extending to the left cavernous sinus. The patient underwent craniotomy and the tissue removed showed features of epithelial-myoepithelial carcinoma similar to the salivary gland, skin and breast counterpart. No primary tumor was found outside the sella. The lesion behaved aggressively despite radio-chemotherapy and the patient died 22 months from the onset. The tumor showed a novel TP53 in-frame deletion (Gly154del) while no variants were found in H-RAS hotspot regions (codons 12, 13 and 61). Our report expands the spectrum of salivary gland-like tumors primarily occurring in the sella and emphasizes the need for specialist review of rare, non-neuroendocrine tumors of the pituitary and sella regions.

PMID: 31900996 [PubMed - as supplied by publisher]

Wnt/Beta-Catenin Signaling and Prostate Cancer Therapy Resistance.

Fetched: January 6th, 2020, 5:00am GMT

Wnt/Beta-Catenin Signaling and Prostate Cancer Therapy Resistance.

Adv Exp Med Biol. 2019;1210:351-378

Authors: Yeh Y, Guo Q, Connelly Z, Cheng S, Yang S, Prieto-Dominguez N, Yu X

Abstract
Metastatic or locally advanced prostate cancer (PCa) is typically treated with androgen deprivation therapy (ADT). Initially, PCa responds to the treatment and regresses. However, PCa almost always develops resistance to androgen deprivation and progresses to castrate-resistant prostate cancer (CRPCa), a currently incurable form of PCa. Wnt/β-Catenin signaling is frequently activated in late stage PCa and contributes to the development of therapy resistance. Although activating mutations in the Wnt/β-Catenin pathway are not common in primary PCa, this signaling cascade can be activated through other mechanisms in late stage PCa, including cross talk with other signaling pathways, growth factors and cytokines produced by the damaged tumor microenvironment, release of the co-activator β-Catenin from sequestration after inhibition of androgen receptor (AR) signaling, altered expression of Wnt ligands and factors that modulate the Wnt signaling, and therapy-induced cellular senescence. Research from genetically engineered mouse models indicates that activation of Wnt/β-Catenin signaling in the prostate is oncogenic, enables castrate-resistant PCa growth, induces an epithelial-to-mesenchymal transition (EMT), promotes neuroendocrine (NE) differentiation, and confers stem cell-like features to PCa cells. These important roles of Wnt/β-Catenin signaling in PCa progression underscore the need for the development of drugs targeting this pathway to treat therapy-resistant PCa.

PMID: 31900917 [PubMed - in process]

Permalink for 'Neuroendocrine tumor with diarrhea: not always the usual suspects - a case report of metastatic calcitoninoma with literature review.'

Neuroendocrine tumor with diarrhea: not always the usual suspects - a case report of metastatic calcitoninoma with literature review.

Fetched: January 6th, 2020, 5:00am GMT

Neuroendocrine tumor with diarrhea: not always the usual suspects - a case report of metastatic calcitoninoma with literature review.

Acta Clin Belg. 2020 Jan 03;:1-5

Authors: Vlaemynck K, De Man M, De Man K, Hoorens A, Geboes K

Abstract
We describe a case of a 59-year-old man without relevant past medical history, presenting with chronic diarrhea and weight loss. Extensive laboratory analysis, stool cultures and gastro- and ileocolonoscopy could not identify a diagnosis. Abdominal imaging revealed a mass in the uncinate process of the pancreas with mesenteric adenopathies and liver metastases. Fine needle aspiration was compatible with a pancreatic neuroendocrine tumor with low proliferative capacity (Ki-67 <1%). Immunohistochemical staining was positive for calcitonin and serum calcitonin levels were clearly elevated. Surprisingly, 18FDG PET-CT scan was positive, but no tracer uptake was seen on 68Gallium-DOTATOC PET-CT scan. Treatment with somatostatin analogues was not successful, but long-term tumor control could be obtained with Everolimus. However, no significant effect was seen on stool frequency despite additional treatment with multiple symptomatic therapies, liver-directed therapy with radio- and chemoembolization and additional external radiotherapy to the primary pancreatic tumor. Ondansetron, eventually, seems to be the only therapy, until now, causing a decrease in stool frequency.Functioning pancreatic calcitoninomas are considered to be a rare disease entity with few literature on optimal (nuclear) imaging and treatment. We discuss molecular insights regarding these aspects that can be of great interest to nuclear medicine physicians, pathologists, endocrinologists and gastroenterologists.

PMID: 31900071 [PubMed - as supplied by publisher]

Is Somatostatin Receptor and Dopamine Receptor profiling useful in the management of silent somatotroph tumors?

Fetched: January 5th, 2020, 5:01am GMT

Is Somatostatin Receptor and Dopamine Receptor profiling useful in the management of silent somatotroph tumors?

J Endocrinol Invest. 2020 Jan 02;:

Authors: Martínez-López S, García-Martínez A, Torregrosa-Quesada ME, López-Muñoz B, Cámara R, Fajardo C, Lamas C, Picó A

Abstract
Silent somatotroph tumors (sSTs) are pituitary neuroendocrine tumors (PitNETs) which do not give rise to the clinical syndrome of acromegaly. Differently to their functioning counterparts, the adjuvant medical treatment with somatostatin analogues (SSAs) or dopamine receptors agonists (DAs) has been scarcely addressed in these tumors. As preliminary results of an ongoing research on silencing mechanisms involved in the pathogenesis of sSTs, we have characterized by qRT-PCR the expression of SSTRs and DRDs in a large series of 18 silent and 68 functioning STs. Although the expression of SSTR2 and SSTR5 was lower in sSTs than in functioning ones, we found a negative correlation between SSTR2 and the tumor size of the sSTs. Additionally, levels of expression of DRD2 were similar between the two subtypes suggesting a possible basis for the treatment of these tumors with SSAs and DAs.

PMID: 31898311 [PubMed - as supplied by publisher]

MRI texture analysis in acromegaly and its role in predicting response to somatostatin receptor ligands.

Fetched: January 5th, 2020, 5:01am GMT

MRI texture analysis in acromegaly and its role in predicting response to somatostatin receptor ligands.

Pituitary. 2020 Jan 02;:

Authors: Galm BP, Buckless C, Swearingen B, Torriani M, Klibanski A, Bredella MA, Tritos NA

Abstract
PURPOSE: Given the paucity of reliable predictors of tumor recurrence, progression, or response to somatostatin receptor ligand (SRL) therapy in acromegaly, we attempted to determine whether preoperative MR image texture was predictive of these clinical outcomes. We also determined whether image texture could differentiate somatotroph adenomas from non-functioning pituitary adenomas (NFPAs).
METHODS: We performed a retrospective study of patients with acromegaly due to a macroadenoma who underwent transsphenoidal surgery at our institution between 2007 and 2015. Clinical data were extracted from electronic medical records. MRI texture analysis was performed on preoperative non-enhanced T1-weighted images using ImageJ (NIH). Logistic and Cox models were used to determine if image texture parameters predicted outcomes.
RESULTS: Eighty-nine patients had texture parameters measured, which were compared to that of NFPAs, while 64 of these patients had follow-up and were included in the remainder of analyses. Minimum pixel intensity, skewness, and kurtosis were significantly different in somatotroph adenomas versus NFPAs (area under the receiver operating characteristic curve, 0.7771, for kurtosis). Furthermore, those with a maximum pixel intensity above the median had an increased odds of IGF-I normalization on SRL therapy (OR 5.96, 95% CI 1.33-26.66), which persisted after adjusting for several potential predictors of response. Image texture did not predict tumor recurrence or progression.
CONCLUSION: Our data suggest that MRI texture analysis can distinguish NFPAs from somatotroph macroadenomas with good diagnostic accuracy and can predict normalization of IGF-I with SRL therapy.

PMID: 31897778 [PubMed - as supplied by publisher]

Permalink for 'Pancreatic neuroendocrine tumors (pNETs): the predictive value of MDCT characteristics in the differentiation of histopathological grades.'

Pancreatic neuroendocrine tumors (pNETs): the predictive value of MDCT characteristics in the differentiation of histopathological grades.

