Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (524 unread)

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Merkel Cell Carcinoma in a Patient With CLL/Atypical AML.

Fetched: December 16th, 2018, 5:01am GMT

Merkel Cell Carcinoma in a Patient With CLL/Atypical AML.

J Cutan Med Surg. 2018 May/Jun;22(3):324

Authors: Lipner SR

PMID: 29865947 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma.

Fetched: December 16th, 2018, 5:01am GMT

Merkel Cell Carcinoma.

J Cutan Med Surg. 2017 Sep/Oct;21(5):438

Authors: Vangipuram R, Tyring SK

PMID: 28920480 [PubMed - indexed for MEDLINE]

Antitumor and Anti-Hepatitis C Viral Response After Administration of the Anti-Programmed Death 1 Antibody Pembrolizumab.

Fetched: December 16th, 2018, 5:01am GMT

Antitumor and Anti-Hepatitis C Viral Response After Administration of the Anti-Programmed Death 1 Antibody Pembrolizumab.

J Oncol Pract. 2017 07;13(7):462-464

Authors: Jang S, Venna S

PMID: 28562196 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma in the HIV-1/AIDS Patient.

Fetched: December 15th, 2018, 5:01am GMT

Merkel Cell Carcinoma in the HIV-1/AIDS Patient.

Cancer Treat Res. 2019;177:211-229

Authors: Goldstein RH, DeCaprio JA

Abstract
Merkel cell carcinoma (MCC) is a highly aggressive, primary neuroendocrine cancer of the skin. The majority of MCC cases are associated with the recently discovered Merkel cell polyomavirus (MCPyV), while the remaining are caused by ultraviolet (UV) light-induced mutations from excessive sunlight exposure. The risk of developing MCC is much higher in the white population relative to all other races. Approximately 10% of all patients with MCC have some form of immunosuppression including HIV-1/AIDS, chronic inflammatory conditions, solid organ transplantation, or hematological malignancies. The age of onset of MCC is lower and the mortality is higher in immunosuppressed individuals than in immune-competent patients. It is plausible that HIV-1/AIDS predisposes to virus-positive MCC, but it should be noted that HIV-1/AIDS increases the risk for developing of UV-induced skin cancers such as cutaneous squamous cell carcinoma and basal cell carcinoma and therefore may also increase the risk for virus-negative MCC. Surgical management is considered standard of care for localized Merkel cell carcinoma with current recommendations advising a wide local excision of the lesion. Most international guidelines support the use of local adjuvant radiotherapy coupled with tumor staging to improve the frequency of cure. For advanced, metastatic, and recurrent MCC, checkpoint blockade inhibitors targeting PD-1 and PD-L1 have shown remarkable activity including durable long-term. MCC in patients living with HIV-1/AIDS are treated with similar modalities as HIV-1 uninfected individuals with MCC.

PMID: 30523626 [PubMed - in process]

Permalink for 'Human Oncoviruses: Mucocutaneous Manifestations, Pathogenesis, Therapeutics, and Prevention (Part I: Papillomaviruses and Merkel cell polyomavirus).'

Human Oncoviruses: Mucocutaneous Manifestations, Pathogenesis, Therapeutics, and Prevention (Part I: Papillomaviruses and Merkel cell polyomavirus).

Fetched: December 8th, 2018, 5:00am GMT

Human Oncoviruses: Mucocutaneous Manifestations, Pathogenesis, Therapeutics, and Prevention (Part I: Papillomaviruses and Merkel cell polyomavirus).

J Am Acad Dermatol. 2018 Nov 28;:

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

Abstract
In 1964, the first human oncovirus, Epstein-Barr virus (EBV), was identified in Burkitt lymphoma cells. Since then, six other human oncoviruses have been identified: human papillomavirus (HPV), Merkel cell polyomavirus (MCPyV), hepatitis B and C viruses (HBV and HCV), human T-cell lymphotropic virus-1 (HTLV-1), and human herpesvirus-8 (HHV-8). These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. Additionally, oncoviruses are associated with multiple benign mucocutaneous diseases. Research regarding the pathogenic mechanisms of oncoviruses as well as virus-specific treatment and prevention is rapidly evolving. Preventative vaccines for HPV and HBV are already available. This review discusses the mucocutaneous manifestations, pathogenesis, diagnosis, treatment, and prevention of oncovirus-related diseases. Part I of the review focuses on diseases associated with HPV and MCPyV, while part II focuses on diseases associated with HBV, HCV, HTLV-1, HHV-8, and EBV.

PMID: 30502418 [PubMed - as supplied by publisher]

Editorial: Human Papillomaviruses and Polyomaviruses in Skin Cancer.

Fetched: December 2nd, 2018, 5:00am GMT

Editorial: Human Papillomaviruses and Polyomaviruses in Skin Cancer.

Front Microbiol. 2018;9:2778

Authors: Pfister HJ, Gariglio M, Smola S

PMID: 30498488 [PubMed]

Merkel Cell Carcinoma Review.

Fetched: December 2nd, 2018, 5:00am GMT

Merkel Cell Carcinoma Review.

Hematol Oncol Clin North Am. 2019 Feb;33(1):39-52

Authors: Xue Y, Thakuria M

Abstract
Merkel cell carcinoma is a rare and aggressive cutaneous malignancy of neuroendocrine origin-an often-missed diagnosis due to the wide histopathologic differential diagnosis of malignant small blue cell tumors. The advent of electron microscopy and immunohistochemistry staining for cytokeratin 20, a shared neuroendocrine marker, greatly improved diagnostic accuracy. Over the past decade, staging, treatment, and surveillance of the cancer have progressed at a remarkably rapid pace. Herein, the authors provide an update on the current guidelines around diagnosis and management and review the exciting advancements on the horizon.

PMID: 30497676 [PubMed - in process]

Permalink for 'Management of Regional Lymph Nodes in Patients with Merkel Cell Carcinoma Following a Positive Sentinel Node Biopsy: Less May be More, But is Either Enough?'

Management of Regional Lymph Nodes in Patients with Merkel Cell Carcinoma Following a Positive Sentinel Node Biopsy: Less May be More, But is Either Enough?

Fetched: December 1st, 2018, 5:00am GMT

Management of Regional Lymph Nodes in Patients with Merkel Cell Carcinoma Following a Positive Sentinel Node Biopsy: Less May be More, But is Either Enough?

Ann Surg Oncol. 2018 Nov 27;:

Authors: Hruby G, Guminski A, Thompson JF

Abstract

PMID: 30483975 [PubMed - as supplied by publisher]

Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy.

Fetched: December 1st, 2018, 5:00am GMT

Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy.

J Immunother Cancer. 2018 Nov 27;6(1):131

Authors: Miller NJ, Church CD, Fling SP, Kulikauskas R, Ramchurren N, Shinohara MM, Kluger HM, Bhatia S, Lundgren L, Cheever MA, Topalian SL, Nghiem P

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer that frequently responds to anti-PD-1 therapy. MCC is associated with sun exposure and, in 80% of cases, Merkel cell polyomavirus (MCPyV). MCPyV-specific T and B cell responses provide a unique opportunity to study cancer-specific immunity throughout PD-1 blockade therapy.
METHODS: Immune responses were assessed in patients (n = 26) with advanced MCC receiving pembrolizumab. Peripheral blood mononuclear cells (PBMC) were collected at baseline and throughout treatment. MCPyV-oncoprotein antibodies were quantified and T cells were assessed for MCPyV-specificity via tetramer staining and/or cytokine secretion. Pre-treatment tumor biopsies were analyzed for T cell receptor clonality.
RESULTS: MCPyV oncoprotein antibodies were detectable in 15 of 17 (88%) of virus-positive MCC (VP-MCC) patients. Antibodies decreased in 10 of 11 (91%) patients with responding tumors. Virus-specific T cells decreased over time in patients who had a complete response, and increased in patients who had persistent disease. Tumors that were MCPyV(+) had a strikingly more clonal (less diverse) intratumoral TCR repertoire than virus-negative tumors (p = 0.0001).
CONCLUSIONS: Cancer-specific T and B cell responses generally track with disease burden during PD-1 blockade, in proportion to presence of antigen. Intratumoral TCR clonality was significantly greater in VP-MCC than VN-MCC tumors, suggesting expansion of a limited number of dominant clones in response to fewer immunogenic MCPyV antigens. In contrast, VN-MCC tumors had lower clonality, suggesting a diverse T cell response to numerous neoantigens. These findings reveal differences in tumor-specific immunity for VP-MCC and VN-MCC, both of which often respond to anti-PD-1 therapy.

PMID: 30482247 [PubMed - in process]

Product review: avelumab, an anti-PD-L1 antibody.

Fetched: November 29th, 2018, 5:00am GMT

Product review: avelumab, an anti-PD-L1 antibody.

Hum Vaccin Immunother. 2018 Nov 27;:

Authors: Collins JM, Gulley JL

Abstract
Although immunotherapies have been employed for many decades, immune checkpoint inhibitors have only recently entered the oncologic landscape. Avelumab is a fully human monoclonal antibody that blocks the interaction between PD-L1 on tumor cells and PD-1 on T cells, thereby inhibiting immunosuppression in the tumor microenvironment and reducing tumor growth. Most early clinical trials of avelumab as monotherapy and in combination regimens were part of the international JAVELIN clinical trial program, which included more than 7000 patients in more than 30 trials with at least 15 tumor types. Avelumab has been approved by the U.S. FDA for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma that has progressed during or following treatment with a platinum-based regimen. Its acceptable safety profile and ability to induce durable responses in otherwise deadly tumors provide the rationale for its use in other tumor types and in combination with other therapies.

PMID: 30481100 [PubMed - as supplied by publisher]

Clinical features and outcomes of Merkel cell carcinoma in 20 cats.

Fetched: November 29th, 2018, 5:00am GMT

Clinical features and outcomes of Merkel cell carcinoma in 20 cats.

Vet Comp Oncol. 2018 Dec;16(4):554-561

Authors: Sumi A, Chambers JK, Doi M, Kudo T, Omachi T, Uchida K

Abstract
The biological behaviour and prognostic factors of Merkel cell carcinoma (MCC) in 20 cats were studied. The tumours were surgically removed and histopathologically examined. The animals were 8 to 20 years old (median age: 14 years), and the tumours were predominantly located in the neck and head. Follow-up data were available in 17 cases, and 12 cats died within a year of surgery. The overall median survival time after resection was 243 days (range 16-360 days). Recurrence occurred in 11 cases, although 6 of them (55%) were found to be margin-negative. Possible metastasis occurred after the surgery in 10 cases, although 6 of them (60%) were found to be margin-negative. The histopathological features of MCC included tumour necrosis in 16 cases (80%), vascular invasion in 6 cases (38%) and high mitotic counts (median: 28.5 per high-power field). Irregular acanthosis was noted adjacent to the tumours in 9 cases (60%). Immunohistochemically, the tumour cells were positive for cytokeratin (CK) 20 and p63 in all cases, synaptophysin in 19 (95%) cases, and CK18 in 16 cases (80%). The study shows that feline MCC is associated with a poor prognosis and exhibited a strong tendency towards local recurrence, regional lymph node metastasis and distant spread.

PMID: 30022593 [PubMed - indexed for MEDLINE]

Permalink for 'Unusual Neuroendocrine Differentiation in a Small Round Cell Angiosarcoma: A Potential Histologic Mimicker of Superficial Ewing Sarcoma.'

Unusual Neuroendocrine Differentiation in a Small Round Cell Angiosarcoma: A Potential Histologic Mimicker of Superficial Ewing Sarcoma.

Fetched: November 28th, 2018, 5:00am GMT

Unusual Neuroendocrine Differentiation in a Small Round Cell Angiosarcoma: A Potential Histologic Mimicker of Superficial Ewing Sarcoma.

Am J Dermatopathol. 2018 Sep;40(9):671-675

Authors: Machado I, Santonja C, Huerta V, Cruz J, Requena C, Requena L, Llombart-Bosch A

Abstract
Neuroendocrine differentiation or aberrant expression of neuroendocrine markers is very uncommon in angiosarcomas (AS) and creates a challenging differential diagnosis with other superficial or soft tissue tumors. Herein, we report a new case of superficial AS presenting as a tumor lesion on the little finger of the right hand of a 52-year-old man. The tumor displayed CD56, chromogranin-A, and synaptophysin immunoreactivity. Tumor cells were positive for vascular markers (CD31, FLI1, ERG, D2-40, VE-cadherin, VEGR1,2, and 3), CD99, and EMA, but were negative for S100, CK (AE1/AE3), CK20, polyomavirus, and myogenic (desmin and myogenin) and melanocyte markers (melan-A and HMB45). Ki67 immunostains indicated high proliferative activity (>50%). The whole-body computed tomography did not reveal distant disease. The initial assessment considered several tumor subtypes as possible histological diagnoses, including Ewing sarcoma, Ewing-like sarcoma, Merkel cell carcinoma, and undifferentiated "small round cell sarcoma". Fluorescence in situ hybridization analysis was negative for EWSR1 translocation and molecular analysis failed to detect any EWSR1, CIC, SYT or BCOR rearrangement. As a follow-up investigation, we tested 17 cutaneous/superficial AS for neuroendocrine markers; however, only one of these showed focal CD56 and synaptophysin expression. In conclusion, the present findings indicate that neuroendocrine differentiation is a very infrequent feature in AS. We report an AS of the finger with an uncommon histological appearance and immunohistochemical profile: predominant round cell tumor proliferation and neuroendocrine differentiation. Pathologists should be aware of these potential histological and immunohistochemical pitfalls in AS.

PMID: 29533277 [PubMed - indexed for MEDLINE]

Merkel cell carcinomas infiltrated with CD33+ myeloid cells and CD8+ T cells are associated with improved outcome.

Fetched: November 28th, 2018, 5:00am GMT

Merkel cell carcinomas infiltrated with CD33+ myeloid cells and CD8+ T cells are associated with improved outcome.

J Am Acad Dermatol. 2018 05;78(5):973-982.e8

Authors: Kervarrec T, Gaboriaud P, Berthon P, Zaragoza J, Schrama D, Houben R, Le Corre Y, Hainaut-Wierzbicka E, Aubin F, Bens G, Domenech J, Guyétant S, Touzé A, Samimi M

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumor of the skin that has an aggressive behavior. Immunity is the main regulator of MCC development, and many interactions between lymphocytes and tumor cells have been proven. However, the impact of tumor-infiltrating myeloid cells needs better characterization.
OBJECTIVE: To characterize tumor-infiltrating myeloid cells in MCC and their association with other immune effectors and patient outcome.
METHODS: MCC cases were reviewed from an ongoing prospective cohort study. In all, 103 triplicate tumor samples were included in a tissue microarray. Macrophages, neutrophils, and myeloid-derived suppressor cells were characterized by the following markers: CD68, CD33, CD163, CD15, CD33, and human leukocyte antigen-DR. Associations of these cell populations with programmed cell death ligand 1 expression, CD8 infiltrates, and vascular density were assessed. Impact on survival was analyzed by log-rank tests and a Cox multivariate model.
RESULTS: The median density of macrophages was 216 cells/mm2. CD68+ and CD33+ macrophage densities were associated with CD8+ T-cell infiltrates and programmed cell death ligand 1 expression. In addition, MCC harboring CD8+ T cell infiltrates and brisk CD33+ myeloid cell infiltrates were significantly and independently associated with improved outcomes (recurrence-free and overall survival).
LIMITATIONS: Sampling bias and the retrospective design were potential study limitations.
CONCLUSION: Infiltration of CD33+ myeloid cells and CD8+ T lymphocytes defines a subset of MCC associated with improved outcome.

PMID: 29273486 [PubMed - indexed for MEDLINE]

Permalink for 'Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary skin tumor from other metastatic neuroendocrine carcinomas: The ELECTHIP criteria.'

Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary skin tumor from other metastatic neuroendocrine carcinomas: The ELECTHIP criteria.

Fetched: November 28th, 2018, 5:00am GMT

Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary skin tumor from other metastatic neuroendocrine carcinomas: The ELECTHIP criteria.

J Am Acad Dermatol. 2018 05;78(5):964-972.e3

Authors: Kervarrec T, Zaragoza J, Gaboriaud P, Le Gouge A, Beby-Defaux A, Le Corre Y, Hainaut-Wierzbicka E, Aubin F, Bens G, Michenet P, Maillard H, Touzé A, Samimi M, Guyétant S

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) can present as a cutaneous tumor or a lymph node metastasis without a primary tumor. MCC presenting without a primary tumor (MCCWOPT) can be misinterpreted on histologic examination as lymph node metastasis (LNM) from another neuroendocrine carcinoma (LNMNEC). However, this distinction is crucial for therapeutic management.
OBJECTIVE: To determine the discriminative criteria for the differential diagnosis of MCCWOPT, LNM from cutaneous MCC, and LNMNECs.
METHODS: Clinical, morphologic, and immunohistochemical data (expression of cytokeratins AE1, AE3, 7, 19, and 20; chromogranin A, synaptophysin, thyroid transcription factor-1 [TTF-1]), as well as the presence of Merkel cell polyomavirus (by immunohistochemistry and PCR) were compared in patients with MCCWOPT (n = 17), LNM from a cutaneous MCC (n = 11), and LNMNEC (n = 20; 8 lung, 7 thyroid, 3 digestive tract, 2 other).
RESULTS: MCC (including MCCWOPT and LNM from a cutaneous MCC) differed from LNMNEC by 7 discriminative criteria: 1) elderly age, 2) location of the tumor, 3) extent of the disease, 4) cytokeratin expression, 5) TTF-1 expression, 6) histologic type, and 7) Merkel cell polyomavirus detection, summarized under the acronym ELECTHIP. All MCC patients had ≥5 of the ELECTHIP criteria, whereas all patients with LNMNEC (except 1) had <3 criteria.
LIMITATIONS: The discriminant ability of the ELECTHIP criteria should be validated in a second independent set.
CONCLUSION: MCCWOPT can be distinguished from other LNMNEC by the ELECTHIP criteria.

PMID: 29180096 [PubMed - indexed for MEDLINE]

Utilization of Indocyanine Green to Aid in Identifying Sentinel Lymph Nodes in Merkel Cell Cancer.

Fetched: November 24th, 2018, 5:00am GMT

Utilization of Indocyanine Green to Aid in Identifying Sentinel Lymph Nodes in Merkel Cell Cancer.

J Surg Res. 2018 Dec;232:365-368

Authors: Knackstedt RW, Knackstedt T, Gastman B

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a relatively rare skin cancer with high rates of regional lymph node involvement and metastatic spread. National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for staging purposes. The goal of this study is to report our experience utilizing indocyanine green (ICG) fluorescence-based technology to aid in SLNB detection in MCC.
METHODS: Consecutive MCC patients who underwent SLNB with radioisotope lymphoscintigraphy, with intraoperative handheld gamma probe, and ICG-based fluorescence imaging from 2012 to 2017 were prospectively studied (Cohort A). A group of historical controls that underwent SLNB for MCC with radioisotope lymphoscintigraphy and vital blue dye (VBD) (lymphazurin or methylene blue dye) was also analyzed (Cohort B).
RESULTS: Twenty-four consecutive patients underwent SLNB with lymphoscintigraphy and ICG-based fluorescence and 11 controls underwent SLNB with lymphoscintigraphy and VBD. The localization rate by node with VBD was 63.6% and ICG-based fluorescence was 94.8%. For two patients, a positive sentinel lymph node (SLN) was detected only by ICG-based fluorescence and the nodes were not detected by gamma probe and one patient's only positive node was identified via ICG fluorescence only. VBD or gamma probe did not identify any unique positive SLNs in either cohort B or either cohort, respectively.
CONCLUSIONS: In this study, we indicate that ICG-based fluorescence is not only feasible to augment SLN identification, but it has a higher node localization rate as compared to blue dye and it was able to identify positive SLNs otherwise missed by gamma probe. This study suggests the importance of utilizing two modalities to augment SLN identification and that ICG-based fluorescence may be able to identify nodes that would have been otherwise missed by gamma probe. We will continue to follow these patients and enroll more patients in this prospective study to further determine the role that ICG-based fluorescence has in identifying sentinel lymph nodes in MCC.

PMID: 30463742 [PubMed - in process]

Evidence of proliferative activity in human Merkel cells: implications in the histogenesis of Merkel cell carcinoma.

Fetched: November 23rd, 2018, 5:00am GMT

Evidence of proliferative activity in human Merkel cells: implications in the histogenesis of Merkel cell carcinoma.

Arch Dermatol Res. 2018 Nov 20;:

Authors: Narisawa Y, Inoue T, Nagase K

Abstract
The cellular origin of Merkel cell carcinoma (MCC) is controversial. We previously hypothesized that MCC originates from hair follicle stem cells or Merkel cell (MC) progenitors residing within the hair follicle bulge. Examination of three cases of combined MCC led to the unexpected discovery that numerous keratin 20 (CK20)-positive MCs within the squamous cell carcinoma (SCC) component of combined MCC appeared morphologically normal with dendritic and oval shapes. Moreover, one extremely rare case of combined SCC and MCC showed both intra-epidermal and dermal MCCs. These three cases represent the first documentation of MC hyperplasia in MCC, besides various benign follicular neoplasms associated with MC hyperplasia. Therefore, to elucidate the proliferating potential of MCs and their histogenetic relationship with MCCs, we further investigated these cases based on pathological observations. We identified numerous cells co-expressing CK20 and the proliferation marker Ki-67, identical to the morphological and immunohistochemical features of normal MCs. This finding indicated that MCs can no longer be considered as pure post-mitotic cells. Instead, they have proliferative potential under specific conditions in the diseased or wounded skin, or adjacent to various skin tumors, including MCC. Intimate co-existence of two malignant cell components composed of intradermal and intra-epidermal MCCs, with the proliferation of normal-appearing MCs in the same lesion, lends support to the hypothesis that MCs and MCC cells are derived from MC progenitors residing within the hair follicle bulge. Specifically, MCCs are derived from transformed MC progenitors with potential for dual-directional differentiation towards neuroendocrine and epithelial lineages.

PMID: 30460510 [PubMed - as supplied by publisher]

Merkel cell carcinoma with seborrheic keratosis: A unique association.

Fetched: November 23rd, 2018, 5:00am GMT

Icon for Medknow Publications and Media Pvt Ltd

Merkel cell carcinoma with seborrheic keratosis: A unique association.

Indian J Pathol Microbiol. 2018 Jan-Mar;61(1):101-102

Authors: Anand MS, Krishnamurthy S, Ravindranath S, Ranganathan J

Abstract
Merkel cell carcinoma (MCC) is a rare, clinically aggressive neuroendocrine carcinoma of the skin; MCC is 40 times less common as compared to melanoma. The most frequently reported sites have been the head and neck, extremities, and trunk. Potential mimics include malignant melanoma, lymphoma, or metastatic small cell (neuroendocrine) carcinomas. Histopathology of MCC resembles small cell carcinoma both morphologically and on IHC. The possible cell of origin was proposed as the Merkel cell, which functions as a mechanoreceptor. It has a high chance of local recurrence, regional and distant spread. In recent times, Merkel cell polyomavirus has been implicated as the causative agent for this tumor. The same agent has a reported etiologic association with other skin lesions, including seborrheic keratosis.

PMID: 29567894 [PubMed - indexed for MEDLINE]

A novel report of a primary Merkel cell carcinoma lesion in the nasal vestibule.

Fetched: November 22nd, 2018, 5:00am GMT

A novel report of a primary Merkel cell carcinoma lesion in the nasal vestibule.

Clin Case Rep. 2018 Nov;6(11):2033-2036

Authors: Khatchaturian EM, Zohrabian N

Abstract
Merkel cell carcinoma (MCC) accounts for less than 1% of cutaneous malignancies. As the lesion may mimic benign entities, clinicians' differential should include rare entities to improve outcomes by early intervention. We present a case of primary MCC in the nasal vestibule requiring partial rhinectomy, suprahyoid lymphadenectomy, and radiation therapy.

PMID: 30455885 [PubMed]

Permalink for 'Long-Term Follow-Up of 90Y-Ibritumomab Tiuxetan, Fludarabine, and Total Body Irradiation-Based Nonmyeloablative Allogeneic Transplant Conditioning for Persistent High-Risk B Cell Lymphoma.'

Long-Term Follow-Up of 90Y-Ibritumomab Tiuxetan, Fludarabine, and Total Body Irradiation-Based Nonmyeloablative Allogeneic Transplant Conditioning for Persistent High-Risk B Cell Lymphoma.

Fetched: November 22nd, 2018, 5:00am GMT

Long-Term Follow-Up of 90Y-Ibritumomab Tiuxetan, Fludarabine, and Total Body Irradiation-Based Nonmyeloablative Allogeneic Transplant Conditioning for Persistent High-Risk B Cell Lymphoma.

Biol Blood Marrow Transplant. 2018 Nov;24(11):2211-2215

Authors: Puronen CE, Cassaday RD, Stevenson PA, Sandmaier BM, Flowers ME, Green DJ, Maloney DG, Storb RF, Press OW, Gopal AK

Abstract
Nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) can provide prolonged remissions in patients with advanced B cell lymphoma (B-NHL) via the graft-versus-lymphoma effect, although inferior results are seen in patients with chemoresistant, bulky, or aggressive disease. Radioimmunotherapy can safely induce responses in B-NHL with minimal nonhematologic toxicity. Initial results of 90Y-ibritumomab tiuxetan-based allografting demonstrated early safety and disease control in nonremission patients but with short follow-up. Here we report the long-term outcomes of patients treated on this study with specific emphasis on patients achieving early remissions. Eleven of 40 patients were alive at a median follow-up of 9 years (range, 5.3 to 10.2). Fourteen (35%) deaths were due to disease progression and 14 (35%) deaths to complications from HCT. One patient died of a Merkel cell carcinoma. The 5-year overall and progression-free survival for patients with indolent B-NHL was 40% and 27.5%, respectively. None of the patients with diffuse large B cell lymphoma was a long-term disease-free survivor regardless of early remission status. 90Y-ibritumomab tiuxetan-based allografting represents a viable option in patients with indolent histologies. Improved strategies are needed for aggressive B-NHL. The original trial was registered at www.clinicaltrials.gov as NCT00119392.

PMID: 30454872 [PubMed - in process]

Permalink for 'Investigation of the Diagnostic Precision and Utility of Sentinel Lymph Node Biopsy in the Treatment of Patients with Merkel Cell Carcinoma.'

Investigation of the Diagnostic Precision and Utility of Sentinel Lymph Node Biopsy in the Treatment of Patients with Merkel Cell Carcinoma.

Fetched: November 22nd, 2018, 5:00am GMT

Investigation of the Diagnostic Precision and Utility of Sentinel Lymph Node Biopsy in the Treatment of Patients with Merkel Cell Carcinoma.

Am Surg. 2018 May 01;84(5):e173-e175

Authors: Lamb EP, Shaw FR, Fleming MD

PMID: 30454322 [PubMed - in process]

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

Fetched: November 21st, 2018, 5:00am GMT

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

Australas J Dermatol. 2018 Nov 18;:

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

PMID: 30450568 [PubMed - as supplied by publisher]

MiR-375 Regulation of LDHB Plays Distinct Roles in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma.

Fetched: November 19th, 2018, 5:00am GMT

MiR-375 Regulation of LDHB Plays Distinct Roles in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma.

Cancers (Basel). 2018 Nov 14;10(11):

Authors: Kumar S, Xie H, Scicluna P, Lee L, Björnhagen V, Höög A, Larsson C, Lui WO

Abstract
MicroRNA-375 (miR-375) is deregulated in multiple tumor types and regulates important targets involved in tumorigenesis and metastasis. This miRNA is highly expressed in Merkel cell carcinoma (MCC) compared to normal skin and other non-MCC skin cancers, and its expression is high in Merkel cell polyomavirus (MCPyV)-positive (MCPyV+) and low in MCPyV-negative (MCPyV-) MCC tumors. In this study, we characterized the function and target of miR-375 in MCPyV+ and MCPyV- MCC cell lines. Ectopic expression of miR-375 in MCPyV- MCC cells resulted in decreased cell proliferation and migration, as well as increased cell apoptosis and cell cycle arrest. However, in MCPyV+ MCC cells, inhibition of miR-375 expression reduced cell growth and induced apoptosis. Additionally, the expression of lactate dehydrogenase B (LDHB), a known target of miR-375, was inversely correlated with miR-375. Silencing of LDHB reduced cell growth in MCPyV- cell lines, while its silencing in MCPyV+ cell lines rescued the cell growth effect mediated by miR-375 inhibition. Together, our results suggest dual roles of miR-375 and LDHB in MCPyV and non-MCPyV-associated MCCs. We propose that LDHB could be a therapeutic target in MCC and different strategies should be applied in virus- and non-virus-associated MCCs.

PMID: 30441870 [PubMed]

Heterogeneity of PD-L1 Expression in a Case of Merkel Cell Carcinoma Exhibiting Complete Regression After Multiple Metastases.

Fetched: November 17th, 2018, 5:00am GMT

Heterogeneity of PD-L1 Expression in a Case of Merkel Cell Carcinoma Exhibiting Complete Regression After Multiple Metastases.

Br J Dermatol. 2018 Nov 15;:

Authors: Nakamura M, Magara T, Kobayashi Y, Kato H, Watanabe S, Morita A

Abstract
Merkel cell carcinoma (MCC) is a highly malignant skin cancer with a propensity for local recurrence and regional lymph node metastases. Once recurrence occurs, tumour progression becomes hard to be controlled. Overexpression of programmed death-ligand 1 (PD-L1) in MCC correlates with better clinical outcomes, in contrast to other solid carcinomas, e.g., malignant melanoma. The successful results of treatment with the immune checkpoint inhibitor avelumab for metastatic MCC highlight this unusual relationship between MCC and PD-L1 expression. This article is protected by copyright. All rights reserved.

PMID: 30431150 [PubMed - as supplied by publisher]

New and emerging treatments for metastatic Merkel cell carcinoma.

Fetched: November 17th, 2018, 5:00am GMT

New and emerging treatments for metastatic Merkel cell carcinoma.

Panminerva Med. 2018 03;60(1):39-40

Authors: Cestaro G, Quarto G, DE Monti M, Fasolini F, DE Fazio M, Furino E, Gentile M

PMID: 29332376 [PubMed - indexed for MEDLINE]

Radiotherapy for Skin Cancers of the Face, Head, and Neck.

Fetched: November 15th, 2018, 5:00am GMT

Radiotherapy for Skin Cancers of the Face, Head, and Neck.

Facial Plast Surg Clin North Am. 2019 Feb;27(1):131-138

Authors: Mierzwa ML

Abstract
Radiotherapy plays a role in the definitive or adjuvant management of early and late stage skin cancers including nonmelanoma basal cell carcinoma and cutaneous squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The role of radiotherapy in skin cancers of the head and neck is reviewed including early and advanced-stage nonmelanoma skin cancers, melanoma, and Merkel cell carcinoma. In particular, the indications, oncologic outcomes, and technical aspects of radiotherapy for these diseases are discussed.

PMID: 30420066 [PubMed - in process]

Nonmelanoma Skin Cancer.

Fetched: November 15th, 2018, 5:00am GMT

Nonmelanoma Skin Cancer.

Facial Plast Surg Clin North Am. 2019 Feb;27(1):1-13

Authors: Brandt MG, Moore CC

Abstract
This article reviews the most common nonmelanoma skin cancers affecting the head and neck region. Although the most common of these malignancies rarely result in mortality, local morbidity caused by the tumors and their extirpation cannot be underestimated. Complete tumor extirpation with pathologically confirmed negative margins is the gold standard. Regional and distant metastases are rare, but must be treated appropriately should they occur. Although reconstructive surgery can be life changing for the patients and rewarding for the clinicians, it behooves the treating surgeons to remain true to oncologic principles above all else.

PMID: 30420063 [PubMed - in process]

A case of combined Merkel cell carcinoma and squamous cell carcinoma: Molecular insights and diagnostic pitfalls.

Fetched: November 14th, 2018, 5:00am GMT

A case of combined Merkel cell carcinoma and squamous cell carcinoma: Molecular insights and diagnostic pitfalls.

JAAD Case Rep. 2018 Nov;4(10):996-999

Authors: Falto Aizpurua LA, Wang M, Ruiz HA, Sánchez JL, Chan MP, Andea AA, Harms PW

PMID: 30417062 [PubMed]

Neuroendocrine Key Regulator Gene Expression in Merkel Cell Carcinoma.

Fetched: November 12th, 2018, 5:00am GMT

Neuroendocrine Key Regulator Gene Expression in Merkel Cell Carcinoma.

Neoplasia. 2018 Nov 07;20(12):1227-1235

Authors: Chteinberg E, Sauer CM, Rennspiess D, Beumers L, Schiffelers L, Eben J, Haugg A, Winnepenninckx V, Kurz AK, Speel EJ, Zenke M, Zur Hausen A

Abstract
Merkel cell carcinoma (MCC) is a highly aggressive non-melanoma skin cancer of the elderly which is associated with the Merkel cell polyomavirus (MCPyV). MCC reveals a trilinear differentiation characterized by neuroendocrine, epithelial and pre/pro B-cell lymphocytic gene expression disguising the cellular origin of MCC. Here we investigated the expression of the neuroendocrine key regulators RE1 silencing transcription factor (REST), neurogenic differentiation 1 (NeuroD1) and the Achaete-scute homolog 1 (ASCL1) in MCC. All MCCs were devoid of REST and were positive for NeuroD1 expression. Only one MCC tissue revealed focal ASCL1 expression. This was confirmed in MCPyV-positive MCC cell lines. Of interest, MCPyV-negative cell lines did express REST. The introduction of REST expression in REST-negative, MCPyV-positive MCC cells downregulated the neuroendocrine gene expression. The lack of the neuroendocrine master regulator ASCL1 in almost all tested MCCs points to an important role of the absence of the negative regulator REST towards the MCC neuroendocrine phenotype. This is underlined by the expression of the REST-regulated microRNAs miR-9/9* in REST-negative MCC cell lines. These data might provide the basis for the understanding of neuroendocrine gene expression profile which is expected to help to elucidate the cellular origin of MCC.

PMID: 30414538 [PubMed - as supplied by publisher]

Prevalence and risk factors of human polyomavirus infections in non-malignant tonsils and gargles: the SPLIT study.

Fetched: November 10th, 2018, 5:00am GMT

Prevalence and risk factors of human polyomavirus infections in non-malignant tonsils and gargles: the SPLIT study.

J Gen Virol. 2018 Nov 08;:

Authors: Kourieh A, Combes JD, Tommasino M, Dalstein V, Clifford GM, Lacau St Guily J, Clavel C, Franceschi S, Gheit T, For The Split Study Group

Abstract
The prevalence of 13 polyomaviruses (PyVs) in the tonsil brushings and gargles of immunocompetent children and adults was assessed. Patients undergoing tonsillectomy for benign indications were recruited in 19 centres in France. After resection, the entire outer surface of the right and left halves of the tonsils was brushed extensively. Gargles were also collected prior to surgery in selected adults. A species-specific multiplex assay was used to detect the DNA of 13 PyVs. In tonsil brushings (n=689), human PyV 6 (HPyV6) and Merkel cell PyV (MCPyV) were the most prevalent (≈15 %), followed by trichodysplasia spinulosa-associated PyV (TSPyV), BKPyV, Washington University PyV (WUPyV) and human PyV 9 (HPyV9) (1 to 5 %), and human PyV 7 (HPyV7), John Cunningham PyV (JCPyV) and Simian virus 40 (SV40) (<1 %), while no Karolinska Institute PyV (KIPyV), Malawi PyV (MWPyV), human PyV 12 (HPyV12) or Lyon IARC PyV (LIPyV) were detected. The prevalence of TSPyV and BKPyV was significantly higher in children versus adults, whereas for HPyV6 the opposite was found. HPyV6 and WUPyV were significantly more prevalent in men versus women. In gargles (n=139), MCPyV was the most prevalent (≈40 %), followed by HPyV6, HPyV9 and LIPyV (2 to 4 %), and then BKPyV (≈1 %), while other PyVs were not detected. MCPyV and LIPyV were significantly more prevalent in gargles compared to tonsil brushings, in contrast to HPyV6. We described differing patterns of individual PyV infections in tonsils and gargles in a large age-stratified population. Comparison of the spectrum of PyVs in paired tonsil samples and gargles adds to the current knowledge on PyV epidemiology, contributing towards a better understanding of PyV acquisition and transmission and its potential role in head and neck diseases.

PMID: 30407150 [PubMed - as supplied by publisher]

Investigation of the Diagnostic Precision and Utility of Sentinel Lymph Node Biopsy in the Treatment of Patients with Merkel Cell Carcinoma.

Fetched: November 9th, 2018, 5:00am GMT

Investigation of the Diagnostic Precision and Utility of Sentinel Lymph Node Biopsy in the Treatment of Patients with Merkel Cell Carcinoma.

Am Surg. 2018 May 01;84(5):e173-e175

Authors: Lamb EP, Shaw FR, Fleming MD

PMID: 30401168 [PubMed - in process]

Permalink for 'Pharmacological inhibition of serine palmitoyl transferase and sphingosine kinase-1/-2 inhibits Merkel Cell Carcinoma cell proliferation.'

Pharmacological inhibition of serine palmitoyl transferase and sphingosine kinase-1/-2 inhibits Merkel Cell Carcinoma cell proliferation.

Fetched: November 8th, 2018, 5:00am GMT

Pharmacological inhibition of serine palmitoyl transferase and sphingosine kinase-1/-2 inhibits Merkel Cell Carcinoma cell proliferation.

J Invest Dermatol. 2018 Nov 03;:

Authors: Bhat VK, Bernhart E, Plastira I, Fan K, Tabrizi-Wizsy NG, Wadsack C, Rechberger G, Eichmann T, Asslaber M, Spassova I, Verhaegen ME, Malle E, Becker JC, Sattler W

Abstract
The majority of Merkel cell carcinoma (MCC), a highly aggressive neuroendocrine cancer of the skin, is associated with Merkel cell polyomavirus (MCPyV) infection. Polyomavirus binding, internalization and infection is mediated by glycosphingolipids (GSL). Besides receptor function, bioactive sphingolipids (SL) are increasingly recognized as potent regulators of several hallmarks of cancer. MCPyV+ and MCPyV- cells express serine palmitoyltransferase (SPT) subunits and sphingosine kinase (SK)1/2 mRNA. Induced expression of MCPyV-large tumor antigen in human lung fibroblasts resulted in upregulation of SPTLC1-3 and SK1/2 expression. Therefore we exploited pharmacological inhibition of SL metabolism as an option to interfere with proliferation of MCPyV+ MCC cell lines. We used myriocin (a SPT antagonist) and two SK inhibitors (SKI-II and ABC294640). In MKL-1 and WaGa cells myriocin decreased cellular ceramide, sphingomyelin, and sphingosine-1-phosphate (S1P) content. SKI-II increased ceramide species but decreased sphingomyelin and S1P concentrations. Aberrant SL homeostasis was associated with reduced cell viability, increased necrosis, procaspase-3 and PARP processing, caspase-3 activity, and decreased AKTS473 phosphorylation. Myriocin and SKI-II decreased tumor size and Ki-67 staining of xenografted MKL-1 and WaGa tumors on the chorioallantoic membrane. Our data suggest that pharmacological inhibition of SL synthesis could represent a potential therapeutic approach in MCC.

PMID: 30399362 [PubMed - as supplied by publisher]

Multi-modal chip-based fluorescence and quantitative phase microscopy for studying inflammation in macrophages.

