Surgery of the primary tumour in 201 patients with high‐grade gastroenteropancreatic neuroendocrine and mixed neuroendocrine‐non‐neuroendocrine neoplasms

2021 ◽  
Author(s):  
Hans‐Christian Pommergaard ◽  
Kirstine Nielsen ◽  
Halfdan Sorbye ◽  
Birgitte Federspiel ◽  
Elizaveta M. Tabaksblat ◽  
...  
Keyword(s):  
Primary Tumour ◽  
Neuroendocrine Neoplasms ◽  
High Grade

scholarly journals The molecular characteristics of high-grade gastroenteropancreatic neuroendocrine neoplasms

2021 ◽  
Author(s):  
Andreas Venizelos ◽  
Hege Elvebakken ◽  
Aurel Perren ◽  
Oleksii Nikolaienko ◽  
Wei Deng ◽  
...  
Keyword(s):  
Copy Number ◽  
Primary Tumour ◽  
Treatment Strategies ◽  
Morphological Differentiation ◽  
Molecular Characteristics ◽  
Neuroendocrine Neoplasms ◽  
High Grade ◽  
Braf Mutations ◽  
Molecular Features ◽  
Net G3

High-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are rare but have a very poor prognosis and represent a severely understudied class of tumours. Molecular data for HG GEP-NEN are limited and treatment strategies for the carcinoma subgroup (HG GEP-NEC) are extrapolated from small-cell lung cancer (SCLC). After pathological re-evaluation, we analysed DNA from tumours and matched blood samples from 181 HG GEP-NEN patients; 152 neuroendocrine carcinomas (NEC) and 29 neuroendocrine tumours (NET G3). Based on sequencing of 360 cancer related genes, we assessed mutations and copy number alterations (CNA). For NEC, frequently mutated genes were TP53 (64%), APC (28%), KRAS (22%) and BRAF (20%). RB1 was only mutated in 14%, but CNAs affecting RB1 were seen in 34%. Other frequent copy number losses were ARID1A (35%), ESR1 (25%) and ATM (31%). Frequent amplifications/gains were found in MYC (51%) and KDM5A (45%). While these molecular features had limited similarities with SCLC, we found potentially targetable alterations in 66% of the NEC samples. Mutations and CNA varied according to primary tumour site with BRAF mutations mainly seen in colon (49%), and FBXW7 mutations mainly seen in rectal cancers (25%). 8/152 (5.3%) NEC were microsatellite instable (MSI). NET G3 had frequent mutations in MEN1 (21%), ATRX (17%), DAXX, SETD2 and TP53 (each 14%). We show molecular differences in HG GEP-NEN, related to morphological differentiation and site of origin. Limited similarities to SCLC and a high fraction of targetable alterations indicates a high potential for better personalized treatments.

scholarly journals The Expression of Chromogranin A, Syanptophysin and Ki67 in Detecting Neuroendocrine Neoplasma at High Grade Colorectal Adenocarcinoma

2021 ◽  
Vol 9 (A) ◽  
pp. 1142-1147
Author(s):  
W. A. Gusti Deasy ◽  
M. Husni Cangara ◽  
Andi Alfian Zainuddin ◽  
Djumadi Achmad ◽  
Syarifuddin Wahid ◽  
...  
Keyword(s):  
Chromogranin A ◽  
Colorectal Adenocarcinoma ◽  
Final Diagnosis ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
High Grade ◽  
Neuroendocrine Markers ◽  
Study Results ◽  
Cell Neoplasm ◽  
Sample Characteristics

BACKGROUND: Neuroendocrine neoplasm (NEN) is an epithelial cell neoplasm that can give a histopathological appearance resembling high-grade colorectal adenocarcinoma. Immunohistochemical assays with specific neuroendocrine markers of chromogranin A and synaptophysin are required to establish a definite diagnosis of NEN. AIM: This study aimed to determine whether there was an expression of chromogranin A, synaptophysin and Ki67 which indicated the presence of neuroendocrine neoplasms in samples that have been diagnosed as high-grade colorectal adenocarcinoma. MATERIALS AND METHODS: A study of the expression of chromogranin A, synaptophysin and Ki67 in paraffin blocks was carried out as a result of biopsy and tissue surgery of 70 samples of colorectal tumor specimens diagnosed with colorectal adenocarcinoma. Descriptive analyses were used to assess the study results of the amount of chromogranin A, synaptophysin, and sample characteristics. RESULTS: We discovered that eight (8) samples (11.4%) were NEN from 70 previously diagnosed samples as high-grade colorectal adenocarcinoma using immunohistochemical assay with neuroendocrine markers, namely chromogranin A and synaptophysin. CONCLUSION: The final diagnosis obtained from 8 samples diagnosed as NEN were Neuroendocrine tumor (NET) G1, G2, and G3, respectively 1.4% and LCNEC 7.1% based on the specific neuroendocrine markers of chromogranin A, synaptophysin and Ki67.