Fetched: January 5th, 2020, 5:01am GMT

Pancreatic neuroendocrine tumors (pNETs): the predictive value of MDCT characteristics in the differentiation of histopathological grades.

Abdom Radiol (NY). 2020 Jan 02;:

Authors: Salahshour F, Mehrabinejad MM, Zare Dehnavi A, Alibakhshi A, Dashti H, Ataee MA, Ayoobi Yazdi N

Abstract
PURPOSE: To investigate the correlation between multiple detector computed tomography (MDCT) features of pancreatic neuroendocrine tumors (pNETs) and histopathologic grade and find valuable imaging criteria for grade prediction.
MATERIAL AND METHODS: MDCT of 61 patients with 65 masses, which pNETs were approved histopathologically, underwent revision retrospectively. Each MDCT was evaluated for various radiologic characteristics. Absolute and relative (R: tumor/pancreas, D: tumor-pancreas) tumor enhancements were calculated in multiple post contrast phases.
RESULTS: 61 patients [mean age = 50.70 ± 14.28 y/o and 30(49.2%) were male] were evaluated and classified into 2 groups histopathologically: G1: 32 (49.2%) and G2,3: 33 (50.8%). Significant relationships were observed between histopathologic tumor grade regarding age (p = 0.006), the longest tumor size (p = 0.006), presence of heterogeneity (p < 0.0001), hypodense foci in delayed phase (p = 0.004), lobulation (p = 0.002), vascular encasement (p < 0.0001), adjacent organ invasion (p = 0.01), presence (p < 0.0001) and number (0.02) of liver metastases, presence of lymphadenopathy with short axis of more than 10 mm (LAP) (p = 0.008), pathologic lymph node size (p = 0.004), relative (R and D) (p = 0.05 and 0.02, respectively), and percentage of arterial hyper-enhancing area (p = <0.0001). Tumor grades, however, had no significant relationship with gender, tumor location, tumor outline, calcification, cystic change, or pancreatic (PD) or biliary duct (BD) dilation (p = 0.21, 0.60, 0.05, 0.05 1, 0.10, and 0.51, respectively). Then, we suggested a novel imaging criteria consisting of six parameters (tumor size > 33 mm, relative (R) tumor enhancement in arterial phase ≤ 1.33, relative (D) tumor enhancement in arterial phase ≤ 16.5, percentage of arterial hyper-enhancing area ≤ 75%, vascular encasement, and lobulation), which specificity and accuracy of combination of all findings (6/6) for predicting G2,3 were 100% and 70.1%, respectively. The highest accuracy (84.21%) was seen in combinations of at least 4 of 6 findings, with 80.00% sensitivity, 87.5% specificity, 83.33% PPV, and 84.85% NPV.
CONCLUSION: We suggested reliable imaging criteria with high specificity and accuracy for predicting the histopathologic grade of pNETs.

PMID: 31897681 [PubMed - as supplied by publisher]

A case of gallbladder neuroendocrine carcinoma diagnosed preoperatively using somatostatin receptor scintigraphy.

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A case of gallbladder neuroendocrine carcinoma diagnosed preoperatively using somatostatin receptor scintigraphy.

Oncol Lett. 2020 Jan;19(1):247-254

Authors: Kamikihara Y, Tanoue S, Kawahira M, Iwaya H, Arima S, Sasaki F, Nasu Y, Hashimoto S, Kanmura S, Higashi M, Gejima K, Ido A

Abstract
Gallbladder neuroendocrine carcinoma (NEC) is a rare gallbladder tumor. The current report is a case of a patient preoperatively diagnosed with gallbladder NEC using somatostatin receptor scintigraphy (SRS). A 63-year-old man was admitted to our hospital by a family doctor after abdominal ultrasonography revealed thickened walls of the neck of his gallbladder. At Kagoshima University Hospital, CT and MRI of the abdomen and endoscopic ultrasonography confirmed the thickening of the walls of the neck of the gallbladder. However, it did not resemble a typical gallbladder cancer or tumor, such as a neuroendocrine tumor or malignant lymphoma. Positron emission tomography and SRS showed abnormal accumulation at the tumor site. Endoscopic retrograde cholangiopancreatography was performed, adenocarcinoma was suspected based on intra-gallbladder bile cytology, and a cholecystectomy with lymphadenectomy was performed. The postoperative pathological diagnosis was small cell NEC (pT3a, N0, M0, stage II). Immunohistochemistry indicated that the gallbladder tumor cells were positive for synaptophysin, chromogranin A, and cluster of differentiation (CD) 56, and negative for somatostatin receptors (SSTR) 2 and 5. Gene expression assays revealed the expression of all SSTR subtypes (SSTR1-5) in the tumor. Generally, NECs exhibit poor accumulation in SRS, however, the results of the current case suggest that SRS may be useful in the preoperative diagnosis of NEC.

PMID: 31897136 [PubMed]

A primer on the genetics of medullary thyroid cancer.

Fetched: January 5th, 2020, 5:01am GMT

A primer on the genetics of medullary thyroid cancer.

Curr Oncol. 2019 Dec;26(6):389-394

Authors: Larouche V, Akirov A, Thomas CM, Krzyzanowska MK, Ezzat S

Abstract
Medullary thyroid cancer is a rare type of neuroendocrine tumour that arises from the parafollicular cells (C cells) of the thyroid gland. It accounts for 3%-5% of thyroid cancer cases. Close to 25% of cases are familial, and 75% are considered sporadic. Familial cases are associated with a germline RET mutation; 43%-65% of sporadic cases harbour a somatic event in the gene. Germline RET mutations are associated with the autosomal-dominant inherited multiple endocrine neoplasia (men) 2a and 2b syndromes and the isolated familial medullary thyroid cancer syndrome. More than 100 RET codon mutations have been reported to date, with genotype-phenotype correlations that include the extent and aggressiveness of the medullary thyroid cancer and the presence of other features of the men2 syndromes. The latter include pheochromocytoma-paraganglioma, hyperparathyroidism, cutaneous lichen amyloidosis, and Hirschsprung disease. In this narrative review, we focus on RET proto-oncogene physiology and pathogenesis induced by germline and somatic RET mutations, the genotype-phenotype correlation, and the management and follow-up of patients with germline-mutated medullary thyroid cancer.

PMID: 31896937 [PubMed - in process]

Permalink for 'Baicalein restrains proliferation, migration, and invasion of human malignant melanoma cells by down-regulating colon cancer associated transcript-1.'

Baicalein restrains proliferation, migration, and invasion of human malignant melanoma cells by down-regulating colon cancer associated transcript-1.

Fetched: January 5th, 2020, 5:01am GMT

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Baicalein restrains proliferation, migration, and invasion of human malignant melanoma cells by down-regulating colon cancer associated transcript-1.

Braz J Med Biol Res. 2019;52(12):e8934

Authors: Yang X, Jiang J, Zhang C, Li Y

Abstract
Baicalein (BAI) is an acknowledged flavonoids compound, which is regarded as a useful therapeutic pharmaceutical for numerous cancers. However, its involvement in melanoma is largely unknown. This study aimed to examine the anti-melanoma function of BAI and unraveled the regulatory mechanism involved. A375 and SK-MEL-28 were treated with BAI for 24 h. Then, CCK-8 assay, flow cytometry, and transwell assay were carried out to investigate cell growth, migration, and invasion. RT-qPCR was applied to detect the expression of colon cancer associated transcript-1 (CCAT1) in melanoma tissues and cells. The functions of CCAT1 in melanoma cells were also evaluated. Western blot was utilized to appraise Wnt/β-catenin or MEK/ERK pathways. BAI restrained cell proliferation and stimulated cell apoptotic capability of melanoma by suppressing cleaved-caspase-3 and cleaved-PARP. Cell migratory and invasive abilities were restrained by BAI via inhibiting MMP-2 and vimentin. CCAT1 was over-expressed in melanoma tissues and down-regulated by BAI in melanoma cells. Overexpressed CCAT1 reversed the BAI-induced anti-growth, anti-migratory, and anti-invasive effects. Furthermore, BAI inhibited Wnt/β-catenin and MEK/ERK pathways-axis via regulating CCAT1. Our study indicated that BAI blocked Wnt/β-catenin and MEK/ERK pathways via regulating CCAT1, thereby inhibiting melanoma cell proliferation, migration, and invasion.