Fetched: November 7th, 2018, 5:00am GMT

Multi-modal chip-based fluorescence and quantitative phase microscopy for studying inflammation in macrophages.

Opt Express. 2018 Aug 06;26(16):19864-19876

Authors: Dubey V, Ahmad A, Singh R, Wolfson DL, Basnet P, Acharya G, Mehta DS, Ahluwalia BS

Abstract
Total internal reflection fluorescence (TIRF) microscopy benefits from high-sensitivity, low background noise, low photo-toxicity and high-contrast imaging of sub-cellular structures close to the membrane surface. Although, TIRF microscopy provides high-contrast imaging it does not provide quantitative information about morphological features of the biological cells. Here, we propose an integrated waveguide chip-based TIRF microscopy and label-free quantitative phase imaging (QPI). The evanescent field present on top of a waveguide surface is used to excite the fluorescence and an upright microscope is used to collect the signal. The upright microscope is converted into a Linnik-type interferometer to sequentially extract both the quantitative phase information and TIRF images of the cells. Waveguide chip-based TIRF microscopy benefits from decoupling of illumination and collection light path, large field of view imaging and pre-aligned configuration for multi-color TIRF imaging. The proposed multi-modal microscopy is used to study inflammation caused by lipopolysaccharide (LPS) on rat macrophages. The TIRF microscopy showed that LPS inflammatory molecule disrupts the cell membrane and causes cells to significantly expand across a substrate. While, QPI module quantified changes in the sub-cellular content of the LPS challenged macrophages, showing a net decrease in its maximum phase values.

PMID: 30119307 [PubMed - indexed for MEDLINE]

In brief: Avelumab (Bavencio) for metastatic merkel cell carcinoma.

Fetched: November 7th, 2018, 5:00am GMT

Icon for Medical Letter on Drugs and Therapeutics

In brief: Avelumab (Bavencio) for metastatic merkel cell carcinoma.

Med Lett Drugs Ther. 2017 07 17;59(1521):e120

Authors:

PMID: 28699934 [PubMed - indexed for MEDLINE]

Permalink for 'Lymph Node Metastasis With Both Components of Combined Cutaneous Squamous Cell Carcinoma/Merkel Cell (Neuroendocrine) Carcinoma.'

Lymph Node Metastasis With Both Components of Combined Cutaneous Squamous Cell Carcinoma/Merkel Cell (Neuroendocrine) Carcinoma.

Fetched: November 7th, 2018, 5:00am GMT

Lymph Node Metastasis With Both Components of Combined Cutaneous Squamous Cell Carcinoma/Merkel Cell (Neuroendocrine) Carcinoma.

Am J Dermatopathol. 2018 08;40(8):626-628

Authors: Navarrete J, Gugelmeier N, Mazzei ME, González S, Barcia JJ, Magliano J

PMID: 28570390 [PubMed - indexed for MEDLINE]

Permalink for 'Infection and coinfection by human papillomavirus, Epstein-Barr virus and Merkel cell polyomavirus in patients with squamous cell carcinoma of the larynx: a retrospective study.'

Infection and coinfection by human papillomavirus, Epstein-Barr virus and Merkel cell polyomavirus in patients with squamous cell carcinoma of the larynx: a retrospective study.

Fetched: November 4th, 2018, 5:00am GMT

Infection and coinfection by human papillomavirus, Epstein-Barr virus and Merkel cell polyomavirus in patients with squamous cell carcinoma of the larynx: a retrospective study.

PeerJ. 2018;6:e5834

Authors: Vazquez-Guillen JM, Palacios-Saucedo GC, Rivera-Morales LG, Alonzo-Morado MV, Burciaga-Bernal SB, Montufar-Martinez M, Ortiz-Lopez R, Gonzalez-Villasana V, Martinez-Torres AC, Serna-Hernandez JC, Hernandez-Martinez SJ, Castelan-Maldonado EE, Zavala-Pompa A, Montalvo-Bañuelos MS, Garcia-Cabello R, Sanchez-Fresno EC, Rodriguez-Padilla C

Abstract
Background: Human papillomavirus (HPV) is recognized as an important risk factor for laryngeal carcinogenesis. Although HPV-16 and 18 have been strongly implicated, the presence of other high-risk HPV (HR-HPV) genotypes or the coinfection with Epstein-Barr virus (EBV) or Merkel cell polyomavirus (MCPV) may increase the risk, but their etiological association has not been definitively established.
Methods: We characterized the genotype-specific HPV and the frequency of EBV and MCPV infections through the detection of their DNA in 195 laryngeal specimens of squamous cell carcinoma (SCC) histologically confirmed.
Results: HPV DNA was detected in 93 (47.7%) specimens. HPV-11 was the most frequent with 68 cases (73.1%), and HPV-52 was the most frequently HR-HPV found with 51 cases, which corresponds to 54.8% of all HPV-positive specimens. EBV DNA was detected in 54 (27.7%) tumor tissue specimens of which 25 (46.3%) were in coinfection with HPV. MCPV DNA was detected only in 11 (5.6%) cases of which 5 (45.4%) were in coinfection with an HR-HPV. No association between the presence of DNA of the three examined viruses and the patient smoking habits, alcohol consumption, age, the keratinization status, differentiation grade, or localization of the tumor in the larynx were found.
Discussion: HPV-52 was the most prevalent HR-HPV, which may suggest that this and other genotypes in addition to HPV-16 and 18 could be considered for prophylaxis. However, further studies including non-cancer larynx cases and the evaluation of other molecular markers and viral co-infection mechanisms are needed to determine the role of the different HR-HPV genotypes, EBV, and MCPV in the etiology of SCC of the larynx.

PMID: 30386708 [PubMed]

A case report of recurrent Merkel cell carcinoma with synchronous metastases to the heart and stomach.

Fetched: November 3rd, 2018, 5:00am GMT

A case report of recurrent Merkel cell carcinoma with synchronous metastases to the heart and stomach.

Medicine (Baltimore). 2018 Nov;97(44):e13032

Authors: Ha JY, Park SE, Kim HS, Won H, Kim BJ, Hwang IG

Abstract
RATIONALE: Merkel cell carcinoma (MCC) is an aggressive, rare neuroendocrine skin cancer. MCC metastasis to the heart is exceedingly rare and gastric metastases from MCC have rarely been reported.
PATIENT CONCERNS: We described the case of an 82-year-old man diagnosed with recurrent MCC with cardiac and gastric metastasis who presented with poor oral intake and severe weight loss. The patient was diagnosed with MCC 3 years ago and treated with surgical resection and radiation.
INTERVENTIONS: We performed stomach biopsy in edematous lesion. And fluoroscopy and ultrasound guided biopsy of the cardiac mass was performed.
DIAGNOSES: MCC with synchronous metastases to the heart and stomach.
OUTCOMES: The primary lesion had complete resolution and the patient remained disease free on regular follow-up every 6 months for 2 and half years. After MCC recurred, palliative anti-cancer therapy was considered but could not be performed due to the patient's poor performance status involved elderly, combined recurrent pneumonia.
LESSONS: To our best knowledge, this is the first report of synchronous cardiac and gastric metastasis from cutaneous MCC worldwide. Although uncommon, MCC should be considered in clinical cases of synchronous metastasis.

PMID: 30383666 [PubMed - in process]

NKX2.2 immunohistochemistry in the distinction of ewing sarcoma from cytomorphologic mimics: Diagnostic utility and pitfalls.

Fetched: November 1st, 2018, 5:00am GMT

NKX2.2 immunohistochemistry in the distinction of ewing sarcoma from cytomorphologic mimics: Diagnostic utility and pitfalls.

Cancer Cytopathol. 2018 Oct 30;:

Authors: Russell-Goldman E, Hornick JL, Qian X, Jo VY

Abstract
BACKGROUND: Ewing sarcoma (ES) is a round cell sarcoma that can be challenging to diagnose on cytologic material given its significant overlap with numerous mesenchymal, epithelial, and lymphoid cytomorphologic mimics. The objective of this study was to assess the utility of a novel marker, NKX2.2, in the diagnosis of ES in cytologic material and its ability to distinguish ES from its mimics.
METHODS: NKX2.2 immunohistochemistry was performed on cell blocks from 107 fine-needle aspirations, and nuclear expression was scored semiquantitatively for extent and intensity. The study cohort included ES (n = 10), well differentiated neuroendocrine tumor (n = 20), melanoma (n = 11), Merkel cell carcinoma (n = 10), small cell carcinoma (n = 10), alveolar rhabdomyosarcoma (n = 2), spindle cell/sclerosing rhabdomyosarcoma (n = 2), synovial sarcoma (n = 12), solitary fibrous tumor (n = 2), chronic lymphocytic leukemia (n = 10), lymphoblastic lymphoma (n = 11), adenoid cystic carcinoma (n = 6), and CIC-rearranged sarcoma (n = 1).
RESULTS: NKX2.2 had high sensitivity (100%) and moderate specificity (85%) for the diagnosis of ES in cytologic material. NKX2.2 expression also was present in a subset of mesenchymal and epithelial mimics, and staining was most commonly observed in small cell carcinoma (80%) and well differentiated neuroendocrine tumor (45%). Among mesenchymal mimics, 42% exhibited NKX2.2 expression. NKX2.2 staining was absent in melanoma, adenoid cystic carcinoma, and lymphoproliferative neoplasms.
CONCLUSIONS: NKX2.2 is a highly sensitive but only moderately specific marker for ES. Neuroendocrine neoplasms exhibit variable NKX2.2 expression and remain a significant potential diagnostic pitfall. Thus, NKX2.2 expression should be interpreted in the context of an appropriate immunohistochemical panel (and often with confirmatory molecular testing) for the accurate diagnosis of ES.

PMID: 30376220 [PubMed - as supplied by publisher]

A case series of Merkel cell carcinoma of the eyelid: a rare entity often misdiagnosed.

Fetched: November 1st, 2018, 5:00am GMT

A case series of Merkel cell carcinoma of the eyelid: a rare entity often misdiagnosed.

Orbit. 2018 Oct 29;:1-6

Authors: Iuliano A, Tranfa F, Clemente L, Fossataro F, Strianese D

Abstract
Merkel cell carcinoma (MCC) is one of the rarest eyelid tumors, with high mortality rate due to lymphatic and metastatic spread. We hereby report six cases of patients with histological diagnosis of MCC referred to our Orbit Unit between 2012 and 2018, focusing on diagnosis, treatment, and subsequent follow up. All patients underwent surgical excision and systemic work-up. Both MCC TNM and eyelid MCC TNM were used to stage lesions. MCC of the eyelid is usually misdiagnosed as benign or other malignant lesions. A prompt examination and a wide local excision are mandatory. A close follow-up of these patients is advised due to high recurrence rate and lymphatic spread.

PMID: 30373432 [PubMed - as supplied by publisher]

Outcome of Combined Treatment of Surgery and Adjuvant Radiotherapy in Merkel Cell Carcinoma.

Fetched: October 31st, 2018, 5:00am GMT

Outcome of Combined Treatment of Surgery and Adjuvant Radiotherapy in Merkel Cell Carcinoma.

Acta Derm Venereol. 2018 Jul 11;98(7):699-703

Authors: Fiedler E, Vordermark D

Abstract
In recent analyses of Merkel cell carcinoma, prognosis is poor even in stages I and II. We performed a monocentric retrospective study of 37 consecutive cases with Merkel cell carcinoma stage I to III treated with a combination of surgery and adjuvant radiation to evaluate progression-free and overall survival. The median primary tumour diameter was 17.9 mm. Cases consisted of 31 primary tumours, of which 13 had negative sentinel lymph node biopsy (IA n = 10 and IIA n = 3) and 18 no sentinel lymph node biopsy (IB n = 15 and IIB n = 3), 2 tumours with positive sentinel lymph node biopsy (IIIA) and 4 with local macrometastasis (IIIB). The median age was 71 years and the median follow-up was 60.4 months. The 5-year progression-free survival was 83.8% and 5-year disease-specific survival was 95.7% (overall survival 93.0%). So far, our results show a high survival rate with combined treatment of surgery and adjuvant radiotherapy in early tumour stages of Merkel cell carcinoma.

PMID: 29379978 [PubMed - indexed for MEDLINE]

Letter to the Editor in reference to: Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease.

Fetched: October 29th, 2018, 5:00am GMT

Letter to the Editor in reference to: Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease.

Clin Otolaryngol. 2018 Oct 26;:

Authors: Narayanan D, Doan H, Simonette R, Rady PL, Tyring SK

Abstract
We read with interest the recent article titled 'Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease'. Frochman-Frana and colleagues concluded that ALOX15 expression is seen in primary MCC tumor samples as well as lymph node metastasis samples. Primary tumors of metastatic MCC had a higher expression rate of ALOX15 compared to samples without metastatic disease, providing evidence in support of ALOX15's association with cancer development. This article is protected by copyright. All rights reserved.

PMID: 30367539 [PubMed - as supplied by publisher]

Preserved Renal-Allograft Function and successful treatment of metastatic Merkel cell cancer post Nivolumab therapy.

Fetched: October 28th, 2018, 5:00am GMT

Preserved Renal-Allograft Function and successful treatment of metastatic Merkel cell cancer post Nivolumab therapy.

Transplantation. 2018 Oct 26;:

Authors: Singh P, Visger J, Prosek J, Olencki T, Pandey D, Rovin B, Pesavento TE

PMID: 30365468 [PubMed - as supplied by publisher]

A case report of eyelid Merkel cell carcinoma occurring under treatment with nivolumab for a lung adenocarcinoma.

Fetched: October 25th, 2018, 5:00am GMT

A case report of eyelid Merkel cell carcinoma occurring under treatment with nivolumab for a lung adenocarcinoma.

BMC Cancer. 2018 Oct 22;18(1):1024

Authors: Lavacchi D, Nobili S, Brugia M, Paderi A, Fancelli S, Caliman E, Vergoni F, Mini E

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine malignancy of the skin characterized by high aggressiveness. Four main factors are implicated in its development: immunosuppression, ultraviolet radiation, age and the Merkel cell polyomavirus (MCPyV). In recent years, immune checkpoint inhibitors have shown clinical activity in MCC treatment.
CASE PRESENTATION: We report the case of an 82-year-old man with a lung adenocarcinoma diagnosis, who underwent immunotherapy with nivolumab as second-line treatment. Seven months after the diagnosis of lung cancer during the nivolumab treatment, the patient developed an eyelid MCC, initially misdiagnosed as a chalazion. A palliative radiotherapy was performed with clinical benefit. After a total of seven cycles of nivolumab, computed tomography showed a lung and cerebral disease progression. In addition, clinical conditions worsened leading to the patient's death 13 months after the initial lung cancer diagnosis.
CONCLUSIONS: Cases of co-occurrence of MCC and non-small cell lung cancer (NSCLC) have rarely been reported. Interestingly, common risk factors may be postulated for both cancers. Considering the rarity of this adverse event, its short-term temporal relation with the administration of the drug, which makes a relation improbable, and the coexistence of other risk factors, which may provide plausible explanations, it is possible to conclude according to the WHO Adverse Reaction Terminology that a causal relation between the occurrence of this serious adverse event and the exposure to the drug is unlikely. However, the case deserves to be reported in the literature.

PMID: 30348121 [PubMed - in process]

Revisiting PAX-8's Labeling of Merkel Cell Carcinoma.

Fetched: October 25th, 2018, 5:00am GMT

Revisiting PAX-8's Labeling of Merkel Cell Carcinoma.

Am J Dermatopathol. 2017 11;39(11):873-874

Authors: Wang DP, Stevens RA, Wisell JA

PMID: 28002100 [PubMed - indexed for MEDLINE]

PDQ Cancer Information Summaries

Fetched: October 25th, 2018, 5:00am GMT

PDQ Cancer Information Summaries

Book. 2002

Authors:

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

PMID: 26389202

Expression of Proton-sensing G-Protein-coupled receptors in selected skin tumors.

Fetched: October 21st, 2018, 5:00am GMT

Expression of Proton-sensing G-Protein-coupled receptors in selected skin tumors.

Exp Dermatol. 2018 Oct 19;:

Authors: Nassios A, Wallner S, Haferkamp S, Klingelhöffer C, Brochhausen C, Schreml S

Abstract
BACKGROUND: In humans, there are four known proton-sensing G-Protein-coupled receptors (pH-GPCRs): GPR4 (GPR19), TDAG8 (GPR65, T-cell death-associated gene 8), OGR1 (GPR68, ovarian cancer GPCR1), and G2A (GPR132, G2 accumulation protein). They are known to be involved in sensing changes of extracellular proton-concentrations in the acidic microenvironment of tumors, which leads to altered cell proliferation, migration, metastasis, immune cell function and inflammation. However, little is known about the expression of pH-GPCRs in the skin and especially skin cancers.
AIM: We studied the expression of pH-GPCRs in selected skin cancers, i.e. Merkel cell carcinoma (MCC), dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS).
METHODS: We did immunohistochemistry and immunofluorescence to analyze the expression of GPR4, TDAG8, OGR1 and G2A using paraffin-embedded tissue samples (n = 4, exceptions: PDS GPR4/GPR65 n = 5, AFX GPR132 n = 3) from patients suffering from MCC, DFSP, AFX and PDS.
RESULTS: (1) GPR4 was expressed on all AFX and PDS specimens. All AFX and MCC showed a positive expression of G2A. All PDS exhibited a strong positive expression of G2A. (2) MCCs neither expressed GPR4 nor TDAG8. All DFSP showed no expression of TDAG8. (3) For any other combination of GPCR and skin disease we found positive/negative mixed results.
CONCLUSIONS: These are the first results on pH-GPCRs in selected skin cancers. We provide evidence that these GPCRs are differentially expressed on the various types of skin cancers and that they can potentially be addressed as a therapeutic target in extensive disease. This article is protected by copyright. All rights reserved.

PMID: 30339292 [PubMed - as supplied by publisher]

Human polyomaviruses and cancer: an overview.

Fetched: October 19th, 2018, 5:00am GMT

Human polyomaviruses and cancer: an overview.

Clinics (Sao Paulo). 2018 Oct 11;73(suppl 1):e558s

Authors: Prado JCM, Monezi TA, Amorim AT, Lino V, Paladino A, Boccardo E

Abstract
The name of the family Polyomaviridae, derives from the early observation that cells infected with murine polyomavirus induced multiple (poly) tumors (omas) in immunocompromised mice. Subsequent studies showed that many members of this family exhibit the capacity of mediating cell transformation and tumorigenesis in different experimental models. The transformation process mediated by these viruses is driven by viral pleiotropic regulatory proteins called T (tumor) antigens. Similar to other viral oncoproteins T antigens target cellular regulatory factors to favor cell proliferation, immune evasion and downregulation of apoptosis. The first two human polyomaviruses were isolated over 45 years ago. However, recent advances in the DNA sequencing technologies led to the rapid identification of additional twelve new polyomaviruses in different human samples. Many of these viruses establish chronic infections and have been associated with conditions in immunosuppressed individuals, particularly in organ transplant recipients. This has been associated to viral reactivation due to the immunosuppressant therapy applied to these patients. Four polyomaviruses namely, Merkel cell polyomavirus (MCPyV), Trichodysplasia spinulosa polyomavirus (TSPyV), John Cunningham Polyomavirus (JCPyV) and BK polyomavirus (BKPyV) have been associated with the development of specific malignant tumors. However, present evidence only supports the role of MCPyV as a carcinogen to humans. In the present review we present a summarized discussion on the current knowledge concerning the role of MCPyV, TSPyV, JCPyV and BKPyV in human cancers.

PMID: 30328951 [PubMed - in process]

A case of locally-advanced Merkel cell carcinoma progressing with disseminated bone marrow metastases.

Fetched: October 18th, 2018, 5:00am GMT

A case of locally-advanced Merkel cell carcinoma progressing with disseminated bone marrow metastases.

Eur J Dermatol. 2018 Oct 15;:

Authors: Kobrinski DA, Choudhury AM, Shah RP

Abstract

PMID: 30325324 [PubMed - as supplied by publisher]

Moderately Differentiated Neuroendocrine Cell Carcinoma of the Vulva: A Case Report and Review of the Literature.

Fetched: October 17th, 2018, 5:00am GMT

Moderately Differentiated Neuroendocrine Cell Carcinoma of the Vulva: A Case Report and Review of the Literature.

Gulf J Oncolog. 2016 Sep;1(22):72-75

Authors: Aminimoghaddam S, Maghsoudnia A, Shafiee S

Abstract
Primary vulvar neuroendocrine carcinoma are extremely rare. There have been few cases of these tumors most of which have been considered as Merkel cell carcinoma. This report describes a moderately differentiated neuroendocrine cell carcinoma that was not compatible to any of previously reported cases. The patient underwent left hemivulvectomy and bilateral inguinal lymph node dissection. Pathology examination revealed a 5×5 cm mass with no lymph node involvement. Post-op evaluation ruled out any regional and distant metastasis and thereby did not receive chemotherapy or radiotherapy. Four years of close follow up evidenced no signs of recurrence, regional involvement or distant metastasis.

PMID: 28191812 [PubMed - indexed for MEDLINE]

Management of Sentinel Lymph Node Metastasis in Merkel Cell Carcinoma: Completion Lymphadenectomy, Radiation, or Both?

Fetched: October 14th, 2018, 5:00am GMT

Management of Sentinel Lymph Node Metastasis in Merkel Cell Carcinoma: Completion Lymphadenectomy, Radiation, or Both?

Ann Surg Oncol. 2018 Oct 11;:

Authors: Perez MC, Oliver DE, Weitman ES, Boulware D, Messina JL, Torres-Roca J, Cruse CW, Gonzalez RJ, Sarnaik AA, Sondak VK, Wuthrick EJ, Harrison LB, Zager JS

Abstract
BACKGROUND: Approximately 30% of patients with clinically localized Merkel cell carcinoma (MCC) show nodal involvement on sentinel lymph node biopsy (SLNB). Optimal management of SLNB-positive disease has not been defined. This study compared outcomes after completion lymphadenectomy (CLND), radiation, and combined CLND plus radiation after a positive SLNB.
METHODS: All patients treated at a single institution for SLNB-positive MCC (1998-2015) were retrospectively evaluated, with examination of patient demographics, clinicopathologic characteristics, outcomes, and regional toxicity.
RESULTS: The study identified 71 evaluable patients with SLNB-positive disease. The median age of these patients was 76 years, and 76.1% were men. Of the 71 patients, 11 (15.5%) underwent CLND, 40 (56.3%) received radiation, and 20 (28.2%) underwent CLND plus postoperative radiation. Lymphovascular invasion was significantly more common in the radiation-alone cohort (p = 0.04). For the three cohorts, the median percentages of nodal involvement were respectively 2, 10, and 30% (p = 0.06). After a median follow-up period of 22.3 months, four patients had recurrence in their regional nodal basin (3 radiation-alone patients and 1 CLND + radiation patient). The three cohorts did not differ significantly in the development of distant metastases (p = 0.68) or overall survival (p = 0.72). Six patients experienced surgical-site infections (2 CLND and 4 CLND + radiation patients), and three patients experienced symptomatic lymphedema (1 CLND patient and 2 CLND + radiation patients).
CONCLUSIONS: Regional failure was infrequent (≤ 10%) regardless of treatment, and morbidity appeared to be low with all approaches. Given that multiple treatment approaches can be successful in treating micrometastatic MCC, future efforts should be directed at refining criteria for allocating patients to a specific method, or possibly no further nodal basin treatment, in an effort to maximize regional control at the lowest cost and morbidity.

PMID: 30311164 [PubMed - as supplied by publisher]

Merkel cell carcinoma: An update and review: Current and future therapy.

Fetched: October 14th, 2018, 5:00am GMT

Merkel cell carcinoma: An update and review: Current and future therapy.

J Am Acad Dermatol. 2018 03;78(3):445-454

Authors: Tello TL, Coggshall K, Yom SS, Yu SS

Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin associated with a high risk of local recurrence and distant metastases. It most commonly occurs on sun-exposed areas of white patients >65 years of age. The Merkel cell polyomavirus (MCV) is thought to be responsible for malignant transformation in approximately 80% of cases in the northern hemisphere, while ultraviolet radiation-induced DNA damage is implicated in MCV-negative tumors. The overall incidence of MCC is low, with approximately 1600 cases diagnosed annually in the United States. The rate is much higher in patients with lymphoproliferative malignancies, solid organ transplants, and HIV infection. The low overall incidence of this tumor makes it challenging to conduct prospective clinical trials with sufficient power. As a result, most management recommendations are based on case series, retrospective reviews, and expert opinion. The pathogenesis, diagnosis, and staging of MCC was discussed in the first article in this continuing medical education series. This article focuses on current management guidelines and promising new therapies in development. Because of the complexity, aggressive nature, and individuality of each case, MCC is best treated by a multidisciplinary team.

PMID: 29229573 [PubMed - indexed for MEDLINE]

A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma.

Fetched: October 13th, 2018, 5:00am GMT

A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma.

Histopathology. 2018 Jul;73(1):162-166

Authors: Pelletier DJ, Czeczok TW, Bellizzi AM

Abstract
AIMS: Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus-associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but, if antibodies against SV40 also cross-reacted with MCPyV, that would be advantageous from a resource-utilisation perspective.
METHODS AND RESULTS: Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small-cell lung carcinomas, and 18 extrapulmonary visceral small-cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC and MCPyV large T antigens, focusing on areas recognised by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumours; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognised by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by two long stretches of amino acids unique to MCPyV. The CM2B4 clone recognises a unique epitope in one of these stretches.
CONCLUSIONS: The PAb416 antibody against the SV40 large T antigen does not cross-react with MCPyV large T antigen, and thus does not label Merkel cell carcinoma.

PMID: 29430700 [PubMed - indexed for MEDLINE]

Analysis of cutaneous Merkel Cell Carcinoma outcomes after different surgical interventions.

Fetched: October 10th, 2018, 5:00am GMT

Analysis of cutaneous Merkel Cell Carcinoma outcomes after different surgical interventions.

J Am Acad Dermatol. 2018 Oct 05;:

Authors: Yan L, Sun L, Guan Z, Wei S, Wang Y, Li P

Abstract
BACKGROUND: Current guidelines recommend local excision margin (EM) with 1 to 2cm on primary merkel cell carcinoma (MCC) site.
OBJECTIVE: We compared survival outcomes of MCC patients treated with different surgical interventions.
METHODS: A retrospective analysis of MCC cases in the SEER database was performed by Kaplan-Meier, competing risk and Cox proportional hazards regression model analyses. Influence of age, T stage, AJCC stage, adjuvant radiotherapy and other subgroups were also analyzed by pair-wise log-rank test.
RESULTS: Our results indicated significant association between local destruction method and inferior survival, while EM>2cm showed significantly higher overall survival (OS). In addition, competing risk analysis depicted similar trend as Kaplan-Meier analysis, and considerably reduced estimated cumulative incidence. Further subgroup pair-wise analysis demonstrated that EM>2cm method had better survival in patients younger than 60 years, having smaller tumor diameters (T1 and T2) or undergone adjuvant radiotherapy (p<0.05). In contrast, different EMs did not show any significant association with survival rate in patients older than 75 years or stage III tumors.
LIMITATIONS: This study was not prospectively randomized without relapse data.
CONCLUSIONS: It is challenging to make optimal EM recommendations, as surgical options may depend on individual case situations. Further prospective randomized studies are warranted.

PMID: 30296537 [PubMed - as supplied by publisher]

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities.

Fetched: October 7th, 2018, 5:00am GMT

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities.

Nat Rev Clin Oncol. 2018 Oct 04;:

Authors: Harms PW, Harms KL, Moore PS, DeCaprio JA, Nghiem P, Wong MKK, Brownell I, International Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer associated with advanced age and immunosuppression. Over the past decade, an association has been discovered between MCC and either integration of the Merkel cell polyomavirus, which likely drives tumorigenesis, or somatic mutations owing to ultraviolet-induced DNA damage. Both virus-positive and virus-negative MCCs are immunogenic, and inhibition of the programmed cell death protein 1 (PD-1)-programmed cell death 1 ligand 1 (PD-L1) immune checkpoint has proved to be highly effective in treating patients with metastatic MCC; however, not all patients have a durable response to immunotherapy. Despite these rapid advances in the understanding and management of patients with MCC, many basic, translational and clinical research questions remain unanswered. In March 2018, an International Workshop on Merkel Cell Carcinoma Research was held at the US National Cancer Institute, at which academic, government and industry experts met to identify the highest-priority research questions. Here, we review the biology and treatment of MCC and report the consensus-based recommendations agreed upon during the workshop.

PMID: 30287935 [PubMed - as supplied by publisher]

Permalink for 'Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab.'

Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab.

Fetched: October 6th, 2018, 5:00am GMT

Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab.

J Immunother Cancer. 2018 Oct 01;6(1):99

Authors: Giraldo NA, Nguyen P, Engle EL, Kaunitz GJ, Cottrell TR, Berry S, Green B, Soni A, Cuda JD, Stein JE, Sunshine JC, Succaria F, Xu H, Ogurtsova A, Danilova L, Church CD, Miller NJ, Fling S, Lundgren L, Ramchurren N, Yearley JH, Lipson EJ, Cheever M, Anders RA, Nghiem PT, Topalian SL, Taube JM

Abstract
BACKGROUND: We recently reported a 56% objective response rate in patients with advanced Merkel cell carcinoma (MCC) receiving pembrolizumab. However, a biomarker predicting clinical response was not identified.
METHODS: Pretreatment FFPE tumor specimens (n = 26) were stained for CD8, PD-L1, and PD-1 by immunohistochemistry/immunofluorescence (IHC/IF), and the density and distribution of positive cells was quantified to determine the associations with anti-PD-1 response. Multiplex IF was used to test a separate cohort of MCC archival specimens (n = 16), to identify cell types expressing PD-1.
RESULTS: Tumors from patients who responded to anti-PD-1 showed higher densities of PD-1+ and PD-L1+ cells when compared to non-responders (median cells/mm2, 70.7 vs. 6.7, p = 0.03; and 855.4 vs. 245.0, p = 0.02, respectively). There was no significant association of CD8+ cell density with clinical response. Quantification of PD-1+ cells located within 20 μm of a PD-L1+ cell showed that PD-1/PD-L1 proximity was associated with clinical response (p = 0.03), but CD8/PD-L1 proximity was not. CD4+ and CD8+ cells in the TME expressed similar amounts of PD-1.
CONCLUSIONS: While the binomial presence or absence of PD-L1 expression in the TME was not sufficient to predict response to anti-PD-1 in patients with MCC, we show that quantitative assessments of PD-1+ and PD-L1+ cell densities as well as the geographic interactions between these two cell populations correlate with clinical response. Cell types expressing PD-1 in the TME include CD8+ T-cells, CD4+ T-cells, Tregs, and CD20+ B-cells, supporting the notion that multiple cell types may potentiate tumor regression following PD-1 blockade.

PMID: 30285852 [PubMed - in process]

Paraneoplastic neuronal intermediate filament autoimmunity.

Fetched: October 6th, 2018, 5:00am GMT

Paraneoplastic neuronal intermediate filament autoimmunity.

Neurology. 2018 Oct 03;:

Authors: Basal E, Zalewski N, Kryzer TJ, Hinson SR, Guo Y, Dubey D, Benarroch EE, Lucchinetti CF, Pittock SJ, Lennon VA, McKeon A

Abstract
OBJECTIVE: To describe paraneoplastic neuronal intermediate filament (NIF) autoimmunity.
METHODS: Archived patient and control serum and CSF specimens were evaluated by tissue-based indirect immunofluorescence assay (IFA). Autoantigens were identified by Western blot and mass spectrometry. NIF specificity was confirmed by dual tissue section staining and 5 recombinant NIF-specific HEK293 cell-based assays (CBAs, for α-internexin, neurofilament light [NfL], neurofilament medium, or neurofilament heavy chain, and peripherin). NIF-immunoglobulin Gs (IgGs) were correlated with neurologic syndromes and cancers.
RESULTS: Among 65 patients, NIF-IgG-positive by IFA and CBAs, 33 were female (51%). Median symptom onset age was 62 years (range 18-88). Patients fell into 2 groups, defined by the presence of NfL-IgG (21 patients, who mostly had ≥4 NIF-IgGs detected) or its absence (44 patients, who mostly had ≤2 NIF-IgGs detected). Among NfL-IgG-positive patients, 19/21 had ≥1 subacute onset CNS disorders: cerebellar ataxia (11), encephalopathy (11), or myelopathy (2). Cancers were detected in 16 of 21 patients (77%): carcinomas of neuroendocrine lineage (10) being most common (small cell [5], Merkel cell [3], other neuroendocrine [2]). Two of 257 controls (0.8%, both with small cell carcinoma) were positive by both IFA and CBA. Five of 7 patients with immunotherapy data improved. By comparison, the 44 NfL-IgG-negative patients had findings of unclear significance: diverse nervous system disorders (p = 0.006), as well as limited (p = 0.003) and more diverse (p < 0.0001) cancer accompaniments.
CONCLUSIONS: NIF-IgG detection by IFA, with confirmatory CBA testing that yields a profile including NfL-IgG, defines a paraneoplastic CNS disorder (usually ataxia or encephalopathy) accompanying neuroendocrine lineage neoplasia.

PMID: 30282771 [PubMed - as supplied by publisher]

Spontaneous regression of Merkel cell carcinoma.

Fetched: October 5th, 2018, 5:00am GMT

Spontaneous regression of Merkel cell carcinoma.

Cutis. 2018 Apr;101(4):301-305

Authors: Branch S, Maloney K, Purcell SM

Abstract
A 96-year-old woman presented with a rapidly enlarging lesion overlying the suprasternal notch. The lesion originated as a small, erythematous, scaly macule that rapidly increased in size over 8 weeks and became an ulcerated nodule measuring 5 cm in diameter and 4.5 cm in thickness. A 4-mm punch biopsy showed a poorly differentiated tumor with cells that were positive for CAM 5.2 and cytokeratin 20 in a dotlike paranuclear pattern and negative for cytokeratin 5/6, human melanoma black 45, and leukocyte common antigen. Two weeks after the punch biopsy, the lesion noticeably decreased in size, and within 8 weeks of the biopsy the tumor had completely resolved with no further intervention. Regression of Merkel cell carcinoma (MCC) is a very rare event, with as few as 30 cases reported. The mechanism of this phenomenon remains unclear; however, T-cell-mediated immunity and apoptosis appear to play a major role.

PMID: 29763480 [PubMed - indexed for MEDLINE]

Mechanisms of persistence by small DNA tumor viruses.

Fetched: October 4th, 2018, 5:00am GMT

Mechanisms of persistence by small DNA tumor viruses.

Curr Opin Virol. 2018 Sep 29;32:71-79

Authors: Krump NA, Liu W, You J

Abstract
Virus infection contributes to nearly 15% of human cancers worldwide. Many of the oncogenic viruses tend to cause cancer in immunosuppressed individuals, but maintain asymptomatic, persistent infection for decades in the general population. In this review, we discuss the tactics employed by two small DNA tumor viruses, Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV), to establish persistent infection. We will also highlight recent key findings as well as outstanding questions regarding the mechanisms by which HPV and MCPyV evade host immune control to promote their survival. Since persistent infection enables virus-induced tumorigenesis, identifying the mechanisms by which small DNA tumor viruses achieve latent infection may inform new approaches for preventing and treating their respective human cancers.

PMID: 30278284 [PubMed - as supplied by publisher]

Primary cutaneous ganglioneuroma: anatomico-clinical study of 4 cases with focus on Merkel cells.

Fetched: October 4th, 2018, 5:00am GMT

Primary cutaneous ganglioneuroma: anatomico-clinical study of 4 cases with focus on Merkel cells.

J Cutan Pathol. 2018 Jun;45(6):403-411

Authors: Romero-Pérez D, Jegou MH, Lecointre C, Penchet I, Cribier B

Abstract
Cutaneous ganglioneuromas (CGNs) are exceptional. We aim to describe the anatomico-clinical profile of primary CGN and report 4 cases. Patients were 2 men and 2 women aged 53 to 76 years, who had flesh-colored nodules on the back, associated with adjacent keratotic changes, that is, epidermal nevus (1 case) or seborrheic keratosis (3 cases). Histopathology showed ganglion cells within a proliferation of Schwann cells. The epidermis was acanthotic, associated with sebaceous induction in 2 cases, with follicular hyperplasia as in fibroepithelial tumors (1 case) or with tricholemmoma (2 cases). Cytokeratin-20 immunostaining showed Merkel cells in the epidermis. A higher density of Merkel cells was observed in BerEP4+ follicular structures. Along with 16 published cases, our study indicates that a nodule associated with seborrheic keratosis on the back may represent a CGN, a complex mesenchymal and epidermal/follicular lesion of neuroectodermal lineage, associating neuronal proliferation and Merkel cell hyperplasia with follicular induction.

PMID: 29569258 [PubMed - indexed for MEDLINE]

Permalink for 'Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03.'

Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03.

Fetched: October 3rd, 2018, 5:00am GMT

Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03.

J Med Imaging Radiat Oncol. 2018 Jun;62(3):412-419

Authors: Poulsen M, Macfarlane D, Veness M, Estall V, Hruby G, Kumar M, Pullar A, Tripcony L, Rischin D

Abstract
INTRODUCTION: TROG 09.03 prospectively studied the utility of Fluorine-18 Fluorodeoxyglucose (18-FDG) PET in the management of Merkel cell carcinoma of skin.
METHODS: Following consent and registration, a pre-treatment FDG-PET/CT was performed. Sites of avid disease were confirmed by cytology where practicable. Following surgery, patients with AJCCv7 Stages IIA-IIIB disease were treated with chemo-radiotherapy and reassessed with a post-treatment PET.
RESULTS: Fifty-eight subjects (45 males and 13 females, median age 68 years) were enrolled between 2011 and 2015, 43 patients of whom went on to receive chemo-radiotherapy. An occult primary was present in 22 (37.9%), T1 in 22 (37.9%) and T2 disease in 14 (24.1%). Nodal disease was present in 69% of cases. Fifty per cent of subjects had gross residual disease at the primary site and/or nodal site at the time of registration. 18-FDG PET/CT had a sensitivity of 94.74% (95% CI 82-99.3%) and a specificity of 88.24% (95% CI 63.56-98.54). The positive predictive value was 94.74% (83.01-98.51) and the negative predictive value was 88.24% (95% CI 65.81-96.69). The pre-treatment PET influenced a treatment decision in 27.6% of cases. Upstaging occurred in 15 (25.9%), with no down staging. Other diseases were identified in 4 (6.9%) patients. Univariate analysis failed to demonstrate that pre-treatment SUV levels or a negative post-treatment PET had any impact on overall survival. PET staged patients had 89% 3-year in-field loco-regional control and 76% 3-year overall survival.
CONCLUSION: Staging 18-FDG-PET significantly influenced treatment decisions in approximately one-third of cases of MCC and should be considered in the routine pre-treatment work-up. Post-treatment PET was not found to be prognostic. Funding through the Medicare Benefits Schedule needs to be considered for high risk MCC.

PMID: 29405630 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma arising on a pre-existing Bowen's disease: is it just by chance?

Fetched: October 3rd, 2018, 5:00am GMT

Merkel cell carcinoma arising on a pre-existing Bowen's disease: is it just by chance?