First-Line Irinotecan Combined with 5-Fluorouracil and Leucovorin for High-Grade Metastatic Gastrointestinal Neuroendocrine Carcinoma

2013 ◽  
Vol 99 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Zedong Du ◽  
Yi Wang ◽  
Yi Zhou ◽  
Feng Wen ◽  
Qiu Li
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Progression Free Survival ◽  
Disease Stage ◽  
Neuroendocrine Neoplasms ◽  
High Grade ◽  
First Line ◽  
Laboratory Findings ◽  
Poorly Differentiated ◽  
Prospective Trials ◽  
Line Setting

Aim and background High-grade gastrointestinal neuroendocrine neoplasms, ie, poorly differentiated neuroendocrine carcinomas, with no effective therapeutic approaches, have a high ability to metastasize. Methods A review of the hospital information system was performed. Patients with histologically proven gastrointestinal neuroendocrine carcinoma who were treated with irinotecan combined with 5-fluorouracil and leucovorin in a first-line setting were eligible for analysis. We extracted information on age, sex, disease stage, laboratory findings, radiological findings, pathological findings, chemotherapy, effectiveness and adverse events of therapy, and outcomes. Results Eleven patients were included in the study. Partial response was observed in 7 patients. Median progression-free survival and overall survival were 6.5 (95% CI, 5.1–7.9) and 13.0 (95% CI, 9.8–16.2) months, respectively. No treatment-related deaths occurred. Conclusions The results demonstrated that irinotecan combined with 5-fluorouracil and leucovorin is an active regimen with acceptable toxicity for patients with metastatic high-grade gastointestinal neuroendocrine carcinoma that merits further investigation in prospective trials.

EpiCO (epirubicin, cyclophosphamide and vincristine) as treatment for extrapulmonary high-grade neuroendocrine neoplasms

2020 ◽  
Vol 58 (02) ◽  
pp. 133-136
Author(s):  
Stefan Munker ◽  
Martin Vogelhuber ◽  
Jan Bornschein ◽  
Christian Stroszczynski ◽  
Matthias Evert ◽  
...  
Keyword(s):  
Case Series ◽  
Small Cell ◽  
Neuroendocrine Neoplasms ◽  
Significant Activity ◽  
High Grade ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
Cell Lung Carcinoma

AbstractHigh-grade neuroendocrine neoplasms (NEN) comprise a rare entity. Due to the lack of randomized controlled trials, therapy recommendations were mainly extrapolated from its pulmonary analogue, small cell lung cancer and mostly validated in small retrospective case series. The multicentric Nordic NEC Study of gastro-entero-pancreatic (GEP) and cancer of unknown primary (CUP) high-grade neuroendocrine neoplasms showed a significant disease control upon treatment with etoposide and platinum-based chemotherapies 1. Such a combination with etoposide and a platinum (CE) compound is currently considered standard first-line treatment for high-grade GEP/CUP NEN. High-grade mixed-neuroendocrine-non-neuroendocrine neoplasms (MiNEN) formerly termed mixed adeno-neuroendocrine carcinomas (MANEC) also have a poor prognosis and are generally treated like other high-grade NEN. The CE protocol has significant activity in high-grade NEN and MiNEN, but the response is short-lived in most cases with response rates around 50–60 %. Second-line treatment alternatives are not established so far. The need for additional treatment options is evident.Combination chemotherapy with doxorubicin, cyclophosphamide and vincristine (CAV) showed efficacy in small cell lung carcinoma (SCLC) and was considered standard first-line therapy before the era of etoposide and platinum combinations. Due to a better toxicity profile, doxorubicin was replaced by epirubicin, resulting in the combination of epirubicin, cyclophosphamide and vincristine (abbreviated as EpiCO or CEV).In analogy to SCLC, selected patients with high-grade NEN were treated with the EpiCO regimen in second line (or in one patient first line) at our center. In this report we present the retrospective series of 5 cases with metastatic high-grade GEP/CUP NEN/MiNEN who received chemotherapy according to this protocol.