PMID: 31778440 [PubMed - indexed for MEDLINE]

Understanding a sentinel lymph node biopsy service for patients with malignant melanoma.

Fetched: January 5th, 2020, 5:01am GMT

Understanding a sentinel lymph node biopsy service for patients with malignant melanoma.

Br J Nurs. 2019 Sep 26;28(17):S10-S14

Authors: Stothers S

Abstract
Malignant melanoma cases represented the seventh most common cancer type in Northern Ireland between 2011 and 2015, and the incidence of melanoma cases is expected to rise. Sentinel lymph node biopsy (SLNB) is commonly offered to patients in the UK with malignant melanoma to help in staging their disease, but a commissioned SLNB service is not available in Northern Ireland. This article describes a Florence Nightingale Foundation Travel Scholarship to gain knowledge and experience with the aim of developing and implementing an effective and efficient SLNB service for patients with malignant melanoma in Northern Ireland. A 3-week visit was made to an eminent centre of excellence in skin oncology in the UK.

PMID: 31556746 [PubMed - indexed for MEDLINE]

Antiproliferative and Antitumour Effect of Nongenotoxic Silver Nanoparticles on Melanoma Models.

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Antiproliferative and Antitumour Effect of Nongenotoxic Silver Nanoparticles on Melanoma Models.

Oxid Med Cell Longev. 2019;2019:4528241

Authors: Valenzuela-Salas LM, Girón-Vázquez NG, García-Ramos JC, Torres-Bugarín O, Gómez C, Pestryakov A, Villarreal-Gómez LJ, Toledano-Magaña Y, Bogdanchikova N

Abstract
During the last 3 decades, there has been a slow advance to obtain new treatments for malignant melanoma that improve patient survival. In this work, we present a systematic study focused on the antiproliferative and antitumour effect of AgNPs. These nanoparticles are fully characterized, are coated with polyvinylpyrrolidone (PVP), and have an average size of 35 ± 15 nm and a metallic silver content of 1.2% wt. Main changes on cell viability, induction of apoptosis and necrosis, and ROS generation were found on B16-F10 cells after six hours of exposure to AgNPs (IC50 = 4.2 μg/mL) or Cisplatin (IC50 = 2.0 μg/mL). Despite the similar response for both AgNPs and Cisplatin on antiproliferative potency (cellular viability of 53.95 ± 1.88 and 53.62 ± 1.04) and ROS production (20.27 ± 1.09% and 19.50 ± 0.35%), significantly different cell death pathways were triggered. While AgNPs induce only apoptosis (45.98 ± 1.88%), Cisplatin induces apoptosis and necrosis at the same rate (22.31 ± 1.72% and 24.07 ± 1.10%, respectively). In addition to their antiproliferative activity, in vivo experiments showed that treatments of 3, 6, and 12 mg/kg of AgNPs elicit a survival rate almost 4 times higher (P < 0.05) compared with the survival rate obtained with Cisplatin (2 mg/kg). Furthermore, the survivor mice treated with AgNPs do not show genotoxic damage determined by micronuclei frequency quantification on peripheral blood cells. These results exhibit the remarkable antitumour activity of a nongenotoxic AgNP formulation and constitute the first advance toward the application of these AgNPs for melanoma treatment, which could considerably reduce adverse effects provoked by currently applied chemotherapeutics.

PMID: 31428226 [PubMed - indexed for MEDLINE]

Inhibitory Effect of Cuphea aequipetala Extracts on Murine B16F10 Melanoma In Vitro and In Vivo.

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Inhibitory Effect of Cuphea aequipetala Extracts on Murine B16F10 Melanoma In Vitro and In Vivo.

Biomed Res Int. 2019;2019:8560527

Authors: Uscanga-Palomeque AC, Zapata-Benavides P, Saavedra-Alonso S, Zamora-Ávila DE, Franco-Molina MA, Arellano-Rodríguez M, Manilla-Muñoz E, Martínez-Torres AC, Trejo-Ávila LM, Rodríguez-Padilla C

Abstract
Cuphea aequipetala (C. aequipetala) has been used in Mexican traditional medicine since prehispanic times to treat tumors. In this paper, we evaluated the antiproliferative and apoptotic effect of the methanolic and aqueous extracts of C. aequipetala on several cancer cell lines including the B16F10 cell line of murine melanoma and carried a murine model assay. In vitro assay analyzed the effect in the cellular cycle and several indicators of apoptosis, such as the caspase-3 activity, DNA fragmentation, phosphatidylserine exposure (Annexin-V), and induction of cell membrane permeabilization (propidium iodide) in the B16F10 cells. In vivo, groups of C57BL/6 female mice were subcutaneously injected with 5x105 B16F10 cells and treated with 25 mg/mL of C. aequipetala extracts via oral. Aqueous and methanolic extracts showed a cytotoxic effect in MCF-7, HepG2, and B16F10 cell lines. The methanolic extract showed more antiproliferative effect with less concentration, and for this reason, the in vitro experiments were only continued with it. This extract was able to induce accumulation of cells on G1 phase of the cell cycle; moreover, it was able to induce DNA fragmentation and increase the activity of caspase-3 in B16F10 cells. On the other hand, in the murine model of melanoma, the aqueous extract showed a greater reduction of tumor size in comparison with the methanolic extract, showing an 80% reduction versus one of around 31%, both compared with the untreated control, indicating a better antitumor effect of C. aequipetala aqueous extract via oral administration. In conclusion, the in vitro data showed that both C. aequipetala extracts were able to induce cytotoxicity through the apoptosis pathway in B16F10 cells, and in vivo, the oral administration of aqueous extract reduces the melanoma tumoral mass, suggesting an important antitumoral effect and the perspective to search for effector molecules involved in it.

PMID: 31275985 [PubMed - indexed for MEDLINE]

Permalink for 'The evaluation of vestibular compensation by vestibular rehabilitation and prehabilitation in short-term postsurgical period in patients following surgical treatment of vestibular schwannoma.'

The evaluation of vestibular compensation by vestibular rehabilitation and prehabilitation in short-term postsurgical period in patients following surgical treatment of vestibular schwannoma.

Fetched: January 5th, 2020, 5:01am GMT

The evaluation of vestibular compensation by vestibular rehabilitation and prehabilitation in short-term postsurgical period in patients following surgical treatment of vestibular schwannoma.

Eur Arch Otorhinolaryngol. 2019 Oct;276(10):2681-2689

Authors: Hrubá S, Chovanec M, Čada Z, Balatková Z, Fík Z, Slabý K, Zvěřina E, Betka J, Plzak J, Čakrt O

Abstract
PURPOSE: Vestibular schwannoma removal causes unilateral vestibular deafferentation, which results in dizziness and postural unsteadiness. Vertigo and balance problems together are among the most important aspects affecting quality of life. Intensive vestibular rehabilitation, which starts before surgery, with following postsurgical supervised rehabilitation, using visual biofeedback propose an instrument to accelerate a recovery process. Another option how to accelerate the vestibular compensation, is employment of presurgical gentamicin ablation together with vestibular rehabilitation (prehabilitation) of vestibular function. Purpose of present study was to examine the dynamics of vestibular compensation process using supervised intensive vestibular rehabilitation with visual biofeedback in the short-term postsurgical period. The second aim was to compare both studied groups mainly to evaluate if prehabilitation has potential to accelerate the compensation process in the early postoperative course.
METHODS: The study included 52 patients who underwent the retrosigmoid vestibular schwannoma removal. They were divided into two groups. The first group was prehabilitated with intratympanic application of gentamicin before surgery to cause unilateral vestibular loss (14 patients), the second group (38 patients) was treated in standard protocol without prehabilitation. All patients underwent at home vestibular training before surgery to learn new movement patterns. Following the surgery supervised intensive vestibular rehabilitation including visual biofeedback was employed daily in both groups between the 5th and 14th postoperative day. Outcome measurements included an evaluation of subjective visual vertical (SVV), posturography and the Activities-Specific Balance Confidence Scale (ABC). ANOVA for repeated measurements was used for statistical analysis.
RESULTS: We observed significant improvement in SVV (p < 0.05), posturography parameters (p < 0.05) and ABC scores (p < 0.05) with postoperative rehabilitation program following surgery in both groups. There was no statistically significant difference between group treated by prehabilitation and group without prehabilitation.
CONCLUSIONS: Results of this study showed that intensive postsurgical rehabilitation represents key factor in compensation process following retrosigmoid vestibular schwannoma surgery. Prehabilitation did not speed up recovery process.