G Ital Dermatol Venereol. 2018 Apr;153(2):273-275

Authors: Casari A, Argenziano G, Piana S, Lallas A, Moscarella E, Lombardi M, Raucci M, Pellacani G, Longo C

Abstract
Merkel cell carcinoma (MCC) is a cutaneous carcinoma with neuroendocrine differentiation. It arises typically on sun-exposed areas of elderly men as an asymptomatic, rapidly growing, red nodule. Although it is usually found as a solitary nodule, in almost one third of cases MCC may be associated with other malignancies such as basal cell or squamous cell carcinomas. Merkel cell carcinoma should be considered as differential diagnosis every time we have a rapidly growing, red nodule, arising in an elderly patient with signs of sun-damage. We report a case of MCC developing in association with a pre-existing Bowen's disease. The association between MCC and Bowen's disease is quite common and their area of occurrence is usually a sun-exposed area. Ultraviolet radiation contributes to the etiology of both the malignancies.

PMID: 26222729 [PubMed - indexed for MEDLINE]

Computed tomography accelerates staging in patients with Merkel cell carcinoma.

Fetched: October 1st, 2018, 5:00am GMT

Computed tomography accelerates staging in patients with Merkel cell carcinoma.

Eur Arch Otorhinolaryngol. 2018 Sep 28;:

Authors: Foki E, Fochtmann-Frana A, Haymerle G, Nemec S, Loader B, Perisanidis C, Erovic BM

Abstract
PURPOSE: No imaging algorithms for diagnostic imaging in patients suffering from Merkel cell carcinoma (MCC) have been established so far and thus staging work-up is challenging. Long presentation-to-treatment intervals determine further treatment course and, consequently, have an impact on clinical outcome in patients with MCC.
METHODS: In this retrospective study, diagnostic imaging of 37 MCC patients was analyzed. CT, ultrasound, and PET/PET-CT imaging for primary staging work-up with time frames from patients´ initial presentation and imaging until completion of tumor staging were analyzed.
RESULTS: Tumor staging could be completed earlier when (1) less examinations (35 vs. 42 days) were carried out or (2) computed tomography was used as the initial imaging modality (28 vs. 35 days). Furthermore, CT imaging, when used as the initial imaging study, was linked to less follow-up imaging (3 vs. 6).
CONCLUSION: Computed tomography as the first-staging imaging technique in MCC patients leads to less follow-up studies and fastest completion of tumor staging.

PMID: 30267216 [PubMed - as supplied by publisher]

Complete remission of metastatic Merkel cell carcinoma in a patient with severe psoriasis.

Fetched: September 29th, 2018, 5:00am GMT

Complete remission of metastatic Merkel cell carcinoma in a patient with severe psoriasis.

Cutis. 2018 01;101(1):E24-E27

Authors: Yousif J, Yousif B, Kuriata MA

PMID: 29529118 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma of the Buccal Mucosa and Lower Lip.

Fetched: September 29th, 2018, 5:00am GMT

Merkel Cell Carcinoma of the Buccal Mucosa and Lower Lip.

Head Neck Pathol. 2018 Jun;12(2):279-285

Authors: Islam MN, Chehal H, Smith MH, Islam S, Bhattacharyya I

Abstract
Merkel cell carcinoma (MCC) is an uncommon relatively aggressive neuroendocrine dermal neoplasm first described in 1972 as a tumor of the sun exposed skin. Although most MCC affect the skin of the head and neck, rare primarily oral mucosal cases have been documented. Merkel cells are nondendritic neuroendocrine cells that are found not only in the skin but also the oral mucosa and give rise to MCC. Neuroendocrine cells may be found as aggregates in organs or as diffuse or isolated cells within organs and their epithelial lining. They contain peptide hormones and biogenic amines and occur in two forms: dendritic, which are not associated with nerve fibers and non-dendritic, which are associated with nerve fibers. Merkel cells as well as MCC express simple epithelium-type Cytokeratins (8, 18, 19, 20), neurosecretory substances; chromogranin A, synaptophysin, neuron-specific enolase (NSE), adhesion molecules, and villin (intermediate filament). Though weakly, they also express neural markers such as S-100 protein. Cytokeratin 20, and Cluster of differentiation 56, are the two key diagnostic markers for Merkel cells and MCC. Etiology includes UV radiation, the recently described Merkel cell polyomavirus, and long term systemic immunosuppression. The cutaneous and mucosal variants of MCC are considered aggressive tumors with a high risk for local recurrence and metastasis and should be considered in the differential diagnosis of head and neck mucosal lesions. We present two cases of primary Merkel cell carcinoma, one on the buccal mucosa and the other on the lower lip, and discuss the salient histologic, immunohistochemical and clinical features.

PMID: 28980225 [PubMed - indexed for MEDLINE]

The ALPPS procedure: hepatocellular carcinoma as a main indication. An Italian single-center experience.

Fetched: September 28th, 2018, 5:00am GMT

The ALPPS procedure: hepatocellular carcinoma as a main indication. An Italian single-center experience.

Updates Surg. 2018 Sep 25;:

Authors: Vennarecci G, Ferraro D, Tudisco A, Sandri GBL, Guglielmo N, Berardi G, Sperduti I, Ettorre GM

Abstract
The ALPPS is a technique that allows achieving hepatic resection by a rapid future liver remnant hypertrophy. The aim of this study was to report the experience of an Italian center with ALPPS in patients with liver tumors. A retrospective analysis of patients undergoing ALPPS between 2012 and 2017 was performed. Patients' characteristics and disease presentation, increase in future liver remnant (FLR) as well as intraoperative and postoperative short- and long-term outcomes were evaluated. A total of 24 patients underwent the ALPPS procedure: 17 procedures for hepatocarcinoma (HCC), 5 for colorectal liver metastases (CRLM), 1 for cholangiocarcinoma (CC) and 1 for Merkel Cell Carcinoma liver metastasis (MCCLM). Macrovascular invasion (MVI) was recorded in 10 (41.6%) patients: 8 (33.3%) patients with HCC had invasion of portal vein (5), middle hepatic vein (2) and inferior vena cava (1). One patient with CRLM had involvement of middle hepatic vein and one patient with CC had involvement of right portal vein and middle hepatic vein. A p-ALPPS in 14 cases (58.3%), 10 t-ALPPS (41.6%) and hanging maneuver in 19 patients (80%) were performed. Median postoperative stay was 26 days (range 16-68 days). 90-day mortality was 8.3% (two patients, one with CC and one with HCC), 90-day mortality for HCC was 5.8%. After stage 1, we counted 15 complications all of grade I; after stage 2 the number of complications was increased to 37:33 were of grade I and 4 were of grade IV. R0 resection was achieved in all patients with 100% oncology feasibility. After a median follow-up of 10 months (range 2-54), disease recurrence has been recorded in 6 patients with HCC and in 2 with CRLM. Eleven patients died, nine affected by HCC, one by CRLM, and one by CC. 2-years OS and disease-free survival (DFS) for the entire group were 47.3% and 47.5%, respectively. Concerning patients operated on for HCC, the 2-years OS and DFS were 38.5% and 60%, respectively. The ALPPS procedure is an interesting approach for large primary or secondary liver tumor with small FLR above all for large HCC associated with MVI, with acceptable OS and DFS.

PMID: 30255436 [PubMed - as supplied by publisher]

Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA.

Fetched: September 27th, 2018, 5:00am GMT

Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA.

Nat Commun. 2018 Sep 24;9(1):3868

Authors: Paulson KG, Voillet V, McAfee MS, Hunter DS, Wagener FD, Perdicchio M, Valente WJ, Koelle SJ, Church CD, Vandeven N, Thomas H, Colunga AG, Iyer JG, Yee C, Kulikauskas R, Koelle DM, Pierce RH, Bielas JH, Greenberg PD, Bhatia S, Gottardo R, Nghiem P, Chapuis AG

Abstract
Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular immunotherapy trials offer a means to probe complex tumor-immune interfaces through defined T cell/antigen interactions. We treated two patients with metastatic Merkel cell carcinoma with autologous Merkel cell polyomavirus specific CD8+ T cells and immune-checkpoint inhibitors. In both cases, dramatic remissions were associated with dense infiltration of activated CD8+s into the regressing tumors. However, late relapses developed at 22 and 18 months, respectively. Here we report single cell RNA sequencing identified dynamic transcriptional suppression of the specific HLA genes presenting the targeted viral epitope in the resistant tumor as a consequence of intense CD8-mediated immunologic pressure; this is distinguished from genetic HLA-loss by its reversibility with drugs. Transcriptional suppression of Class I loci may underlie resistance to other immunotherapies, including checkpoint inhibitors, and have implications for the design of improved immunotherapy treatments.

PMID: 30250229 [PubMed - in process]

Permalink for 'Expression of the IDO1/TDO2-AhR pathway in tumor cells or the tumor microenvironment is associated with MCPyV status and prognosis in Merkel cell carcinoma.'

Expression of the IDO1/TDO2-AhR pathway in tumor cells or the tumor microenvironment is associated with MCPyV status and prognosis in Merkel cell carcinoma.

Fetched: September 23rd, 2018, 5:00am GMT

Expression of the IDO1/TDO2-AhR pathway in tumor cells or the tumor microenvironment is associated with MCPyV status and prognosis in Merkel cell carcinoma.

Hum Pathol. 2018 Sep 18;:

Authors: Wardhani LO, Matsushita M, Iwasaki T, Kuwamoto S, Nonaka D, Nagata K, Kato M, Kitamura Y, Hayashi K

Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer, with approximately 80% of cases related to Merkel cell polyomavirus (MCPyV). Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) are the key rate-limiting enzymes of the tryptophan to kynurenine (KYN) metabolic pathway. With aryl hydrocarbon receptor (AhR), an intracellular transcription factor, they play a role in escaping the immunosurveillance process in several cancers. IDO1/TDO2/AhR expression associated with the MCPyV status and prognosis in MCC was investigated. Samples included 24 MCPyV-positive MCCs, 12 MCPyV-negative MCCs with squamous cell carcinoma, and seven MCPyV-negative pure MCCs. They were stained immunohistochemically with IDO1, TDO2, and AhR antibodies and analyzed. Higher IDO1 expression in MCC tumor cells was found in MCPyV-negative than in MCPyV-positive MCC (P < .001). The tumor microenvironment (TME) in MCPyV-negative MCC expressed higher TDO2 than MCPyV-positive MCC (P < .001). Kaplan-Meier and log-rank tests showed that MCC with lower IDO1 expression in tumor cells and with lower TDO2 and AhR expressions in TME had better overall survival than otherwise (P = .043, .008, and .035, respectively); lower TDO2 expression in TME was also associated with longer disease-specific survival (P = .016). This suggests that IDO1, TDO2, and AhR express differentially in tumor cells or TME and play different roles in tumorigenesis between MCPyV-positive and -negative MCC that may affect the MCC biology. Evaluating IDO1/TDO2/AhR expression is important for selecting the most likely patients with MCC for immunotherapies targeting the IDO1/TDO2-AhR pathway.

PMID: 30240768 [PubMed - as supplied by publisher]

Immunotherapy for Merkel Cell Carcinoma.

Fetched: September 23rd, 2018, 5:00am GMT

Immunotherapy for Merkel Cell Carcinoma.

Curr Treat Options Oncol. 2018 Sep 20;19(11):57

Authors: Nagase K, Narisawa Y

Abstract
OPINION STATEMENT: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin, with frequent recurrences, metastasis, and a high mortality rate. For primary or locoregional MCC, a wide local excision followed by radiation therapy is the basic treatment modality for preventing recurrence at the primary site and involved lymph nodes. Cytotoxic chemotherapy has been commonly used to treat patients with metastatic MCC, but not as an adjuvant therapy for high-risk resected MCC. Although MCC is often chemotherapy-sensitive in the first-line setting, responses are rarely durable and most patients subsequently relapse and develop metastasis. Treatment with checkpoint inhibitors (CPIs) has shown a major advancement in the treatment of advanced MCC. Systemic therapy against programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) is associated with a high objective response rate (ORR), prolonged durable responses, and good tolerability in advanced-stage MCC. CPIs are now included in the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of patients with metastatic MCC. Multiple clinical trials of CPIs administered as monotherapy or in combination with other agents or modalities, including the adjuvant setting, are ongoing. Immunotherapy offers a promising future for patients with MCC. In this review, we present an overview of emerging data on immunotherapy, especially CPIs of the PD-1/PD-L1 pathway, for patients with advanced MCC.

PMID: 30238195 [PubMed - in process]

Virus-related Merkel cell carcinoma complicating fingolimod treatment for multiple sclerosis.

Fetched: September 23rd, 2018, 5:00am GMT

Virus-related Merkel cell carcinoma complicating fingolimod treatment for multiple sclerosis.

Neurology. 2016 12 13;87(24):2595-2597

Authors: Beadnall HN, Gill AJ, Riminton S, Barnett MH

PMID: 27856777 [PubMed - indexed for MEDLINE]

Permalink for 'Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.'

Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.

Fetched: September 15th, 2018, 5:00am GMT

Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.

Am J Clin Oncol. 2018 Sep 11;:

Authors: Cook M, Baker K, Redman M, Lachance K, Nguyen MH, Parvathaneni U, Bhatia S, Nghiem P, Tseng YD

Abstract
OBJECTIVES: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with higher incidence among whites, elderly, and immunosuppressed patients. Although immunosuppressed MCC patients are at higher risk of recurrence and MCC-related death, it is unknown whether immunosuppression type is associated with differential outcomes.
MATERIALS AND METHODS: We retrospectively evaluated 89 nonmetastatic MCC patients with a diagnosis of chronic immunosuppression. Immunosuppression was categorized as chronic lymphocytic leukemia (31% of cohort), other hematologic malignancies (18%), solid organ transplant (21%), autoimmune disease (21%), and human immunodeficiency virus acquired deficiency syndrome (8%). Progression-free survival (PFS) and MCC-specific survival (MSS) were estimated with the cumulative incidence function. Overall survival (OS) was estimated by the Kaplan-Meier method.
RESULTS: With a median follow-up of 52 months, 53 deaths occurred (42 from MCC, 7 unknown, and 4 non-MCC). Two-year PFS, MSS, and OS were 30%, 55%, and 52%, respectively. Human immunodeficiency virus/acquired deficiency syndrome and solid organ transplant patients were diagnosed with MCC at a younger age (median 55 and 59 y, respectively) and with more advanced stage disease compared with other immunosuppressed subgroups. PFS did not significantly differ among the 5 immunosuppression subgroups (P=0.30), but significant differences were observed in MSS and OS (both P=0.01). Controlling for potential confounders for OS, including age and stage, immunosuppression type was still significantly associated with risk of death (P=0.01).
CONCLUSIONS: Among immunosuppressed MCC patients, recurrent MCC is the major cause of mortality. The risk of death from MCC differs among immunosuppression types, suggesting important biological differences in host-tumor immune interactions.

PMID: 30211723 [PubMed - as supplied by publisher]

PDQ Cancer Information Summaries

Fetched: September 13th, 2018, 5:00am GMT

PDQ Cancer Information Summaries

Book. 2002

Authors:

PMID: 26389158

Venous thromboembolism leading to diagnosis of de novo malignancy in an organ transplant recipient.

Fetched: September 11th, 2018, 5:00am GMT

Venous thromboembolism leading to diagnosis of de novo malignancy in an organ transplant recipient.

BMJ Case Rep. 2018 Sep 08;2018:

Authors: Mitchell N, Connell A, Kurth B

Abstract
We report the case of a patient with remote orthotopic liver transplant who was ultimately diagnosed with Merkel cell carcinoma following admission for initial venous thromboembolism. Additionally, we review pertinent literature related to the risk of skin cancer in solid organ transplant recipients and discuss the importance of yearly skin exams in this patient population.

PMID: 30196255 [PubMed - in process]

Epidemiology of Merkel Cell Carcinoma. A population-based study from 1985 to 2013, in Northeastern of France.

Fetched: September 10th, 2018, 5:00am GMT

Epidemiology of Merkel Cell Carcinoma. A population-based study from 1985 to 2013, in Northeastern of France.

Int J Cancer. 2018 Sep 08;:

Authors: Kieny A, Cribier B, Meyer N, Velten M, Jégu J, Lipsker D

Abstract
Merkel Cell Carcinoma (MCC) is an aggressive skin cancer with an increasing incidence. Population-based epidemiologic data about MCC in France are rare. This study aims to describe the epidemiology of MCC in Bas-Rhin, Northeastern of France, between 1985 and 2013. Data were collected from the Bas-Rhin Cancer Registry. We measured age-adjusted incidence rates (per 100,000 person-years) and effect of age, sex and period of diagnosis on survival. The world age-standardized incidence rate was 0.17 and it quadrupled between 1985 and 2013. Cases (n=111) occurred mostly in women (60%) and in persons ≥ 70 years of age (74%). Incidence rates was close for men (0.18) and women (0.16) and was 25-time higher in people ≥ 70 years of age but incidence rate similarly increased between 1985 and 2013 in persons older and younger than 70 years. Net five-year survival was 48.5 %; female sex and younger age were positive predictors of survival. Given the low number of cases, incidence and survival data should be interpreted with caution. Incidence of MCC in Bas-Rhin quadrupled between 1985 and 2013. The highest incidence rate was observed in people ≥ 70 years. Better survival was associated with female sex and younger age. We hypothesize that MCC will still increase and be diagnosed in increasingly younger patients in next generations. This article is protected by copyright. All rights reserved.

PMID: 30194728 [PubMed - as supplied by publisher]

Permalink for 'Effect of Patient Immune Status on the Efficacy of Radiation Therapy and Recurrence-Free Survival Among 805 Patients With Merkel Cell Carcinoma.'

Effect of Patient Immune Status on the Efficacy of Radiation Therapy and Recurrence-Free Survival Among 805 Patients With Merkel Cell Carcinoma.

Fetched: September 9th, 2018, 5:00am GMT

Effect of Patient Immune Status on the Efficacy of Radiation Therapy and Recurrence-Free Survival Among 805 Patients With Merkel Cell Carcinoma.

Int J Radiat Oncol Biol Phys. 2018 Oct 01;102(2):330-339

Authors: Tseng YD, Nguyen MH, Baker K, Cook M, Redman M, Lachance K, Bhatia S, Liao JJ, Apisarnthanarax S, Nghiem PT, Parvathaneni U

Abstract
PURPOSE: Patients with Merkel cell carcinoma (MCC) with chronic immunosuppression (IS) have worse outcomes, but the mechanisms are not well understood. We hypothesized that these differences may be mediated in part by differential response to treatment, and we evaluated whether radiation therapy (RT) efficacy is altered among IS compared with immune-competent (IC) patients with MCC.
METHODS AND MATERIALS: Among 805 patients with MCC, recurrence-free survival (RFS) and patterns of first recurrence were compared between 89 IS and 716 IC patients with stage I to III MCC treated with curative intent. We used a Fine and Gray's competing risk multivariable analysis to estimate associations with RFS.
RESULTS: IS and IC patients with MCC had similar demographic and disease characteristics. Most (77% IC, 86% IS) were irradiated (median, 50.4 Gy IC, 50.3 Gy IS), although more IS patients were irradiated to the primary site (97% vs 81%). With a median follow-up of 54.4 months, IS patients had inferior RFS (2-year: 30% vs 57%; P < .0001) and higher rates of local recurrence as the first site of relapse (25% vs 12%; P = .0002). The association between RT and RFS differed by immune status (interaction P = .01). Although RT was associated with significantly improved RFS among IC patients (hazard ratio 0.56, 95% confidence interval 0.44-0.72), no difference in RFS was observed with RT among IS patients (hazard ratio 1.49, 95% confidence interval 0.70-3.17).
CONCLUSIONS: Radiation therapy efficacy at current standard RT doses for MCC is impaired among immunosuppressed patients with MCC. Although a strong link between durability of RT response and immune function does not appear to be evident in most cancers, our results may reflect an especially dynamic interaction between immune status and RT efficacy in MCC.

PMID: 30191867 [PubMed - in process]

Permalink for 'Morphological and immunocytochemical features of Merkel cell carcinoma metastatic to the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration.'

Morphological and immunocytochemical features of Merkel cell carcinoma metastatic to the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Fetched: September 9th, 2018, 5:00am GMT

Morphological and immunocytochemical features of Merkel cell carcinoma metastatic to the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Diagn Cytopathol. 2017 Jul;45(7):629-630

Authors: Lucci R, D' Anna M, Marano A, Vigliar E, Avellino M, Napolitano V, Troncone G, Bellevicine C

PMID: 28387053 [PubMed - indexed for MEDLINE]

Permalink for 'Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness.'

Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness.

Fetched: September 8th, 2018, 5:00am GMT

Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness.

PLoS Pathog. 2018 Sep 06;14(9):e1007276

Authors: Nwogu N, Boyne JR, Dobson SJ, Poterlowicz K, Blair GE, Macdonald A, Mankouri J, Whitehouse A

Abstract
Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is recognised as the causative factor in the majority of MCC cases. The MCPyV small tumour antigen (ST) is considered to be the main viral transforming factor, however potential mechanisms linking ST expression to the highly metastatic nature of MCC are yet to be fully elucidated. Metastasis is a complex process, with several discrete steps required for the formation of secondary tumour sites. One essential trait that underpins the ability of cancer cells to metastasise is how they interact with adjoining tumour cells and the surrounding extracellular matrix. Here we demonstrate that MCPyV ST expression disrupts the integrity of cell-cell junctions, thereby enhancing cell dissociation and implicate the cellular sheddases, A disintegrin and metalloproteinase (ADAM) 10 and 17 proteins in this process. Inhibition of ADAM 10 and 17 activity reduced MCPyV ST-induced cell dissociation and motility, attributing their function as critical to the MCPyV-induced metastatic processes. Consistent with these data, we confirm that ADAM 10 and 17 are upregulated in MCPyV-positive primary MCC tumours. These novel findings implicate cellular sheddases as key host cell factors contributing to virus-mediated cellular transformation and metastasis. Notably, ADAM protein expression may be a novel biomarker of MCC prognosis and given the current interest in cellular sheddase inhibitors for cancer therapeutics, it highlights ADAM 10 and 17 activity as a novel opportunity for targeted interventions for disseminated MCC.

PMID: 30188954 [PubMed - as supplied by publisher]

Onset of Kaposi sarcoma and Merkel cell carcinoma during low-dose steroid therapy for rheumatic polymyalgia.

Fetched: September 7th, 2018, 5:00am GMT

Onset of Kaposi sarcoma and Merkel cell carcinoma during low-dose steroid therapy for rheumatic polymyalgia.

Clin Exp Dermatol. 2017 Aug;42(6):702-704

Authors: Brambilla L, Esposito L, Nazzaro G, Tourlaki A

PMID: 28598021 [PubMed - indexed for MEDLINE]

Sentinel lymph node biopsy in Merkel cell carcinoma: The Mayo Clinic experience of 150 patients.

Fetched: September 6th, 2018, 5:00am GMT

Sentinel lymph node biopsy in Merkel cell carcinoma: The Mayo Clinic experience of 150 patients.

Surg Oncol. 2018 Mar;27(1):11-17

Authors: Sims JR, Grotz TE, Pockaj BA, Joseph RW, Foote RL, Otley CC, Weaver AL, Jakub JW, Price DL

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy of neuroendocrine origin with a high propensity for lymph node metastasis. Sentinel lymph node (SLN) status is important for accurate staging; however, the optimal treatment following SLN biopsy, regardless of nodal status, remains unclear.
METHODS: 150 patients with MCC who underwent SLN biopsy from 1995 to 2011 at 3 Mayo Clinic sites were reviewed.
RESULTS: Of 150 patients with MCC who underwent SLN biopsy, 39 (26%) were positive and 111 (74%) were negative. There was no significant difference between the sex, age, tumor location, or size of primary in the positive and negative SLN groups. While there was no difference in the cumulative incidence of any regional recurrence between SLN groups, the rate of in-transit recurrences was significantly higher in patients with a positive SLN (p = 0.022). The disease-specific survival for MCC was 97.0%, 82.4%, and 82.4% at 1, 3, and 5 years with a positive SLN and 99.0%, 94.9%, and 86.8% with a negative SLN (p = 0.31). Among those alive at last follow up, the median follow up was 3.8 years (IQR, 2.1-8.4) and 2.9 years (IQR, 1.8-6.1) for positive and negative SLN cohorts respectively.
CONCLUSIONS: Occult nodal metastasis is common in MCC(26%). No tumor or patient characteristics were identified to predict SLN positivity. Patients with a positive SLN have a higher risk of in-transit recurrence and may benefit from adjuvant radiation with inclusion of the in-transit field in amenable cases. When patients with a positive SLN receive additional treatment to the at-risk nodal basin, both OS and DSS are similar to patients with a negative SLN.

PMID: 29549898 [PubMed - indexed for MEDLINE]

Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report.

Fetched: September 3rd, 2018, 5:00am GMT

Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report.

J Immunother Cancer. 2018 Aug 31;6(1):82

Authors: Appelbaum J, Wells D, Hiatt JB, Steinbach G, Stewart FM, Thomas H, Nghiem P, Kapur RP, Thompson JA, Bhatia S

Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) are the treatment of choice for several cancers and can be associated with remarkable clinical benefit, but can also cause serious immune-related adverse events (irAEs). Management of rare and severe irAEs is challenged by an incomplete knowledge of their natural history and pathogenetic mechanisms. We report a case of fatal acute-onset gastro-intestinal (GI) hypomotility from myenteric plexus neuropathy following a single dose of ipilimumab plus nivolumab given for treatment of Merkel cell carcinoma (MCC).
CASE PRESENTATION: A 66-year-old man with recurrent metastatic MCC involving several organs (liver, bones and disseminated retroperitoneal lymphadenopathy) developed profound pharyngeal dysphagia and ileus that started 7 days after receiving a single administration of combination immune checkpoint blockade consisting of nivolumab (3 mg/kg) and low-dose ipilimumab (1 mg/kg). A swallowing study showed oropharyngeal dysfunction and aspiration. Imaging studies were consistent with diffuse intestinal paresis. An extensive work-up did not reveal obvious causes of these symptoms, and enteric plexopathy was suspected. Empiric immune suppressive therapy was initiated urgently. Despite an escalating immunosuppressive regimen that included high dose steroids, tacrolimus and therapeutic plasma exchange, no improvement in GI motility was seen and the patient suffered repeated episodes of aspiration. Seven weeks after the onset of GI hypomotility, the patient succumbed to sepsis from intestinal perforations. At autopsy, histologic specimens obtained from the entire GI tract (pharynx to rectum) showed near complete loss of ganglion cells within the myenteric and submucosal plexuses. An associated inflammatory infiltrate was not seen, suggesting a 'burned out' phase of illness. C4d complement deposition was found at the ganglionic sites, suggesting antibody-mediated pathogenesis. Remarkably, at sites of previously suspected Merkel cell metastases, no residual viable Merkel cell carcinoma was identified.
CONCLUSIONS: GI-tract paresis due to myenteric neuritis is a rarely reported toxicity of ICIs. Because the window of reversibility is likely to be very brief, quick and decisive interventions are warranted. Subtle functional and anatomic perturbations of the myenteric nervous system from the use of ICIs may be more prevalent than realized and should be suspected and addressed in both clinical and investigational settings.

PMID: 30170630 [PubMed - in process]

Permalink for 'Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma-An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin.'

Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma-An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin.

Fetched: September 2nd, 2018, 5:00am GMT

Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma-An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin.

Head Neck Pathol. 2018 Mar;12(1):13-21

Authors: Chernock RD, Duncavage EJ

Abstract
Salivary neuroendocrine carcinomas are rare and the overwhelming majority is high-grade. The parotid gland is the most commonly involved site followed by the submandibular gland. Most arise de novo but rare examples occurring as a high-grade transformation of another type of salivary gland neoplasm exist. There is significant morphologic and immunophenotypic overlap with neuroendocrine carcinomas of other sites, especially the skin. Like cutaneous neuroendocrine (or Merkel cell) carcinomas, approximately three-fourths are cytokeratin 20 positive. Cytokeratin 20 positive salivary neuroendocrine carcinomas are often referred to as being of the 'Merkel cell type' since most other non-cutaneous neuroendocrine carcinomas are cytokeratin 20 negative. Salivary neuroendocrine carcinomas may be challenging to separate from Merkel cell carcinomas of the head and neck on pathologic grounds because the latter often metastasize to the parotid gland. Clinical history is often relied upon to separate primary salivary tumors from cutaneous metastases but may not be helpful in all cases. Here we review the clinical, pathologic and molecular features of salivary neuroendocrine carcinomas focusing on high-grade major salivary gland tumors. The difficulty in separating salivary tumors from metastatic Merkel cell carcinoma will be highlighted.

PMID: 29556963 [PubMed - indexed for MEDLINE]

Color Doppler Sonography of Merkel Cell Carcinoma.

Fetched: September 2nd, 2018, 5:00am GMT

Color Doppler Sonography of Merkel Cell Carcinoma.

J Ultrasound Med. 2018 Jan;37(1):285-292

Authors: Catalano O, Alfageme Roldán F, Scotto di Santolo M, Solivetti FM, Wortsman X

Abstract
We illustrate the color Doppler sonographic findings in primary cutaneous Merkel cell carcinoma. Eight cases (4 female and 4 male; mean age, 75.4 years) were collected. The most common affected regions were the face (63%) and the hip/buttock (25%). The mean transverse diameter and thickness were 21 and 14 mm, respectively. Fifty percent were oval, and 50% were dome shaped. All lesions were hypoechoic, with variable degrees of heterogeneity. All but 2 lesions were poorly defined. An acoustic reinforcement artifact was present in 3 and epidermal thickening in 2. All tumors had prominent and chaotic hypervascularity with arterial vessels (mean peak velocity, 11 cm/s; mean resistive index, 0.57).

PMID: 28726278 [PubMed - indexed for MEDLINE]

Permalink for 'One in a hundred million: Merkel cell carcinoma in pediatric and young adult patients is rare but more likely to present at advanced stages based on US registry data.'

One in a hundred million: Merkel cell carcinoma in pediatric and young adult patients is rare but more likely to present at advanced stages based on US registry data.

Fetched: September 1st, 2018, 5:00am GMT

One in a hundred million: Merkel cell carcinoma in pediatric and young adult patients is rare but more likely to present at advanced stages based on US registry data.

J Am Acad Dermatol. 2018 Aug 27;:

Authors: Paulson KG, Nghiem P

PMID: 30165170 [PubMed - as supplied by publisher]

Do cancer registries play a role in determining the incidence of non-melanoma skin cancers?

Fetched: September 1st, 2018, 5:00am GMT

Do cancer registries play a role in determining the incidence of non-melanoma skin cancers?

Eur J Dermatol. 2018 Apr 01;28(2):169-176

Authors: Anselmo Lima C, Sampaio Lima M, Maria Da Silva A, Prado Nunes MA, Macedo Lima MM, Oliveira Santos M, Lyra D, Kleber Alves C

Abstract
Non-melanoma skin cancers have the highest incidence of all malignancies worldwide. However, cancer registries rarely include data on non-melanoma skin cancers because they tend to be under-reported. To determine incidence rates and changes over time for non-melanoma skin cancers in a mid-sized Brazilian population. We calculated age-standardized rates, adjusted to the world population using the direct method, from 1996-2012 in the Aracaju Cancer Registry and then calculated incidence trends using the Joinpoint Regression Program. We analysed 11,476 cases (5,695 men and 5,781 women) of non-melanoma skin cancer collected during the study period. The histological subtypes in men were 84.5% basal cell carcinoma, 14.5% squamous cell carcinoma, and 1% other histological subtypes, whereas the corresponding percentages in women were 89.1%, 10%, and 0.9%, respectively. Average incidence age-standardized rates were 228.6 (95% CI: 221.6; 235.6) per 100,000 men and 145.4 (95% CI: 141.0; 149.9) per 100,000 women. The incidence mostly increased in the first years for the series and then stabilized. The under-reporting of non-melanoma skin cancers, due to removal of lesions without histopathological confirmation, decisions to keep skin lesions under observation instead of excising them, and deferring medical examination, is a potential pitfall of this study. Age-standardized incidence of non-melanoma skin cancer was high during the study period, but tended to stabilise in the latter years of the study.

PMID: 29619990 [PubMed - indexed for MEDLINE]

Permalink for 'Definitive radiotherapy for a head and neck Merkel cell carcinoma and comprehensive nodal volumes: a case for using a computer-designed variable-thickness compensator to reduce risk and severity of mucositis.'

Definitive radiotherapy for a head and neck Merkel cell carcinoma and comprehensive nodal volumes: a case for using a computer-designed variable-thickness compensator to reduce risk and severity of mucositis.

Fetched: September 1st, 2018, 5:00am GMT

Definitive radiotherapy for a head and neck Merkel cell carcinoma and comprehensive nodal volumes: a case for using a computer-designed variable-thickness compensator to reduce risk and severity of mucositis.

Med Dosim. 2018 Spring;43(1):69-73

Authors: Ahamad A, Weed DT, Pruett DD, Saulpaugh D, Neeranjun W, Fernandez E

Abstract
When contemplating how to treat head and neck primary cancers and regional lymph nodes with radiotherapy, we often select the contemporary intensity-modulated radiotherapy (IMRT) without much consideration of older methods that may give fewer side effects and be more cost-effective. For an 87-year-old female with a 1.5-cm Merkel cell carcinoma (MCC) located 1.5 cm lateral to the orbital rim, we were challenged to deliver 50 Gy to comprehensive elective nodal regions and 70 Gy to the primary. We were particularly concerned about the potential adverse acute effects of radiotherapy to mucosal structures in this elderly female. Acute mucositis could impair nutrition, quality of life, and treatment intensity especially given her age. We compared 3 techniques that are appropriate for this target: step-and-shoot IMRT, matched electron fields (MEF), and electron conformal therapy (BolusECT™). We selected and treated her with BolusECT™ because of better sparing of larynx, pharynx, oral cavity and lips, and shortest treatment time. This is a reasonable option for treating ipsilateral head and neck target volumes at centers where only these 3 techniques are available.

PMID: 29031904 [PubMed - indexed for MEDLINE]

ASO Author Reflections: Resection Margins in Merkel Cell Carcinoma: Is a 1 cm Margin Wide Enough?

Fetched: August 30th, 2018, 5:00am GMT

ASO Author Reflections: Resection Margins in Merkel Cell Carcinoma: Is a 1 cm Margin Wide Enough?

Ann Surg Oncol. 2018 Aug 27;:

Authors: Perez MC, Zager JS

PMID: 30151562 [PubMed - as supplied by publisher]

Merkel-cell carcinoma of the upper limb.

Fetched: August 30th, 2018, 5:00am GMT

Icon for Silverchair Information Systems

Merkel-cell carcinoma of the upper limb.

J Surg Case Rep. 2018 Aug;2018(8):rjy190

Authors: M Rojoa D, Katsogridakis E, Madan M, Rao M

Abstract
Merkel-cell carcinoma is a rare form of aggressive cutaneous cancer that is associated with a poor prognosis. Despite significant advances, its pathogenesis is still poorly understood, and treatment remains controversial. Timely diagnosis and early management is essential in improving survival rate. We present a case of a 63-year-old patient with a rapidly growing upper limb Merkel-cell carcinoma. It was treated with wide-local excision and adjuvant radiotherapy.

PMID: 30151102 [PubMed]

Image Gallery: Merkel cell carcinoma under the rainbow.

Fetched: August 30th, 2018, 5:00am GMT

Image Gallery: Merkel cell carcinoma under the rainbow.

Br J Dermatol. 2017 10;177(4):e166

Authors: di Meo N, Vernoni S, Longone M, Trevisan G

PMID: 29052882 [PubMed - indexed for MEDLINE]

Coincident Metastatic Melanoma and Merkel Cell Carcinoma with Complete Remission on Treatment with Pembrolizumab.

Fetched: August 29th, 2018, 5:00am GMT

Coincident Metastatic Melanoma and Merkel Cell Carcinoma with Complete Remission on Treatment with Pembrolizumab.

Acta Derm Venereol. 2017 Nov 15;97(10):1252-1254

Authors: Thiem A, Kneitz H, Schummer P, Herz S, Schrama D, Houben R, Goebeler M, Schilling B, Gesierich A

PMID: 28761962 [PubMed - indexed for MEDLINE]

CCL17/TARC and CCR4 expression in Merkel cell carcinoma.

Fetched: August 26th, 2018, 5:00am GMT

CCL17/TARC and CCR4 expression in Merkel cell carcinoma.

Oncotarget. 2018 Jul 31;9(59):31432-31447

Authors: Rasheed K, Abdulsalam I, Fismen S, Grimstad Ø, Sveinbjørnsson B, Moens U

Abstract
Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine skin cancer. In more than 80% of the cases, Merkel cell polyomavirus (MCPyV) is a causal factor. The oncogenic potential of MCPyV is mediated through its viral oncoproteins, large T antigen (LT) and small t antigen (sT). To investigate the role of cytokines in MCC, a PCR array analysis for genes encoding inflammatory cytokines and receptors was performed on MCPyV-negative and MCPyV-positive MCC cell lines, respectively. We detected an increased expression of CCL17/TARC in the MCPyV-positive MKL2 cell line compared to the MCPyV-negative MCC13 cell line. Transfection studies in MCC13 cells with LT expression plasmid, and a luciferase reporter plasmid containing the CCL17/TARC promoter, exhibited stimulated promoter activity. Interestingly, the ectopic expression of CCL17/TARC upregulated MCPyV early and late promoter activities in MCC13 cells. Furthermore, recombinant CCL17/TARC activated both the mitogen-activated protein kinase and the NF-κB pathways. Finally, immunohistochemical staining on human MCC tissues showed a strong staining of CCL17/TARC and its receptor CCR4 in both LT-positive and -negative MCC. Taken together, CCL17/TARC and CCR4 may be a potential target in MCC therapy providing MCC patients with a better overall survival outcome.

PMID: 30140381 [PubMed]

$Permalink for 'Favorable Response to Treatment with Avelumab in an HIV-Positive Patient with Advanced Merkel Cell Carcinoma Previously Refractory to Chemotherapy.'$

Favorable Response to Treatment with Avelumab in an HIV-Positive Patient with Advanced Merkel Cell Carcinoma Previously Refractory to Chemotherapy.

Fetched: August 26th, 2018, 5:00am GMT

Favorable Response to Treatment with Avelumab in an HIV-Positive Patient with Advanced Merkel Cell Carcinoma Previously Refractory to Chemotherapy.

Case Rep Oncol. 2018 May-Aug;11(2):467-475

Authors: Al Homsi MU, Mostafa M, Fahim K

Abstract
Avelumab is indicated for the management of Merkel cell carcinoma, a rare and aggressive neuroendocrine skin cancer. Its regulatory approval followed the positive outcome of a Phase 2 trial on 88 patients with stage IV disease, which excluded patients with immunodeficiency due to HIV, a risk factor for this cancer type. We report a positive and sustained response to avelumab in an HIV-positive patient with stage IV Merkel cell carcinoma refractory to previous chemotherapy (cisplatin/etoposide) and radiotherapy. Five cycles of avelumab 10 mg/m2 resulted in the resolution of tumor activity visualized using PET-CT scanning in all affected lymph nodes. The only major side effect associated with avelumab was thyroiditis and mild hypothyroidism, a known adverse effect of this treatment, which was well controlled by L-thyroxine treatment. Treatment is ongoing and the positive response has been sustained during 5 further cycles of treatment up to date. This apparently durable response is consistent with the earlier clinical trial experience with avelumab, but seen here in a patient with HIV-associated immunodeficiency as a predisposing factor (an exclusion criterion from the previous trial). Further clinical trials with avelumab in a broader patient population with Merkel cell carcinoma are warranted.

PMID: 30140209 [PubMed]

Merkel cell polyomavirus and Langerhans cell neoplasm.

Fetched: August 25th, 2018, 5:00am GMT

Merkel cell polyomavirus and Langerhans cell neoplasm.