scholarly journals TMIC-13. FEELING THE FORCE: DIFFERENCES IN THE MECHANOREGULATED MIGRATION OF HIGH GRADE GLIOMA BETWEEN INDIVIDUAL CELLS AND THOSE IN CONTACT WITH OTHER TUMOUR CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi249-vi250
Author(s):  
Thuvarahan Jegathees ◽  
Victoria Prior ◽  
Geraldine O’Neill
Keyword(s):  
Cell Migration ◽  
Single Cell ◽  
Primary Tumour ◽  
Automated Image Analysis ◽  
Migration And Invasion ◽  
Tumour Mass ◽  
High Grade ◽  
Migratory Behaviour ◽  
Tissue Elasticity

Abstract A major limitation in the treatment of High Grade Gliomas (HGG) is their highly disseminating nature. While it is increasingly appreciated that the mechanical properties of the extracellular matrix, (measured as tissue elasticity, Young’s modulus, E), can independently cue cancer cell migration and invasion, to date there has been little consideration of this mechanism in HGG invasion. This is particularly important given that the brain parenchyma is a mechanically soft tissue (E values varying between 1 - 10 kPa). By measuring single cell migration we have previously demonstrated that molecular subclasses of HGGs exhibit different rigidity-sensitive and -insensitive migration. Following these findings, the present project aimed to determine whether these mechanosensitive phenotypes are maintained in the dissemination of multicellular tumour spheroids (MCTSs) that represent in vivo organisation of the primary tumour bulk. Therefore MCTSs composed of primary patient-derived HGG cells with pre-established single cell mechanosensitive phenotypes were cultured on mechanically tuneable polyacrylamide hydrogels, mimicking the range of physiological tissue rigidities. Bright-field time-lapse images were then captured over a period of 48 hours, 6 images per hour. In order to quantitate the migratory behaviours, we adapted a previously published automated image analysis program to segment the MCTS images into proliferative and migratory regions. Our analysis suggests that the cellular mechano-phenotype is affected by contact with neighbouring cells, as the migratory response to tissue stiffness is quantitatively different in the MCTSs. Our results highlight different migratory behaviour between HGG cells within the primary tumour mass versus individual cells that escape. Our results reveal the complex migratory behaviour of HGG cells and suggests that successful anti-invasive therapies will need different strategies depending on tumour cell location.

Comparative Outcomes in Patients With Small- and Large-Cell Neuroendocrine Carcinoma (NEC) and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the Stomach

2020 ◽  
pp. 000313482095000
Author(s):  
Nam Young Choi ◽  
Byung-Sik Kim ◽  
Sung Tae Oh ◽  
Jeong Hwan Yook ◽  
Beom Su Kim
Keyword(s):  
Clinical Outcomes ◽  
Disease Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
High Grade ◽  
Intermediate Grade ◽  
Free Survival ◽  
Neuroendocrine Carcinomas

Background Gastric neuroendocrine carcinomas (NECs), consisting of both large- and small-cell NECs, and mixed adenoneuroendocrine carcinomas (MANECs), including mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), are a group of high-grade malignancies. Few studies to date have reported clinical outcomes, including prognosis, in patients with these tumors. This study therefore evaluated the clinicopathologic outcomes and prognosis in patients with NECs and MANECs. Methods This study included 36 patients diagnosed with gastric NECs, including 23 with large-cell and 13 with small-cell NECs, and 85 with MiNENs, including 70 with high-grade and 15 with intermediate-grade MiNENs. Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed. Results DFS was significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN ( P < .05), whereas both OS and DFS were similar in patients with NEC and high-grade MiNEN ( P > .05). Patients with large-cell NEC were more likely to undergo aggressive surgery than patients with high-grade MiNEN ( P < .05). Lymphovascular invasion was more frequent and DFS poorer in patients with large-cell than small-cell NECs ( P < .05 each). Conclusion DFS is significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN and significantly lower in patients with large-cell than small-cell NECs.

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