PMID: 31187238 [PubMed - indexed for MEDLINE]

Establishment and characterization of a novel cell line of medullary thyroid carcinoma from a dog.

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Establishment and characterization of a novel cell line of medullary thyroid carcinoma from a dog.

In Vitro Cell Dev Biol Anim. 2019 Aug;55(7):559-566

Authors: Okano K, Uematsu Y, Nibe K, Yamashita M, Suzuki S, Uchida K, Ono K, Hirao H

Abstract
A novel cell line of canine medullary thyroid carcinoma (MTC) was established from the neck mass, diagnosed histopathologically and immunohistochemically as ectopic MTC. The neoplastic cells arranging trabecular structures were characterized as pleomorphic cells with eosinophilic cytoplasm and nucleus, containing often clear nucleolus. These tumor cells were immuno-positive for calcitonin gene-related protein (CGRP), somatostatin, and chromogranin A. In addition, 8th passaged cultured cells were also immuno-positive for CGRP, somatostatin, and chromogranin A. The cloned tumor cells showed logarithmic cell growth with a doubling time of 33.3 h. From the results of DNA sequencing of rearranged during transfection (RET) proto-oncogene, the cloned tumor cells had four single base substitution, including exon 5 codon 82, exon 16 codon 750, exon 17 codon 777, and exon 24 codon 1085, all of which were single nucleotide polymorphism reported in RET gene of dogs. After the xenotransplantation into severe combined immunodeficiency (SCID) mice, the cloned cells showed tumorigenicity potentials. The morphological and immunohistochemical features of the xenotransplanted tumor were almost in conformity with those of the original tumor, including positive immunoreactivity for calcitonin, CGRP, and chromogranin A. To our knowledge, this is the first report of canine MTC cell line, which provides useful in vitro tool for understanding oncogenic mechanism and pathophysiological state of MTC in dogs.

PMID: 31144267 [PubMed - indexed for MEDLINE]

A rare initial clinical presentation of pheochromocytoma.

Fetched: January 5th, 2020, 5:01am GMT

A rare initial clinical presentation of pheochromocytoma.

BMJ Case Rep. 2019 May 24;12(5):

Authors: Burgan H, Celi J

PMID: 31129631 [PubMed - indexed for MEDLINE]

How to treat esophageal neuroendocrine carcinoma with proper stratification?

Fetched: January 5th, 2020, 5:01am GMT

How to treat esophageal neuroendocrine carcinoma with proper stratification?

Dis Esophagus. 2019 Jun 01;32(6):

Authors: Deng HY

PMID: 31022730 [PubMed - indexed for MEDLINE]

Pseudomelanoma (with Cataract) in a Child Caused by Amniocentesis.

Fetched: January 5th, 2020, 5:01am GMT

Pseudomelanoma (with Cataract) in a Child Caused by Amniocentesis.

Ophthalmology. 2019 04;126(4):590

Authors: Abramson DH, Francis JH

PMID: 30910042 [PubMed - indexed for MEDLINE]

Understanding Uveal Melanoma Metastasis to the Liver: The Zimmerman Effect and the Zimmerman Hypothesis.

Fetched: January 5th, 2020, 5:01am GMT

Understanding Uveal Melanoma Metastasis to the Liver: The Zimmerman Effect and the Zimmerman Hypothesis.

Ophthalmology. 2019 04;126(4):483-487

Authors: Grossniklaus HE

PMID: 30910033 [PubMed - indexed for MEDLINE]

The Need for Increased Melanoma Awareness among Non-dermatology Secondary Care Colleagues.

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The Need for Increased Melanoma Awareness among Non-dermatology Secondary Care Colleagues.

Acta Derm Venereol. 2019 Jun 01;99(7):693-694

Authors: Quinlan C, McCracken S, Tierney E, Heffron C, Fitzgibbon J, Murphy C, Bourke JF, Murphy M

PMID: 30896782 [PubMed - indexed for MEDLINE]

Permalink for 'Linking dose delivery accuracy and planning target margin in radiosurgery based on dose-volume histograms derived from measurement-guided dose reconstruction.'

Linking dose delivery accuracy and planning target margin in radiosurgery based on dose-volume histograms derived from measurement-guided dose reconstruction.

Fetched: January 5th, 2020, 5:01am GMT

Linking dose delivery accuracy and planning target margin in radiosurgery based on dose-volume histograms derived from measurement-guided dose reconstruction.

Phys Med Biol. 2019 02 11;64(4):045009

Authors: Chan MKH, Leung RWK, Lee VWY, Wong MYP, Chiang CL, Law GML, Blanck O

Abstract
In radiosurgery (SRS), the geometric uncertainties of machine-related delivery including image-guidance and hence the planning target volume (PTV) are often evaluated by the end-to-end gamma (γ) comparison that carries no information about the clinical relevance of deviations of individual SRS plans during delivery quality assurance (DQA). A proof-of-concept method was proposed to derive the PTV against both the plan- and the machine-specific delivery errors directly from the clinically relevant dose-volume histograms (DVHs) using measured-guided dose reconstruction (MGDR) during DQA. A liquid-filled detector array and a rotating phantom were used to measure sixteen arc-based radiosurgery treatments with 1 and 2 mm gross tumor volume (GTV)-to-PTV margins, producing MGDR-3D dose distribution on both the phantom and the patient CT for γ index and clinical DVH evaluations, respectively. The PTV was considered optimal when the MGDR showed the desired prescription dose coverage (V pres ) of the GTV (100% in this study). Associations of the binary V pres outcomes (<or =100%) of the GTV with the acceptance level of percent γ pass rate (γPR%) at 90 versus 95% were assessed. Further receiver operator characteristic (ROC) analysis was performed to assess the distance-to-agreement (DTA) and local dose difference (ΔD) criteria that may be suitable for treatment acceptance. From the MGDR, 100% GTV V pres was achieved in 68.8% and 100% of plans with 1 and 2 mm PTV, respectively. V pres outcomes were neither associated with γPR% at 1-2 mm DTA and 1%-3% ΔD nor the acceptance level for MGDR in the patient CT. ROC analysis shows statistically significant AUC values from 0.78-0.84 and 0.79-0.80 for MGDR phantom and patient doses, respectively. DQA by MGDR-DVH objectives offers the unique opportunity of direct assessment of the dose delivery accuracy and hence the optimal PTV without subject to the statistical correlation between γPR% and clinical metrics. Based on multi-criteria DVH objectives, clinical decision can be instantly made to adjust the treatment plan prescription.

PMID: 30630157 [PubMed - indexed for MEDLINE]

Permalink for 'Data Set for the Reporting of Mucosal Melanomas of the Head and Neck: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.'

Data Set for the Reporting of Mucosal Melanomas of the Head and Neck: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Fetched: January 5th, 2020, 5:01am GMT

Data Set for the Reporting of Mucosal Melanomas of the Head and Neck: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Arch Pathol Lab Med. 2019 05;143(5):603-609

Authors: Williams MD, Franchi A, Helliwell T, Müller S, Thompson LDR

Abstract
Standardized pathologic reporting for cancers allows for improved communication for patient care and prognostic determination. If used universally, synoptic reporting enhances comparing data globally for scientific leverage. The International Collaboration on Cancer Reporting is a nonprofit organization whose mission is to develop evidence-based, universally available surgical pathology reporting data sets. Multiple different sites within the head and neck may be affected by mucosal melanoma, whose behavior and patient outcome are not equivalent to carcinomas of the corresponding sites. Factors such as Breslow thickness and Clark depth of invasion applied to cutaneous melanomas do not yield any prognostic significance in mucosal sites, and thus are not meaningful. Likewise, margin assessment is unique in head and neck sites. Further, the genetic profile of mucosal melanomas is different from that of most cutaneous tumors. Thus, within the head and neck region, mucosal melanoma is a distinct entity for which a dedicated data set was developed for implementation. The elements that comprise the core (required) and noncore (recommended) elements are discussed.