Cell Commun Signal. 2018 Aug 22;16(1):49

Authors: Murakami I, Wada N, Nakashima J, Iguchi M, Toi M, Hashida Y, Higuchi T, Daibata M, Matsushita M, Iwasaki T, Kuwamoto S, Horie Y, Nagata K, Hayashi K, Oka T, Yoshino T, Imamura T, Morimoto A, Imashuku S, Gogusev J, Jaubert F

Abstract
BACKGROUND: The relationship between various external agents such as pollen, food, and infectious agents and human sensitivity exists and is variable depending upon individual's health conditions. For example, we believe that the pathogenetic potential of the Merkel cell polyomavirus (MCPyV), the resident virus in skin, is variable and depends from the degree of individual's reactivity. MCPyV as well as Epstein-Barr virus, which are normally connected with humans under the form of subclinical infection, are thought to be involved at various degrees in several neoplastic and inflammatory diseases. In this review, we cover two types of Langerhans cell neoplasms, the Langerhans cell sarcoma (LCS) and Langerhans cell histiocytosis (LCH), represented as either neoplastic or inflammatory diseases caused by MCPyV.
METHODS: We meta-analyzed both our previous analyses, composed of quantitative PCR for MCPyV-DNA, proteomics, immunohistochemistry which construct IL-17 endocrine model and interleukin-1 (IL-1) activation loop model, and other groups' data.
RESULTS: We have shown that there were subgroups associated with the MCPyV as a causal agent in these two different neoplasms. Comparatively, LCS, distinct from the LCH, is a neoplastic lesion (or sarcoma) without presence of inflammatory granuloma frequently observed in the elderly. LCH is a proliferative disease of Langerhans-like abnormal cells which carry mutations of genes involved in the RAS/MAPK signaling pathway. We found that MCPyV may be involved in the development of LCH.
CONCLUSION: We hypothesized that a subgroup of LCS developed according the same mechanism involved in Merkel cell carcinoma pathogenesis. We proposed LCH developed from an inflammatory process that was sustained due to gene mutations. We hypothesized that MCPyV infection triggered an IL-1 activation loop that lies beneath the pathogenesis of LCH and propose a new triple-factor model.

PMID: 30134914 [PubMed - in process]

Merkel Cell Carcinoma in a Steer.

Fetched: August 23rd, 2018, 5:00am GMT

Merkel Cell Carcinoma in a Steer.

J Comp Pathol. 2018 Jan;158:17-21

Authors: Teh APP, Izzati UZ, Diep NV, Hirai T, Yamaguchi R

Abstract
Merkel cell carcinoma is a rare and aggressive cutaneous neuroendocrine tumour reported only in man, dogs and cats. A 20-month-old Japanese black fattening steer was presented with necrotic protruding skin masses over the left thoracic area and a 20 × 25 cm subcutaneous mass in the left abdominal area. Microscopical evaluation of the masses revealed cords of small to medium-sized round tumour cells with marked anisocytosis and anisokaryosis and clear and vacuolated cytoplasm, which were separated by a delicate fibrovascular stroma and arranged in a trabecular and nested pattern. Necropsy examination revealed multiple solid white nodular masses in the lungs. Immunohistochemistry (IHC) for cytokeratin (CK) 20 and CKAE1/3 revealed focal perinuclear labelling of tumour cells. IHC for the neuroendocrine markers chromogranin A and neuron specific enolase, the neuroepithelial stem cell marker nestin and the hormonal markers adrenocorticotropic hormone and calcitonin revealed diffuse cytoplasmic labelling of all tumour cells. Ultrastructurally, the tumour cells contained few neurosecretory granules and abundant glycogen pools. The tumours were diagnosed as Merkel cell carcinoma with pulmonary metastases and this case represents the first such diagnosis in cattle.

PMID: 29422311 [PubMed - indexed for MEDLINE]

Hedgehog Signaling Inhibitors Fail to Reduce Merkel Cell Carcinoma Viability.

Fetched: August 22nd, 2018, 5:00am GMT

Hedgehog Signaling Inhibitors Fail to Reduce Merkel Cell Carcinoma Viability.

J Invest Dermatol. 2017 05;137(5):1187-1190

Authors: Carroll TM, Williams JS, Daily K, Rogers T, Gelb T, Coxon A, Wang SQ, Crago AM, Busam KJ, Brownell I

PMID: 28130073 [PubMed - indexed for MEDLINE]

Comparative effectiveness of avelumab versus chemotherapy in Merkel cell carcinoma: innovative use of patient insights.

Fetched: August 17th, 2018, 5:00am GMT

Comparative effectiveness of avelumab versus chemotherapy in Merkel cell carcinoma: innovative use of patient insights.

J Comp Eff Res. 2018 Aug 15;:

Authors: Bharmal M, Marrel A, Hennessy M, Fofana F, Lambert J, Arnould B

Abstract
AIM: To assess patient experience with chemotherapy and avelumab in metastatic Merkel cell carcinoma (mMCC).
METHODS: In the JAVELIN Merkel 200 trial, chemotherapy-refractory mMCC patients could participate in optional qualitative interviews at baseline documenting recollection of previous chemotherapy experience, and at weeks 13/25 documenting current experience with avelumab. Functional Assessment of Cancer Therapy subscale for melanoma questionnaire (FACT-M) was administered in parallel.
RESULTS: In our sample, chemotherapy was associated with an unpleasant experience. On selected FACT-M items addressing chemotherapy-impacted concepts, most patients receiving avelumab were improved or stable; few worsened. In addition, a few patients spontaneously reported experiencing less toxicity with avelumab than experienced during previous chemotherapy.
CONCLUSION: This approach merging qualitative and quantitative data suggests that mMCC patients report a better experience with avelumab than with chemotherapy.

PMID: 30107762 [PubMed - as supplied by publisher]

Management of cutaneous Merkel cell carcinoma.

Fetched: August 17th, 2018, 5:00am GMT

Management of cutaneous Merkel cell carcinoma.

Acta Oncol. 2018 Mar;57(3):320-323

Authors: Mendenhall WM, Morris CG, Kirwan JM, Amdur RJ, Shaw C, Dziegielewski PT

Abstract
PURPOSE: To report the outcomes of patients with previously untreated cutaneous Merkel cell carcinoma (MCC) managed with curative intent.
MATERIAL AND METHODS: Between December 1984 and August 2015, 59 patients with previously untreated cutaneous MCC were managed with curative intent with surgery and adjuvant radiotherapy (54 patients) or radiotherapy alone (5 patients) at the University of Florida. Primary sites included head and neck (45 patients), extremities (11 patients) and trunk (3 patients). Adjuvant chemotherapy was employed in 14 patients. Patients were staged according to the AJCC staging system: stage I, 25 patients; stage IIA, 7 patients; and, stage III, 27 patients. No patients had distant metastases. Median follow-up for all patients was 3.2 years (range, 0.3-20.9 years). Median follow-up for survivors was 6.7 years (range, 1.6-20.9 years).
RESULTS: The 5-year outcomes were as follows: local control, 91%; regional control, 79%; local-regional control, 77%; disease metastasis-free survival, 60%; cause-specific survival, 53%; and overall survival, 39%. The 5-year outcomes for patients with stage I-IIA versus stage-III disease were the following: local-regional control, 90% versus 57% (p = .0115); distant metastasis-free survival, 78% versus 36% (p = .0002); cause-specific survival, 68% versus 35% (p = .0050); and overall survival, 48% versus 27% (p = .0377). Local-regional recurrences occurred in 12 patients; no patients were successfully salvaged. Severe late complications were observed in four patients.
CONCLUSIONS: Although radiotherapy alone or combined with surgery results in a relatively high likelihood of local-regional control, the majority of recurrences are distant and approximately half of patients are cured. Patients with regional disease at diagnosis have significantly worse outcomes.

PMID: 28712323 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma: new insights into pathogenesis.

Fetched: August 17th, 2018, 5:00am GMT

Merkel cell carcinoma: new insights into pathogenesis.

Eur J Dermatol. 2017 06 01;27(3):307-309

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

PMID: 28382918 [PubMed - indexed for MEDLINE]

Skin cancer management-updates on Merkel cell carcinoma.

Fetched: August 16th, 2018, 5:00am GMT

Skin cancer management-updates on Merkel cell carcinoma.

Ann Transl Med. 2018 Jul;6(14):282

Authors: Tai P, Au J

Abstract
There are many different types of skin tumors in the World Health Organization (WHO) classification. The natural course and treatment varies according to the histological type. This review summarizes clinical experience for treatment decision. Contemporary radiotherapy and systemic therapy are improving. Landmark studies for basal cell and Merkel cell carcinomas (MCC) trigger further research and impetus for improving treatment outcome. Avelumab, nivolumab, pembrolizumab, ipilimumab appear to be promising for treatment of advanced MCCs and adjuvant trials are underway.

PMID: 30105232 [PubMed]

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

Fetched: August 16th, 2018, 5:00am GMT

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

Future Oncol. 2017 Aug;13(19):1699-1710

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

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

PMID: 28605939 [PubMed - indexed for MEDLINE]

Importance of Sentinel Lymph Node Biopsy in Merkel Cell Carcinoma.

Fetched: August 15th, 2018, 5:00am GMT

Importance of Sentinel Lymph Node Biopsy in Merkel Cell Carcinoma.

J Oncol Pract. 2016 07;12(7):647-8

Authors: Angeles CV, Wong SL

PMID: 27407161 [PubMed - indexed for MEDLINE]

Permalink for 'Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma.'

Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma.

Fetched: August 12th, 2018, 5:00am GMT

Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma.

ESMO Open. 2018;3(5):e000388

Authors: Dummer R, Michielin O, Nägeli MC, M Goldinger S, Campigotto F, Kriemler-Krahn U, Schmid H, Pedroncelli A, Micaletto S, Schadendorf D

Abstract
Introduction: Somatostatin analogues exert antitumour activity via direct and indirect mechanisms. The present study was designed to assess the safety and efficacy of pasireotide in patients with BRAF-wild type (WT) and NRAS-WT metastatic melanoma.
Patients and methods: Patients with unresectable and/or metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was administered at different doses for ≤8 weeks in dose-escalation phase, followed by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up phase up to six additional months. Primary endpoint was safety in the first 8 weeks of dose-escalation phase.
Results: The study was terminated early due to slow recruitment. Of the 10 patients with metastatic melanoma enrolled, only four reached the high dose level: two patients reached 3600 µg in dose-escalation and follow-up phases and two patients reached 3600 µg in dose-escalation and long-acting pasireotide 80 mg in follow-up phases and were stable for >5 months. Most common adverse events (AEs) during dose-escalation phase in ≥2 patients (20%) were: diarrhoea (50%), nausea (50%), fatigue (20%), hyperglycaemia (20%), hypophosphatemia (20%), chills (20%) and tumour pain (20%). Grade 3 or 4 study drug-related AEs were diarrhoea and nausea, reported in one patient. Partial response was documented in one patient and stable disease in another.
Conclusions: Pasireotide was well tolerated, and safety results were similar to those previously reported in other indications. Further studies are needed to evaluate its antitumour activity alone and in combination with other drugs in melanoma.

PMID: 30094073 [PubMed]

Permalink for 'Intratumoral G100, a TLR4 agonist, induces anti-tumor immune responses and tumor regression in patients with Merkel cell carcinoma.'

Intratumoral G100, a TLR4 agonist, induces anti-tumor immune responses and tumor regression in patients with Merkel cell carcinoma.

Fetched: August 12th, 2018, 5:00am GMT

Intratumoral G100, a TLR4 agonist, induces anti-tumor immune responses and tumor regression in patients with Merkel cell carcinoma.

Clin Cancer Res. 2018 Aug 09;:

Authors: Bhatia S, Miller NJ, Lu H, Vandeven NV, Ibrani D, Shinohara M, Byrd D, Parvathaneni U, Kulikauskas RM, Ter Meulen J, Hsu FJ, Koelle DM, Nghiem P

Abstract
PURPOSE: G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive anti-tumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC).
EXPERIMENTAL DESIGN: Patients with loco-regional MCC (n=3; Cohort A) received neoadjuvant IT G100 (2 weekly doses at 5 μg/dose) followed by surgery and radiotherapy; patients with metastatic MCC (n=7; Cohort B) received 3 doses in a 6-week cycle and could receive additional cycles with/without radiotherapy.
RESULTS: IT G100 was safe and feasible in both neoadjuvant and metastatic settings. Treatment-related adverse events were mostly grade 1 or 2 injection site reactions. IT G100 led to increased inflammation in the injected tumors with infiltration of CD8+and CD4+T cells and activation of immune-related genes. These pro-inflammatory changes were associated with local tumor regression and appeared to promote systemic immunity. All 3 Cohort A patients successfully completed therapy; 2 patients remain recurrence-free at 44+ and 41+ months, including one with a pathologic complete response after G100 alone. In Cohort B, 2 patients achieved sustained partial responses, both lasting 33+ months after 2 cycles of therapy.
CONCLUSIONS: In this first-in-human study, IT G100 induced anti-tumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity.

PMID: 30093453 [PubMed - as supplied by publisher]

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 Disorders
Interventions: Biological: Autologous T Cells modified to recognize Merkel Cell Polyomavirus (FH-MCVA2TCR); Drug: Avelumab; Radiation: Radiation Therapy
Sponsor: Fred Hutchinson Cancer Research Center
Not yet 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; Resected Mass
Interventions: Other: Best Practice; Biological: Pembrolizumab; Radiation: Radiation Therapy
Sponsor: National Cancer Institute (NCI)
Recruiting

A Phase 1b/2 Study of 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.
Not yet recruiting

A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies

Posted: August 29th, 2018, 2:00pm GMT

Conditions: Cervical Cancer; Gastric Cancer; Stomach Cancer; Gastroesophageal Junction Cancer; Esophageal Cancer; Hepatocellular Carcinoma; Melanoma; Uveal Melanoma; Merkel Cell Carcinoma; Mesothelioma; MSI; Non-small Cell Lung Cancer; NSCLC; Ovarian Cancer; Squamous Cell Carcinoma of the Head and Neck; Small Cell Lung Cancer; Renal Cell Carcinoma; RCC; Triple-negative Breast Cancer; Urothelial Carcinoma; Mismatch Repair Deficiency
Intervention: Drug: INCAGN02390
Sponsor: Incyte Corporation
Recruiting

A Study to Evaluate the Safety and Tolerability of AB154 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; Renal Cell Carcinoma; Breast Cancer; Colorectal Cancer; Melanoma; Bladder Cancer; Ovarian Cancer; Endometrial Cancer; Merkel Cell Carcinoma; GastroEsophageal Cancer
Interventions: Drug: AB154; Drug: AB122
Sponsor: Arcus Biosciences, 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
Interventions: Drug: AB928; Drug: AB122
Sponsor: Arcus Biosciences, Inc.
Recruiting

A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma

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

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

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

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

Conditions: Cervical Cancer; Microsatellite Instability (MSI)-High Endometrial Cancer; Gastric Cancer (Including Stomach and Gastroesophageal Junction [GEJ]); Esophageal Cancer; Hepatocellular Carcinoma; Melanoma (Uveal Melanoma Excluded); Merkel Cell Carcinoma; Mesothelioma; MSI-high Colorectal Cancer; Non-small Cell Lung Cancer (NSCLC); Ovarian Cancer; Squamous Cell Carcinoma of the Head and Neck (SCCHN); Small Cell Lung Cancer (SCLC); Renal Cell Carcinoma (RCC); Triple-negative Breast Cancer; Urothelial Carcinoma; Diffuse Large B-cell Lymphoma
Intervention: Biological: INCAGN02385
Sponsor: Incyte Biosciences International Sàrl
Recruiting

Pfizer Immunotherapy Combinations for Acute Myeloid Leukemia (AML) Multi-Arm Study 1

Posted: January 4th, 2018, 3:00pm GMT

Condition: Acute Myeloid Leukemia
Interventions: Drug: PF-04518600; Drug: Avelumab; Drug: Azacitidine; Drug: Utomilumab; Drug: Gemtuzumab Ozogamicin; Drug: Glasdegib
Sponsors: M.D. Anderson Cancer Center; Pfizer
Recruiting

Permalink for 'Pembrolizumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Merkel Cell Cancer'

Pembrolizumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Merkel Cell Cancer

Posted: October 9th, 2017, 2:00pm GMT

Conditions: Stage III Merkel Cell Carcinoma AJCC v7; Stage IIIA Merkel Cell Carcinoma AJCC v7; Stage IIIB Merkel Cell Carcinoma AJCC v7; Stage IV Merkel Cell Carcinoma AJCC v7
Interventions: Biological: Pembrolizumab; Radiation: Stereotactic Body Radiation Therapy
Sponsor: National Cancer Institute (NCI)
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)
Recruiting

Phase 1 Study of CK-301 as a Single Agent in Subjects With Advanced Cancers

Posted: July 11th, 2017, 2:00pm GMT

Conditions: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Malignant Mesothelioma, Advanced; Head and Neck Cancer; Melanoma; Merkel Cell Carcinoma; Renal Cell Carcinoma; Urothelial Carcinoma; Classical Hodgkin Lymphoma; Colorectal Cancer; Cutaneous Squamous Cell Carcinoma; Non Hodgkin Lymphoma; Endometrial Cancer
Intervention: Drug: CK-301
Sponsors: Checkpoint Therapeutics, Inc.; Novotech (Australia) Pty Limited
Recruiting

French National Database of Rare Dermatological Cancers

Posted: July 7th, 2017, 2:00pm GMT

Conditions: Adnexal Tumor of Skin; Merkel Cell Carcinoma; Advanced Basal Cell Carcinoma Requiring Systemic Treatment
Intervention:
Sponsor: University Hospital, Lille
Recruiting

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

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

Posted: April 24th, 2017, 2:00pm GMT

Conditions: Advanced Malignancies; Metastatic Cancer
Interventions: Drug: INCAGN01876; Drug: Nivolumab; Drug: Ipilimumab
Sponsor: Incyte Biosciences International Sàrl
Recruiting

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

Posted: March 24th, 2017, 2:00pm GMT

Condition: Metastatic Merkel Cell Carcinoma
Intervention: Drug: Avelumab
Sponsors: Merck KGaA; Pfizer
Available

Atezolizumab and Bevacizumab in Rare Solid Tumors

Posted: March 8th, 2017, 3:00pm GMT

Conditions: Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs
Interventions: Drug: Atezolizumab; Drug: Bevacizumab; Behavioral: Phone Call
Sponsors: M.D. Anderson Cancer Center; Genentech, Inc.
Recruiting

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

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

Posted: March 7th, 2017, 3:00pm GMT

Condition: Advanced Solid Tumors Cancer
Interventions: Drug: ABBV-368; Drug: ABBV-181
Sponsor: AbbVie
Recruiting

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

Posted: December 22nd, 2016, 3:00pm GMT

Condition: Advanced Solid Tumors Cancer
Interventions: Drug: Rovalpituzumab Tesirine; Drug: ABBV-181
Sponsor: AbbVie
Recruiting

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

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

Posted: December 1st, 2016, 3:00pm GMT

Conditions: Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma
Interventions: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: Talimogene Laherparepvec
Sponsor: National Cancer Institute (NCI)
Recruiting

$Permalink for 'Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides'$

Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides

Posted: September 7th, 2016, 2:00pm GMT

Conditions: Solid Tumors; Mycosis Fungoides; Melanoma; Merkel-cell Carcinoma; Squamous Cell Carcinoma; Breast Carcinoma; Human Papillomavirus-Related Malignant Neoplasm; Soft Tissue Sarcoma
Interventions: Drug: TTI-621 Monotherapy; Drug: TTI-621 + PD-1/PD-L1 Inhibitor; Drug: TTI-621 + pegylated interferon-α2a; Other: TTI-621 + T-Vec; Other: TTI-621 + radiation
Sponsor: Trillium Therapeutics Inc.
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; Lymphoma, Cutaneous T-Cell
Interventions: Drug: Durvalumab; Drug: Tremelimumab; Drug: Poly ICLC
Sponsors: Ludwig Institute for Cancer Research; MedImmune LLC; Cancer Research Institute, New York City
Recruiting

Study of Intratumoral G100 With Or Without Pembrolizumab or Rituximab In Patients With Follicular Non-Hodgkin's Lymphoma

Posted: July 17th, 2015, 2:00pm GMT

Condition: Follicular Low Grade Non-Hodgkin's Lymphoma
Interventions: Drug: G100; Drug: Pembrolizumab; Drug: Rituximab
Sponsors: Immune Design; Merck Sharp & Dohme Corp.
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

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

An Exploratory Study of Pembrolizumab Plus Entinostat in Non-Inflamed Stage III/IV Melanoma

Posted: December 5th, 2018, 3:00pm GMT

Condition: Melanoma
Interventions: Drug: Entinostat; Drug: Pembrolizumab
Sponsors: UNC Lineberger Comprehensive Cancer Center; Syndax Pharmaceuticals, Inc.
Not yet recruiting

A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3)

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

Conditions: Melanoma (Excluding Uveal Melanoma); Cervical Carcinoma; Pancreatic Carcinoma; Breast Carcinoma That is Estrogen Receptor, Progesterone Receptor, and Her2 Negative; Hepatocellular Carcinoma; Urothelial Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Nasopharyngeal Carcinoma; Renal Cell Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Non-small Cell Lung Carcinoma; Small Cell Lung Cancer; Gastric or Gastroesophageal Junction Adenocarcinoma; Advanced Solid Tumors
Intervention: Biological: XmAb®23104
Sponsors: Xencor, Inc.; ICON plc
Not yet recruiting

Neuroendocrine Tumors of Old Patients in the West of France

Posted: November 21st, 2018, 3:00pm GMT

Condition: Neuroendocrine Tumors
Intervention:
Sponsors: University Hospital, Brest; Novartis
Not yet recruiting

Observation Study of Pancreatic Neuroendocrine Tumours

Posted: November 15th, 2018, 3:00pm GMT

Condition: Pancreatic Neuroendocrine Tumor
Interventions: Radiation: 18F-FDG-PET; Radiation: 68Ga-DOTATOC-PET; Radiation: Computed tomography; Other: Core needle biopsy; Other: Phlebotomy
Sponsor: Uppsala University
Not yet recruiting

Genomic Investigation of Unusual Responders

Posted: November 14th, 2018, 3:00pm GMT

Conditions: Cancer; Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Gynecological Cancer; Upper Aerodigestive Tract Cancer; Pancreatobiliary Gastrointestinal Cancer; Melanoma (Skin); Rare Cancer; Carcinoma of Unknown Primary
Intervention:
Sponsor: University Health Network, Toronto
Recruiting

$Permalink for 'Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin'$

Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin

Posted: November 9th, 2018, 3:00pm GMT

Conditions: Locally Advanced Digestive System Neuroendocrine Carcinoma; Locally Advanced Pancreatic Neuroendocrine Carcinoma; Metastatic Digestive System Neuroendocrine Carcinoma; Metastatic Pancreatic Neuroendocrine Carcinoma; Refractory Digestive System Neuroendocrine Carcinoma; Refractory Pancreatic Neuroendocrine Carcinoma; Unresectable Digestive System Neuroendocrine Carcinoma; Unresectable Pancreatic Neuroendocrine Carcinoma
Interventions: Drug: Fluorouracil; Drug: Leucovorin; Drug: Liposomal Irinotecan; Procedure: Quality-of-Life Assessment
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI)
Not yet recruiting

A Phase 1 Study of ZSP1602 in Participants With Advanced Solid Tumors

Posted: November 8th, 2018, 3:00pm GMT

Conditions: Basal Cell Carcinoma; Medulloblastoma; Adenocarcinoma of Esophagogastric Junction; Small Cell Lung Cancer; Neuroendocrine Neoplasm; Glioblastoma
Intervention: Drug: ZSP1602
Sponsor: Guangdong Zhongsheng Pharmaceutical Co., Ltd.
Not yet recruiting

$Permalink for 'Nivolumab and Temozolomide in Treating Patients With Recurrent or Refractory Small-Cell Lung Cancer or Advanced Neuroendocrine Cancer'$

Nivolumab and Temozolomide in Treating Patients With Recurrent or Refractory Small-Cell Lung Cancer or Advanced Neuroendocrine Cancer

Posted: November 2nd, 2018, 2:00pm GMT

Conditions: Grade I Neuroendocrine Carcinoma; Grade II Neuroendocrine Carcinoma; Grade III Neuroendocrine Carcinoma; Metastatic Neuroendocrine Carcinoma; Neuroendocrine Carcinoma; Recurrent Small Cell Lung Carcinoma; Refractory Small Cell Lung Carcinoma; Lung Cancer Stage IV; Large Cell Neuroendocrine Carcinoma; Neuroendocrine Tumors; Small Cell Lung Cancer Metastatic; Small-cell Lung Cancer
Interventions: Biological: Nivolumab; Drug: Temozolomide
Sponsors: Dwight Owen; National Cancer Institute (NCI)
Not yet recruiting

Spontaneous Regression in Metastatic Melanoma and Renal Cell Carcinoma

Posted: November 2nd, 2018, 2:00pm GMT

Condition: Melanoma; Renal Cell Carcinoma
Interventions: Other: Blood collection for laboratory studies; Other: Data collection from medical record
Sponsor: Indiana University
Recruiting

CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

Posted: November 1st, 2018, 2:00pm GMT

Conditions: Advanced Cutaneous Melanoma of the Extremity; Advanced Sarcoma of the Extremity; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Recurrent Cutaneous Melanoma of the Extremity; Recurrent Sarcoma of the Extremity; Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IIIA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IIIB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
Intervention: Drug: FACT Complex-targeting Curaxin CBL0137
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI)
Not yet recruiting

Selective Intra-arterial Injection of PRRT in Neuroendocrine Tumor Patients With Liver Metastases

Posted: October 30th, 2018, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: [90]Y-DOTATOC
Sponsors: Sandeep Laroia; National Institutes of Health (NIH); Holden Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting

Evaluating an Amino Acid Based Medical Food w/ Diarrhea in Carcinoid Syndrome & Other NETs

Posted: October 29th, 2018, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Carcinoid Tumor of GI System; Diarrhea; Carcinoid Syndrome
Intervention: Dietary Supplement: Amino Acid Based Medical Food/Drink
Sponsors: University of Kentucky; Entrinsic Health Solutions, Inc.
Not yet 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
Not yet 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.
Not yet 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

Enzalutamide and Decitabine in Treating Patients With Metastatic Castration Resistant Prostate Cancer

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

Conditions: Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma in the Soft Tissue; Prostate Carcinoma Metastatic in the Bone; PSA Level Greater Than or Equal to Two; PSA Progression; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8
Interventions: Drug: Decitabine; Drug: Enzalutamide
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI)
Not yet recruiting

Bronchoscopic Laser Ablation of Peripheral Lung Tumors

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

Conditions: Lung Carcinoid Tumor; Non-Small Cell Lung Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8
Interventions: Procedure: Cone-Beam Computed Tomography; Procedure: Conventional Surgery; Procedure: Laser Ablation
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Precise DCE-MRI in Diagnosing Participants With Recurrent High Grade Glioma or Melanoma Brain Metastases

Posted: October 5th, 2018, 2:00pm GMT

Conditions: Brain Metastases; Glioma of Brain; Brain Tumor; Metastatic Melanoma
Interventions: Device: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Drug: Bevacizumab Injection
Sponsors: University of Southern California; National Cancer Institute (NCI)
Not yet recruiting

Selective Treatment According to Molecular Subtype of Prostate Cancer

Posted: October 4th, 2018, 2:00pm GMT

Conditions: Castration-resistant Prostate Cancer; Prostate Cancer Metastatic
Interventions: Drug: Luminal type-1; Drug: Luminal type-2; Drug: Neuroendocrine type-1; Drug: Neuroendocrine type-2; Drug: Atypical type-1; Drug: Atypical type-2
Sponsor: Tianjin Medical University Second Hospital
Recruiting

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

Post-Authorization Long-Term Safety Study of LUTATHERA

Posted: October 1st, 2018, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: LUTATHERA
Sponsor: Advanced Accelerator Applications
Recruiting

Evaluation of Melatonin Application of Immediate Dental Implant

Posted: October 1st, 2018, 2:00pm GMT

Condition: Immediate Dental Implant
Intervention: Procedure: immediate implant placement
Sponsor: Cairo University
Not yet recruiting

Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors

Posted: September 28th, 2018, 2:00pm GMT

Conditions: Non Small Cell Lung Cancer; Urothelial Carcinoma; Malignant Melanoma; Ovarian Cancer; Colorectal Cancer; Breast Cancer; Squamous Cell Carcinoma of the Head and Neck; Metastatic Cancer
Intervention: Biological: ARG1-18,19,20
Sponsor: Inge Marie Svane
Recruiting

A Phase 1b/2 Study of AST-008 Combined With Pembrolizumab in Patients With Advanced Solid Tumors

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

A Study of INCMGA00012 in Participants With Selected Solid Tumors (POD1UM-203)

Posted: September 20th, 2018, 2:00pm GMT

Conditions: Metastatic Non-small Cell Lung Cancer; Locally Advanced Urothelial Cancer; Metastatic Urothelial Cancer; Unresectable Melanoma; Metastatic Melanoma; Locally Advanced Renal Cell Carcinoma; Metastatic Clear-Cell Renal Cell Carcinoma
Intervention: Drug: INCMGA00012
Sponsor: Incyte Corporation
Not yet recruiting

Permalink for 'Young Melanoma Family Facebook Intervention or Healthy Lifestyle Facebook Intervention in Improving Skin Examination in Participants With Melanoma and Their Families'

Young Melanoma Family Facebook Intervention or Healthy Lifestyle Facebook Intervention in Improving Skin Examination in Participants With Melanoma and Their Families

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

Conditions: Clinical Stage 0 Cutaneous Melanoma AJCC v8; Clinical Stage I Cutaneous Melanoma AJCC v8; Clinical Stage IA Cutaneous Melanoma AJCC v8; Clinical Stage IB Cutaneous Melanoma AJCC v8; Clinical Stage II Cutaneous Melanoma AJCC v8; Clinical Stage IIA Cutaneous Melanoma AJCC v8; Clinical Stage IIB Cutaneous Melanoma AJCC v8; Clinical Stage IIC Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; First Degree Relative; Pathologic Stage 0 Cutaneous Melanoma AJCC v8; Pathologic Stage I Cutaneous Melanoma AJCC v8; Pathologic Stage IA Cutaneous Melanoma AJCC v8; Pathologic Stage IB Cutaneous Melanoma AJCC v8; Pathologic Stage II Cutaneous Melanoma AJCC v8; Pathologic Stage IIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIC Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
Interventions: Other: Informational Intervention; Other: Survey Administration
Sponsors: Rutgers, The State University of New Jersey; National Cancer Institute (NCI)
Not yet recruiting

Imaging of Patients With Known or Suspected Somatostatin Receptor Positive Neuroendocrine Tumors Using Cu64-DOTATATE

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

Condition: Neuroendocrine Tumors
Intervention: Drug: 64Cu-DOTATATE
Sponsor: Radiomedix, Inc.
Recruiting

Elderly Cancer PatIents, Safety and qualiTy of Life Under immunOtheraPies

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

Conditions: Advanced or Metastatic Melanoma; Advanced or Metastatic NSCLC
Intervention: Drug: immune-checkpoint inhibitors therapies
Sponsors: Institut Paoli-Calmettes; Société Francophone d'Onco-Gériatrie
Not yet recruiting

Permalink for 'A Study to Test the Effectiveness of ABI-009 in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System'

A Study to Test the Effectiveness of ABI-009 in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System

Posted: September 13th, 2018, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: ABI-009
Sponsors: Robert Ramirez; Aadi, LLC
Not yet recruiting

Exploration of Molecular Biomarkers for Lu-177 DOTATATE Therapy in Midgut Neuroendocrine Tumor

Posted: September 12th, 2018, 2:00pm GMT

Condition: Midgut Neuroendocrine Tumors
Intervention: Biological: non-drug intervention type
Sponsor: University Hospital, Toulouse
Recruiting

Vegetative Monitoring During Brainstem-associated Surgery

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

Conditions: Brain Tumor, Recurrent; Vestibular Schwannoma; Brainstem Neoplasm; Brainstem Glioma
Intervention: Procedure: Intraoperative Monitoring during resection of brain tumor
Sponsor: University Hospital Tuebingen
Recruiting

Effects of Epidural Block on the Prognosis in Patients With Pancreatic Cancer Undergoing Distal Pancreatectomy

Posted: September 6th, 2018, 2:00pm GMT

Condition: Cancer of Pancreas
Interventions: Other: GEA; Other: PCEA; Other: GA; Other: PCIA
Sponsors: Fudan University; Washington University School of Medicine
Not yet recruiting

pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

Posted: August 31st, 2018, 2:00pm GMT

Conditions: Cutaneous Melanoma, Stage III; Cutaneous Melanoma, Stage IV
Intervention: Biological: IFx-Hu2.0
Sponsors: Morphogenesis, Inc.; H. Lee Moffitt Cancer Center and Research Institute
Recruiting

High Intensity Interval Training (HIIT) for Patients With Cancer-related Lymphedema in the Lower Limbs

Posted: August 31st, 2018, 2:00pm GMT

Conditions: Lymphedema of Leg; Cancer of Cervix; Cancer, Ovarian; Cancer, Endometrial; Cancer of the Prostate; Malignant Melanoma
Interventions: Other: First exercise session + compression; Other: First exercise session - compression
Sponsors: Herlev and Gentofte Hospital; University of Copenhagen
Recruiting

A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies

Posted: August 29th, 2018, 2:00pm GMT

177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer

Posted: August 27th, 2018, 2:00pm GMT

Condition: Thyroid Cancer, Medullary
Interventions: Drug: 177Lu-PP-F11N; Drug: Sacuitril
Sponsors: University Hospital, Basel, Switzerland; Krebsforschung Schweiz, Bern, Switzerland; Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland; University Hospital, Zürich; University Hospital Freiburg
Not yet recruiting

[68Ga]DOTATATE-PET/MRI in Hepatocellular Carcinoma

Posted: August 27th, 2018, 2:00pm GMT

Condition: Hepatocellular Carcinoma
Intervention: Diagnostic Test: [68Ga]DOTATATE-PET/MRI
Sponsor: University of Alabama at Birmingham
Not yet recruiting

18F-Fluorocholine PET/CT in Medullary Thyroid Cancer

Posted: August 22nd, 2018, 2:00pm GMT

Condition: Medullary Thyroid Cancer
Intervention: Diagnostic Test: 18F-fluorocholine PET/CT
Sponsors: University Medical Centre Ljubljana; Institute of Oncology Ljubljana
Recruiting

Safety, Tolerability, Immunogenicity, and Antitumor Activity of GEN-009 Adjuvanted Vaccine

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

Conditions: Cutaneous Melanoma; Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Urothelial Carcinoma; Renal Cell Carcinoma
Interventions: Biological: GEN-009 Adjuvanted Vaccine; Drug: Nivolumab
Sponsor: Genocea Biosciences, Inc.
Recruiting

Treatment of Neuroendocrine Tumors (NETs) With Combination of Everolimus and Radiolabeled Somatostatin Analogue

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

Condition: Neuroendocrine Tumors
Intervention: Drug: Everolimus
Sponsor: King Faisal Specialist Hospital & Research Center
Recruiting

Adaptive Tyrosine Kinase Inhibitor (TKI) Therapy In Patients With Thyroid Cancer

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

Conditions: Thyroid Cancer; Thyroid Cancer, Medullary; Differentiated Thyroid Cancer; Papillary Thyroid Cancer; Follicular Thyroid Cancer; Poorly Differentiated Thyroid Gland Carcinoma
Interventions: Drug: Lenvatinib; Drug: Sorafenib; Drug: Cabozantinib; Drug: Vandetanib
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Recruiting

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

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

A Study to Evaluate the Safety and Tolerability of AB154 in Participants With Advanced Malignancies

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

Molecular-Guided Surgery for Pancreatic and GI Neuroendocrine Cancers

Posted: August 9th, 2018, 2:00pm GMT

Conditions: Neuroendocrine Carcinoma of Pancreas; Carcinoid
Intervention: Drug: Gallium Dotatate
Sponsor: University of Alabama at Birmingham
Not yet recruiting

Permalink for 'Clinic, Pathologic and Genetic Characterization of Patients With Familial Carcinoid Tumors (Study From the GTE, Groupe d'étude Des Tumeurs Endocrines)'

Clinic, Pathologic and Genetic Characterization of Patients With Familial Carcinoid Tumors (Study From the GTE, Groupe d'étude Des Tumeurs Endocrines)

Posted: August 9th, 2018, 2:00pm GMT

Condition: Small Intestinal Carcinoid Tumors
Intervention: Genetic: Research of constitutional genetic alterations
Sponsor: CHU de Reims
Recruiting

Denosumab + Pembrolizumab in Patients With Stage IV Melanoma

Posted: August 8th, 2018, 2:00pm GMT

Conditions: Melanoma Stage Iii; Melanoma Stage Iv; Melanoma; Melanoma (Skin); Cutaneous Melanoma
Interventions: Drug: Denosumab; Drug: Pembrolizumab
Sponsors: UNC Lineberger Comprehensive Cancer Center; Amgen
Recruiting

CMP-001 in Combo With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease

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

Conditions: Melanoma; Lymph Node Cancer
Interventions: Drug: CMP-001; Biological: Nivolumab
Sponsors: Diwakar Davar; Checkmate Pharmaceuticals
Recruiting

$Permalink for 'EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults'$

EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

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

Conditions: Pediatric Solid Tumor; Germ Cell Tumor; Retinoblastoma; Hepatoblastoma; Wilms Tumor; Rhabdoid Tumor; Carcinoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Clear Cell Sarcoma; Malignant Peripheral Nerve Sheath Tumors; Desmoplastic Small Round Cell Tumor; Soft Tissue Sarcoma; Neuroblastoma
Interventions: Biological: second generation 4-1BBζ EGFR806-EGFRt; Biological: second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG
Sponsor: Seattle Children's Hospital
Recruiting

Pancreatic Cancer Dietary Assessment Study

Posted: August 6th, 2018, 2:00pm GMT

Conditions: Pancreatic Neoplasm; Pancreas Adenocarcinoma; Well-Differentiated Neuroendocrine Carcinoma; Malignant Neoplasm of Pancreas
Intervention: Diagnostic Test: Pancreo-KIT breath test
Sponsors: The Christie NHS Foundation Trust; Pancreatic Cancer UK
Recruiting

A Study of APG-115 in Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors

Posted: August 2nd, 2018, 2:00pm GMT

Condition: Unresectable or Metastatic Melanoma or Advanced Solid Tumors
Intervention: Drug: APG-115+Pembrolizumab
Sponsor: Ascentage Pharma Group Inc.
Recruiting

Liquid Biopsy-based Detection of Resistance to Targeted Therapy in Prostate Cancer Patients

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

Condition: Castration-resistant Prostate Cancer
Intervention: Other: Blood samples prior to a new line of AR-targeted therapy
Sponsor: Technische Universität München
Recruiting

Permalink for 'A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies'

A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies

Posted: July 18th, 2018, 2:00pm GMT

Conditions: Stage III Cutaneous Melanoma; Stage IV Cutaneous Melanoma; Locally Advanced Melanoma; Locally Advanced Solid Neoplasm; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Urothelial Carcinoma; Non-Small Cell Lung Carcinoma; Stage IB Lung Cancer AJCC v7; Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage III Lung Cancer AJCC v8; Stage III Ureter Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Ureter Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8
Interventions: Drug: Abexinostat; Biological: Pembrolizumab
Sponsors: Rahul Aggarwal; Xynomic Pharmaceuticals, Inc.
Recruiting