PMID: 30500297 [PubMed - indexed for MEDLINE]

Permalink for 'MicroRNA-378 regulates epithelial-mesenchymal transition and metastasis of melanoma by inhibiting FOXN3 expression through the Wnt/β-catenin pathway.'

MicroRNA-378 regulates epithelial-mesenchymal transition and metastasis of melanoma by inhibiting FOXN3 expression through the Wnt/β-catenin pathway.

Fetched: January 5th, 2020, 5:01am GMT

MicroRNA-378 regulates epithelial-mesenchymal transition and metastasis of melanoma by inhibiting FOXN3 expression through the Wnt/β-catenin pathway.

Cell Biol Int. 2019 Oct;43(10):1113-1124

Authors: Sun M, Ma X, Tu C, Wang X, Qu J, Wang S, Xiao S

Abstract
MicroRNAs (miRNAs) participate in the development and progression of melanoma. However, while dysregulation of microRNA-378 (miR-378) has been seen in various cancer types, its clinical importance and function in melanoma are poorly elucidated. In this work, miR-378 expression in melanoma and in adjacent non-cancerous tissue was evaluated with a quantitative real-time polymerase chain reaction. A series of assays (wound healing, Transwell, and nude mouse subcutaneous tumor model) were used to investigate the implications of abnormal miR-378 regulation on melanoma cell migration and invasion in vitro, and on tumorigenicity in vivo. Prediction and conformation of the miR-378 target gene was undertaken using bioinformatic analysis and luciferase reporter system. Expression of miR-378 was often increased in melanoma, and shown to potentiate its migration, invasion, and tumorigenicity. miR-378 acted, at least partially, through inhibition of the potential target FOXN3 and via Wnt/β-catenin pathway activation. The findings indicate that miR-378 triggers melanoma development and progression. This miRNA could be a novel diagnostic and prognostic biological marker and provide utility for targeted treatment of melanoma.

PMID: 29972255 [PubMed - indexed for MEDLINE]

Permalink for 'Adrenomedullary function, obesity and permissive influences of catecholamines on body mass in patients with chromaffin cell tumours.'

Adrenomedullary function, obesity and permissive influences of catecholamines on body mass in patients with chromaffin cell tumours.

Fetched: January 5th, 2020, 5:01am GMT

Adrenomedullary function, obesity and permissive influences of catecholamines on body mass in patients with chromaffin cell tumours.

Int J Obes (Lond). 2019 02;43(2):263-275

Authors: An Y, Reimann M, Masjkur J, Langton K, Peitzsch M, Deutschbein T, Fassnacht M, Rogowski-Lehmann N, Beuschlein F, Fliedner S, Stell A, Prejbisz A, Januszewicz A, Lenders J, Bornstein SR, Eisenhofer G

Abstract
BACKGROUND: Obesity-associated activation of sympathetic nervous outflow is well documented, whereas involvement of dysregulated adrenomedullary hormonal function in obesity is less clear. This study assessed relationships of sympathoadrenal function with indices of obesity and influences of circulating catecholamines on body mass.
METHODS: Anthropometric and clinical data along with plasma and 24-h urine samples were collected from 590 volunteers and 1368 patients tested for phaeochromocytoma and paraganglioma (PPGL), among whom tumours were diagnosed in 210 individuals.
RESULTS: Among patients tested for PPGL, those with tumours less often had a body mass index (BMI) above 30 kg/m2 (12 vs. 31%) and more often a BMI under 25 kg/m2 (56 vs. 32%) than those without tumours (P < 0.0001). Urinary outputs of catecholamines in patients with PPGL were negatively related to BMI (r = -0.175, P = 0.0133). Post-operative weight gain (P < 0.0001) after resection of PPGL was positively related to presurgical tumoural catecholamine output (r = 0.257, P = 0.0101). Higher BMI in men and women and percent body fat in women of the volunteer group were associated with lower plasma concentrations and urinary outputs of adrenaline and metanephrine, the former indicating obesity-related reduced adrenaline secretion and the latter obesity-related reduced adrenomedullary adrenaline stores. Daytime activity was associated with substantial increases in urinary adrenaline and noradrenaline excretion, with blunted responses in obese subjects.
CONCLUSIONS: The findings in patients with PPGL support an influence of high circulating catecholamines on body weight. Additional associations of adrenomedullary dysfunction with obesity raise the possibility of a permissive influence of the adrenal medulla on the regulation of body weight.

PMID: 29717268 [PubMed - indexed for MEDLINE]

VEGF Induce Vasculogenic Mimicry of Choroidal Melanoma through the PI3k Signal Pathway.

Fetched: January 4th, 2020, 5:01am GMT

VEGF Induce Vasculogenic Mimicry of Choroidal Melanoma through the PI3k Signal Pathway.

Biomed Res Int. 2019;2019:3909102

Authors: Xu X, Zong Y, Gao Y, Sun X, Zhao H, Luo W, Jia S

Abstract
Purpose: To explore the effect of VEGF (vascular endothelial growth factor) on the vasculogenic mimicry (VM) formation of Choroidal Melanoma (CM) through PI3k signal pathway, to find novel targets for CM therapy.
Methods: This research investigated the molecular mechanism of VEGF promoting VM formation of CM. First, we evaluated the expressions of VEGF in 20 CM specimens by immunohistochemical determination. Then we detected expressions of VEGF, AKT, MT1-MMP, MMP2, and MMP9 of OCM-1 in hypoxia. siRNA was used to inhibit the expression of VEGF, to realize the control of the VM formation. The VM formation was evaluated through wound healing assay, transwell assay, and apoptosis. And then we testify the correlation of the VM and the factors in protein and mRNA level preliminarily.
Results: VEGF protein was expressed in CM in all 20 cases of CM, especially along the VM. In hypoxia, the expression of VEGF in OCM-1 increased significantly. VEGF gene deletion reduced the proliferation, migration, and invasion of OCM-1. VEGF gene deletion impaired the expression of invasive associated genes like VEGF, p-AKT, AKT, MT1-MMP, MMP2, and MMP9. These results indicate that VEGF induce VM formation in CM by activating PI3K/AKT signaling pathway.
Conclusions: VEGF promoted VM formation by the PI3K signal transduction pathway, indicating a molecular mechanism which may be used to develop new therapeutic targets for the clinical treatment of CM.

PMID: 31380420 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma with kidney metastasis in a 81-year-old man. A rare case report.

Fetched: January 4th, 2020, 5:01am GMT

Merkel cell carcinoma with kidney metastasis in a 81-year-old man. A rare case report.

Arch Ital Urol Androl. 2019 Jul 02;91(2):

Authors: Anastasiou A, Moulavasilis N, Leotsakos I, Nerantzis CE, Anastasiou I

PMID: 31266284 [PubMed - indexed for MEDLINE]

Oral malignant melanoma of alveolar ridge.

Fetched: January 4th, 2020, 5:01am GMT

Oral malignant melanoma of alveolar ridge.

BMJ Case Rep. 2019 May 31;12(5):

Authors: Astekar M, Choubey RR, Manjunatha BS, Gupta S

Abstract
Malignancy of melanocytes, a pigment-producing cell, is referred as malignant melanoma (MM) which occur basically on skin and oral mucous membrane, but as well found in ears, eyes, gastrointestinal tract and genital mucosa. Oral melanomas has propensity to metastasise and invade more voluntarily than other malignant counterparts. Here we present a case of 52-year-old male patient with a chief symptom of blackening of gums in the upper front tooth region. In dental history, the patient revealed history of faulty artificial prosthesis fixed in the same region since 6 months. On the basis of a through clinical assessment, a provisional opinion of oral malignant melanoma, was prepared. On histopathological and immunohistochemical analysis with S-100 and homatropine methylbromide 45 the diagnosis of MM was confirmed.