Trial of Ixazomib Combined With Gemcitabine and Doxorubicin in Patients With Renal Medullary Carcinoma

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

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

Permalink for 'Pembrolizumab With Combination Chemotherapy in Treating Participants With Locally Advanced or Metastatic Small Cell/Neuroendocrine Cancers of Urothelium or Prostate'

Pembrolizumab With Combination Chemotherapy in Treating Participants With Locally Advanced or Metastatic Small Cell/Neuroendocrine Cancers of Urothelium or Prostate

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

Conditions: Bladder Small Cell Neuroendocrine Carcinoma; Castration-Resistant Prostate Carcinoma; Metastatic Bladder Urothelial Carcinoma; Metastatic Urethral Urothelial Carcinoma; Prostate Carcinoma Metastatic in the Bone; Prostate Neuroendocrine Neoplasm; Prostate Small Cell Carcinoma; Stage III Bladder Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage III Urethral Cancer AJCC v8; Stage IV Bladder Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IV Urethral Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8; Ureter Small Cell Carcinoma; Urothelial Carcinoma
Interventions: Drug: Carboplatin; Drug: Cisplatin; Drug: Docetaxel; Drug: Etoposide; Biological: Pembrolizumab
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Not yet recruiting

Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer

Posted: June 27th, 2018, 2:00pm GMT

Conditions: ATM Biallelic Inactivation; ATM Gene Mutation; ATM Monoallelic Inactivation; BRCA1 Biallelic Inactivation; BRCA1 Gene Mutation; BRCA2 Biallelic Inactivation; BRCA2 Gene Mutation; FANCA Biallelic Inactivation; Homologous Recombination Deficiency; PALB2 Biallelic Inactivation; PALB2 Gene Mutation; Prostate Adenocarcinoma Without Evidence of Neuroendocrine Differentiation; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8
Interventions: Drug: Olaparib; Procedure: Radical Prostatectomy
Sponsors: University of Washington; 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

Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

Posted: June 1st, 2018, 2:00pm GMT

Conditions: Melanoma (Skin); Skin Cancer; Skin Melanoma; Skin Carcinoma
Interventions: Drug: Vemurafenib; Drug: Cobimetinib
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Recruiting

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

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

Analysis of the Modulation of the Tumor Microenvironment by MK-3475 (Pembrolizumab) Using a Systems Biology Approach (PEMSYS)

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

Condition: Metastatic Melanoma Naive to Immune Therapy in Metastatic Setting
Interventions: Drug: Pembrolizumab; Drug: Pembrolizumab - additional treatment
Sponsor: Centre Hospitalier Universitaire Vaudois
Recruiting

Permalink for 'Methylphenidate and Physical Activity in Reducing Cancer-Related Fatigue in Participants With Metastatic Melanoma Who Receive Anti-PD1 Immunotherapy'

Methylphenidate and Physical Activity in Reducing Cancer-Related Fatigue in Participants With Metastatic Melanoma Who Receive Anti-PD1 Immunotherapy

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

Condition: Metastatic Melanoma
Interventions: Other: Laboratory Biomarker Analysis; Drug: Methylphenidate; Other: Physical Activity; Other: Placebo; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

A Study of Anlotinib in Patients With Gastroenteropancreatic Neuroendocrine Tumor G3

Posted: March 8th, 2018, 3:00pm GMT

Condition: Gastroenteropancreatic Neuroendocrine Tumor G3
Intervention: Drug: Anlotinib
Sponsor: Jiangsu Chia-tai Tianqing Pharmaceutical Co.,Ltd
Recruiting

Permalink for 'SARC031: MEK Inhibitor Selumetinib (AZD6244) in Combination With the mTOR Inhibitor Sirolimus for Patients With Malignant Peripheral Nerve Sheath Tumors'

SARC031: MEK Inhibitor Selumetinib (AZD6244) in Combination With the mTOR Inhibitor Sirolimus for Patients With Malignant Peripheral Nerve Sheath Tumors

Posted: February 14th, 2018, 3:00pm GMT

Conditions: Malignant Peripheral Nerve Sheath Tumors; Neurofibromatosis 1
Interventions: Drug: Selumetinib; Drug: Sirolimus
Sponsors: Sarcoma Alliance for Research through Collaboration; United States Department of Defense; AstraZeneca
Not yet 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 'Propranolol Hydrochloride and Pembrolizumab in Treating Patients With Stage IIIC-IV Melanoma That Cannot Be Removed by Surgery'

Propranolol Hydrochloride and Pembrolizumab in Treating Patients With Stage IIIC-IV Melanoma That Cannot Be Removed by Surgery

Posted: December 27th, 2017, 3:00pm GMT

Conditions: Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
Interventions: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Drug: Propranolol Hydrochloride
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI)
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; Enterochromaffin Cell Serotonin-Producing Pancreatic Neuroendocrine Tumor; Functional 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; Nonfunctional Pancreatic Neuroendocrine Tumor; 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; Other: Quality-of-Life Assessment
Sponsor: National Cancer Institute (NCI)
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

Pembrolizumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Merkel Cell Cancer

Posted: October 9th, 2017, 2:00pm GMT

Permalink for 'Ability of a Dendritic Cell Vaccine to Immunize Melanoma or Epithelial Cancer Patients Against Defined Mutated Neoantigens Expressed by the Autologous Cancer'

Ability of a Dendritic Cell Vaccine to Immunize Melanoma or Epithelial Cancer Patients Against Defined Mutated Neoantigens Expressed by the Autologous Cancer

Posted: October 4th, 2017, 2:00pm GMT

Conditions: Melanoma; Gastrointestinal Cancer; Breast Cancer; Ovarian Cancer; Pancreatic Cancer
Intervention: Biological: Peptide loaded dendritic cell vaccine
Sponsor: National Cancer Institute (NCI)
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

Permalink for 'A Study to Evaluate Patient Experience in the Therapy of Neuroendocrine Tumors Treated With Octreotide Long Acting Release Versus Lanreotide'

A Study to Evaluate Patient Experience in the Therapy of Neuroendocrine Tumors Treated With Octreotide Long Acting Release Versus Lanreotide

Posted: September 21st, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: Octreotide; Drug: LAR Lanreotide; Behavioral: Questionnaires
Sponsor: Memorial Sloan Kettering Cancer Center
Recruiting

Pembrolizumab in Advanced Poorly Differentiated and/or High Grade Neuroendocrine Tumors/Carcinomas

Posted: September 21st, 2017, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma; Neuroendocrine Cancer
Intervention: Drug: Pembrolizumab
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Merck Sharp & Dohme Corp.
Recruiting

Permalink for 'Local Control, Quality of Life and Toxicities in Adults With Benign or Indolent Brain Tumors Undergoing Proton Radiation Therapy'

Local Control, Quality of Life and Toxicities in Adults With Benign or Indolent Brain Tumors Undergoing Proton Radiation Therapy

Posted: September 18th, 2017, 2:00pm GMT

Condition: Brain Tumor
Intervention: Radiation: Proton Radiation
Sponsor: Massachusetts General Hospital
Recruiting

Avelumab in G2-3 NET

Posted: September 11th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: Avelumab
Sponsors: Sunnybrook Health Sciences Centre; Merck KGaA
Recruiting

Nivolumab Plus Ipilimumab in Patients With Renal Medullary Carcinoma

Posted: September 6th, 2017, 2:00pm GMT

Conditions: Renal Medullary Carcinoma; Other Disorders of Kidney and Ureter
Interventions: Drug: Nivolumab; Drug: Ipilimumab
Sponsors: M.D. Anderson Cancer Center; Bristol-Myers Squibb
Recruiting

Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC)

Posted: September 6th, 2017, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Meningioma; Neuroblastoma; Medulloblastoma
Interventions: Radiation: 90Y-DOTA tyr3-Octreotide; Diagnostic Test: 68Ga-DOTATOC PET Positron Emission Tomography (PET) whole body scan; Drug: Amino Acids
Sponsors: Sue O'Dorisio; National Institutes of Health (NIH); National Cancer Institute (NCI)
Recruiting

Adjuvant Avelumab in Merkel Cell Cancer

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

Phase Ib of L-NMMA and Pembrolizumab

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

Conditions: Non-Small Cell Lung Cancer; Malignant Melanoma; Head and Neck Squamous Cell Carcinoma; Classical Hodgkin Lymphoma; Urothelial Carcinoma Bladder; DNA Repair-Deficiency Disorders
Interventions: Drug: L-NMMA; Drug: Pembrolizumab
Sponsor: Jorge G. Darcourt
Recruiting

Permalink for 'To Evaluate the Optimal Dose of 68Ga-OPS202 as a PET (Positron Emission Tomography) Imaging Agent in Subjects With Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)'

To Evaluate the Optimal Dose of 68Ga-OPS202 as a PET (Positron Emission Tomography) Imaging Agent in Subjects With Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)

Posted: July 18th, 2017, 2:00pm GMT

Condition: Gastro-Enteropancreatic Neuroendocrine Tumor
Intervention: Drug: Satoreotide trizoxetan
Sponsor: Ipsen
Recruiting

Phase 1 Study of CK-301 as a Single Agent in Subjects With Advanced Cancers

Posted: July 11th, 2017, 2:00pm GMT

French National Database of Rare Dermatological Cancers

Posted: July 7th, 2017, 2:00pm GMT

Conditions: Adnexal Tumor of Skin; Merkel Cell Carcinoma; Advanced Basal Cell Carcinoma Requiring Systemic Treatment
Intervention:
Sponsor: University Hospital, Lille
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; Other: F-18-FDG; Drug: Amino Acid solution
Sponsor: National Cancer Institute (NCI)
Recruiting

A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001)

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

Conditions: Mesothelioma; Uveal Melanoma; Renal Cell Carcinoma; Cholangiocarcinoma
Intervention: Drug: Niraparib
Sponsors: University of Florida; Tesaro, Inc.
Recruiting

Tissue Predictors of Abiraterone Benefit

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

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

Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Posted: May 31st, 2017, 2:00pm GMT

Conditions: Urothelial Carcinoma; Renal Cell Carcinoma; Non-Small Cell Lung Cancer; Castration-resistant Prostate Cancer
Interventions: Drug: cabozantinib; Drug: atezolizumab
Sponsor: Exelixis
Recruiting

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

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

Posted: May 30th, 2017, 2:00pm GMT

Condition: Neuroendocrine Carcinoma
Interventions: Drug: irinotecan cisplatin; Drug: Etoposide cisplatin
Sponsor: Peking University
Recruiting

Study of JS001 in Patients With Advanced Neuroendocrine Tumors

Posted: May 30th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Biological: humanized anti-PD-1 monoclonal antibody
Sponsors: Peking University; Shanghai Junshi Biosciencee Co.,Ltd
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: Australia and New Zealand Melanoma Trials Group; Peter MacCallum Cancer Centre, Australia; Amgen; Bristol-Myers Squibb
Recruiting

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

Posted: May 18th, 2017, 2:00pm GMT

Conditions: Advanced Ovarian Cancer; Malignant Melanoma
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Pembrolizumab; Biological: Tumor-Infiltrating Lymphocytes (TILs); Biological: Interleukin-2 (IL-2)
Sponsors: University Health Network, Toronto; Merck Sharp & Dohme Corp.
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; Solid Tumor
Intervention: Drug: LOXO-292
Sponsor: Loxo Oncology, Inc.
Recruiting

Health Care Coach Support in Reducing Acute Care Use and Cost in Patients With Cancer

Posted: May 16th, 2017, 2:00pm GMT

Conditions: Acute Myeloid Leukemia; Brain Glioblastoma; Estrogen Receptor Negative; Extensive Stage Small Cell Lung Carcinoma; Head and Neck Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Limited Stage Small Cell Lung Carcinoma; Myelodysplastic Syndrome; Progesterone Receptor Negative; Progressive Disease; Recurrent Carcinoma; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage III Colon Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer; Stage III Non-Small Cell Lung Cancer; Stage III Ovarian Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Skin Melanoma; Stage IIIA Colon Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Colon Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Colon Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Bone Sarcoma; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IV Soft Tissue Sarcoma; Stage IVA Bone Sarcoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Bone Sarcoma; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Triple-Negative Breast Carcinoma
Interventions: Other: Best Practice; Other: Laboratory Biomarker Analysis; Procedure: Supportive Care; Other: Survey Administration
Sponsor: Stanford University
Recruiting

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

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

Posted: May 9th, 2017, 2:00pm GMT

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

DIVIT Study Diet and Vitamin Supplementation in Patients With a Neuroendocrine Tumor

Posted: May 8th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumor
Interventions: Dietary Supplement: Vitamin supplement;; Other: Diet advice
Sponsor: University Medical Center Groningen
Recruiting

Multi-Institutional Registry for Malignant Peripheral Nerve Sheath Tumors

Posted: May 4th, 2017, 2:00pm GMT

Condition: Malignant Peripheral Nerve Sheath Tumors
Intervention:
Sponsor: Washington University School of Medicine
Recruiting

Permalink for 'A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) and of NKTR-214 in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Select Advanced or Metastatic Solid Tumors'

A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) and of NKTR-214 in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Select Advanced or Metastatic Solid Tumors

Posted: May 3rd, 2017, 2:00pm GMT

Conditions: Non-Small Cell Lung Cancer; Urinary Bladder Neoplasms; Neoplasm Metastasis; Melanoma
Interventions: Drug: NKTR-214; Drug: Pembrolizumab; Drug: Atezolizumab
Sponsor: Nektar Therapeutics
Recruiting

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

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

Conditions: Carcinoma, Renal Cell; Melanoma
Interventions: Drug: Pembrolizumab; Drug: Interleukin-2
Sponsor: William Grosh, MD
Recruiting

Cobimetinib and Atezolizumab in Advanced Rare Tumors

Posted: April 11th, 2017, 2:00pm GMT

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

Durvalumab (MEDI4736) Plus Tremelimumab for Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin

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

Conditions: Neuroendocrine Tumors; Neuroendocrine Neoplasm of Lung
Interventions: Drug: Durvalumab; Drug: Tremelimumab
Sponsor: Grupo Espanol de Tumores Neuroendocrinos
Recruiting

Permalink for 'Clinical Outcomes of Patients with Small Rectal Neuroendocrine Tumors Treated Using Endoscopic Submucosal Resection with a Ligation Device.'

Clinical Outcomes of Patients with Small Rectal Neuroendocrine Tumors Treated Using Endoscopic Submucosal Resection with a Ligation Device.

Fetched: December 18th, 2018, 5:00am GMT

Icon for S. Karger AG, Basel, Switzerland

Clinical Outcomes of Patients with Small Rectal Neuroendocrine Tumors Treated Using Endoscopic Submucosal Resection with a Ligation Device.

Digestion. 2018 Dec 14;99(1):72-78

Authors: Takita M, Sakai E, Nakao T, Kimoto Y, Ishii R, Konishi T, Ueno S, Kanda K, Negishi R, Muramoto T, Hashimoto H, Morikawa T, Matsuhashi N, Ohata K

Abstract
BACKGROUND/AIMS: The therapeutic strategies for small rectal neuroendocrine tumors (NETs) have not been standardized. We examined the efficacy and safety of endoscopic submucosal resection with a ligation device (ESMR-L) and the long-term outcomes after endoscopic treatment.
METHODS: A total of 181 patients with rectal NETs <10 mm who were treated between May 2002 and May 2017 were retrospectively enrolled. All the lesions had been resected using ESMR-L, and the follow-up strategies were determined according to the pathological examinations. The long-term outcomes after a 53-month follow-up period were also evaluated.
RESULTS: R0 resection was achieved in 180 cases (99.4%). Lymphovascular invasion was confirmed in 67 cases (37.0%), while a curative resection was achieved in 114 cases (63.0%). One perforation (0.6%) and 11 cases with delayed bleeding (6.1%) were observed. A multivariate logistic regression analysis revealed that a tumor size > 5 mm (OR 2.06; 95% CI 1.04-4.08, p = 0.04) was a significant independent predictor of the presence of lymphovascular invasion. Of the 67 patients with non-curative resections, 11 patients underwent additional surgery; lymph node metastasis was confirmed in 2 cases (18.2%). No local or distant metastases were observed during the follow-up period in 77 patients with a curative resection, 9 patients who received additional surgery, and 50 patients with non-curative resections.
CONCLUSION: ESMR-L is an easy, safe and effective treatment for rectal NETs <10 mm in diameter, and the prognosis of patients seems to be good, despite a relatively high rate of lymphovascular invasion.

PMID: 30554202 [PubMed - as supplied by publisher]

Synchronous neuroendocrine tumor and signet-ring cell carcinoma in the stomach.

Fetched: December 18th, 2018, 5:00am GMT

Synchronous neuroendocrine tumor and signet-ring cell carcinoma in the stomach.

Clin Res Hepatol Gastroenterol. 2018 Dec 12;:

Authors: He F, Nie L

PMID: 30553756 [PubMed - as supplied by publisher]

Permalink for 'Adenocarcinoma is not always the diagnosis - colon neoplasia in patient with long-standing ulcerative colitis under long-term prednisone maintenance therapy.'

Adenocarcinoma is not always the diagnosis - colon neoplasia in patient with long-standing ulcerative colitis under long-term prednisone maintenance therapy.

Fetched: December 18th, 2018, 5:00am GMT

Adenocarcinoma is not always the diagnosis - colon neoplasia in patient with long-standing ulcerative colitis under long-term prednisone maintenance therapy.

Clin Res Hepatol Gastroenterol. 2018 Dec 12;:

Authors: Costa JM, Rodrigues AP, Fernandes D, Costeira F, Vieira F, Gonçalves R, Teixeira M, Soares JB

PMID: 30553755 [PubMed - as supplied by publisher]

[A misleading breast metastasis of medullary thyroid carcinoma].

Fetched: December 18th, 2018, 5:00am GMT

[A misleading breast metastasis of medullary thyroid carcinoma].

Ann Pathol. 2018 Dec 12;:

Authors: Gardair C, Drabent P, Charveriat P, Bertheau P, Cahen-Doidy L, de Roquancourt A

Abstract
Recognition of mammary metastases by pathologists is fundamental because their prognosis and treatment are different from those of primary mammary carcinomas. We report the case of a 54-year-old woman presenting on her mammography a left breast nodule known for 5 years, having discreetly increased in size. Breast ultrasound showed a regular 1.2cm hypoechogenic nodular formation. A microbiopsy was performed. On microscopic examination, we observed a tumor proliferation realizing nests within a small, richly vascularized stroma. The tumor cells had a moderately abundant, eosinophilic, granular cytoplasm and a rounded, slightly atypical nucleus. One mitosis was found for 10 fields at×400 magnification. Tumor cells did not express hormone receptors but chromogranin A, synaptophysin, TTF1 and thyrocalcitonin. The proliferation index established by the anti-Ki67 antibody was 5 %. The diagnosis was a secondary localization of a well-differentiated neuroendocrine tumor which immunohistochemical profile firstly suggests a thyroid origin. We later learned that the patient had a history of total thyroidectomy 13 years ago. It was a sporadic medullary carcinoma of the thyroid. Bone scintigraphy revealed a lacunar lesion of the posterior part of the right iliac wing suspicious of secondary location. This right iliac lesion was biopsied. It was also a localization of the medullary thyroid carcinoma. The final diagnosis is a metastatic medullary thyroid carcinoma, slowly progressive, the mammary metastasis having probably existed for 5 years.

PMID: 30553643 [PubMed - as supplied by publisher]

Impact of systemic and tumor lipid metabolism on everolimus efficacy in advanced pancreatic neuroendocrine tumors (pNETs).

Fetched: December 8th, 2018, 5:00am GMT

Impact of systemic and tumor lipid metabolism on everolimus efficacy in advanced pancreatic neuroendocrine tumors (pNETs).

Int J Cancer. 2018 Dec 05;:

Authors: Vernieri C, Pusceddu S, Fucà G, Indelicato P, Centonze G, Castagnoli L, Ferrari E, Ajazi A, Pupa S, Casola S, Foiani M, Mazzaferro V, Pruneri G, Milione M, de Braud F

Abstract
The mTOR inhibitor everolimus is effective against advanced pancreatic neuroendocrine tumors (pNETs). However, it can cause metabolic adverse events, such as hyperglycemia, hypertriglyceridemia and hypercholesterolemia. In this work we aimed at evaluating the impact of systemic and tumor lipid metabolism on everolimus efficacy. We carried out a monocentric, retrospective study to correlate plasma triglyceride and cholesterol levels with the progression free survival (PFS) of advanced pNET patients treated with everolimus. In formalin fixed, paraffin embedded (FFPE) tumor specimens, we also assessed by mRNA quantification and immunohistochemistry the expression of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), two enzymes crucially involved in fatty acid biosynthesis, and we analyzed their impact on PFS. We evaluated 58 consecutive pNET patients who started everolimus between December 2006 and January 2015. Patients with higher plasma triglycerides during the first three months of treatment had an increased risk of disease progression (aHR 3.08, 95% CIs 1.15-8.21; p = 0.025). In 23 FFPE tumor specimens amenable for IHC evaluations, we found a positive correlation between ACC1 and FASN at both mRNA (r = 0.87, p = 0.00045) and protein (r = 0.68, p = 0.0004) level. Patients with higher ACC1 protein expression in metastatic lesions had significantly lower PFS when compared to patients with lower ACC1 levels (5.5 vs 36 months; aHR 4.49, 95% CIs 1.08-18.72; p = 0.039). In conclusion, systemic and tumor lipid metabolism are associated with the PFS of everolimus-treated patients with advanced pNETs; based on these findings, dietary and pharmacological interventions targeting lipid metabolism could improve everolimus efficacy in this patient population. Pancreatic neuroendocrine tumors (pNETs) are highly heterogeneous, so to improve treatment, it's critical to learn more about how different tumor types respond to therapy. The mTOR inhibitor everolimus is a standard therapy for pNETs. Here, the authors conducted a retrospective study to evaluate how circulating triglyceride and cholesterol levels affect the efficacy of everolimus. Patients with higher plasma triglyceride levels at the start of treatment, they found, had worse outcomes. In addition, they noted a correlation between disease progression and higher intratumoral levels of ACC1, a key enzyme in fatty acid biosynthesis. This article is protected by copyright. All rights reserved.

PMID: 30520016 [PubMed - as supplied by publisher]

Permalink for 'Ectopic corticotropin-releasing hormone syndrome caused by pancreatic neuroendocrine tumor localized by 68Ga-DOTATATE PET/CT.'

Ectopic corticotropin-releasing hormone syndrome caused by pancreatic neuroendocrine tumor localized by 68Ga-DOTATATE PET/CT.

Fetched: December 8th, 2018, 5:00am GMT

Ectopic corticotropin-releasing hormone syndrome caused by pancreatic neuroendocrine tumor localized by 68Ga-DOTATATE PET/CT.

Eur J Nucl Med Mol Imaging. 2018 Dec 05;:

Authors: Hou G, Jiang Y, Cheng W

Abstract

PMID: 30519868 [PubMed - as supplied by publisher]

Prevalence of Small Intestine Carcinoid Tumors: A US Population-Based Study 2012-2017.

Fetched: December 8th, 2018, 5:00am GMT

Prevalence of Small Intestine Carcinoid Tumors: A US Population-Based Study 2012-2017.

Dig Dis Sci. 2018 Dec 05;:

Authors: Abou Saleh M, Mansoor E, Anindo M, Isenberg G

Abstract
BACKGROUND AND AIMS: Most carcinoid tumors of the gastrointestinal tract are located in the small bowel (SB). Epidemiological studies of these tumors have been limited by small sample sizes. Our aim was to evaluate the epidemiology of SB carcinoids (SBCs) using a large database.
METHODS: We queried a commercial database (Explorys), an aggregate of electronic health data from 26 US healthcare systems. We identified patients with SBCs between 2012 and 2017. We evaluated the epidemiology of SBC and identified possible risk factors.
RESULTS: Of the 35,798,290 individuals in the database between 2012 and 2017, we identified 3280 patients with SBCs, with a prevalence of 9.2/100,000. Prevalence was higher in men [odds ratio (OR) 1.23, 95% confidence interval (CI) 1.153-1.322, p < 0.0001], whites [OR 2.031, 95% CI 1.872-2.203, p < 0.0001], and elderly (aged > 65) [OR 4.856, 95% CI 4.533-5.203, p < 0.0001]. Patients with SBCs were more likely to have a history of smoking [OR 2.749, 95% CI 2.549-2.970, p < 0.0001], alcohol use [OR 2.031, 95% CI 1.864-2.21, p < 0.0001], obesity (BMI > 30) [OR 3.476, 95% CI 3.213-3.761, p < 0.0001], diabetes mellitus [OR 4.198, 95% CI 3.900-4.519, p < 0.0001], and a family history of cancer [OR 5.902, 95% CI 5.396-6.456, p < 0.0001].
CONCLUSIONS: This is one of the largest studies done on the prevalence of SBC. The prevalence of 9.2/100,000 individuals is higher than previously reported. Further genetic and environmental studies are needed to understand the potential mechanisms for the risk factors identified in this study.

PMID: 30519851 [PubMed - as supplied by publisher]

ASO Author Reflections: Pancreatic Neuroendocrine Tumor Recurrence and Survival Predicted by Ki67.

Fetched: December 8th, 2018, 5:00am GMT

ASO Author Reflections: Pancreatic Neuroendocrine Tumor Recurrence and Survival Predicted by Ki67.

Ann Surg Oncol. 2018 Dec 05;:

Authors: Nieveen van Dijkum EJM

Abstract

PMID: 30519760 [PubMed - as supplied by publisher]

CX-3543 Promotes Cell Apoptosis through Downregulation of CCAT1 in Colon Cancer Cells.

Fetched: December 8th, 2018, 5:00am GMT

CX-3543 Promotes Cell Apoptosis through Downregulation of CCAT1 in Colon Cancer Cells.

Biomed Res Int. 2018;2018:9701957

Authors: Yao YX, Xu BH, Zhang Y

Abstract
Aim: Colon cancer-associated transcript-1 (CCAT1), located in the vicinity of transcription factor c-Myc, was first identified in colon cancer. A small-molecule compound CX3543 (Quarfloxin) selectively targeting Myc G-quadruplexes has entered phase II clinical trials for neuroendocrine carcinomas. The aim of the study was to explore the relationship between CX3543, CCAT1, and cell apoptosis in colon cancer cells.
Methods: Semiquantitative PCR was used to detect the relative expression of CCAT1 in colon cancer (CC) tissues and HT29 cell lines. Real-time PCR (RT-PCR) was also used to investigate the expression of CCAT1 and c-Myc after HT29 cells being treated by CX3543 for 24 h. Cell apoptosis assay and cell proliferation assay were conducted in HT29 cells after being treated by CX3543.
Results: The results showed that the expression of CCAT1 was remarkably increased in CC tissues and HT29 cells compared to controls. CX3543 treatment reduced the expression of c-Myc and CCAT1 and promoted cell apoptosis and inhibited cell proliferation. After the expression of CCAT1 was inhibited by sh-CCAT1 transfection, the cell apoptosis rate was higher than that of control group. After the cells were treated by CCAT1 overexpression plasmid transfection and CX3543, the cell apoptosis rate was lower than that of control group. In vivo results showed that CX3543 inhibited the xenograft tumor growth of rats through downregulation of CCAT1.
Conclusion: Our study demonstrated that CX3543 could inhibit the progression of colon cancer by downregulating CCAT1 expression and might be a potential drug for the treatment of colon cancer.

PMID: 30519593 [PubMed - in process]

An Extragastrointestinal Stromal Tumor Originating from the Pancreas.

Fetched: December 8th, 2018, 5:00am GMT

An Extragastrointestinal Stromal Tumor Originating from the Pancreas.

Case Rep Gastroenterol. 2018 Sep-Dec;12(3):671-678

Authors: Yeo SJ, Cho CM, Kwon HJ, Cho SH, Kim GC, Seo AN, Bae HI

Abstract
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract (GIT). In fewer than 5% of cases, GIST originates primarily from outside the GIT. The occurrence of GIST originating from the pancreas is rare. Sometimes, neuroendocrine tumors should be differentiated from GISTs because of their hyperenhancing nature in radiologic images. We report a case of GIST arising in the pancreas that was confirmed by surgical resection.

PMID: 30519153 [PubMed]

Prognosis of patients with neuroendocrine tumor: a SEER database analysis.

Fetched: December 8th, 2018, 5:00am GMT

Prognosis of patients with neuroendocrine tumor: a SEER database analysis.

Cancer Manag Res. 2018;10:5629-5638

Authors: Man D, Wu J, Shen Z, Zhu X

Abstract
Background: Neuroendocrine tumors (NETs) are a group of heterogeneous cancers arising from a variety of anatomic sites. Their incidence has increased in recent years. This study aimed to analyze the prognosis of NETs originating from different anatomic sites.
Methods: We identified 73,782 patients diagnosed with NETs from the Surveillance Epidemiology and Ends Results (SEER) database from 1973 to 2014. Clinical data were compared between patients with different primary tumor sites using the chi-squared test. Differences in survival among NET patients with different tumor sites were compared by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify the prognostic factors of overall survival.
Results: In this cohort, the lung/bronchus was the most common site of NETs, accounting for 30.6%, followed by the small intestine (22.2%), rectum (16.2%), colon (13.4%), pancreas (10.8%), and stomach (6.8%). Totally, 73,782 patients were selected for this cohort from 1973 to 2014. The median survival duration was 41 months. The 1-, 3-, 5-, and 10-year overall survival rates for patients with NETs were 72.8%, 52.7%, 39.4%, and 18.1%, respectively. Patients with NETs located in the rectum had the best prognosis, followed by those with NETs in the small intestine (HR, 1.660, 95% CI, 1.579, 1.744), lung/bronchus (HR, 1.786, 95% CI, 1.703, 1.874), stomach (HR, 1.865, 95% CI, 1.755, 1.982), and colon (HR, 1.896, 95% CI, 1.799, 1.999). Patients with NETs in the pancreas had the highest risk of mortality (HR, 2.034, 95% CI, 1.925, 2.148).
Conclusion: Significant differences in survival were found among various primary tumor sites. NETs in the rectum had the best prognosis, while those in the pancreas had the worst. Primary tumor sites might be one of the most useful outcome predictors in patients with NETs.

PMID: 30519109 [PubMed]

Permalink for 'Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial.'

Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial.

Fetched: December 8th, 2018, 5:00am GMT

Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial.

Eur J Nucl Med Mol Imaging. 2018 Nov 30;:

Authors: Del Prete M, Buteau FA, Arsenault F, Saighi N, Bouchard LO, Beaulieu A, Beauregard JM

Abstract
PURPOSE: Peptide receptor radionuclide therapy (PRRT) is mostly administered using a fixed injected activity (IA) per cycle. This empiric regime results in highly variable absorbed doses to the critical organs and undertreatment of the majority of patients. We conceived a personalized PRRT protocol in which the IA is adjusted to deliver a prescribed absorbed dose to the kidney, with the aim to safely increase tumour irradiation. We herein report on the initial results of our prospective study of personalized PRRT, the P-PRRT Trial (NCT02754297).
METHODS: PRRT-naïve patients with progressive and/or symptomatic neuroendocrine tumour (NET) were scheduled to receive a four-cycle induction course of 177Lu-octreotate with quantitative SPECT/CT-based dosimetry. The IA was personalized according to the glomerular filtration rate and the body surface area for the first cycle, and according to the prior renal Gy/GBq for the subsequent cycles. The prescribed renal absorbed dose of 23 Gy was reduced by 25-50% in case of significant renal or haematological impairment. Responders were allowed to receive consolidation or maintenance cycles, for each of which 6 Gy to the kidney were prescribed. We simulated the empiric PRRT regime by fixing the IA at 7.4 GBq per cycle, with the same percentage reductions as above. Radiological, molecular imaging, biochemical, and quality of life responses, as well as safety, were assessed.
RESULTS: Fifty-two patients underwent 171 cycles. In 34 patients who completed the induction course, a median cumulative IA of 36.1 (range, 6.3-78.6) GBq was administered, and the median cumulative kidney and maximum tumour absorbed doses were 22.1 (range, 8.3-24.3) Gy and 185.7 (range: 15.2-443.1) Gy respectively. Compared with the simulated fixed-IA induction regime, there was a median 1.26-fold increase (range, 0.47-2.12 fold) in the cumulative maximum tumour absorbed dose, which was higher in 85.3% of patients. In 39 assessable patients, the best objective response was partial response in nine (23.1%), minor response in 14 (35.9%), stable disease in 13 (33.3%) and progressive disease in three patients (7.7%). In particular, 11 of 13 patients (84.6%) with pancreatic NET had partial or minor response. The global health status/quality of life score significantly increased in 50% of patients. Acute and subacute side-effects were all of grade 1 or 2, and the most common were nausea (in 32.7% of patients) and fatigue (in 30.8% of patients) respectively. Subacute grade 3 or 4 toxicities occurred in less than 10% of patients, with the exception of lymphocytopenia in 51.9% of patients, without any clinical consequences however. No patient experienced severe renal toxicity.
CONCLUSIONS: Personalized PRRT makes it possible to safely increase tumour irradiation in the majority of patients. Our first results indicate a favourable tolerance profile, which appears similar to that of the empiric regime. The response rates are promising, in particular in patients with NET of pancreatic origin.

PMID: 30506283 [PubMed - as supplied by publisher]

Permalink for 'Erratum to liver transplantation for unresectable pancreatic neuroendocrine tumors with liver metastases in an era of transplant oncology.'

Erratum to liver transplantation for unresectable pancreatic neuroendocrine tumors with liver metastases in an era of transplant oncology.

Fetched: December 8th, 2018, 5:00am GMT

Erratum to liver transplantation for unresectable pancreatic neuroendocrine tumors with liver metastases in an era of transplant oncology.

Gland Surg. 2018 Oct;7(5):499-500

Authors: Shimata K, Sugawara Y, Hibi T

Abstract
[This corrects the article DOI: 10.21037/gs.2017.12.11.].

PMID: 30505773 [PubMed - in process]

Lobar versus sub-lobar surgery for pulmonary typical carcinoid, a population-based analysis.

Fetched: December 8th, 2018, 5:00am GMT

Lobar versus sub-lobar surgery for pulmonary typical carcinoid, a population-based analysis.

J Thorac Dis. 2018 Oct;10(10):5850-5859

Authors: Furqan M, Tien YY, Schroeder MC, Parekh KR, Keech J, Allen BG, Thomas A, Zhang J, Clamon G, Abu Hejleh T

Abstract
Background: The optimal surgery for resectable pulmonary typical carcinoid (TC), e.g., lobar resection (L-R) vs. sub-lobar resection (SL-R), is controversial. This is further explored in this population-based study.
Methods: The Surveillance, Epidemiology, and End Results (SEER) Program was used to select patients ≥66 years old, and diagnosed between 2000 and 2012 with pulmonary TC. A similar cohort was developed using the SEER-Medicare database (diagnosed from 2000-2007) to identify chemotherapy (CTX) use and co-morbidity. Five-year survival was calculated using univariate and multivariate analysis.
Results: A total of 1,506 and 512 patients were identified from SEER and SEER-Medicare, respectively. In the SEER cohort, 49%, 29% and 21% received L-R, SL-R, and no surgery (NS), respectively. Those who received NS were older (P<0.001), had a higher stage (P<0.001), greater comorbidity (P<0.001), and were more likely to receive radiotherapy (XRT) (P<0.001) and CTX (P<0.001). Relative survival was nearly 100% for those who received L-R or SL-R as opposed to 72% for those who received NS (P<0.001). Cox models showed no survival difference for L-R vs. SL-R (HR 1.1, P=0.663), but worse survival for those who received NS vs. L-R or SL-R (HR 3.6, P<0.001). XRT in NS cohort was associated with increased risk of death (HR 2.3, P=0.017).
Conclusions: SL-R was better than NS, and similar to L-R in terms of survival. SL-R should be considered over NS if L-R is unfeasible. Role of adjuvant CTX and XRT is unclear as these did not improve survival in this study.

PMID: 30505493 [PubMed]

Chemotherapy in Patients with Hereditary Angioedema.

Fetched: December 8th, 2018, 5:00am GMT

Chemotherapy in Patients with Hereditary Angioedema.

Anticancer Res. 2018 Dec;38(12):6801-6807

Authors: Morelli C, Formica V, Pellicori S, Menghi A, Guarino MD, Perricone R, Roselli M

Abstract
BACKGROUND: Hereditary angioedema (HAE) is an autosomal dominant hereditary disorder characterized by episodic swelling of many body regions (especially throat and abdomen), potentially triggered by medication. No data are available for HAE in patients with cancer assigned to standard chemotherapy. The aim of our study was to identify circulating mediators potentially predictive of acute HAE attacks during chemotherapy.
PATIENT AND METHODS: Repeated blood testing (approximately every week) for complement system members (C3, C4, CH50, C1 inhibitor, C1-inhibitor functional C1Q), D-dimers and for routine haematochemistry were performed in a 42-year-old male affected by type 2 HAE during standard adjuvant oxaliplatin/fluorouracil-based chemotherapy administered for stage III radically resected rectal cancer. Pre-medication with 1,000 U Berinert inhibitor C1 was administered every week throughout treatment. Mann-Whitney U-test was used to determine statistical differences in measures between the first 30 days of therapy and beyond day 30 of therapy.
RESULTS: Pre-chemotherapy values of tested variables (day 0) were: C3: 101 mg/dl, C4: 5.71 mg/dl, CH50: 74%, C1 inhibitor: 43.4 mg/dl, C1-inhibitor functional: 18%, C1Q: 150 mg/dl, and D-dimers: 113 g/ml. A significant change in circulating values was observed for C3, D-dimers and C1-inhibitor functional. Four HAE attacks were observed, they started from the forth cycle of treatment and all were manageable. Changes in C3, D-dimers and C1-inhibitor functional preceded the attacks.
CONCLUSION: The stress induced by chemotherapy such a standard oxaliplatin/fluorouracil increases the risk of attacks in patients with HAE. However, circulating biomarkers such as D-dimers, C3 and C1-inhibitor functional may serve as early predictors of acute HAE crisis.

PMID: 30504393 [PubMed - in process]

Permalink for 'The benign-malignant paradigm in pituitary neuroendocrine tumors and the metaphor of the semaphore: Reflections of a pathologist.'

The benign-malignant paradigm in pituitary neuroendocrine tumors and the metaphor of the semaphore: Reflections of a pathologist.

Fetched: December 8th, 2018, 5:00am GMT

The benign-malignant paradigm in pituitary neuroendocrine tumors and the metaphor of the semaphore: Reflections of a pathologist.

Endocrinol Diabetes Nutr. 2018 Nov 29;:

Authors: Tortosa F

PMID: 30503910 [PubMed - as supplied by publisher]

Malignant Pancreatic insulinoma with large hepatic metastasis.

Fetched: December 8th, 2018, 5:00am GMT

Malignant Pancreatic insulinoma with large hepatic metastasis.

Am J Med. 2018 Nov 29;:

Authors: Gojwari TA, Ilyas M, Dar MA, Malik AH, Kazimi MJA

PMID: 30503878 [PubMed - as supplied by publisher]

Permalink for 'Carcinoid tumors of the thymus and Cushing's syndrome: Clinicopathologic features and current best evidence regarding the cell of origin of these unusual neoplasms.'

Carcinoid tumors of the thymus and Cushing's syndrome: Clinicopathologic features and current best evidence regarding the cell of origin of these unusual neoplasms.

Fetched: December 8th, 2018, 5:00am GMT

Carcinoid tumors of the thymus and Cushing's syndrome: Clinicopathologic features and current best evidence regarding the cell of origin of these unusual neoplasms.

Ann Diagn Pathol. 2018 Nov 22;38:71-79

Authors: Walts AE, Frye J, Engman DM, Marchevsky AM

Abstract
It is uncertain whether thymic neuroendocrine tumors (NET) associated with Cushing's syndrome (CS) produce corticotropin-releasing hormone (CRH) and adrenocorticotropin hormone (ACTH) and whether the thymus contains ACTH and/or CRH cells that could originate NET. The clinicopathologic features of 5 typical (TC) and 6 atypical carcinoids (ATC), 10 additional non-neoplastic thymi, 6 adrenal glands with bilateral nodular hyperplasia and 8 adrenal cortical adenomas were reviewed. Representative slides were immunostained for ACTH and CRH. Four (36.4%) of the 11 patients had CS. The incidence of Masaoka stage IV was higher (p < 0.0001) in patients with ATC than TC. Only 2 (18.1%) of the 11 patients were alive at follow-up. Ten NET were CRH immunoreactive and 6 were ACTH immunoreactive. Thymic NET with CS exhibited stronger immunoreactivity for ACTH and CRH than those without CS. Non-neoplastic thymi exhibited scattered ACTH and CRH immunoreactive cells. Normal adrenal cortex and glands with bilateral nodular hyperplasia showed diffuse CRH immunoreactivity while adrenal adenomas showed no or only focal CRH immunoreactivity. Literature review showed no association between thymic NET and adrenal adenomas. The thymus contains CRH and ACTH immunoreactive cells that are probably the origin of thymic NET. Neoplasms associated with CS exhibit strong immunoreactivity for both hormones, suggesting that CRH probably plays a role in the pathogenesis of CS. As adrenals with bilateral nodular hyperplasia exhibit diffuse CRH immunoreactivity and adrenal cortical adenomas either lack this finding or show few immunoreactive cells, this marker may be useful to distinguish these lesions.

PMID: 30502716 [PubMed - as supplied by publisher]

Insulinoma-associated protein 1 immunostaining on cytology specimens: an institutional experience.

Fetched: December 8th, 2018, 5:00am GMT

Insulinoma-associated protein 1 immunostaining on cytology specimens: an institutional experience.

Hum Pathol. 2018 Nov 28;:

Authors: Rodriguez EF, Judd Fite J, Chowsilpa S, Maleki Z

Abstract
Neuroendocrine tumors (NET) are epithelial neoplasms with prominent neuroendocrine differentiation. Cytologic examination and utilization of immunohistochemical (IHC) markers are important diagnostic tools for the evaluation of these tumors. Herein we report our experience with the application of INSM1 in cytology samples. We searched our pathology system for cytological specimens with INSM1 IHC performed from 2017-2018. Patients' demographics were recorded, and cytology materials were reviewed including all neuroendocrine IHC markers performed. A total of 134 (67M, 67F) specimens with INSM1 immunohistochemistry were identified. Specimens included 91 (68.2%) neuroendocrine tumors (NET) or tumors with neuroendocrine features (TNEF), 33 (24.3%) non-neuroendocrine lesions (non-NET) and 10 (7.5%) non-neoplastic diagnoses. INSM1 was positive in 90 (99%) of the NET/TNEF and negative in 32 (97%) non-NET. CD56 was positive in 42 (95.5%) of the NET/TNEF and negative on 9 (69.2%) of the non-NET. The sensitivity of INSM1 was 99% and specificity was 97%, while the sensitivity of CD56 was 95.5% and specificity was 69.2%. Chromogranin had the lowest sensitivity (82.5%) and synaptophysin had the lowest specificity (66.7%). Both positive and negative predictive values of INSM1 were higher than CD56 (99% versus 91.3% and 97% versus 81.8%, respectively). INSM1 is a sensitive and specific marker for detection of neuroendocrine tumors in cytology samples independent of primary site.

PMID: 30502379 [PubMed - as supplied by publisher]

Impact of Nutritional Status on Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) Aggressiveness.

Fetched: December 7th, 2018, 5:00am GMT

Impact of Nutritional Status on Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) Aggressiveness.

Nutrients. 2018 Dec 01;10(12):

Authors: Barrea L, Altieri B, Muscogiuri G, Laudisio D, Annunziata G, Colao A, Faggiano A, Savastano S

Abstract
Neuroendocrine tumors (NETs) are rare neoplasms mostly originating from the gastroenteropancreatic tract (GEP-NETs). Data regarding nutritional status in GEP-NET patients are limited. The aim of the study was to investigate the nutritional status and adherence to the Mediterranean Diet (MD) in GEP-NET patients and to correlate them with tumor aggressiveness. A cross-sectional case-control observational study was conducted enrolling 83 patients with well-differentiated G1/G2 GEP-NETs after resection, as well as 83 healthy subjects, age, sex and body mass index-matched. Nutritional status was assessed by evaluating with Bioelectrical Impedance analysis and its phase angle (PhA), adherence to the MD according to PREDIMED score, dietary assessment, anthropometric parameters, and clinico-pathological characteristics. GEP-NET patients consumed less frequently vegetables, fruits, wine, fish/seafood, nuts, and more frequently red/processed meats, butter, cream, margarine, and soda drinks than controls. Patients with more aggressive disease presented a lower adherence to MD according to PREDIMED categories in comparison to G1, localized and free/stable disease status. A smaller PhA value and a lower PREDIMED score were significantly correlated with G2 tumor, metastases, and progressive disease. To the best of our knowledge, this is the first study reporting an association between nutritional status and tumor aggressiveness in a selected group of GEP-NETs. Moreover, higher intakes of food of MD, may represent a potential tool for prevention of tumor aggressiveness. Thus, a skilled nutritionist should be an integral part of the multidisciplinary management of GEP-NET patients.

PMID: 30513732 [PubMed - in process]

Permalink for 'Localized pancreatic Castleman disease presenting with extrahepatic dilatation of bile ducts: A case report and review of published cases.'

Localized pancreatic Castleman disease presenting with extrahepatic dilatation of bile ducts: A case report and review of published cases.

Fetched: December 6th, 2018, 5:00am GMT

Localized pancreatic Castleman disease presenting with extrahepatic dilatation of bile ducts: A case report and review of published cases.

Int J Surg Case Rep. 2018 Nov 20;54:28-33

Authors: Ferreira Junior EG, Apolinario Costa P, Freire Golveia Silveira LM, Valois Vieira R, Lima Martins Soares HA, Menon Loureiro B, Pertile Salvioni NC, Coelho Ferreira Rocha JR

Abstract
INTRODUCTION: Castleman disease (CD) is a rare polyclonal lymphoproliferative disorder of unknown etiology, which usually develops in the mediastinum. It can also occur in the cervical, retroperitoneal and axillary regions. Localized pancreatic CD is quite rare [1].
PRESENTATION OF CASE: The authors herein present a case of a 34 years old female that was diagnosed during a symptomatic cholelithiasis evaluation. During the evaluation, an abdominal ultrasonography revealed a tumor at the head of the pancreas, which went on to generate a dilatation of the extrahepatic bile ducts. This finding was confirmed by abdominal magnetic resonance imaging (MRI). Subsequently, the patient underwent a laparotomy, where a capsulated tumor was found at the head of the pancreas with well-defined margins. The decision was made for tumor excision. The histopathology and immunohistochemistry established CD, hyaline vascular variation.
DISCUSSION: The authors of the present paper also performed a literature review concerning Pancreatic CD, where there were found only 33 cases until the time of the writing of this paper, and we have subsequently carried out a retrospective analysis of all cases. In a patient with atypical images, there might be a benefit from a preoperative diagnosis of CD, by using immunohistochemistry analysis in an image guided biopsy. Thus, avoiding unnecessary procedures and surgeries.
CONCLUSION: Localized pancreatic CD is a very rare condition with good prognosis, but it can mimic many common diseases, such as gastrointestinal stromal tumor (GIST), pancreatic neuroendocrine tumor or pancreatic adenocarcinoma.

PMID: 30513495 [PubMed - as supplied by publisher]

Permalink for 'First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors.'

First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors.

Fetched: December 6th, 2018, 5:00am GMT

First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors.

Invest New Drugs. 2018 Dec 04;:

Authors: Doi T, Yoh K, Shitara K, Takahashi H, Ueno M, Kobayashi S, Morimoto M, Okusaka T, Ueno H, Morizane C, Okano N, Nagashima F, Furuse J

Abstract
Background This first-in-human phase 1 study assessed the safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 to determine its maximum tolerated dose (MTD) and recommended dose (RD). Methods In this dose-escalation study with a 3 + 3 design, TAS-114 and S-1 were concurrently administered orally under fasting conditions at 5-240 mg/m2 and 30-36 mg/m2, respectively, in patients with advanced solid tumors. Safety, efficacy, and pharmacokinetics (PK) were evaluated. Results Seventy-six patients were enrolled. The MTD and RD were TAS-114 200 mg/m2 plus S-1 36 mg/m2 and TAS-114 240 mg/m2 plus S-1 30 mg/m2, respectively. Common treatment-related adverse events were anemia, lymphocytopenia, leukopenia, neutropenia, decreased appetite, rash, nausea, and pigmentation disorder. Partial response (PR) was observed in 10 patients (non-small cell lung cancer [NSCLC], n = 5; pancreatic neuroendocrine tumor, n = 2; gastric cancer, n = 2; gallbladder cancer, n = 1). Of these, four patients achieved PR despite prior treatment history with S-1. Patients administered TAS-114 exhibited linear PK and CYP3A4 induction, with no effect on the PK of S-1. Conclusion TAS-114 plus S-1 showed tolerable, safe, and potentially effective results. To confirm safety and efficacy, two phase 2 studies are ongoing in NSCLC and gastric cancer patients. Clinical trial registration ClinicalTrials.gov ( NCT01610479 ) .

PMID: 30511200 [PubMed - as supplied by publisher]

The Loss of ATRX Increases Susceptibility to Pancreatic Injury and Oncogenic KRAS in Female But Not Male Mice.

Fetched: December 6th, 2018, 5:00am GMT

The Loss of ATRX Increases Susceptibility to Pancreatic Injury and Oncogenic KRAS in Female But Not Male Mice.

Cell Mol Gastroenterol Hepatol. 2019;7(1):93-113

Authors: Young CC, Baker RM, Howlett CJ, Hryciw T, Herman JE, Higgs D, Gibbons R, Crawford H, Brown A, Pin CL

Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for >30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler ɑ-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS's ability to promote PDAC. ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. The hypothesis was that deletion of Atrx in pancreatic acinar cells will increase susceptibility to injury and oncogenic KRAS.
Methods: Mice allowing conditional loss of Atrx within pancreatic acinar cells were examined after induction of recurrent cerulein-induced pancreatitis or oncogenic KRAS (KRAS G12D ). Histologic, biochemical, and molecular analysis examined pancreatic pathologies up to 2 months after induction of Atrx deletion.
Results: Mice lacking Atrx showed more progressive damage, inflammation, and acinar-to-duct cell metaplasia in response to injury relative to wild-type mice. In combination with KRASG12D, Atrx-deficient acinar cells showed increased fibrosis, inflammation, progression to acinar-to-duct cell metaplasia, and pre-cancerous lesions relative to mice expressing only KRASG12D. This sensitivity appears only in female mice, mimicking a significant prevalence of ATRX mutations in human female PDAC patients.
Conclusions: Our results indicate the absence of ATRX increases sensitivity to injury and oncogenic KRAS only in female mice. This is an instance of a sex-specific mutation that enhances oncogenic KRAS's ability to promote pancreatic intraepithelial lesion formation.

PMID: 30510993 [PubMed - in process]

Foxa2 activates the transcription of androgen receptor target genes in castrate resistant prostatic tumors.

Fetched: December 6th, 2018, 5:00am GMT

Foxa2 activates the transcription of androgen receptor target genes in castrate resistant prostatic tumors.

Am J Clin Exp Urol. 2018;6(5):172-181

Authors: Connelly ZM, Yang S, Chen F, Yeh Y, Khater N, Jin R, Matusik R, Yu X

Abstract
Prostate cancer (PCa) is the leading cancer among men. Androgen Deprivation Therapy (ADT) is a common treatment for advanced PCa. However, ADT eventually fails and PCa relapses, developing into castration-resistant prostate cancer (CRPCa). Although alternative pathways such as cancer stem-cell pathway and neuroendocrine differentiation bypass androgen receptor (AR) signaling, AR remains the central player in mediating CRPCa. In this study, we identified a mechanism that retains AR signaling after androgen deprivation. The TRAMP SV40 T antigen transgenic mouse is a model for PCa. The expression of SV40 T-antigen is driven by the androgen-responsive, prostate specific, Probasin promoter. It has been recognized that in this model, T-antigen is still expressed even after androgen ablation. It is unclear how the androgen-responsive Probasin promoter remains active and drives the expression of T-antigen in these tumors. In our study, we found that the expression of Foxa2, a forkhead transcription factor that is expressed in embryonic prostate and advanced stage prostate cancer, is co-expressed in T-antigen positive cells. To test if Foxa2 activates AR-responsive promoters and promotes the expression of T-antigen, we established the prostate epithelial cells that stably express Foxa2, NeoTag1/Foxa2 cells. Neotag1 cells were derived from the Probasin promoter driven SV40 T-antigen transgenic mouse. We found ectopic expression of Foxa2 drives the T-antigen expression regardless of the presence of androgens. Using this model system, we further explored the mechanism that activates AR-responsive promoters in the absence of androgens. Chromatin immunoprecipitation revealed the occupancy of both H3K27Ac, an epigenetic mark of an active transcription, and Foxa2 at the known AR target promoters, Probasin and FKBP5, in the absence of androgen stimulation. In conclusion, we have identified a mechanism that enables PCa to retain the AR signaling pathway after androgen ablation.

PMID: 30510969 [PubMed]

The European Society of Thoracic Surgeons (ESTS) lung neuroendocrine tumors (NETs) database.

Fetched: December 6th, 2018, 5:00am GMT

The European Society of Thoracic Surgeons (ESTS) lung neuroendocrine tumors (NETs) database.

J Thorac Dis. 2018 Oct;10(Suppl 29):S3528-S3532

Authors: Filosso PL, Falcoz PE, Solidoro P, Pellicano D, Passani S, Guerrera F, Ruffini E, ESTS Lung Neuroendocrine Working-Group Participating Centers*

Abstract
Histological characteristics and clinical behaviour define lung neuroendocrine tumors (NETs), which are classified into four groups: typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine carcinomas (LCNCs) and small-cell lung cancers (SCLCs). Historically, outcome and treatment of these rare neoplasms have been based on small, usually mono-institutional clinical series. Furthermore, their rarity makes quite impossible to design randomised clinical trial to compare different treatments especially in unusual clinical presentations. In 2012, the European Society of Thoracic Surgeons (ESTS) launched a new working-group, specifically dedicated to lung NETs, with the aim to develop modern knowledge on biology and behaviour of these tumors, and to disseminate it within the scientific community. A dedicated retrospective database was at first developed and sent to all the ESTS centres interested to this project. More than 2,000 operated NETs cases have been rapidly collected, and they represented the clinical substrate of several published scientific studies. The retrospective data collection intrinsic limitations in term of patients' selection and treatment, along with the problem of possible missing data, were the reasons why the ESTS NETs working-group decided in 2015 to design and promote a new prospective database, employing the official ESTS platform. The aim of this review paper is to report the ESTS Lung NETs working-group history and to explain the architecture and use of the lung NETs databases.

PMID: 30510790 [PubMed]

The European Society of Thoracic Surgeons (ESTS) thymic database.

Fetched: December 6th, 2018, 5:00am GMT

The European Society of Thoracic Surgeons (ESTS) thymic database.

J Thorac Dis. 2018 Oct;10(Suppl 29):S3516-S3520

Authors: Ruffini E, Falcoz PE, Guerrera F, Filosso PL, Thomas P, Novoa N, Moser B, Pellicano D, Passani S

Abstract
The European Society of Thoracic Surgeons (ESTS) thymic database is a satellite database of the ESTS registry collecting patients with thymic tumors (thymomas, thymic carcinomas and neuroendocrine thymic tumors) among the ESTS Institutions. The database is free of charge for any ESTS member, easily accessible to any ESTS institution, web-based, prospective, periodically maintained and updated. It may serve as an institutional database for the storage of data about patients with thymic tumors at no cost for each participating institution. It may be used by any ESTS member to propose studies using one of the largest thymic databases worldwide. The present review focuses on the history and the development of the ESTS thymic database (retrospective and prospective) and its structure with a particular reference to the concept of the minimum dataset and the Clinical Care Analysis (CCA) box. A brief overview about the role of the ESTS thymic database in the global effort for the new TNM staging system of thymic tumors is also provided. In the supplementary, there are clear instructions to get access to the thymic database using the ESTS official website. The ESTS thymic database represents a powerful tool available to all ESTS members which can be used for studies on the management of these rare tumors.

PMID: 30510788 [PubMed]

Permalink for 'Combined Volumetric and Density Analyses of Contrast-Enhanced CT Imaging to Assess Drug Therapy Response in Gastroenteropancreatic Neuroendocrine Diffuse Liver Metastasis.'

Combined Volumetric and Density Analyses of Contrast-Enhanced CT Imaging to Assess Drug Therapy Response in Gastroenteropancreatic Neuroendocrine Diffuse Liver Metastasis.

Fetched: December 6th, 2018, 5:00am GMT

Combined Volumetric and Density Analyses of Contrast-Enhanced CT Imaging to Assess Drug Therapy Response in Gastroenteropancreatic Neuroendocrine Diffuse Liver Metastasis.

Contrast Media Mol Imaging. 2018;2018:6037273

Authors: Wang Y, Huang K, Chen J, Luo Y, Zhang Y, Jia Y, Xu L, Chen M, Huang B, Ni D, Li ZP, Feng ST

Abstract
Objective: We propose a computer-aided method to assess response to drug treatment, using CT imaging-based volumetric and density measures in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and diffuse liver metastases.
Methods: Twenty-five patients with GEP-NETs with diffuse liver metastases were enrolled. Pre- and posttreatment CT examinations were retrospectively analyzed. Total tumor volume (volume) and mean volumetric tumor density (density) were calculated based on tumor segmentation on CT images. The maximum axial diameter (tumor size) for each target tumor was measured on pre- and posttreatment CT images according to Response Evaluation Criteria In Solid Tumors (RECIST). Progression-free survival (PFS) for each patient was measured and recorded.
Results: Correlation analysis showed inverse correlation between change of volume and density (Δ(V + D)), change of volume (ΔV), and change of tumor size (ΔS) with PFS (r = -0.653, P=0.001; r = -0.617, P=0.003; r = -0.548, P=0.01, respectively). There was no linear correlation between ΔD and PFS (r = -0.226, P=0.325).
Conclusion: The changes of volume and density derived from CT images of all lesions showed a good correlation with PFS and may help assess treatment response.

PMID: 30510495 [PubMed - in process]

Therapeutic strategies of melatonin in cancer patients: a systematic review and meta-analysis.

Fetched: December 6th, 2018, 5:00am GMT

Therapeutic strategies of melatonin in cancer patients: a systematic review and meta-analysis.

Onco Targets Ther. 2018;11:7895-7908

Authors: Wang Y, Wang P, Zheng X, Du X

Abstract
Background: Melatonin (MLT), a kind of neuroendocrine active substance, has been reported to function in the treatment of tumors. However, there remain controversies about the curative effect of MLT in tumors in clinical studies. This study investigates the efficacy of MLT on tumor therapeutic strategies by meta-analysis.
Methods: After searching several main literature databases, a total of 5,057 articles were obtained and screened by inclusion and exclusion criteria. The tumor remission rate, overall survival rate, and incidence of side effects were recorded and analyzed in the included study patients. Group analysis and sensitivity analysis were performed to examine the sources of heterogeneity in the pooled studies.
Results: The tumor remission rate in the MLT group was significantly higher than that in the control group (relative risk [RR] =2.25; 95% CI, 1.86-2.71; P<0.00001; I 2=9%). Likewise, the MLT group had an overall survival rate of 28.24% (n=294/1,041), which was greatly increased compared with the control group (RR =2.07; 95% CI, 1.55-2.76; P<0.00001; I 2=55%). And, MLT could significantly enhance the overall survival rate in non-small-cell lung cancer patients (RR =2.13; 95% CI, 1.41-3.24; P=0.0004; I 2=0%) and various solid tumor patients (RR =2.31; 95% CI, 1.78-2.99; P<0.00001; I 2=0%). It was further proved that MLT could effectively reduce the incidence of neurotoxicity (RR =0.30, 95% CI, 0.19-0.45; P<0.00001), thrombocytopenia (RR =0.23; 95% CI, 0.16-0.33; P<0.00001), and asthenia (RR =0.43, 95% CI, 0.38-0.49; P<0.00001) during chemotherapy.
Conclusion: MLT exerts positive influence in tumor therapeutic strategies, including improving tumor remission rate and overall survival rate, while reducing the incidence of chemotherapy side effects. Further large-scale randomized clinical trials (RCTs) are urgently required to verify therapeutic effects of MLT in tumors by various clinical research centers.

PMID: 30510430 [PubMed]

Androgen signaling is essential for development of prostate cancer initiated from prostatic basal cells.

Fetched: December 6th, 2018, 5:00am GMT

Androgen signaling is essential for development of prostate cancer initiated from prostatic basal cells.

Oncogene. 2018 Dec 03;:

Authors: He Y, Hooker E, Yu EJ, Cunha GR, Liao L, Xu J, Earl A, Wu H, Gonzalgo ML, Sun Z

Abstract
Emerging evidence has shown that both prostatic basal and luminal cells are able to initiate oncogenic transformation. However, despite the diversity of tumor-initiating cells, most prostate cancer cells express the androgen receptor (AR) and depend on androgens for their growth and expansion, implicating an essential role of androgen signaling in prostate tumorigenesis. Prostatic basal cells express p63 and are able to differentiate into luminal, neuroendocrine, and basal cells. Here, we directly assessed the essential role of androgen signaling in prostatic p63-expressing cell initiated oncogenic transformation and tumor formation. Using novel and relevant mouse models, we demonstrated that, with stabilized β-catenin expression, prostatic p63-expressing cells possess the ability to initiate oncogenic transformation and, in the presence of androgens, they further transdifferentiate into luminal-like tumor cells and develop adenocarcinomas. Castration prior to activating stabilized β-catenin sensitizes p63-expressing cells and increases their sensitivity to androgens, resulting in aggressive and fast growing tumor phenotypes. These findings are consistent with what have been observed in human prostate cancers, demonstrating an essential role for androgen signaling in prostate cancer initiation and progression. This study also provides fresh insight into developing new therapeutic strategies for better treating prostate cancer patients.

PMID: 30510232 [PubMed - as supplied by publisher]

Permalink for 'A Spontaneous Regression of an Isolated Lymph Node Metastasis from a Primary Unknown Merkel Cell Carcinoma in a Patient with an Idiopathic Hyper-Eosinophilic Syndrome.'

A Spontaneous Regression of an Isolated Lymph Node Metastasis from a Primary Unknown Merkel Cell Carcinoma in a Patient with an Idiopathic Hyper-Eosinophilic Syndrome.

Fetched: December 6th, 2018, 5:00am GMT

A Spontaneous Regression of an Isolated Lymph Node Metastasis from a Primary Unknown Merkel Cell Carcinoma in a Patient with an Idiopathic Hyper-Eosinophilic Syndrome.

Am J Case Rep. 2018 Dec 04;19:1437-1440

Authors: Longo R, Balasanu O, Chastenet de Castaing M, Chatelain E, Yacoubi M, Campitiello M, Marcon N, Plastino F

Abstract
BACKGROUND Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine tumor frequently associated with Merkel cell polyomavirus infection. Despite its aggressiveness, a few reports of spontaneous MCC regression have been described in the literature, most of them following incisional biopsy supporting a hypothetical role of surgery-induced inflammation in the process of regression. CASE REPORT We report a case of 69-year-old Caucasian male who was followed for an idiopathic hyper-eosinophilic syndrome. A positron emission tomography (PET) scan documented a hyper-metabolic, left, inguinal adenopathy, histologically corresponding to a metastasis of a poorly differentiated neuroendocrine carcinoma. This lesion spontaneously regressed at clinical examination and radiological imaging. After its excisional dissection, histology was negative. Five months later, a nearby adenopathy reappeared. The patient underwent another excisional biopsy. Histology and immunohistochemistry were compatible with a lymph node metastasis of a MCC. As the patient refused radical surgery, a regional radiotherapy was performed. As of a follow-up at 10 months, he was alive and free of tumor recurrence. The hyper-eosinophilic syndrome was stable; however, the serum levels of chromogranin-A were inexplicably elevated in the absence of any tumor evidence at the PET scan. CONCLUSIONS The particularity of this case relies on the rarity of MCC complete spontaneous regression in a patient without a primary tumor and with a synchronous, idiopathic hyper-eosinophilic syndrome.

PMID: 30510152 [PubMed - in process]

Hypervascular lesions of the pancreas: Think before you act.

Fetched: December 6th, 2018, 5:00am GMT

Hypervascular lesions of the pancreas: Think before you act.

Am J Surg. 2018 Nov 27;:

Authors: Wcislak SM, Stiles ZE, Deneve JL, Glazer ES, Behrman SW, Farooq FT, Dickson PV

Abstract
BACKGROUND: The "classic" CT appearance of pancreatic neuroendocrine tumors (PNETs) is a solid, hypervascular lesion; however, non-PNET diagnoses may appear similar. In addition, some PNETs have a "non-classic" appearance.
METHODS: Demographic, imaging, endoscopic ultrasound-fine needle aspiration (EUS/FNA) results, and pathology data were analyzed for patients who underwent pancreatectomy for suspected or confirmed diagnosis of PNET from our institutional database.
RESULTS: Forty-three patients with a hypervascular lesion on CT had pancreatectomy for a pre-operative diagnosis of PNET. Final pathology revealed PNET in 30 (70%) and non-PNET diagnoses in 13 (30%). EUS/FNA had a sensitivity of 82% for the pre-operative diagnosis of PNET in patients with "classic" CT. Of 13 non-PNET diagnoses, 7 were benign. Among a total of 41 patients with a final diagnosis of PNET, 11 (27%) had "non-classic" CT (5 hypodense solid lesions, 3 isodense solid lesions, and 3 cystic lesions). Among these patients, EUS/FNA had a sensitivity of 100% in diagnosing PNET.
CONCLUSIONS: Consideration of non-PNET diagnoses is important for patients with hypervascular lesions on CT. Appropriate pre-operative evaluation will optimize treatment plans.

PMID: 30509457 [PubMed - as supplied by publisher]

Implementation of patient dosimetry in the clinical practice after targeted radiotherapy using [177Lu-[DOTA0, Tyr3]-octreotate.

Fetched: December 2nd, 2018, 5:00am GMT

Implementation of patient dosimetry in the clinical practice after targeted radiotherapy using [177Lu-[DOTA0, Tyr3]-octreotate.

EJNMMI Res. 2018 Nov 29;8(1):103

Authors: Santoro L, Mora-Ramirez E, Trauchessec D, Chouaf S, Eustache P, Pouget JP, Kotzki PO, Bardiès M, Deshayes E

Abstract
BACKGROUND: This study's aim was to develop our dosimetric methodology using a commercial workstation for the routine evaluation of the organs at risk during peptide receptor radionuclide therapy (PRRT) with 177Lu.
METHODS: First, planar and SPECT sensitivity factors were determined on phantoms. The reconstruction parameters were optimized by SPECT/CT image acquisition using a NEMA IEC phantom containing a 500 ml bottle of 177Lu, to simulate a kidney. The recovery coefficients were determined on various phantoms. For the red marrow, this was calculated using a NEMA IEC phantom that contained a centrally placed bottle of 80 ml of 177Lu (to model the L2-L4 red marrow) flanked by two 200 ml bottles with 177Lu to simulate the kidneys. Then, SPECT/CT images were acquired at 4, 24, 72, and 192 h after injection in 12 patients with neuroendocrine tumors who underwent PRRT with 177Lu-DOTATATE. SPECT data were reconstructed using the iterative ordered subset expectation maximization (OSEM) method, with six iterations and ten subsets, attenuation, scatter, recovery resolution corrections, and a Gaussian post-filter of 0.11 cm. The liver, spleen, kidneys, and red marrow dose per administered activity (AD/A admin) values were calculated with the Medical Internal Radiation Dose (MIRD) formalism and the residence times (Dosimetry toolkit® application) using standard and CT imaging-based organ masses (OLINDA/EXM® V1.0 software).
RESULTS: Sensitivity factors of 6.11 ± 0.01 and 5.67 ± 0.08 counts/s/MBq were obtained with planar and SPECT/CT acquisitions, respectively. A recovery coefficient of 0.78 was obtained for the modeled L2-L4 red marrow. The mean AD/A admin values were 0.43 ± 0.13 mGy/MBq [0.27-0.91] for kidneys, 0.54 ± 0.58 mGy/MBq [0.12-2.26] for liver, 0.61 ± 0.13 mGy/MBq [0.42-0.89] for spleen, and 0.04 ± 0.02 mGy/MBq [0.01-0.09] for red marrow. The AD/A admin values varied when calculated using the personalized and standard organ mass, particularly for kidneys (p = 1 × 10-7), spleen (p = 0.0069), and red marrow (p = 0.0027). Intra-patient differences were observed especially in organs close to or including tumor cells or metastases.
CONCLUSIONS: The obtained AD/A admin values were in agreement with the literature data. This study shows the technical feasibility of patient dosimetry in clinical practice and the need to obtain patient-specific information.

PMID: 30498938 [PubMed]

Permalink for 'Beyond the Dual Paraneoplastic Syndromes of Small-Cell Lung Cancer with ADH and ACTH Secretion: A Case Report with Literature Review and Future Implications.'

Beyond the Dual Paraneoplastic Syndromes of Small-Cell Lung Cancer with ADH and ACTH Secretion: A Case Report with Literature Review and Future Implications.

Fetched: December 2nd, 2018, 5:00am GMT

Beyond the Dual Paraneoplastic Syndromes of Small-Cell Lung Cancer with ADH and ACTH Secretion: A Case Report with Literature Review and Future Implications.

Case Rep Oncol Med. 2018;2018:4038397

Authors: Agarwal KA, Soe MH

Abstract
We present a case of small-cell lung cancer (SCLC) with syndrome of inappropriate antidiuretic hormone secretion (SIADH) in which serum sodium gradually normalized with the onset of hypertension, refractory hypokalemia, and chloride-resistant metabolic alkalosis due to ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS). In this case report, we discuss the diagnostic challenges of dual paraneoplastic syndromes with SIADH and EAS, management of SCLC with paraneoplastic endocrinopathies, and their prognostic impact on SCLC. In addition, we discuss neuroendocrine differentiation and ectopic hormone production in relation to intratumoral heterogeneity in SCLC and propose tumor microenvironment and hormonal and metabolic dependence as important determinants of tumor growth and survival.

PMID: 30498610 [PubMed]

Clinicopathological characteristics of non-functioning cystic pancreatic neuroendocrine tumors.

Fetched: December 2nd, 2018, 5:00am GMT

Clinicopathological characteristics of non-functioning cystic pancreatic neuroendocrine tumors.

Pancreatology. 2018 Nov 22;:

Authors: Nakashima Y, Ohtsuka T, Nakamura S, Mori Y, Nakata K, Miyasaka Y, Ishigami K, Matsuda R, Oda Y, Nakamura M

Abstract
BACKGROUND/OBJECTIVES: The biological features of cystic pancreatic neuroendocrine tumors (PNETs) remain unclear. The aim of this study was to clarify the clinicopathological characteristics of non-functioning PNETs (NF-PNETs) with a cystic component.
METHODS: The medical records of 75 patients with NF-PNETs who had undergone resection in our institution were retrospectively reviewed. Clinicopathological factors were compared between PNETs with and without a cystic component. Expression of somatostatin 2 receptor (SSTR-2) was also analyzed.
RESULTS: Cystic PNETs were diagnosed in 14 patients (19%). The proportion of men was significantly higher for cystic than solid PNETs (79% vs. 44%, P < 0.05) and cystic PNETs were significantly larger than solid PNETs (25 mm vs. 17 mm, P < 0.01). However, there were no significant differences in the prevalence of lymph node metastases (14% vs. 10%, P = 0.64), hepatic metastasis (7% vs. 3%, P = 0.54), or disease-free survival rate (both 86%, P = 0.29) between PNETs with and without a cystic component. SSTR-2 expression was more frequently observed in PNETs with a cystic component than in those without (100% vs. 70%, P < 0.01).
CONCLUSIONS: Although cystic PNETs were larger upon diagnosis than solid PNETs in this study, prognosis after surgical resection did not differ significantly between these types of PNET. Somatostatin receptor scintigraphy and somatostatin analogues may be more useful for diagnosing and treating cystic PNETs, respectively.

PMID: 30497875 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma Review.

Fetched: December 2nd, 2018, 5:00am GMT

Merkel Cell Carcinoma Review.

Hematol Oncol Clin North Am. 2019 Feb;33(1):39-52

Authors: Xue Y, Thakuria M

PMID: 30497676 [PubMed - in process]

[Current diagnosis and treatment progress of small pancreatic neuroendocrine neoplasm].

Fetched: December 1st, 2018, 5:00am GMT

[Current diagnosis and treatment progress of small pancreatic neuroendocrine neoplasm].

Zhonghua Wai Ke Za Zhi. 2018 Dec 01;56(12):951-956

Authors: Jiang JL, Wu WM, Zhao YP

Abstract
Small(≤2 cm)pancreatic neuroendocrine neoplasm(pNEN) is a very special subgroup of pNEN featuring a small size, concealed pathogenesis, indolent course and remarkable heterogeneity.Differences in its diagnosis and interventional criteria have evolved from routine pNEN.During recent years, the incidence of small pNEN has increased sharply, while optimal management strategy of this subgroup still remains controversial.In this paper, the biological characteristics, pathological classification, diagnosis, intervention indication and therapeutic principles of small pNEN are reviewed based on recent researches, and current situations of diagnosis and treatment of small pNEN are summarized.

PMID: 30497122 [PubMed - in process]

Does it matter if it is appendix mucocele instead of appendicitis? Case series and brief review of literature.

Fetched: December 1st, 2018, 5:00am GMT

Does it matter if it is appendix mucocele instead of appendicitis? Case series and brief review of literature.

J Cancer Res Ther. 2018 Oct-Dec;14(6):1355-1360

Authors: Basak F, Hasbahceci M, Yucel M, Sisik A, Acar A, Kilic A, Su Dur MS

Abstract
Aims: Appendiceal mucocele (AM) is a rare pathology, and its reported incidence is 0.3% in all appendectomy specimens. Here, we report a case series of AM and make a brief review of literature.
Subjects and Methods: We conducted a retrospective review of a prospectively collected data of patients who diagnosed as AM by histopathological evaluation between January 2009 and June 2015 were demographic data including age and gender, intraoperative findings, and histopathological reports were recorded. All cases were followed-up by routine examination and telephone interview.
Statistical Analysis Used: Definitive statistical methods (mean, standard deviation, median, frequency, and percentage) were used to evaluate the study data.
Results: Twelve patients were examined in the study with diagnose of AM. The mean age was 51.8 ± 18.6 years (26-83). Female-to-male ratio was 1.4 (7/5). Indications for surgery were acute abdomen in 8 (72.7%) patients with presumptive diagnosis of acute appendicitis and were AM in four patients diagnosed by imaging. Histopathological evaluation revealed mucinous cystadenoma in eight patients, simple retention cysts in three, and borderline mucinous tumor (pseudomyxoma peritonei) in one. The neuroendocrine tumor was obtained on the remaining portion of the appendix in one of the simple retention cysts patients. None of the patients died because of the AM with an average follow-up of 43 months (range: 7-74).
Conclusions: Surgical resection is the first choice therapy for AM. Precise treatment modality can remain unclear in some patients because of insufficient preoperative diagnosis. It is nonmalign AM mostly however having mucocele matters because of the significant association with synchronous tumors.

PMID: 30488856 [PubMed - in process]

Clinicopathologic profiling of lung carcinoids with a Ki67 index greater than 20.

Fetched: December 1st, 2018, 5:00am GMT

Clinicopathologic profiling of lung carcinoids with a Ki67 index greater than 20.

Neuroendocrinology. 2018 Nov 28;:

Authors: Kasajima A, Konukiewitz B, Oka N, Suzuki H, Sakurada A, Okada Y, Kameya T, Ishikawa Y, Sasano H, Weichert W, Klöppel G

Abstract
<br>The clinicopathological features of lung neuroendocrine neoplasms (NEN) with a high proliferative index at the border area between atypical carcinoid and neuroendocrine carcinoma, have not been investigated so far. The aim of this study was, therefore, to search for lung NENs, which are well-differentiated but show Ki67 values that overlap with those of poorly differentiated NENs (PD-NENs). Resected lung NENs from 244 Japanese patients were reviewed and Ki67 index was assessed in all tumors. The data were then correlated to clinicopathological parameters and patient outcome. Among 59 (24%) well-differentiated NENs (WD-NENs) and 185 (76%) lung PD-NENs, seven were defined as WD-NENs with a Ki67 index>20%. The Ki67 index of these tumors (mean 29%, range 24-36) was significantly lower than that of PD-NENs (mean 74%, range 34-99). All WD-NENs with Ki67>20% lacked abnormal p53 and loss of Rb1 expression. In contrast, many PD-NENs expressed p53 (48%) and showed loss of Rb1 (85%). The 2- and 5-year disease free survival rates in WD-NEN Ki67>20% patients were lower than those of WD-NEN Ki67≤20% (p<0.01 for disease free and overall survival). No statistical differences were detected between outcome of patients with WD-NEN Ki67>20% and those of PD-NEN. It is concluded that WD-NENs Ki67>20% share the morphological and immunohistochemical features with WD-NEN Ki67≤20%, but have a worse prognosis, suggesting that this tumor group has to be specifically considered in future classifications and probably need new therapeutic regimes. <br>.

PMID: 30485860 [PubMed - as supplied by publisher]

Imprint cytology of strumal carcinoid of the ovary: A case report with immunocytochemical analysis.

Fetched: December 1st, 2018, 5:00am GMT

Imprint cytology of strumal carcinoid of the ovary: A case report with immunocytochemical analysis.

Diagn Cytopathol. 2018 Nov 28;:

Authors: Ishida M, Arimoto T, Sandoh K, Okano K, Ebisu Y, Ito H, Matsumoto M, Mizokami T, Kita M, Okada H, Tsuta K

Abstract
Strumal carcinoid is a rare ovarian tumor defined as carcinoid associated with struma ovarii. We report here the second cytological case of strumal carcinoid and performed immunocytochemical analysis for the first time. A 68-year-old Japanese female was found to have a solid tumor with small cystic components in the left ovary, and bilateral salpingo-oophorectomy was performed. The Papanicolaou smear of the imprint cytological specimen of the left ovarian tumor revealed presence of two distinct components. The first component included thyroid follicles, which was composed of flat sheets of polygonal epithelial cells without nuclear groove and intranuclear inclusion. The other component was composed of trabecular clusters of columnar cells containing round to slender nuclei with "salt and pepper" chromatin. Immunocytochemical analysis revealed that synaptophysin was expressed in the latter component. Therefore, a cytodiagnosis of strumal carcinoid was made. Histopathological analyses confirmed the diagnosis of strumal carcinoid. Albeit rare, carcinoid tumor occurs in the ovary, and the recognition of characteristic nuclear features and cellular arrangement leads to correct cytodiagnosis. Presence of struma ovarii component suggests an ovarian origin. Moreover, immunocytochemical analysis for neuroendocrine markers aids its differential diagnosis from granulosa cell tumor and carcinoma arising from struma ovarii.