PMID: 31154344 [PubMed - indexed for MEDLINE]

ALDH1 - A new immunohistochemical diagnostic marker for Schwann cell-derived tumors.

Fetched: January 4th, 2020, 5:01am GMT

ALDH1 - A new immunohistochemical diagnostic marker for Schwann cell-derived tumors.

Clin Neuropathol. 2019 Jul/Aug;38(4):168-173

Authors: Liesche F, Griessmair M, Barz M, Gempt J, Schlegel J

Abstract
Although Schwann cell-derived tumors show typical histological features, the broad variety of spindle cell tumors that exist can impede the diagnostic procedure. In this study, we present aldehyde dehydrogenase 1 (ALDH1) as a new, viable diagnostic marker for Schwann cell tumors. Protein expression was examined by immunohistochemistry in schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (MPNST) as well as in non-neoplastic peripheral nerve sheath specimens. Meningiomas and other spindle cell-like tumors served as control tissue. ALDH1 immunohistochemistry was performed on human FFPE samples. Staining evaluation was performed according to a defined immunoreactive score. All schwannomas and neurofibromas were strongly positive for ALDH1. MPNST were positive too, but with a clear reduction of ALDH1 expression. All non-Schwann-cell-derived tumors showed no immunoreaction. This leads to the conclusion that ALDH1 can serve a as viable diagnostic marker for schwannomas and neurofibromas as it was expressed and detected by IHC in all samples. Furthermore, ALDH1 expression seems to be a sign for differentiation as it diminishes during malignization of Schwann cell tumors. Hence, its expression level provides information about the biological behavior of the tumor.

PMID: 31131824 [PubMed - indexed for MEDLINE]

Freiburg Neuropathology Case Conference: a Hemorrhagic Intraspinal Tumor Extending from L3 to S1.

Fetched: January 4th, 2020, 5:01am GMT

Freiburg Neuropathology Case Conference: a Hemorrhagic Intraspinal Tumor Extending from L3 to S1.

Clin Neuroradiol. 2019 Jun;29(2):383-389

Authors: Taschner CA, Schwabenland M, Hubbe U, Urbach H, Stadler A, Prinz M

PMID: 31119325 [PubMed - indexed for MEDLINE]

Metastatic melanoma of the small bowel. Report of a case and review of literature.

Fetched: January 4th, 2020, 5:01am GMT

Metastatic melanoma of the small bowel. Report of a case and review of literature.

Ann Ital Chir. 2019 May 05;89:

Authors: Mazzeo C, Viscosi F, Foti A, Cucinotta E

Abstract
AIM: Malignant melanoma incidence is rapidly growing worldwide. The small bowel is well known to be a preferred site for melanoma metastases. In 60% of patients who died of disseminated melanoma, the gastrointestinal (GI) tract was affected, but only 1% to 4% of GI metastases were clinically diagnosed ante mortem.
CASE REPORT: In this case we describe a report of a 71 years old male admitted to the hospital with a combination of two possible complications of GI metastatic melanoma: obstruction and GI bleeding. Past medical history reveals a malignant cutaneous melanoma excised 5 years before.
DISCUSSION: Symptoms of small bowel involvement are frequently unspecific which leads to a late diagnosis often made only after complications, such as intestinal obstruction, massive gastrointestinal bleeding and perforation. In most cases, the diagnosis of melanoma metastasis was made only after surgery, which proved to be life-saving. We have searched literature for these complications and their relative treatment.
CONCLUSIONS: Modern imaging techniques are recommended in order to obtain an early diagnosis. Surgical resection is the only treatment in patients with resectable metastatic intestinal melanoma.
KEY WORDS: Acute abdomen, Metastatic melanoma, Small-bowel, Surgery.

PMID: 31112516 [PubMed - indexed for MEDLINE]

An investigation of life quality of patients after two different acoustic neuroma resections.

Fetched: January 4th, 2020, 5:01am GMT

An investigation of life quality of patients after two different acoustic neuroma resections.

Acta Otolaryngol. 2019 Jul;139(7):547-551

Authors: Ning F, Zuo H, Guo L, Jiao C, Xu X, Kong B, Yang S

Abstract
Background: Patients may suffer postoperative facial nerve injury, hearing loss, or other postoperative complications after the operation, which seriously affect their postoperative life quality. Aims/objectives: To investigate the differences in QOL (quality of life) of patients with acoustic neuroma resection by the translabyrinthine or retrosigmoid approach. Material and methods: Patients with acoustic neuroma resection in our department were enrolled in this experimental study, among which fifty patients underwent the translabyrinthine approach resection, the other 50 patients underwent the retrosigmoid approach resection. Different scores by the SF-36 scale between these two groups of patients one month after discharge were then analyzed. Results: Scores of patients undergoing the retrosigmoid approach were higher in the three dimensions of Social Functioning, Role-emotional and Mental Health than those of patients undergoing the translabyrinthine approach with statistical significance. However, scores of patients undergoing the translabyrinthine approach were higher in the two dimensions of Body Pain and Vitality than those of the patients undergoing the retrosigmoid approach. Conclusions and significance: The results indicated that individual nursing interventions for different patients are necessary to improve the QOL of patients after hospitalization. Moreover, the operated patients with translabyrinthine approach were more advantage than patients with retrosigmoid approach.

PMID: 31050576 [PubMed - indexed for MEDLINE]

Permalink for 'Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy.'

Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy.

Fetched: January 4th, 2020, 5:01am GMT

Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy.

PLoS One. 2019;14(4):e0214884

Authors: Consoli F, Manganoni AM, Grisanti S, Petrelli F, Venturini M, Rangoni G, Guarneri F, Incardona P, Vermi W, Calzavara Pinton PG, Berruti A

Abstract
Panniculitis and vitiligo-like lesions have been recently identified as rare cutaneous side effects of the combination of BRAF and MEK inhibitors, a standard of care in metastatic and locally advanced BRAF V600 mutated melanoma. An immune-mediated mechanism has been advocated in the pathogenesis of these skin lesions. Herein we retrospectively reviewed our institutional experience with the aim to explore the association between the occurrence of panniculitis and vitiligo-like lesions during combination therapy with dabrafenib (D) and trametinib (T) and outcome of advanced melanoma patients. Among 52 consecutive BRAF V600 mutated melanoma patients submitted to DT in our center, 12 (23%) developed immune related skin lesions (IRSLs): 8 panniculitis and 4 vitiligo. Patients with IRSLs diagnosis obtained a better disease response (83% versus 25%) (p = 0.001) than their counterpart and had a longer progression free survival and overall survival. The association of IRSLs and lower risk of disease progression (HR 0.19; CI 95% 0.04-0.90; p = 0.043) was confirmed after adjusting for major prognostic factors in multivariate analysis. IRSLs might represent an easy predictive surrogate marker for treatment response and favourable outcome in melanoma patients submitted to DT combination therapy.

PMID: 30939167 [PubMed - indexed for MEDLINE]

Application of temporary agglomeration of chitosan-coated nanoparticles for the treatment of lung metastasis of melanoma.

Fetched: January 4th, 2020, 5:01am GMT

Application of temporary agglomeration of chitosan-coated nanoparticles for the treatment of lung metastasis of melanoma.

J Colloid Interface Sci. 2019 May 15;544:266-275

Authors: Lee SY, Koo JS, Yang M, Cho HJ

Abstract
Temporary association of chitosan (CS)-coated nanoparticles (NPs) including phloretin (Phl) in the blood stream can be applied to treat lung metastasis of melanoma. Phl was entrapped in poly(d,l-lactide-co-glycolide) (PLGA) NPs as an anticancer agent, whereas CS was decorated onto the outer surfaces of the Phl-loaded PLGA NPs (PLGA/Phl NPs). CS-coated PLGA/Phl NPs (CS-PLGA/Phl NPs) with mean hydrodynamic sizes of 342 nm, spherical shapes, unimodal size distribution, positive zeta potentials, and drug encapsulation efficiency larger than 90% were prepared. The presence of the CS layers in the outer surfaces of the CS-PLGA/Phl NPs was elucidated by X-ray photoelectron spectroscopy. Upon blending of the CS-PLGA/Phl NPs with serum albumin, microscale agglomerates formed and easily dissociated into individual NPs by applying external forces. A sustained Phl release from NPs and similar antiproliferation potential of the CS-PLGA/Phl NPs to that of Phl in melanoma (B16F10) cells were observed. After multiple dosing of developed NPs in mouse models with lung metastasis of melanoma, the CS-PLGA/Phl NPs group exhibited significantly lower lung weight and number of metastasis foci than the PLGA/Phl NPs group (p < 0.05). These results suggest that the transient transformation of NPs into microscale aggregates and their facile dissociation into individual NPs can be efficiently and safely applied for the treatment of lung metastasis of melanoma.