PMID: 30485710 [PubMed - as supplied by publisher]

Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms.

Fetched: December 1st, 2018, 5:00am GMT

Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms.

Cancer Cytopathol. 2018 Nov 28;:

Authors: Sigel CS

Abstract
Two-thirds of neuroendocrine neoplasms arising in the human body originate from the gastrointestinal system or pancreas. Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous, comprising both well differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The clinical presentation, molecular characteristics, and behavior are distinct for NETs and NECs. Fine-needle aspiration is an important modality for the primary diagnosis and staging of these neoplasms and can provide information of prognostic and therapeutic significance. Our evolving understanding of neuroendocrine neoplasm biology has led to several iterations of classification. In this review, new concepts and issues most relevant to cytology diagnosis of gastroenteropancreatic neuroendocrine neoplasms are discussed, such as newer detection methods that aid in diagnosis and staging, recent changes in World Health Organization classification, practical issues related to grading these neoplasms on cytology, guidelines for diagnostic reporting, and panels of immunohistochemical stains for the diagnosis of metastasis. The current understanding of genetic and epigenetic events related to tumor development and potential applications for cytology also are presented as they relate to prognostication and recent therapeutic advances.

PMID: 30485690 [PubMed - as supplied by publisher]

Poorly Differentiated Small-Cell-Type Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review.

Fetched: December 1st, 2018, 5:00am GMT

Poorly Differentiated Small-Cell-Type Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review.

Case Rep Oncol. 2018 Sep-Dec;11(3):676-681

Authors: Kumar K, Ahmed R, Chukwunonso C, Tariq H, Niazi M, Makker J, Ihimoyan A

Abstract
Neuroendocrine cells are widespread throughout the body and can give rise of neuroendocrine tumors due to abnormal growth of the chromaffin cells. Neuroendocrine tumors divide into many subtypes based on tumor grade (Ki-67 index and mitotic count) and differentiation. These tumors can be further divided into secretory and nonsecretory types based on the production of peptide hormone by tumor cells. Poorly differentiated small-cell-type neuroendocrine tumors are one of the subtypes of neuroendocrine tumors. These tumors are less common; however, they tend to be locally invasive and aggressive in behavior with poor overall median survival. Treatment of the nonsecretory small-cell type is modeled to small-cell lung cancer with a regimen consisting of platinum-based chemotherapy and etoposide with variable response. Here, we present a case of poorly differentiated small-cell neuroendocrine tumor originating from the prostate.

PMID: 30483097 [PubMed]

High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study.

Fetched: December 1st, 2018, 5:00am GMT

High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study.

Oncologist. 2018 Nov 27;:

Authors: Alese OB, Jiang R, Shaib W, Wu C, Akce M, Behera M, El-Rayes BF

Abstract
BACKGROUND: High-grade neuroendocrine carcinomas are rare in the gastrointestinal tract. However, treatment patterns and outcomes have not been well described.
SUBJECTS, MATERIALS, AND METHODS: The National Cancer Database was analyzed. The primary objective was to describe the clinical outcomes and identify prognostic factors. Univariate and multivariate analyses were done to identify factors associated with patient outcome.
RESULTS: A total of 1,861 patients were identified between 2004 and 2013. The mean age was 63 years (standard deviation ±13). The majority of the patients (78.1%) were non-Hispanic whites. The most common primary sites were pancreas (pancreatic neuroendocrine tumor [PNET] = 19.4%), large intestine (18.1%), esophagus (17.8%), and rectum (15.5%). Stage at presentation was I (6.6%), II (10.5%), III (18%) and IV (64.6%). Only 1.6% of the patients had brain metastases. Surgical resection was the primary therapy in 27.9%, and their median overall survival (OS) was 13.3 months. Patients treated with palliative chemotherapy had a median OS of 11.2 months, compared with 1.7 months for untreated patients. The median OS for high-grade PNET was 6 months, compared with 9.9 months for other high-grade gastrointestinal neuroendocrine carcinomas (HG GI NEC). On univariable analysis, age < 65 years (hazard ratio [HR] 0.72; 0.66-0.8; p < .001) and treatment at an academic center (HR 0.88; 0.79-0.99; p < .034) were associated with improved survival. Multivariable analysis confirmed prognostic advantage of treatment at an academic center.
CONCLUSION: This is the largest series of HG GI NEC. Most patients present with metastatic disease, and overall survival remains poor. Treatment at an academic center, younger age, and use of chemotherapy were associated with improved survival. Multiagent chemotherapy was found to be associated with superior survival compared with single-agent chemotherapy, which was superior to no chemotherapy. Temporal sequences of chemotherapy, surgery, and radiation administration were not found to be associated with survival differences on multivariable analysis.
IMPLICATIONS FOR PRACTICE: Management of patients with high-grade gastrointestinal neuroendocrine carcinomas (HG GI NEC) is based on experience with small-cell lung cancer. In this retrospective review, most patients had advanced disease and pancreatic primary had worse outcomes. Treatment at an academic center, younger age, and use of chemotherapy are associated with improved survival. Patients with early-stage disease treated with resection alone had inferior outcomes compared with patients who received neoadjuvant or adjuvant therapy, suggesting that micrometastases contribute to poor surgical outcomes. The relatively high proportion of positive surgical margin favors downstaging with neoadjuvant therapy to improve resection and lower the risk of systemic recurrence.

PMID: 30482824 [PubMed - as supplied by publisher]

Corticotropin secreting pancreatic neuroendocrine tumour, a therapeutic management challenge. A presentation of 2 cases.

Fetched: December 1st, 2018, 5:00am GMT

Corticotropin secreting pancreatic neuroendocrine tumour, a therapeutic management challenge. A presentation of 2 cases.

Endocrinol Diabetes Nutr. 2018 Nov 24;:

Authors: Simó-Servat A, Peiró I, Villabona C

PMID: 30482522 [PubMed - as supplied by publisher]

Leptin in sperm analysis can be a new indicator.

Fetched: December 1st, 2018, 5:00am GMT

Leptin in sperm analysis can be a new indicator.

Acta Histochem. 2018 Oct 25;:

Authors: Önel T, Ayla S, Keskin İ, Parlayan C, Yiğitbaşı T, Kolbaşı B, Yelke TV, Ustabaş TŞ

Abstract
Purpose Radiotherapy, chemotherapy, various tumors and invasive surgery can result in ejaculatory dysfunction and testicular insufficiency. Sperm cryopreservation is the only method which can provide a baby for couples. Cryopreservation freezes tissues and cells, allowing them to be stored for future use by stopping all biological activities. Cryopreservation can cause some harmful changes in the structure and function of the sperm. Leptin molecule plays many roles in most biological processes including the satiety and cell renewal, proliferation, angiogenesis, modulation of energy expenditure and regulation of the neuroendocrine system. Leptin was also reported to be associated with spermatogenesis in several studies. Methods This study aims to use leptin molecule as a parameter for sperm motility and DNA fragmentation before and after the cryopreservation. In this study, semen samples were taken from 30 normospermic male volunteers. Each semen sample was examined for the same parameters before and after the cryopreservation. Samples were analyzed before and after cryopreservation in terms of sperm motility by morphological sperm analysis with spermac stain dye, DNA fragmentation by TUNEL assay, ultrastructural analysis with transmission electron microscopy (TEM), seminal leptin levels by ELISA method and reactive oxygen species (ROS) levels by colorimetric method. Results Decreased sperm motility, distribution of sperm morphology and increased DNA fragmentation were determined after cryopreservation. Similarly, seminal ROS and leptin levels were also increased significantly. There was a negative correlation between seminal leptin and sperm motility. Additionally, there was a positive correlation between seminal leptin and DNA fragmentation. Conclusion According to these results, leptin molecule can be used as a marker for sperm motility and DNA fragmentation before and after cryopreservation. We think that the results of this study can contribute to further studies in the clinical aspect.

PMID: 30482507 [PubMed - as supplied by publisher]

mTOR kinase inhibition reduces tissue factor expression and growth of pancreatic neuroendocrine tumors.

Fetched: November 27th, 2018, 5:00am GMT

mTOR kinase inhibition reduces tissue factor expression and growth of pancreatic neuroendocrine tumors.

J Thromb Haemost. 2018 Nov 25;:

Authors: Lewis CS, Elnakat Thomas H, Orr-Asman M, Green LC, Boody RE, Matiash K, Karve A, Hisada YM, Davis HW, Qi X, Mercer C, Lucas FV, Aronow BJ, Mackman N, Versteeg HH, Bogdanov VY

Abstract
BACKGROUND: Full-length tissue factor (flTF) and alternatively spliced TF (asTF) contribute to growth and spread of pancreatic ductal adenocarcinoma. It is unknown, however, if flTF and/or asTF contribute to pathobiology of pancreatic neuroendocrine tumors (pNET).
OBJECTIVE: To assess TF expression in pNET and the effects of mTOR complex 1/2 (mTORC1/2) inhibition on pNET growth.
METHODS: Human pNET specimens were immunostained for TF. Human pNET cell lines QGP1 and BON were evaluated for TF expression and responsiveness to mTOR inhibition. shRNA were used to knock down TF in BON. TF cofactor activity was assessed using a two-step FXa generation assay. TF promoter activity was assessed using transient transfection of human TF promoter-driven reporter constructs into cells. Mice bearing orthotopic BON tumors were treated with the mTORC1/2 ATP-site competitive inhibitor sapanisertib / MLN0128 (3 mg/kg, oral gavage) for 34 days.
RESULTS: Immunostaining of pNET tissue revealed flTF and asTF expression. BON and QGP1 expressed both TF isoforms, with BON exhibiting higher levels. shRNA directed against TF suppressed BON proliferation in vitro. Treatment of BON with sapanisertib inhibited mTOR signaling and suppressed TF levels. BON tumors grown in mice treated with sapanisertib had significantly less TF protein and co-factor activity, and were smaller compared to tumors grown in control mice.
CONCLUSIONS: TF isoforms are expressed in pNET. Sapanisertib suppresses TF mRNA and protein expression as well as TF co-factor activity in vitro and in vivo. Thus, further studies are warranted to evaluate the clinical utility of TF-suppressing mTORC1/2 inhibitor sapanisertib in pNET management. This article is protected by copyright. All rights reserved.

PMID: 30472780 [PubMed - as supplied by publisher]

Duodenal gastrointestinal stromal tumors appear similar to pancreatic neuroendocrine tumors: A case report.

Fetched: November 27th, 2018, 5:00am GMT

Duodenal gastrointestinal stromal tumors appear similar to pancreatic neuroendocrine tumors: A case report.

Int J Surg Case Rep. 2018 Nov 15;53:358-361

Authors: Futo Y, Saito S, Miyato H, Sadatomo A, Kaneko Y, Kono Y, Matsubara D, Horie H, Lefor AK, Sata N

Abstract
INTRODUCTION: Duodenal gastrointestinal tumors (GISTs) are rare. Duodenal GISTs and pancreatic neuroendocrine tumors (NETs) may appear similar on imaging studies. GISTs arising from the second or third portions of duodenum may be incorrectly diagnosed as pancreatic NETs.
PRESENTATION OF CASE: The patient is a 79-year-old man who was referred to our hospital with a history of tarry stools and loss of consciousness. Urgent upper digestive tract endoscopy revealed a bleeding submucosal duodenal lesion, which was controlled using endoscopic clips. Enhanced computed tomography scan showed a hyper-vascular mass 50 mm in diameter, at the pancreatic uncus. The patient underwent a pylorus-preserving pancreaticoduodenectomy. Histologically, the tumor was composed of spindle-shaped cells immunohistochemically positive for c-kit and CD34, and the lesion diagnosed as a duodenal GIST.
DISCUSSION: Duodenal GISTs often present with gastrointestinal bleeding, which can necessitate emergency surgery. Surgical resection with regional lymph node dissection is the optimal treatment for pancreatic NETs. In contrast, GISTs are generally treated with a minimal resection and without lymph node dissection. Thus, establishing the diagnosis is important in the management of these tumors. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is effective to establish the diagnosis of these lesions.
CONCLUSION: A tumor located in the pancreatic head or mesenteric side of the duodenum cannot always be diagnosed based on imaging, and is ideally diagnosed histologically to guide the extent of resection. While EUS-FNA can establish the diagnosis, the complications of this procedure must be considered.

PMID: 30472631 [PubMed - as supplied by publisher]

Optimization of Second Window Indocyanine Green for Intraoperative Near-Infrared Imaging of Thoracic Malignancy.

Fetched: November 26th, 2018, 5:00am GMT

Optimization of Second Window Indocyanine Green for Intraoperative Near-Infrared Imaging of Thoracic Malignancy.

J Am Coll Surg. 2018 Nov 21;:

Authors: Newton AD, Predina JD, Corbett CJ, Frenzel-Sulyok LG, Xia L, Petersson EJ, Tsourkas A, Nie S, Delikatny EJ, Singhal S

Abstract
BACKGROUND: Near-infrared (NIR) imaging using the second time window of indocyanine green (ICG) allows localization of pulmonary, pleural, and mediastinal malignancies during surgery. Based on empirical evidence, we hypothesized that different histological tumor types fluoresce optimally at different ICG doses.
STUDY DESIGN: Patients with thoracic tumors biopsy-proven or suspicious for malignancy were enrolled in an NIR imaging clinical trial. Patients received a range of ICG doses one day prior to surgery: 1 mg/kg (n=8), 2 mg/kg (n=8), 3 mg/kg (n=13), 4 mg/kg (n=8), and 5 mg/kg (n=8). Intraoperatively, NIR imaging was performed. The endpoint was to identify the highest tumor-to-background fluorescence ratio (TBR) for each tumor type at each dose. Final pathology confirmed tumor histology.
RESULTS: Of 45 patients, 41 had malignancies (18 non-small cell lung cancer (NSCLC), 3 pulmonary neuroendocrine tumors, 13 thoracic metastases, 3 thymoma, 3 mesothelioma). At doses of 4-5 mg/kg, the TBR from primary NSCLC versus other malignancies was no different (2.70 vs. 3.21, P=1.00). At doses of 1-3 mg/kg, the TBR was greater for the non-NSCLCs (3.19 vs. 1.49, P=0.0006). Background fluorescence from the heart or ribs was observed in 1/16 cases at 1-2 mg/kg, 5/13 cases at 3 mg/kg, and 14/16 cases at 4-5 mg/kg; this was a major determinant of dose optimization.
CONCLUSION: This is the first study to demonstrate that the optimal NIR contrast agent dose varies by tumor histology. Lower dose ICG (2-3 mg/kg) is superior for non-primary lung cancers, and high dose ICG (4-5 mg/kg) is superior for lung cancers. This will have major implications as more intraoperative imaging trials surface in other specialties, will significantly reduce costs, and may facilitate wider application.

PMID: 30471345 [PubMed - as supplied by publisher]

Permalink for 'Association between preoperative Vasostatin-1 and pathological features of aggressiveness in localized nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET).'

Association between preoperative Vasostatin-1 and pathological features of aggressiveness in localized nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET).

Fetched: November 26th, 2018, 5:00am GMT

Association between preoperative Vasostatin-1 and pathological features of aggressiveness in localized nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET).

Pancreatology. 2018 Nov 14;:

Authors: Andreasi V, Partelli S, Manzoni M, Muffatti F, Colombo B, Corti A, Falconi M

Abstract
BACKGROUND: A reliable and accessible biomarker for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET) is currently unavailable. Chromogranin A (CgA) represents the best-described neuroendocrine biomarker, but its accuracy is low. Vasostatin-1 (VS-1), a fragment derived from the cleavage of CgA, was recently investigated and found to be more accurate as tumor biomarker in a cohort of patients affected by mainly metastatic small intestinal NET.
METHODS: Patients submitted to surgery for sporadic localized NF-PanNET at San Raffaele Hospital were included. Preoperative plasma samples were prospectively collected. Circulating levels of total-CgA and VS-1 were retrospectively investigated by sandwich Enzyme-Linked ImmunoSorbent Assays.
RESULTS: Overall, 50 patients were included. VS-1 value (P=0.0001) was the only preoperatively retrievable factor independently associated with NF-PanNET size. No significant correlation between CgA and tumor diameter was found (P = 0.057). A VS-1 value of 0.39 nM was identified as the optimal VS-1 cut-off accurately associated with NF-PanNET larger than 4 cm. Patients with VS-1 > 0.39 nM had a significantly higher frequency of microvascular invasion (P = 0.005) and nodal metastasis (P = 0.027). Median VS-1 plasma level was significantly higher in the presence of microvascular invasion (P = 0.001) and nodal metastasis (P = 0.012). PPI assumption significantly increased total-CgA levels, but not those of VS-1 (P = 0.111).
CONCLUSIONS: In localized, non-metastatic NF-PanNET, VS-1 is strongly associated to tumor dimension and its plasma levels are significantly higher in the presence of microvascular invasion and nodal metastases; moreover, VS-1 value is not affected by the PPI use.

PMID: 30470614 [PubMed - as supplied by publisher]

Neuroendocrine tumors of the lung: A five-year retrospective experience of Egyptian NCI (2010-2014).

Fetched: November 26th, 2018, 5:00am GMT

Neuroendocrine tumors of the lung: A five-year retrospective experience of Egyptian NCI (2010-2014).

J Egypt Natl Canc Inst. 2018 Nov 20;:

Authors: Saber M, Ismail Y, Alieldin N, Loay I, El Zawahry M

Abstract
BACKGROUND: The spectrum of lung neuroendocrine tumors (NETs) encompasses low grade typical carcinoid (TC), intermediate grade atypical carcionid (AC) and high grade, both large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC), with extreme differences in management and survival.
OBJECTIVE: To study clinicopathologic and prognostic factors affecting survival of lung NETs.
PATIENTS AND METHODS: This is a retrospective study evaluating 35 patients with primary lung NETs treated at National Cancer Institute of Egypt (NCI-E) between January 2010 and December 2014. Pathological diagnosis depended on definite morphology and positivity to at least one of the neuroendocrine markers by immunohistochemistry.
RESULTS: The mean age of the patients was 53 ± 11.2 years with male predominance. Performance status (PS) I was encountered in 48.6%. SCLC was the prevalent histology in 68.6%, followed by LCNEC & TC in 20 & 11.4%, respectively. Curative surgery was employed in 100 & 57% of TC & LCNEC patients, respectively. Stage IV was anticipated in 87.5 & 43% of SCLC & LCNEC, respectively. For the entire cohort, the median event-free survival (EFS) and overall survival (OS) were 8.0 and 13.7 months, respectively, whereas the 3-year EFS and OS were 17.8 & 20%, respectively. SCLC patients showed significantly the worst OS compared to other NETs (p = 0.001). Patients who presented with stage IV and PS > I demonstrated significantly shorter OS than those with locoregional and PS I (p = 0.00001 &p = 0.002, respectively).
CONCLUSIONS: SCLC subtype, stage IV and initial PS > I are poor prognostic factors for lung NETs associated with shorter survival. This conclusion needs to be confirmed by larger studies.

PMID: 30470605 [PubMed - as supplied by publisher]

Elevated allostatic load in individuals presenting at psychiatric emergency services.

Fetched: November 26th, 2018, 5:00am GMT

Elevated allostatic load in individuals presenting at psychiatric emergency services.

J Psychosom Res. 2018 Dec;115:101-109

Authors: Juster RP, Sasseville M, Giguère CÉ, Consortium S, Lupien SJ

Abstract
OBJECTIVE: Individuals requiring psychiatric emergency services are often highly distressed and intoxicated. To provide an objective and comprehensive measure of their stress-related physiological dysregulations, we indexed allostatic load with 14 biomarkers collected within 24 h of patients' admission to the largest psychiatric hospital in the Canadian province of Quebec.
METHODS: This study (N = 278) combines data for emergency patients (n = 76; 65.8% women; M age = 44.97, SE = 1.6) and hospital workers who served as sex- and age-matched controls (n = 202; 70.8% women; M age = 40.10, SE = 0.83). Sex-specific allostatic load indices summarized neuroendocrine (cortisol), immune (tumor necrosis factor-α, interleukin-6, c-reactive protein), metabolic (insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, body mass index), and cardiovascular (heart rate, systolic and diastolic blood pressure) functioning. Well-validated questionnaires assessed substance (ab)use.
RESULTS: Individuals presenting at psychiatric emergency showed elevated allostatic load, drug abuse, and tobacco use compared to controls. Elevated allostatic load in emergency patients was driven by elevated cortisol, interleukin-6, systolic blood pressure, and heart rate; however, allostatic load was not explained by substance (ab)use or demographic variables. Sub-group analyses revealed that emergency patients primarily diagnosed with bipolar, depressive, or anxiety disorders showed higher allostatic load than those diagnosed with personality disorder(s).
CONCLUSIONS: This study demonstrates that individuals presenting at psychiatric emergency services show physiological dysregulations associated with chronic stress. Future research should explore the clinical utility of allostatic load in predicting comorbidities among psychiatric patients.

PMID: 30470308 [PubMed - in process]

Pituitary Disorders in Pregnancy.

Fetched: November 26th, 2018, 5:00am GMT

Pituitary Disorders in Pregnancy.

Neurol Clin. 2019 Feb;37(1):63-83

Authors: Woodmansee WW

Abstract
Pregnancy is associated with alterations in pituitary hormonal function and enlargement of the pituitary gland. Pituitary dysfunction diagnosis can be challenging during pregnancy due to known alterations in hormonal status. Pituitary disorders are relatively common; with advancements in medical care, more women with pituitary disorders are becoming pregnant. Management includes optimization of hormonal function and close monitoring for signs of tumor progression during pregnancy. Tumor-directed medical therapy is generally discontinued during pregnancy but can be reinitiated if there is evidence of tumor growth. Most women do not show aggressive tumor growth during pregnancy and can be managed conservatively until delivery.

PMID: 30470276 [PubMed - in process]

Permalink for 'Asynchronous tumour quadruplicity: rectosigmoid adenocarcinoma, renal cell carcinoma, prostate adenocarcinoma and neuroendocrine small-cell lung cancer - a case report.'

Asynchronous tumour quadruplicity: rectosigmoid adenocarcinoma, renal cell carcinoma, prostate adenocarcinoma and neuroendocrine small-cell lung cancer - a case report.

Fetched: November 26th, 2018, 5:00am GMT

Asynchronous tumour quadruplicity: rectosigmoid adenocarcinoma, renal cell carcinoma, prostate adenocarcinoma and neuroendocrine small-cell lung cancer - a case report.

Rozhl Chir. 2018;97(9):427-431

Authors: Adwan R, Prošvic P, Prošvicová J, Tomšová M

Abstract
INTRODUCTION: Multiple tumors belong to rare cancers. Almost all malignancies may occur in combination, the most common combination being gastrointestinal cancer with respiratory or urogenital tract cancer and with breast cancer in females.
CASE REPORT: In 1999, a 66-year-old patient was diagnosed with a rectosigmoid tumor histologically proven as adenocarcinoma. Rectosigmoid resection was performed, followed by adjuvant radiotherapy and the Mayo Clinic FU/FA chemotherapy regimen. Radical nephrectomy was performed in January 2005 due to right kidney tumor, histologically detected as clear cell carcinoma. In February 2006, the patient underwent bilateral pelvic lymphadenectomy for biopsy-verified adenocarcinoma of the prostate with PSA 20.8 ng/ml. Radical prostatectomy was performed in April 2006. Histology demonstrated moderately differentiated adenocarcinoma in both prostatic lobes classified as Gleason score 4 (1+3), without invasion into the capsule or seminal vesicles infiltration. In June 2016, a native X-ray of the lungs revealed a subpleural small dense node in the right upper pulmonary field. PET/CT of the trunk was also performed showing liver metastasis and pulmonary deposits, including enlargement of the mediastinal nodules. In October 2016, liver biopsy was taken and the serum level of neuron-specific enolase (NSE: 93 ng/ml) was measured. Histology demonstrated neuroendocrine carcinoma of the small cell type. In November 2016, palliative chemotherapy with carboplatin and etoposide administered once a month was initiated. After 4 chemotherapy cycles, no deposits on the liver were detected by sonography. A native X-ray image of the lungs still showed a 15mm deposit, but NSE levels returned to normal. In March 2017, treatment continued with palliative radiotherapy of the right lung, mediastinal lymphatic nodes and prophylactic radiotherapy of the skull was planned as a next step. In August 2017, the patient died due to renal function failure and deterioration of the general condition.
CONCLUSION: The patient worked in uranium mines and underwent radio-chemotherapy after the first malignancy - rectosigmoid tumor. Genetic examination was not performed. The patient died of therapeutic complications of the last malignancy. Our case report does not confirm findings described so far - a shortening interval between malignancies - but confirms their increasing aggressiveness. Key words: quadruplicity - rectosigmoid adenocarcinoma - renal-cell carcinoma - prostate adenocarcinoma - neuroendocrine small-cell lung cancer.

PMID: 30470124 [PubMed - in process]

Prenatal Programming of Neuroendocrine System Development by Lipopolysaccharide: Long-Term Effects.

Fetched: November 26th, 2018, 5:00am GMT

Prenatal Programming of Neuroendocrine System Development by Lipopolysaccharide: Long-Term Effects.

Int J Mol Sci. 2018 Nov 21;19(11):

Authors: Izvolskaia M, Sharova V, Zakharova L

Abstract
Various stress factors during critical periods of fetal development modulate the epigenetic mechanisms controlling specific genes, which can affect the structure and function of physiological systems. Maternal immune stress by bacterial infection simulated by lipopolysaccharide (LPS) in an experiment is considered to be a powerful programming factor of fetal development. Studies of the molecular mechanisms controlling the formation and functioning of physiological systems are in the pilot stage. LPSs are the most potent natural inflammation factors. LPS-induced increases in fetal levels of pro- and anti-inflammatory cytokines can affect brain development and have long-term effects on behavior and neuroendocrine functions. The degradation of serotonergic neurons induced by LPS in the fetus is attributed to the increased levels of interleukin (IL)-6 and tumor necrosis factor (TNFα) as well as to anxiety and depression in children. Dopamine deficiency causes dysthymia, learning disability, and Parkinson's disease. According to our data, an LPS-induced increase in the levels of IL-6, leukemia inhibitory factor (LIF), and monocyte chemotactic protein (MCP-1) in maternal and fetal rats during early pregnancy disturbs the development and functioning of gonadotropin-releasing hormone production and reproductive systems. It is important to note the high responsiveness of epigenetic developmental mechanisms to many regulatory factors, which offers opportunities to correct the defects.

PMID: 30469423 [PubMed - in process]

miR-137 inhibits melanoma cell proliferation through downregulation of GLO1.

Fetched: November 25th, 2018, 5:00am GMT

miR-137 inhibits melanoma cell proliferation through downregulation of GLO1.

Sci China Life Sci. 2018 05;61(5):541-549

Authors: Lv N, Hao S, Luo C, Abukiwan A, Hao Y, Gai F, Huang W, Huang L, Xiao X, Eichmüller SB, He D

Abstract
Late-stage melanoma is refractory to current therapies. MicroRNAs (miRNAs) can modulate many physiological and pathological processes of melanoma. Studies have demonstrated that miR-137 acts as a tumor suppressor by inhibiting the proliferation of melanoma cells through targeting multiple mRNAs. The glyoxalase system member glyoxalase 1 (GLO1) is the principal scavenging enzyme of methylglyoxal (MG), a toxic byproduct of glycolysis. Using 35S in vivo/vitro labelling analysis for dynamic proteomics (SiLAD), we found that miR-137 downregulated the expression of GLO1 in melanoma cells. Bioinformatics analysis predicted that GLO1 is a direct target of miR-137. This was validated by dual luciferase reporter assay. Quantitative RT-PCR (qRT-PCR) and western blot analysis indicated that miR-137 could decrease endogenous GLO1 expression. Furthermore, siRNA targeting of GLO1 mimicked inhibition of melanoma cell proliferation caused by miR-137 overexpression. Re-expression of GLO1 was able to restore miR-137-mediated suppression of melanoma cell proliferation. Therefore, these results suggest that miR-137 inhibits the proliferation of melanoma cells by targeting GLO1.

PMID: 29307109 [PubMed - indexed for MEDLINE]

Demonstrating Hickam's Dictum: Metachronous Pulmonary Adenocarcinoma, Carcinoid Tumor, and Histoplasmosis.

Fetched: November 25th, 2018, 5:00am GMT

Demonstrating Hickam's Dictum: Metachronous Pulmonary Adenocarcinoma, Carcinoid Tumor, and Histoplasmosis.

Am J Med. 2017 Nov;130(11):1265-1268

Authors: Icard B, Biscardi F, Sofi U

PMID: 28690073 [PubMed - indexed for MEDLINE]

Permalink for 'Manganese-Based Layered Double Hydroxide Nanoparticles as a T1 -MRI Contrast Agent with Ultrasensitive pH Response and High Relaxivity.'

Manganese-Based Layered Double Hydroxide Nanoparticles as a T1 -MRI Contrast Agent with Ultrasensitive pH Response and High Relaxivity.

Fetched: November 25th, 2018, 5:00am GMT

Manganese-Based Layered Double Hydroxide Nanoparticles as a T1 -MRI Contrast Agent with Ultrasensitive pH Response and High Relaxivity.

Adv Mater. 2017 Aug;29(29):

Authors: Li B, Gu Z, Kurniawan N, Chen W, Xu ZP

Abstract
Recently, Mn(II)-containing nanoparticles have been explored widely as an attractive alternative to Gd(III)-based T1 -weighted magnetic resonance imaging (MRI) contrast agents (CAs) for cancer diagnosis. However, as far as it is known, no Mn-based MRI CAs have been reported to sensitively respond to a very weakly acidic environment (pH 6.5-7.0, i.e., the pH range in a tumor microenvironment) with satisfactory imaging performance. Here, recently devised pH-ultrasensitive Mn-based layered double hydroxide (Mn-LDH) nanoparticles with superb longitudinal relaxivity (9.48 mm-1 s-1 at pH 5.0 and 6.82 mm-1 s-1 at pH 7.0 vs 1.16 mm-1 s-1 at pH 7.4) are reported, which may result from the unique microstructure of Mn ions in Mn-LDH, as demonstrated by extended X-ray absorption fine structure. Further in vivo imaging reveals that Mn-LDH nanoparticles show clear MR imaging for tumor tissues in mice for 2 d post intravenous injection. Thus, this novel Mn-doped LDH nanomaterial, together with already demonstrated capacity for drug and gene delivery, is a very potential theranostic agent for cancer diagnosis and treatment.

PMID: 28585312 [PubMed - indexed for MEDLINE]

A Diagnostic Dilemma in a Patient with Polyarthritis.

Fetched: November 25th, 2018, 5:00am GMT

A Diagnostic Dilemma in a Patient with Polyarthritis.

Am J Med. 2017 Nov;130(11):e497-e498

Authors: Rao P, Coffman N, Ferreira JP

PMID: 28545884 [PubMed - indexed for MEDLINE]

Permalink for 'HuC/D expression in small round cell tumors and neuroendocrine tumors: a useful tool for distinguishing neuroblastoma from childhood small round cell tumors.'

HuC/D expression in small round cell tumors and neuroendocrine tumors: a useful tool for distinguishing neuroblastoma from childhood small round cell tumors.

Fetched: November 25th, 2018, 5:00am GMT

HuC/D expression in small round cell tumors and neuroendocrine tumors: a useful tool for distinguishing neuroblastoma from childhood small round cell tumors.

Hum Pathol. 2018 Nov 20;:

Authors: Takemoto J, Kuda M, Kohashi K, Yamada Y, Koga Y, Kinoshita I, Souzaki R, Taguchi T, Oda Y

Abstract
The RNA-binding protein HuC/D displays a neuron-specific expression and is involved in neuronal differentiation and the maintenance of the nervous system. Here we investigated the diagnostic value of HuC/D in neuroblastomas. We evaluated 85 neuroblastic tumors: 81 neuroblastomas; three ganglioneuroblastomas, intermixed; one ganglioneuroma, maturing, and 101 other tumors consisting of 34 Ewing sarcomas, 14 nephroblastomas, 11 rhabdomyosarcomas, 15 pulmonary small cell carcinomas, 18 pancreatic neuroendocrine tumors, and nine pheochromocytomas. Immunohistochemistry for HuC/D, PHOX2B, and tyrosine hydroxylase was performed. The immunoreactivity for HuC/D was semi-quantified using the total score (TS, range: 0-8). HuC/D positivity was defined as a TS ≥6. The TS of the neuroblastic tumors (mean TS, 7.94) was significantly higher than those of the other small round cell tumors and neuroendocrine tumors (P<.001) except for the pheochromocytomas (mean TS, 6.89; P=.074). HuC/D was positive in all 85 neuroblastic tumors, one (2.9%) Ewing sarcoma, one (6.7%) pulmonary small cell carcinoma, and eight (89%) pheochromocytomas. PHOX2B was positive in all of the neuroblastic tumors and pheochromocytomas. Tyrosine hydroxylase was positive in 80 (94%) neuroblastic tumors, one (9.1%) rhabdomyosarcoma, and all of the pheochromocytomas. Therefore, HuC/D serves as a highly sensitive diagnostic marker to distinguish neuroblastomas from other small round cell tumors. The combination of HuC/D and PHOX2B staining may be valuable for the diagnosis of neuroblastic tumors, especially in the assessment of small sections. HuC/D expression in tumors may be related to catecholamine production or a neural crest-derived cell origin.

PMID: 30468801 [PubMed - as supplied by publisher]

Robotic resection of the uncinate process of the pancreas.

Fetched: November 25th, 2018, 5:00am GMT

Robotic resection of the uncinate process of the pancreas.

J Robot Surg. 2018 Nov 23;:

Authors: Machado MAC, Surjan R, Basseres T, Makdissi F

Abstract
Since the development of the robotic platform, the number of robotic-assisted surgeries has significantly increased. Robotic surgery has gained growing acceptance in recent years, expanding to pancreatic resection. Here, we report a total robotic resection of the uncinate process of the pancreas performed in a patient with a cystic neuroendocrine tumor. To our knowledge, this is the first report of a robotic resection of the uncinate process of the pancreas. A 46-year-old man with no specific medical history was diagnosed with a neuroendocrine tumor after undergoing routine imaging. Biopsy guided by echoendoscopy revealed a well-differentiated neuroendocrine tumor. We decided to perform a robotic resection of the uncinate process of the pancreas after obtaining informed consent for the procedure. According to preoperative echoendoscopy and magnetic resonance imaging, there was a safe margin between the neoplasm and the main pancreatic duct. The technique uses five ports. The duodenum is fully mobilized, and Kocher maneuver is carefully performed. The uncinate process of the pancreas is then identified. The resection of the uncinate process begins with the division of small arterial branches from the inferior pancreaticoduodenal artery in its inferior portion, followed by control of venous tributaries to the superior mesenteric vein. Intraoperative localization of the ampulla of Vater is performed using indocyanine green enhanced fluorescence, thus defining the superior margin of the uncinate process. The pancreatic division is made about 5 mm below its upper margin for safety. Surgical specimen is then retrieved through the umbilical port inside a plastic bag. The raw pancreatic area is covered with hemostatic tissue and drained. The total operation time was 215 min. The docking time was 8 min and console time was 180 min. Blood loss was minimum, estimated at less than 50 mL. The postoperative period was uneventful, except for hyperamylasemia in the drain fluid. The patient was discharged on the 3rd postoperative day. The final pathological report confirmed well-differentiated pancreatic neuroendocrine tumor. Robotic resection of the uncinate process of the pancreas is safe and feasible, providing parenchymal conservation in a minimally invasive setting. Robotic resection should be considered for patients suffering from low-grade pancreatic neoplasms located in this part of the pancreas.

PMID: 30467703 [PubMed - as supplied by publisher]

Comparing Kadish, TNM, and the modified Dulguerov staging systems for esthesioneuroblastoma.

Fetched: November 24th, 2018, 5:00am GMT

Comparing Kadish, TNM, and the modified Dulguerov staging systems for esthesioneuroblastoma.

J Surg Oncol. 2018 Nov 22;:

Authors: Joshi RR, Husain Q, Roman BR, Cracchiolo J, Yu Y, Tsai J, Kang J, McBride S, Lee NY, Morris L, Ganly I, Tabar V, Cohen MA

Abstract
BACKGROUND: Esthesioneuroblastoma (ENB) is a rare neuroendocrine tumor. The purpose of this study was to compare the Kadish, tumor-node-metastasis (TNM), and Dulguerov's modified TNM staging in order to determine the impact of the stage on primary surgical treatment selection, margin status, and survival.
METHODS: The National Cancer Database (NCDB) was used to identify patients diagnosed with ENB between 2004 to 2015. Patients were excluded based on the ability to properly stage their disease as well as the availability of treatment data.
RESULTS: Eight-hundred eighty-three patients had sufficient data for analysis. On multivariate analysis, age and government insurance were associated with primary surgical treatment, whereas tumor stage, gender, race, hospital type and volume, and comorbidity score were not. Age, charlson-deyo comorbidity (CDCC) score, hospital volume, and nodal status were found to be predictors of survival. Multivariate-analysis controlling for stage failed to demonstrate clear survival differences between staging in both TNM and Kadish systems. T-stage and the presence of regional nodal metastasis were associated with an increased risk of positive margins on multivariate analysis.
CONCLUSION: Although primary surgical management and positive margins can be predicted by certain patient and tumor factors, clinical staging systems for ENB poorly predict prognosis over a 10-year horizon.

PMID: 30466166 [PubMed - as supplied by publisher]

Extrahepatic Neuroendocrine Tumor Causing Biliary Obstruction.

Fetched: November 24th, 2018, 5:00am GMT

Extrahepatic Neuroendocrine Tumor Causing Biliary Obstruction.

J Gastrointest Surg. 2018 Nov 21;:

Authors: Rehfuss JP, Thomas RM

Abstract

PMID: 30465186 [PubMed - as supplied by publisher]

Chilean Registry for Neuroendocrine Tumors: A Latin American Perspective.

Fetched: November 24th, 2018, 5:00am GMT

Chilean Registry for Neuroendocrine Tumors: A Latin American Perspective.

Horm Cancer. 2018 Nov 22;:

Authors: Pinto MP, Muñoz Medel M, Carrillo D, Retamal IN, Bravo ML, Valenzuela Y, Nervi B, Sánchez C, Galindo H, Ibañez C, Peña J, Balmaceda C, Madrid J, Briones J, Torres J, Nilo F, Guarda FJ, Quintana JC, Orellana P, Mondaca S, Acevedo F, Vicentini D, Cordova-Delgado M, Owen GI, Garrido M

Abstract
Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.

PMID: 30465145 [PubMed - as supplied by publisher]

Permalink for 'A systematic review and meta-analysis of gastrointestinal events associated with nonoperative therapies for neuroendocrine tumors.'

A systematic review and meta-analysis of gastrointestinal events associated with nonoperative therapies for neuroendocrine tumors.

Fetched: November 24th, 2018, 5:00am GMT

A systematic review and meta-analysis of gastrointestinal events associated with nonoperative therapies for neuroendocrine tumors.