PMID: 30852352 [PubMed - indexed for MEDLINE]

Massively parallel sequencing analysis of benign melanocytic naevi.

Fetched: January 4th, 2020, 5:01am GMT

Massively parallel sequencing analysis of benign melanocytic naevi.

Histopathology. 2019 Jul;75(1):29-38

Authors: Lozada JR, Geyer FC, Selenica P, Brown D, Alemar B, Merghoub T, Berger MF, Busam KJ, Halpern AC, Weigelt B, Reis-Filho JS, Hollmann TJ

Abstract
AIMS: Melanocytic naevi are benign lesions of the skin or mucosa that may constitute non-obligate precursors of malignant melanoma, particularly when they show lentiginous and dysplastic features. The aim of this study was to investigate the repertoire of somatic genetic alterations in melanocytic naevi.
METHODS AND RESULTS: DNA extracted from 12 melanocytic naevi and DNA from matching normal tissue were separately microdissected and subjected to targeted massively parallel sequencing of ≥300 cancer genes. A median of 5.5 (range 1-12) non-synonymous somatic mutations were detected, with 10 cases harbouring mutually exclusive BRAF V600E (6/12) or NRAS (4/12) clonal hotspot mutations. One of the two cases lacking BRAF and NRAS mutations was a dysplastic naevus harbouring an HRAS Q61L hotspot mutation. Analysis of the laser-capture microdissected components of a naevus synchronously diagnosed with in-situ and invasive malignant melanoma revealed a truncal, clonal BRAF V600E mutation, and the acquisition of a CDKN2A homozygous deletion in the invasive component, in conjunction with additional clonal mutations affecting NF2, FAT4 and KDR in both in-situ and invasive malignant components.
CONCLUSION: Melanocytic naevi harbour recurrent BRAF V600E or NRAS hotspot mutations with low mutational burdens. Our findings also show that progression from naevi to malignant melanoma may be driven by the acquisition of additional genetic alterations, including CDKN2A homozygous deletions.

PMID: 30791119 [PubMed - indexed for MEDLINE]

Anaplastic lymphoma kinase expression in small-cell lung cancer.

Fetched: January 4th, 2020, 5:01am GMT

Anaplastic lymphoma kinase expression in small-cell lung cancer.

Histopathology. 2019 Jul;75(1):20-28

Authors: Kondoh C, Horio Y, Hayashi Y, Ebi H, Hida T, Hasegawa Y, Yatabe Y

Abstract
AIMS: Anaplastic lymphoma kinase (ALK) immunohistochemistry has shifted from being a screening tool to being a sole determinant for ALK-targeted therapy. Recent articles have referred to small-cell lung cancer (SCLC) transformation as a resistance mechanism after ALK inhibitor treatments, but few reports have addressed ALK expression in treatment-naive SCLC in a comprehensive manner. Therefore, we examined ALK expression and the mechanisms in treatment-naive SCLCs.
METHODS AND RESULTS: We examined ALK expression in a consecutive series of SCLC tumours, and the expression mechanism was analysed regarding gene rearrangement, copy number changes, and point mutations. We also examined whether SCLC with ALK expression can be suppressed by crizotinib treatment in vitro. Immunohistochemical results revealed that ALK was expressed in 16 of 142 (11.3%) SCLCs. The expression was focal and less intense, which is in contrast to strong and uniform expression in adenocarcinoma with ALK rearrangement. Two combined SCLCs showed a positive reaction restricted to the SCLC component. None of the known genetic alterations, including rearrangement, amplification, copy number gain, or point mutations, were associated with ALK expression. A SCLC cell line, SKLC2, which expressed ALK without known genetic alterations, was not inhibited by a practically achievable serum concentration of crizotinib.
CONCLUSIONS: Anaplastic lymphoma kinase immunohistochemistry for treatment-naive SCLCs should not be used as a predictive biomarker for ALK inhibitor therapy, because the positive reactions were due to intrinsic expression of normal ALK transcript.

PMID: 30790327 [PubMed - indexed for MEDLINE]

Permalink for 'Postanal minimally invasive surgery "PAMIS" assisted extra-levator abdominoperineal excision "ELAPE" for cancer: A novel approach in supine position.'

Postanal minimally invasive surgery "PAMIS" assisted extra-levator abdominoperineal excision "ELAPE" for cancer: A novel approach in supine position.

Fetched: January 4th, 2020, 5:01am GMT

Postanal minimally invasive surgery "PAMIS" assisted extra-levator abdominoperineal excision "ELAPE" for cancer: A novel approach in supine position.

Arab J Gastroenterol. 2019 Mar;20(1):53-55

Authors: Farag A

Abstract
Local recurrences are more common after abdominoperineal excision (APE) than after anterior resection of rectal cancer. Extralevator APE was introduced to address this problem. The post anal minimally invasive approach had been used by other authors for transperineal mesh rectopexy but not in cancer management. Our aim is to use the post-anal minimally invasive approach for better visualization and division of the levator Ani during the Extralevator abdominoprineal excision in 2 cases of carcinoma of the anal canal. After laparoscopic exploration of the abdomen and performing a laparoscopic nerve sparing TME down to the levator ani from the abdominal side, the perineal phase was started by a purse string suture followed by a postanal incision and division of the Anococcygeal ligament, the gel port was inserted where visualization of the levator ani allows its division under vision posteriorly and laterally in order to achieve a good circumferential resection margin in the studied 2 cases. Good circumferential resection margin was reported pathologically and photographed in one of them. Postanal minimally invasive PAMIS assisted technique facilitates the extralevator abdominoperineal "ELAPE" in supine position. However a large multicenter trial comparing this new assisted technique with the traditional ELAPE id needed for a final conclusion.

PMID: 30770261 [PubMed - indexed for MEDLINE]

Phenotypic and genotypic analysis of amelanotic and hypomelanotic melanoma patients.

Fetched: January 4th, 2020, 5:01am GMT

Phenotypic and genotypic analysis of amelanotic and hypomelanotic melanoma patients.

J Eur Acad Dermatol Venereol. 2019 Jun;33(6):1076-1083

Authors: Rayner JE, McMeniman EK, Duffy DL, De'Ambrosis B, Smithers BM, Jagirdar K, Lee KJ, Soyer HP, Sturm RA

Abstract
BACKGROUND: Amelanotic/hypomelanotic melanoma is associated with poorer outcomes due to a more advanced disease stage at diagnosis.
OBJECTIVE: To determine phenotypic risks and genotypic associations with amelanotic/hypomelanotic melanoma to develop a clinical and genetic profile that could assist in identifying high-risk individuals.
METHODS: The Brisbane Naevus Morphology Study conducted from 2009 to 2016 has recruited a core of 1254 participants. Participants were drawn from a combination of volunteers from dermatology outpatient clinics, private dermatology clinics, the Brisbane Longitudinal Twin Study and QSkin study. Case participants had a personal history of melanoma and control participants no personal history of melanoma. We specifically examined seven known candidate pigmentation and melanoma genes and pigmentary phenotypic characteristics in participants with amelanotic/hypomelanotic melanoma compared to pigmented melanomas. This assayed single nucleotide polymorphisms in MC1R, TYR, HERC/OCA2, IRF4, MTAP, PLA2G6 and MITF.
RESULTS: Forty-seven participants had at least one amelanotic/hypomelanotic melanoma, and 389 had pigmented melanomas, with amelanotic/hypomelanotic melanoma patients significantly older than pigmented melanoma participants (63.3 ± 13.0 vs. 54.6 ± 15.3 years; P < 0.001). Amelanotic/hypomelanotic melanoma patients were more likely than pigmented melanoma patients to have red hair (34% vs. 15%; P = 0.01), severe hand freckling (13% vs. 5%; P = 0.01) and propensity to sunburn (63% vs. 44%; P = 0.01). MC1R R/R genotype was much more frequent in our amelanotic/hypomelanotic melanoma population (31.1% vs. 11%; P < 0.001; OR 26.4 vs. 5.9; control 1.0). Amelanotic/hypomelanotic melanoma was associated with TYR rs1126809*A/A [OR (CI 95%) 2.7 (1.1-6.8) vs. 1.2 (0.8-1.9)] and PLA2G6 rs11570734*A/A [OR (CI 95%) 3.7 (1.0-13.6) vs. 1.3 (0.9-2.0)]. The MTAP melanoma risk SNP genotype, associated with darker pigmentation, (rs4636294*A/A) was less common in amelanotic/hypomelanotic melanoma patients [OR (CI 95%) 0.8 (0.3-2.1) vs. 2.0 (1.3-3.1)].
CONCLUSIONS: Knowledge of phenotypic and genotypic associations of amelanotic/hypomelanotic melanoma can help predict risks and associations of this difficult to diagnose melanoma, which may ultimately assist clinical management and patient skin self-examination.

PMID: 30680790 [PubMed - indexed for MEDLINE]

Carboranyl Analogues of Celecoxib with Potent Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines.

Fetched: January 4th, 2020, 5:01am GMT

Carboranyl Analogues of Celecoxib with Potent Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines.

ChemMedChem. 2019 02 05;14(3):315-321

Authors: Buzharevski A, Paskas S, Sárosi MB, Laube M, Lönnecke P, Neumann W, Mijatovic S, Maksimovic-Ivanic D, Pietzsch J, Hey-Hawkins E

Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common way of treating inflammatory disorders. Their widespread use helped reveal their other modes of action as pharmaceuticals, such as a profound effect on various cancers. Celecoxib has proven to be a very prominent member of this group with cytostatic activities. On the other hand, the highly dynamic field of drug design is constantly searching for new ways of modifying known structures to obtain more powerful and less harmful drugs. A very interesting development is the implementation of carboranes in pharmacologically active structures, mostly as phenyl mimetics. Herein we report the synthesis of three carborane-containing derivatives of the COX-2-selective NSAID celecoxib. The new compounds proved to have promising cytostatic potential against various melanoma and colorectal adenocarcinoma cell lines. Inhibited proliferation accompanied by caspase-independent apoptotic cell death was found to be the main cause of decreased cell viability upon treatment with the most efficient celecoxib analogue, 3 b (4-[5-(1,7-dicarba-closo-dodecaboranyl)-3-trifluoromethyl-1H-pyrazol-1-yl]-1-methylsulfonylbenzene).

PMID: 30602073 [PubMed - indexed for MEDLINE]

Succinate dehydrogenase mutations: paraganglioma imaging and at-risk population screening.

Fetched: January 4th, 2020, 5:01am GMT

Succinate dehydrogenase mutations: paraganglioma imaging and at-risk population screening.

Clin Radiol. 2019 03;74(3):169-177

Authors: Cavenagh T, Patel J, Nakhla N, Elstob A, Ingram M, Barber B, Snape K, Bano G, Vlahos I

Abstract
Paragangliomas are rare vascular tumours of the autonomic nervous system. They can be classified as sympathetic or parasympathetic. Sympathetic paragangliomas, which include phaeochromocytomas, tend to be functional and symptomatic. Parasympathetic paragangliomas are usually non-functional and may present with mass effect. Forty percent of paragangliomas are linked to genetic syndromes, most commonly due to mutations of the succinate dehydrogenase (SDH) enzyme complex and are collectively known as paraganglioma syndromes, of which five are described. Genetic testing is recommended for all patients, and their first-degree relatives, diagnosed with paragangliomas. When SDH mutations are discovered, biochemical screening and imaging surveillance is indicated. There is currently no consensus on imaging surveillance protocols. Most advocate full-body imaging, but the choice of technique and frequency varies. If paragangliomas are demonstrated, functional imaging to look for synchronous tumours or metastases is indicated. 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)-computed tomography (CT) is the technique of choice for metastatic evaluation, but [123I]-metaiodobenzylguanidine or [111In]-DTPA-octreotide scintigraphy are also utilised. Current research into emerging positron-emitting radiolabelled somatostatin analogues have yielded promising results, which is likely to be reflected in future guidelines. As genetic testing becomes increasingly prevalent, the need to answer the remaining questions regarding surveillance imaging is paramount.

PMID: 30551795 [PubMed - indexed for MEDLINE]

Permalink for 'Sinonasal inverted papilloma associated with small cell neuroendocrine carcinoma: A case report and literature review of rare malignancies associated with inverted papilloma.'

Sinonasal inverted papilloma associated with small cell neuroendocrine carcinoma: A case report and literature review of rare malignancies associated with inverted papilloma.

Fetched: January 4th, 2020, 5:01am GMT

Sinonasal inverted papilloma associated with small cell neuroendocrine carcinoma: A case report and literature review of rare malignancies associated with inverted papilloma.

Auris Nasus Larynx. 2019 Aug;46(4):641-650

Authors: Nakamura Y, Suzuki M, Ozaki S, Yokota M, Nakayama M, Hattori H, Inagaki H, Murakami S

Abstract
We report a rare case of sinonasal inverted papilloma (IP) associated with small cell neuroendocrine carcinoma (SNEC). To our knowledge, this is the first report to describe SNEC found during the treatment of sinonasal IP. Surgery and five cycles of cisplatin plus etoposide with concurrent intensity modulated radiation therapy were performed. Neither local recurrence nor distant metastasis was noted during 6 years of post-diagnostic follow-up. The prognosis of SNEC is very poor. Treatment planning for sinonasal IP should consider a possible association with this rare but aggressive malignancy, whose treatment is completely different from that of squamous cell carcinoma, a malignancy which is commonly associated with IP. We also performed a PubMed review of the literature to identify the incidence and pathological diagnosis of associated malignancy. Among a total of 5286 cases of sinonasal IP (61 studies), the incidence of associated malignancy was 8.02% in squamous cell carcinoma, 0.19% in transitional cell carcinoma, 0.04% in mucoepidermoid carcinoma, 0.02% in verrucous cell carcinoma and 0.02% in adenocarcinoma. The incidence of associated malignancy was significantly higher in East and Southeast Asia (11.0%) and North America (10.4%) than in Europe (3.9%) (p=0.04 and p=0.03, respectively; T-test).

PMID: 30545727 [PubMed - indexed for MEDLINE]

Enhanced combination cancer therapy using lipid-calcium carbonate/phosphate nanoparticles as a targeted delivery platform.

Fetched: January 4th, 2020, 5:01am GMT

Enhanced combination cancer therapy using lipid-calcium carbonate/phosphate nanoparticles as a targeted delivery platform.

Nanomedicine (Lond). 2019 01;14(1):77-92

Authors: Wu Y, Gu W, Xu ZP

Abstract
AIM: Melanoma, the most life-threatening skin cancer, requires more effective therapies.
METHODOLOGY: A new folic acid (FA) receptor-targeted lipid-coated calcium carbonate/phosphate (LCCP) nanoparticle was synthesized, incorporating two often-used therapeutics, cell death siRNA and α-tocopheryl succinate.
RESULTS: The nanoparticles were spherical, with an average size of 40 nm. The nanoparticles exhibited a high gene/drug loading efficiency (60%), with folic acid-enhanced cellular uptake. The nanoparticles with both therapeutics enhanced inhibition of B16F0 melanoma cell growth, showing a moderate synergistic effect. The mechanism of the inhibition is associated with induction of cell apoptosis and cell cycle arrest at G1 phase.
CONCLUSION: Our data indicate that lipid-coated calcium carbonate/phosphate nanoparticles are a potential platform for targeted therapy for melanoma.

PMID: 30543136 [PubMed - indexed for MEDLINE]

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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Endocrine/Neuroendocrine (466 unread)

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