Onco Targets Ther. 2018;11:7655-7668

Authors: Wu Q, Chen B, Yan G, Yang Z, Xiong L, He J

Abstract
The risk of gastrointestinal (GI) events induced by nonoperative therapies in patients with neuroendocrine tumors (NETs) is unclear. Nonoperative therapies include somatostatin analogs, molecular targeted agents, cytotoxic chemotherapy, interferon-α, and peptide receptor radionuclide therapy. We undertook an up-to-date meta-analysis to determine the incidence and relative risks (RRs) of GI events in NET patients treated with these therapies. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched to identify relevant trials. Eligible trials were selected according to the PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random- and fixed-effects models. We included 2,890 patients from 17 randomized controlled trials in this meta-analysis. The experimental treatments led to increased incidence and risks of GI events compared to the control treatments (P<0.05). Diarrhea was the most common GI event. The experimental treatments were associated with increased risks of high-grade nausea (RR 2.36; 95% CI 1.05-5.25; P<0.01) and vomiting (RR 1.89; 95% CI 1.04-3.44; P<0.05). In regard to specific therapy regimens, everolimus led to increased risks of diarrhea (RR 2.97; 95% CI 1.83-4.83; P<0.05), vomiting (RR 2.19; 95% CI 1.38-3.48; P<0.05), and anorexia (RR 3.20; 95% CI 1.69-6.06; P<0.05), whereas VEGFR inhibitors led to increased risk of diarrhea (RR 2.12; 95% CI 1.39-3.25; P<0.05). Additionally, GI NETs led to higher risk of GI events than pancreatic NETs. Thus, nonoperative therapies are associated with increased risks of GI events in NET patients, and rigorous management is warranted to minimize the adverse impact on treatment outcomes and to improve quality of life.

PMID: 30464514 [PubMed]

Integrative epigenetic taxonomy of primary prostate cancer.

Fetched: November 24th, 2018, 5:00am GMT

Integrative epigenetic taxonomy of primary prostate cancer.

Nat Commun. 2018 Nov 21;9(1):4900

Authors: Stelloo S, Nevedomskaya E, Kim Y, Schuurman K, Valle-Encinas E, Lobo J, Krijgsman O, Peeper DS, Chang SL, Feng FY, Wessels LFA, Henrique R, Jerónimo C, Bergman AM, Zwart W

Abstract
The Androgen Receptor (AR) is the key-driving transcription factor in prostate cancer, tightly controlled by epigenetic regulation. To date, most epigenetic profiling has been performed in cell lines or limited tissue samples. Here, to comprehensively study the epigenetic landscape, we perform RNA-seq with ChIP-seq for AR and histone modification marks (H3K27ac, H3K4me3, H3K27me3) in 100 primary prostate carcinomas. Integrative molecular subtyping of the five data streams revealed three major subtypes of which two were clearly TMPRSS2-ERG dictated. Importantly, we identify a third subtype with low chromatin binding and activity of AR, but with high activity of FGF and WNT signaling. While positive for neuroendocrine-hallmark genes, these tumors were copy number-neutral with low mutational burden, significantly depleted for genes characteristic of poor-outcome associated luminal B-subtype. We present a unique resource on transcriptional and epigenetic control in prostate cancer, revealing tight control of gene regulation differentially dictated by AR over three subtypes.

PMID: 30464211 [PubMed - in process]

Tumor lysis syndrome: a rare, but serious complication of radioligand therapies.

Fetched: November 24th, 2018, 5:00am GMT

Tumor lysis syndrome: a rare, but serious complication of radioligand therapies.

J Nucl Med. 2018 Nov 21;:

Authors: Huang K, Brenner W, Prasad V

Abstract
Radioligand therapy (RLT) is considered a safe treatment for patients with metastasized neuroendocrine tumors (NET) and prostate cancer (PC), and the occurrence of tumor lysis syndrome (TLS) with 177Lutetium (177Lu)-labeled peptides has not been reported so far. We retrospectively screened our patients' database for TLS after RLT in NET and PC. Methods: The database was searched for patients receiving RLT with 177Lu-DOTATATE, -DOTATOC or -PSMA and showing laboratory or clinical abnormalities typical for TLS within 7 days after start of treatment. Results: 205 patients (539 cycles) were screened; 4 patients developed TLS with clinical symptoms and characteristic changes of laboratory parameters, which normalized after appropriate treatment. Follow-up revealed partial remission (n = 2), mixed response (n = 1) and progressive disease (n = 1). Conclusion: Clinical TLS is a rare, but definite complication of RLT suggesting patient monitoring for TLS as mandatory.

PMID: 30464038 [PubMed - as supplied by publisher]

Neutrophil Lymphocyte Ratio and Transarterial Chemoembolization in Neuroendocrine Tumor Metastases.

Fetched: November 24th, 2018, 5:00am GMT

Neutrophil Lymphocyte Ratio and Transarterial Chemoembolization in Neuroendocrine Tumor Metastases.

J Surg Res. 2018 Dec;232:369-375

Authors: McDermott SM, Saunders ND, Schneider EB, Strosberg D, Onesti J, Dillhoff M, Schmidt CR, Shirley LA

Abstract
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been shown to be predictive of outcomes in various cancers, including neuroendocrine tumors (NETs), and cancer-related treatments, including transarterial chemoembolization (TACE). We hypothesized that NLR could be predictive of response to TACE in patients with metastatic NET.
METHODS: We reviewed 262 patients who underwent TACE for metastatic NET at a single tertiary medical center from 2000 to 2016. NLR was calculated from blood work drawn 1 d before TACE, as well as 1 d, 1 wk, and 6 mo after treatment.
RESULTS: The median post-TACE overall survival (OS) of the entire cohort was 30.1 mo. Median OS of patients with a pre-TACE NLR ≤ 4 was 33.3 mo versus 21.1 mo for patients with a pre-TACE NLR >4 (P = 0.005). At 6 mo, the median OS for patients with post-TACE NLR > pre-TACE NLR was 21.4 mo versus 25.8 mo for patients with post-TACE NLR ≤ pre-TACE NLR (P = 0.007). On multivariate analysis, both pre-TACE NLR and 6-mo post-TACE NLR were independent predictors of survival. NLR values from 1-d and 1-wk post-TACE did not correlate with outcome.
CONCLUSIONS: An elevated NLR pre-TACE and an NLR that has not returned to its pre-TACE value several months after TACE correlate with outcomes in patients with NET and liver metastases. This value can easily be calculated from laboratory results routinely obtained as part of preprocedural and postprocedural care, potential treatment strategies.

PMID: 30463743 [PubMed - in process]

Permalink for 'Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A Digestive Endoscopy Society of Tawian (DEST) multicenter study: Erratum.'

Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A Digestive Endoscopy Society of Tawian (DEST) multicenter study: Erratum.

Fetched: November 23rd, 2018, 5:00am GMT

Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A Digestive Endoscopy Society of Tawian (DEST) multicenter study: Erratum.

Medicine (Baltimore). 2018 Nov;97(47):e13472

Authors:

PMID: 30461660 [PubMed - in process]

Metastatic thymic carcinoid responds to chemoradiation and octreotide: A case report.

Fetched: November 23rd, 2018, 5:00am GMT

Metastatic thymic carcinoid responds to chemoradiation and octreotide: A case report.

Medicine (Baltimore). 2018 Nov;97(47):e13286

Authors: Mei Z, Wang H, Ren S, Wei J, Gu Y

Abstract
RATIONALE: Thymic carcinoids are a rare type of malignant neuroendocrine tumors which have a poor prognosis due to their distant metastasis, invasive behaviour, and postoperative recurrence. Surgical resection is still the fundamental mode for treating thymic carcinoids. Here, we report the rapid shrinkage of an atypical thymic carcinoid with multiple metastases following chemoradiation plus octreotide as a first-line therapy PATIENT CONCERNS:: A 39-year-old Chinese man presented with chest tightness, dyspnea with a history of lumbago and untreated malignant thymoma.
DIAGNOSIS: Thoracic computed tomography (CT) scan revealed an anterior mediastinal mass with pulmonary and multiple bone metastases as well as bilateral pleural and pericardial effusions. Percutaneous needle biopsy was performed on the mediastinal mass and the pathological diagnosis was neuroendocrine carcinoma of moderately differentiation (atypical carcinoid) INTERVENTIONS:: The tumor was considered unresectable because of extensive invasion into the lung and various bones. The patient was started on paclitaxel and oxaliplatin per 21 days for 4 cycles, and on 20 mg of depot formulation of octreotide once per 21 days. After 2 cycles of chemotherapy, the patient received concurrently mediastinal radiotherapy (39.6 Gy × 22 fractions).
OUTCOMES: A follow-up CT of the chest at the completion of his fourth chemotherapy regimen demonstrated, approximately 22% of tumor shrinkage. There were no signs of disease progression but the patient refused further chemoradiation treatment. The patient received monthly treatment of octreotide and zoledronate and his progression-free survival reached 18 months. Due to uncontrollable disease progression, the patient expired.
LESSONS: Early diagnosis and radical surgery of thymic carcinoid are very important. However, radiotherapy (combined/noncombined chemotherapy) must be considered if radical resection is not performed. We believe that further study of chemoradiation and octreotide with the palliative intent of preparing tumors for shrinkage is warranted as a strategy to improve curative management of neuroendocrine tumors.

PMID: 30461637 [PubMed - in process]

Diagnostic challenges and good treatment outcomes in pediatric paraganglioma of the abdomen: A case report.

Fetched: November 23rd, 2018, 5:00am GMT

Diagnostic challenges and good treatment outcomes in pediatric paraganglioma of the abdomen: A case report.

Medicine (Baltimore). 2018 Nov;97(47):e13268

Authors: Cui Q, Lu J, Zhang C, Tan S

Abstract
RATIONALE: Paraganglioma is a catecholamine-producing neuroendocrine tumor. Management of paraganglioma including its diagnosis is difficult, because it has no characteristic symptoms and many diseases can manifest as headache and high blood pressure. Herein, we report a rare case of paraganglioma of the abdomen with headache and initial normal blood pressure.
PATIENT CONCERNS: A 9-year-old Chinese girl was hospitalized because of intermittent headache persisting for more than 9 months and recurrent headache for 15 days, accompanied by weight loss, impaired heat tolerance, and otherwise normal blood pressure.
DIAGNOSES: We eventually diagnosed paraganglioma.
INTERVENTIONS: Her paroxysmal hypertension subsided over 1 month after surgical removal of the tumor.
LESSONS: Intermittent headache and normal hypertension as the initial symptoms of paraganglioma can easily lead to misdiagnosis as another disease (e.g., renal artery stenosis, primary hyperaldosteronism, Takayasu's arteritis), and its differential diagnosis is difficult. When a patient presents with intermittent hypertension, clinicians should consider a diagnosis of paraganglioma. The comprehensive use of ultrasonography, computed tomography (including enhanced computed tomography and 3D reconstruction), magnetic resonance imaging, and plasma catecholamine measurement can aid the diagnosis of paraganglioma.

PMID: 30461634 [PubMed - in process]

Permalink for 'Smear cytological features of large cell neuroendocrine carcinoma of the uterine cervix in pregnancy: A case report and review of the literature.'

Smear cytological features of large cell neuroendocrine carcinoma of the uterine cervix in pregnancy: A case report and review of the literature.

Fetched: November 23rd, 2018, 5:00am GMT

Smear cytological features of large cell neuroendocrine carcinoma of the uterine cervix in pregnancy: A case report and review of the literature.

Diagn Cytopathol. 2018 Nov 21;:

Authors: Erdem BE, Çiğdem V, Şener G, Bahar M, Kursat YD, İzzet Y

Abstract
Large-cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare aggressive tumor. The examination of a cervicovaginal smear from a 31-year-old patient diagnosed with LCNEC after a cervical polypectomy during the 32nd week of pregnancy was carried out. The observed atypical cells had large cytoplasm, increased nucleus: cytoplasm ratio with the nucleus containing coarse, dispersed chromatin, and were arranged in a pseudorosette formation, which all confirmed the diagnosis. In addition, adenocarcinoma in situ (AIS) was determined in the histopathological examination of the subsequent hysterectomy material. Given the rarity of this condition, we present and discuss the case herein.

PMID: 30461217 [PubMed - as supplied by publisher]

Evidence of proliferative activity in human Merkel cells: implications in the histogenesis of Merkel cell carcinoma.

Fetched: November 23rd, 2018, 5:00am GMT

Evidence of proliferative activity in human Merkel cells: implications in the histogenesis of Merkel cell carcinoma.

Arch Dermatol Res. 2018 Nov 20;:

Authors: Narisawa Y, Inoue T, Nagase K

PMID: 30460510 [PubMed - as supplied by publisher]

Seneca Valley Virus Exploits TEM8, a Collagen Receptor Implicated in Tumor Growth.

Fetched: November 23rd, 2018, 5:00am GMT

Seneca Valley Virus Exploits TEM8, a Collagen Receptor Implicated in Tumor Growth.

Front Oncol. 2018;8:506

Authors: Evans DJ, Wasinger AM, Brey RN, Dunleavey JM, St Croix B, Bann JG

Abstract
Recent studies reveal that Seneca Valley Virus (SVV) exploits tumor endothelial marker 8 (TEM8) for cellular entry, the same surface receptor pirated by bacterial-derived anthrax toxin. This observation is particularly significant as SVV is a known oncolytic virus which selectively infects and kills tumor cells, particularly those of neuroendocrine origin. TEM8 is a transmembrane glycoprotein that is preferentially upregulated in some tumor cell and tumor-associated stromal cell populations. Both TEM8 and SVV have been evaluated for targeting of tumors of multiple origins, but the connection between the two was previously unknown. Here, we review currently understood interactions between TEM8 and SVV, anthrax protective antigen (PA), and collagen VI, a native binding partner of TEM8, with an emphasis on potential therapeutic directions moving forward.

PMID: 30460197 [PubMed]

Permalink for 'Anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease, successfully treated with modified FOLFOX6: a case report.'

Anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease, successfully treated with modified FOLFOX6: a case report.

Fetched: November 23rd, 2018, 5:00am GMT

Anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease, successfully treated with modified FOLFOX6: a case report.

BMC Cancer. 2018 Nov 20;18(1):1142

Authors: Yamaura M, Yamada T, Watanabe R, Kawai H, Hirose S, Tajima H, Sato M, Uchida Y, Suganuma D, Yamamoto Y, Moriwaki T, Hyodo I

Abstract
BACKGROUND: Anal canal cancer occasionally accompanies extramammary Paget disease. Although most of them are squamous cell carcinoma, anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease has never been reported.
CASE PRESENTATION: Here, we report a 76-year-old man presented with pruritus in the perianal area. Investigation revealed a fist-sized perianal erythema, diffuse liver tumors, and right inguinal lymph node swelling. Pathological examination of biopsies from the erythema suggested secondary extramammary Paget disease with positive cytokeratin-7 and -20 expressions and negative GCDFP-15 expression. The anal canal tumor was confirmed by digital examination and endoscopy. Biopsies from the anal canal tumor, swollen lymph node, and Paget lesion all showed poorly differentiated adenocarcinoma with neuroendocrine features expressing synaptophysin and chromogranin A. Serum CEA and NSE levels were high, 809.4 ng/ml and 85.8 ng/ml, respectively. After chemotherapy with modified FOLFOX6 for 2 months, the Paget lesion disappeared, and the primary anal canal tumor and liver metastases shrunk remarkably. Serum CEA and NSE levels decreased promptly to within normal ranges.
CONCLUSIONS: This is a clinically significant case, as it reveals novel pathological features about anal canal cancer with secondary Paget disease and successfully treated with modified FOLFOX6. Careful pathological investigation and appropriate treatment choice are needed for this rare cancer.

PMID: 30458812 [PubMed - in process]

Immune checkpoint inhibitors of CTLA4 and PD-1 for malignant melanoma arising in ovarian cystic teratoma: A case report.

Fetched: November 23rd, 2018, 5:00am GMT

Immune checkpoint inhibitors of CTLA4 and PD-1 for malignant melanoma arising in ovarian cystic teratoma: A case report.

Medicine (Baltimore). 2018 Oct;97(43):e12937

Authors: Yano M, Asami Y, Nishikawa T, Yoshida S, Kamada K, Katoh T, Teramoto Y, Nakamura Y, Yasuda M

Abstract
RATIONALE: Malignant melanoma (MM) arising in ovarian cystic teratoma (OCT) is a rare disease with poor prognosis. Recently, immune checkpoint inhibitors of cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed death 1 (PD-1) have shown promising results in MM. Herein we report a case of MM arising in OCT.
PATIENT CONCERNS: A 63-year-old Japanese primigravida had lower abdominal pain. Magnetic resonance imaging revealed the presence of an 85-mm mass at the right ovary.
DIAGNOSES: The patient underwent right salpingo-oophorectomy for right ovarian tumor, and histopathological examinations revealed MM arising in OCT. On immunohistochemical analysis, the tumor cells were positive for HMB-45, Melan A, and S-100 protein, and negative for programmed death-ligand 1 (PD-L1). BRAF gene mutations were not detected by the Real-Time PCR. Two months after surgery, liver metastasis was detected.
INTERVENTIONS: The patient underwent immune checkpoint inhibitors of CTLA4 (ipilimumab) and PD-1 (pembrolizumab and nivolumab). She had interstitial pneumonia associated with ipilimumab, but she safely underwent the immune checkpoint inhibitors therapy along with oral prednisolone. Pembrolizumab, ipilimumab, and nivolumab therapies had poor effect on the tumor.
OUTCOMES: Now, the present case has had tumor-bearing survival for 14 months since the initial diagnosis and 12 months since the detection of liver metastasis.
LESSONS: This is the first case of MM arising in OCT treated by immune checkpoint inhibitors, with information of PD-L1 immunohistochemical expression and adverse events. The present case is the longest survivor following the detection of recurrence among all the previous reports. The long survival and slow-growing tumor in the present case may be associated with no PD-L1 expressions.

PMID: 30412106 [PubMed - indexed for MEDLINE]

Paraganglioma with a very rare presentation.

Fetched: November 23rd, 2018, 5:00am GMT

Paraganglioma with a very rare presentation.

Indian J Pathol Microbiol. 2018 Jul-Sep;61(3):404-406

Authors: Khare M, Gupta MK, Sharma UB, Garg KM

Abstract
Paragangliomas (PGLs) are rare tumors of neural crest origin, with a malignancy rate of approximately 10% and a 5-year survival rate of <50%. We present a case of malignant PGL arising from the porta hepatis with metastasis to the portal lymph node and bilateral ovaries. PGLs arising from the porta hepatis are very rare. As per our knowledge, only three cases of hepatic duct PGL have been reported. It is important to detect it earlier because the treatment modality and prognosis of benign and malignant PGL differs and defines the prognosis of the patient.

PMID: 30004066 [PubMed - indexed for MEDLINE]

[Schwannoma of the ethmoid sinus in children: a case report].

Fetched: November 23rd, 2018, 5:00am GMT

[Schwannoma of the ethmoid sinus in children: a case report].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Nov 05;31(21):1693-1694

Authors: Chen JD, Liu P, Sun MX, Song LM, Song L, Zhang LL, Lin J

Abstract
A ten years old male patient，the main symptom was prsented as the left nasal obstruction, repeated hemorrhage with hyposmia. Large translucent neoplasm can be seen in the left side of the nasal cavity. CT and MRI of the nasal sinus showed that the soft tissue density shadow in the left side of the ethmoid sinus and the surrounding bone with no damage. He was treated with nasal endoscopic surgery. Postoperative pathology showed schwannoma. The tumor recurred three years later, and the patient underwent nasal endoscopic surgery again. In the literature we reviewed the case to analyze the reasons of recurrence.

PMID: 29798131 [PubMed - indexed for MEDLINE]

Inhibition of cancer stem cell like cells by a synthetic retinoid.

Fetched: November 23rd, 2018, 5:00am GMT

Inhibition of cancer stem cell like cells by a synthetic retinoid.

Nat Commun. 2018 04 11;9(1):1406

Authors: Chen J, Cao X, An Q, Zhang Y, Li K, Yao W, Shi F, Pan Y, Jia Q, Zhou W, Yang F, Wei F, Wang N, Yu B

Abstract
Developing novel drugs that can abrogate the growth and metastasis of malignant tumors is a major challenge for cancer researchers. Here we describe a novel synthetic retinoid, namely WYC-209, which inhibits proliferation of malignant murine melanoma tumor-repopulating cells (TRCs), known to resist conventional drug treatment, with an IC50 of 0.19 μM in a dose-dependent manner. WYC-209 also inhibits proliferation of TRCs of human melanoma, lung cancer, ovarian cancer, and breast cancer in culture. Interestingly, the treated TRCs fail to resume growth even after the drug washout. Importantly, the molecule abrogates 87.5% of lung metastases of melanoma TRCs in immune-competent wild-type C57BL/6 mice at 0.22 mg kg-1 without showing apparent toxicity. Pretreating the melanoma TRCs with retinoic acid receptor (RAR) antagonists or with RAR siRNAs blocks or reduces the inhibitory effect of the molecule, suggesting that the target of the molecule is RAR. WYC-209 induces TRC apoptosis and pretreating the TRCs with caspase 3 inhibitor or depleting caspase 3 with siRNAs substantially rescues growth of TRCs from WYC-209 inhibition, suggesting that WYC-209 induces TRCs apoptosis primarily via the caspase 3 pathway. Our findings demonstrate the promise of the new retinoid WYC-209 in treating malignant melanoma tumors with high efficacy and little toxicity.

PMID: 29643385 [PubMed - indexed for MEDLINE]

An Epigenetic Switch: From Senescent Melanocytes to Malignant Melanoma (and Back).

Fetched: November 23rd, 2018, 5:00am GMT

An Epigenetic Switch: From Senescent Melanocytes to Malignant Melanoma (and Back).

Cancer Cell. 2018 02 12;33(2):162-163

Authors: Wagner V, Gil J

Abstract
Oncogene-induced senescence is an important barrier during melanomagenesis. In this issue of Cancer Cell, Yu et al. show how elevated expression of structurally unrelated H3K9 demethylases disables senescence and constitutes a liability that can be exploited to restore senescence in melanoma by pharmacological inhibition of these epigenetic regulators.

PMID: 29438692 [PubMed - indexed for MEDLINE]

[Tongue schwannoma：a case report].

Fetched: November 23rd, 2018, 5:00am GMT

[Tongue schwannoma：a case report].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Mar 20;31(6):480-481

Authors: Ren X, Li DJ, Zhu W

Abstract
Neurilemmomas, or called schwannomas, are tumors originating from schwann cells of the nerve sheath.With integrate capsules,the slow growing tumors are presenting benign properties in quite a few clinical cases.Approximately 25%~40% of all schwannomas were reported in the soft tissues of the head and neck. However,as a rare region, schwannomas in oral cavity was only reported less than 1% of all head and neck locations. We contribute the case of a 17 years old girl,who was experiencing progressive odynophagia and dysarthria. The lingual root's Neurilemmoma, as the final diagnosis, was confirmed by preoperative laryngendoscopy and histopathological examination. The surgery was conducted by suspension laryngoscope. Completely excised lesion was histopathological identified,which showed strong and diffuse staining with S100.

PMID: 29871291 [PubMed - indexed for MEDLINE]

Permalink for 'A model for predicting low probability of nonsentinel lymph node positivity in melanoma patients with a single positive sentinel lymph node.'

A model for predicting low probability of nonsentinel lymph node positivity in melanoma patients with a single positive sentinel lymph node.

Fetched: November 21st, 2018, 5:00am GMT

A model for predicting low probability of nonsentinel lymph node positivity in melanoma patients with a single positive sentinel lymph node.

J Surg Oncol. 2018 Nov;118(6):922-927

Authors: Bhutiani N, Egger ME, Stromberg AJ, Gershenwald JE, Ross MI, Philips P, Martin RCG, Scoggins CR, McMasters KM

Abstract
BACKGROUND: Identifying factors associated with nonsentinel lymph node (NSN) metastases in melanoma patients with a single positive sentinel lymph node (SLN) could aid decision making regarding adjuvant therapy. We describe a model for identifying patients with a single positive SLN at low risk for NSN metastasis.
METHODS: Factors associated with NSN metastasis in patients with a primary cutaneous melanoma and a single positive SLN who underwent completion lymph node dissection (CLND) were identified. These factors were used to construct a model for predicting the NSN status. The model was validated using a separate data set from another tertiary referral cancer center.
RESULTS: In the training data set, 111 patients had a single positive SLN. Of these, 27 had positive NSN. SLN tumor deposit diameter ≥0.75 mm (OR, 3.43; P = 0.047), age ≥40 (OR, 12.14; P = 0.024), and multifocal SLN tumor deposit location (OR, 4.16; P = 0.0096) were independently associated with NSN positivity. Patients with 0 to 1 of these risk factors had a low risk of NSN metastasis in both the training (7.5%) and validation (4.6%) data sets.
CONCLUSIONS: A combination of patient and SLN tumor burden characteristics can help to identify patients with a single positive SLN who are at a low risk of NSN metastasis.

PMID: 30259521 [PubMed - indexed for MEDLINE]

Permalink for 'Hemolytic Anemia and Gastric Carcinoid in a Russian Seafarer: Highlighting the Role of Diagnostic Technologies in Modern Clinical Practice.'

Hemolytic Anemia and Gastric Carcinoid in a Russian Seafarer: Highlighting the Role of Diagnostic Technologies in Modern Clinical Practice.

Fetched: November 21st, 2018, 5:00am GMT

Hemolytic Anemia and Gastric Carcinoid in a Russian Seafarer: Highlighting the Role of Diagnostic Technologies in Modern Clinical Practice.

Yale J Biol Med. 2018 09;91(3):243-246

Authors: Chaunzwa TL, O'Shea J, Boggs NA, Schwartz JI, Gibson J, Gielissen KA

Abstract
Vitamin B-12 deficiency, most commonly due to pernicious anemia, can cause intramedullary hemolysis. The pathogenesis is thought to be due to increased membrane rigidity and reduced red blood cell elasticity, which predisposes the patient to hemolysis and microangiopathic hemolytic anemia. In this article, we discuss a Russian engineer who worked aboard a petroleum tanker that presented from his ship with profound B-12 deficiency, microangiopathic anemia, elevated lactate dehydrogenase levels, low haptoglobin, and reticulocyte count in the setting of normal renal and neurologic function. The patient traveled around the world seven months of the year for work and had occupational exposure to fluorinated hydrocarbons. Extensive diagnostic work-up, including endoscopic biopsy, and a radio-labeled octreotide scan was performed. The patient was found to have autoimmune gastritis and a gastric carcinoid tumor. With assistance from his global health insurance provider and a local hospital near his hometown in Russia, care was coordinated to be transitioned there with a plan for repeat endoscopy and mapping biopsies to determine the extent of his tumor burden. This study adds to the now growing base of literature describing this atypical presentation of pernicious anemia with normal neurologic function and underscores the importance of screening for B-12 deficiency in these patients. It also highlights the increased risk of gastric carcinoids in patients with autoimmune gastritis. With the collaboration of different medical specialists, the full gamut of medical technology was utilized in the care of the patient. This included in vitro diagnostics, advanced endoscopic tools, pathology, and radio-isotope based imaging studies.

PMID: 30258311 [PubMed - indexed for MEDLINE]

Permalink for 'Neutrophil to lymphocyte ratio is an independent predictor of outcome for patients undergoing definitive resection for stage IV melanoma.'

Neutrophil to lymphocyte ratio is an independent predictor of outcome for patients undergoing definitive resection for stage IV melanoma.

Fetched: November 21st, 2018, 5:00am GMT

Neutrophil to lymphocyte ratio is an independent predictor of outcome for patients undergoing definitive resection for stage IV melanoma.

J Surg Oncol. 2018 Nov;118(6):915-921

Authors: Kanatsios S, Melanoma Project M, Li Wai Suen CSN, Cebon JS, Gyorki DE

Abstract
BACKGROUND AND OBJECTIVES: The aim of this study was to perform a retrospective analysis of survival rates and determine prognostic indicators for patients who underwent definitive surgical resection of stage IV melanoma.
METHODS: Patients included were those who underwent complete resection of metastatic melanoma. Data was analyzed using IBM SPSS 2.0. Survival estimates were derived from Kaplan-Meier, log-rank, and Breslow tests.
RESULTS: The study population (n = 95) consisted of 60 males and 35 females. Median overall survival (OS) from the first metastasectomy was 49 months (95% confidence interval, 31-67 months). OS at 1, 2, and 5 years was 92%, 87%, and 50% respectively. Predictors of survival included clear surgical margins compared to patients with positive margins (median OS 53 vs 20 months, P = .026). A preoperative neutrophil to lymphocyte ratio less than 5 experienced a median OS of 65 months compared to 15 months ( P = .006; multivariable analysis for OS: hazard ratio 3.590, P = .009).
CONCLUSION: This study's results are consistent with previous findings demonstrating favourable long-term outcomes following selective resection of metastatic melanoma. In addition to achieving clear surgical margins, a low preoperative neutrophil to lymphocyte ratio was associated with improved outcomes. These factors may help identify surgical candidates.

PMID: 30196539 [PubMed - indexed for MEDLINE]

ROCK inhibitor enhances the growth and migration of BRAF-mutant skin melanoma cells.

Fetched: November 21st, 2018, 5:00am GMT

ROCK inhibitor enhances the growth and migration of BRAF-mutant skin melanoma cells.

Cancer Sci. 2018 Nov;109(11):3428-3437

Authors: Chang F, Zhang Y, Mi J, Zhou Q, Bai F, Xu X, Fisher DE, Sun Q, Wu X

Abstract
Rho-associated protein kinase (ROCK) plays crucial roles in the proliferation and migration of different types of cells. ROCK inhibitor Y-27632 was previously reported to inhibit melanoma cell growth, and ROCK signaling was suggested to be a therapeutic target for treating melanoma. However, the negative effect of Y-27632 on melanoma cells was mainly seen in studies on murine B16 melanoma cells. Here, we reported that ROCK inhibitor actually promoted human melanoma cell growth and migration in vitro. Y-27632 increased the growth and migration of BRAF-mutated melanoma cells but had a negative effect on wild-type melanoma cells or primary melanocytes. We discovered that Y-27632 enhanced the growth of BRAF-mutated melanoma cells through increased ATK and ERK activity. The in vivo study further confirmed the in vitro finding. These data suggested that the effect of ROCK inhibitor on melanoma cells is cell-context dependent, and the application of ROCK inhibitor in the treatment of melanoma requires further study.

PMID: 30168234 [PubMed - indexed for MEDLINE]

Applicability of Plant Extracts in Preclinical Studies of Melanoma: A Systematic Review.

Fetched: November 21st, 2018, 5:00am GMT

Applicability of Plant Extracts in Preclinical Studies of Melanoma: A Systematic Review.

Mediators Inflamm. 2018;2018:6797924

Authors: Albuquerque KRS, Pacheco NM, Del Rosario Loyo Casao T, de Melo FCSA, Novaes RD, Gonçalves RV

Abstract
Melanoma is the most aggressive form of skin cancer and arises from melanocyte gene mutation. This disease is multifactorial, but its main cause is the excessive exposure to ultraviolet radiation. Currently, available chemotherapy has shown little expressive results, which may justify the high use of natural products to treat this cancer. We performed a systematic review to compile the results of studies carried out in murine models and investigated the effect of plant extracts on melanoma treatment. Papers were selected in MEDLINE/Pubmed and Scopus according to the PRISM statement. Search filters were developed using three parameters: plant extract, melanoma, and animal model. The 35 identified studies were all submitted to the criteria described in the ARRIVE guidelines. The different extracts showed antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory activity, and also proved to be effective in cell cycle modulation and apoptosis evasion. Bias analysis evidenced the absence of standardized experimental designs, as well as failures in statistical tests and in the presentation of results. The analysis of the studies suggests that the use of plant extracts is effective for the treatment of melanoma in murine models.

PMID: 30147443 [PubMed - indexed for MEDLINE]

Imaging pediatric gastrointestinal stromal tumor (GIST).

Fetched: November 21st, 2018, 5:00am GMT

Imaging pediatric gastrointestinal stromal tumor (GIST).

J Pediatr Surg. 2018 Sep;53(9):1862-1870

Authors: Herzberg M, Beer M, Anupindi S, Vollert K, Kröncke T

Abstract
BACKGROUND: Gastrointestinal stromal tumors (GIST) are extremely rare in children. Imaging plays a key role in staging and monitoring therapy (surgical and with tyrosine kinase inhibitors). The vast majority of articles addressing imaging of GIST base on adults and are based on CT. The subtype "pediatric GIST" - if at all - is only mentioned in a dependent clause. Although the imaging features in children and adults are similar, histology, clinical course and thus imaging approach are different.
METHODS: A PubMed search using the search terms "Gastrointestinal stromal tumor, GIST, WT GIST, children, pediatric, carney's triad, imaging, staging, follow-up, MRI, CEUS, ultrasonography, Positron emission tomography" was conducted. Studies that reported on laparoscopy, endoscopy and surgical techniques only were excluded.
RESULTS: Based on our selective literature review, we present alternative radiological imaging strategies using MRI, contrast enhanced ultrasound (CEUS) and PET-CT to stage and follow-up pediatric GIST patients. As pediatric GIST often is a chronic disease, minimizing exposure to ionizing radiation is mandatory.
CONCLUSION: MRI, contrast enhanced ultrasound and PET-CT instead of CT are the imaging modalities to evaluate pediatric GIST.
TYPE OF STUDY: Systematic review LEVEL OF EVIDENCE: III.

PMID: 29685489 [PubMed - indexed for MEDLINE]

Clinicopathological indicators of survival among patients with pulmonary carcinoid tumor.

Fetched: November 21st, 2018, 5:00am GMT

Clinicopathological indicators of survival among patients with pulmonary carcinoid tumor.

Acta Oncol. 2018 Aug;57(8):1109-1116

Authors: Vesterinen T, Mononen S, Salmenkivi K, Mustonen H, Ilonen I, Knuuttila A, Haglund C, Arola J

Abstract
BACKGROUND: Pulmonary carcinoids (PC) are rare malignant neoplasms that cover approximately 1% of all lung cancers. PCs are classified by histological criteria as either typical (TC) or atypical (AC). Histological subtype is the most studied prognostic factor. The aim of this study was to evaluate if other tissue or clinical features are associated with patient outcomes.
MATERIAL AND METHODS: We retrospectively reviewed clinical records of 133 PC patients who underwent operation in the Helsinki University Hospital between 1990 and 2013. Tissue specimens were re-evaluated, processed into tissue microarray format and stained immunohistochemically with serotonin, calcitonin, adrenocorticotropic hormone (ACTH), thyroid transcription factor-1 (TTF-1) and Ki-67. Survival and risk analyses were performed.
RESULTS: Based on histology, 75% (n = 100) of the tumors were TCs and 25% (n = 33) ACs. TCs had higher 10-year disease-specific survival (DSS) rate than ACs (99% (95% CI, 93-100%) for TCs vs. 82% (95% CI, 61-92%) for ACs). Hormonally active tumors expressing serotonin, calcitonin or ACTH were noted in 53% of the specimens but hormonal expression was not associated with DSS. TTF-1 was positive in 78% of the specimens but was not associated with DSS. Ki-67 index varied between <1% and 15%. Ki-67 ≥ 2.5% was associated with shorter DSS (p = .004). The presence of metastatic disease (p = .001), tumor size ≥30 mm (p = .021) and atypical histology (p = .011) were also associated with disease-specific mortality.
CONCLUSIONS: We conclude that PCs are uncommon tumors. When resected, the long-term survival is in general favorable. In this consecutive, single-institution cohort of patients, presence of metastatic disease, tumor size, histological subtype and Ki-67 index were associated with shorter disease-specific survival. As TC and AC have different clinical behaviors, the correct tumor classification at the time of diagnosis is a necessity.

PMID: 29463166 [PubMed - indexed for MEDLINE]

Permalink for 'Non-genetic engineering of cytotoxic T cells to target IL-4 receptor enhances tumor homing and therapeutic efficacy against melanoma.'

Non-genetic engineering of cytotoxic T cells to target IL-4 receptor enhances tumor homing and therapeutic efficacy against melanoma.

Fetched: November 21st, 2018, 5:00am GMT

Non-genetic engineering of cytotoxic T cells to target IL-4 receptor enhances tumor homing and therapeutic efficacy against melanoma.

Biomaterials. 2018 03;159:161-173

Authors: Gunassekaran GR, Hong CM, Vadevoo SMP, Chi L, Guruprasath P, Ahn BC, Kim HJ, Kang TH, Lee B

Abstract
Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor (IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic efficacy against melanoma. CTLs isolated from mice bearing melanomas were non-genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane anchor composed of dioleylphosphatidylethanolamine. Compared to control CTLs, IL-4R-targeted CTLs showed higher binding to melanoma cells and in vivo tumor homing. They also exerted a more rapid and robust effector response, including increased cytokine secretion and cytotoxicity against melanoma cells and enhanced reprogramming of M2-type macrophages to M1-type macrophages. Moreover, IL-4R-targeted CTLs efficiently inhibited melanoma growth and reversed the immunosuppressive tumor microenvironment. These results suggest that non-genetically engineered CTLs targeting IL-4R have potential as an adoptive T cell therapy against melanoma.

PMID: 29329051 [PubMed - indexed for MEDLINE]

Permalink for 'Injectable polypeptide hydrogel for dual-delivery of antigen and TLR3 agonist to modulate dendritic cells in vivo and enhance potent cytotoxic T-lymphocyte response against melanoma.'

Injectable polypeptide hydrogel for dual-delivery of antigen and TLR3 agonist to modulate dendritic cells in vivo and enhance potent cytotoxic T-lymphocyte response against melanoma.

Fetched: November 21st, 2018, 5:00am GMT

Injectable polypeptide hydrogel for dual-delivery of antigen and TLR3 agonist to modulate dendritic cells in vivo and enhance potent cytotoxic T-lymphocyte response against melanoma.

Biomaterials. 2018 03;159:119-129

Authors: Song H, Huang P, Niu J, Shi G, Zhang C, Kong D, Wang W

Abstract
Transplantation of immune cells manipulated in vitro to dictate immune responses in the body is promising in cancer immunotherapy. However, this approach suffers from low cell survival after administration, insufficient cell homing to lymph nodes, and off-target. Here we demonstrate an injectable and self-assembled poly(l-valine) hydrogel as the delivery carrier of cargoes including antigen and immunopotentiator for DCs modulation. Our results indicate the vaccine formulation composed of tumor cell lysates (TCL), TLR3 agonist, poly(I:C) and polypeptide hydrogel can robustly recruit, activate and mature DCs in vitro and in vivo by sustained release of TCL and poly(I:C). Hydrogel as the delivery system significantly improves antigen persistence at the injection site and antigen drainage to lymph nodes. Strikingly, subcutaneous injection of hydrogel-based vaccine formulations in melanoma-bearing mice elicits good antitumor efficiency by evoking strong cytotoxic T-lymphocyte immune response. Hydrogel vaccine significantly promotes the production of CD8+ T cells in draining lymph nodes and tumor infiltrating T-lymphocytes. These findings suggest that in vivo program of DCs by injectable polypeptide hydrogel encapsulated with antigen and immunopentiator is able to direct immune responses against cancer. Our study also implies that such a hydrogel may serve as a multifunctional delivery platform of vaccines.

PMID: 29324304 [PubMed - indexed for MEDLINE]

Atypical presentation of a primary cardiac malignant peripheral nerve sheath tumor.

Fetched: November 21st, 2018, 5:00am GMT

Atypical presentation of a primary cardiac malignant peripheral nerve sheath tumor.

Int J Cardiovasc Imaging. 2018 Jun;34(6):903-904

Authors: Eindhoven JA, Loonstra EEG, Kik C, van den Bos EJ, Kofflard MJM

PMID: 29318408 [PubMed - indexed for MEDLINE]

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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Endocrine/Neuroendocrine (524 unread)

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