Clinicopathological Characteristics of Extrahepatic Biliary Neuroendocrine Neoplasms in the Gallbladder, Extrahepatic Biliary Tract, and Ampulla of Vater: A Single-Center Cross-Sectional Study

Abstract BackgroundSignificant changes were made in the grading and staging systems for neuroendocrine neoplasms (NENs) in 2017. Therefore, a clinical report to comprehensively update the clinicopathological characteristics, therapeutic approaches, and prognosis of these patients should be drafted.MethodsWe retrospectively reviewed a database of 16 patients who developed NENs or mixed endocrine non-endocrine neoplasms (MiNENs) after curative resection. Among them, eight had ampulla of Vater (AoV) tumors, and eight had non-AoV tumors. One patient had NEN Grade 1, five had NEN Grade 2, and five had NEN Grade 3 (G3); all had poorly differentiated neuroendocrine carcinoma. Five patients had MiNEN or combined carcinoma.ResultsThe mean age was 57.88 years. The overall survival rates after curative surgery at 1, 3, and 5 years were 87.1, 80.4, and 71.4%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 87.1%, 79.8%, and 71.8%, respectively. In univariate analysis, age >65 years, mitotic count (>20/10 high-power fields), Ki-67 index >20%, and presence of stones were significant prognosticators, whereas only the mitotic count was statistically significant in the multivariate analysis. Age >65 years (p=0.039), a Ki-67 index >20% (p=0.03), presence of stones (p=0.021), G3 stage disease, MiNEN (p=0.002), or perineural invasion (p<0.001) were more frequently observed in the non-AoV group than in the AoV group.ConclusionHigh mitosis count had a greater effect on extrahepatic biliary NEN than the tumor-node-metastasis staging system. Patients with AoV tumors had better prognostic predictor factors compared to those with non-AoV tumors.

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Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms

Neuroendocrinology ◽

10.1159/000500135 ◽

2019 ◽

Vol 109 (4) ◽

pp. 333-345 ◽

Cited By ~ 11

Author(s):

Eleftherios Chatzellis ◽

Anna Angelousi ◽

Kosmas Daskalakis ◽

Marina Tsoli ◽

Krystallenia I. Alexandraki ◽

...

Keyword(s):

Univariate Analysis ◽

Area Under The Curve ◽

Progression Free Survival ◽

Clinicopathological Characteristics ◽

Unknown Primary ◽

Neuroendocrine Neoplasms ◽

Significant Prognostic Factor ◽

Characteristic Analysis ◽

Prolonged Administration ◽

Ki 67

Background: Capecitabine and temozolomide combination (CAPTEM) is associated with high response rates in patients with advanced neuroendocrine neoplasms (NENs). We evaluated the real-world activity and safety of CAPTEM from 3 NEN centers. Methods: Clinicopathological characteristics and outcomes of patients treated with CAPTEM for bulky or progressive disease (PD) were retrospectively analyzed. Results: Seventy-nine patients with gastroenteropancreatic (grades 1–2 [n = 38], grade 3 [n = 24]) and lung/thymic (n = 17) NENs were included. Median treatment duration was 12.1 months (range 0.6–55.6). Overall, partial responses (PRs) occurred in 23 (29.1%), stable (SD) in 24 (30.4%), and PD in 28 (35.4%) patients. Median progression-free survival (PFS) and overall survival (OS) were 10.1 (6–14.2) and 102.9 months (43.3–162.5), respectively. On univariate analysis, NENs naive to chemotherapy and low Ki67 were associated with favorable responses (partial response [PR] + SD; p = 0.011 and 0.045), PFS (p < 0.0001 and 0.002) and OS (p = 0.005 and 0.001). Primary site (pancreas and lung/thymus) was also a significant prognostic factor for PFS (p < 0.0001) and OS (p < 0.0001). On multivariate analysis, gastrointestinal and unknown primary NENs (hazard ratio [HR] 0.3, 95% CI 0.1–0.8, p = 0.009 and p = 0.018) and prior surgery (HR 2.4, 95% CI 11–4.9, p = 0.021) were independent prognostic factors for PFS. Ki-67 was a poor predictor for favorable response in receiver operating characteristic analysis (area under the curve 0.678). Safety analysis of CAPTEM indicated rare events of serious (grades 3–4) toxicities (n = 4) and low discontinuation rates (n = 8) even in patients with prolonged administration (>12 months). Conclusions: CAPTEM treatment can be an effective and safe treatment even after prolonged administration for patients with NENs of various sites and Ki67 labeling index, associated with significant favorable responses and PFS.

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Clinical relevance of different WHO grade 3 pancreatic neuroendocrine neoplasms based on morphology

Endocrine Connections ◽

10.1530/ec-17-0388 ◽

2018 ◽

Vol 7 (2) ◽

pp. 355-363 ◽

Cited By ~ 9

Author(s):

Xu Han ◽

Xuefeng Xu ◽

Hongyun Ma ◽

Yuan Ji ◽

Dansong Wang ◽

...

Keyword(s):

Vascular Invasion ◽

Who Classification ◽

Univariate Analysis ◽

Tnm Staging ◽

Mitotic Count ◽

Biological Behavior ◽

Neuroendocrine Neoplasms ◽

Ki 67 ◽

Who Grade ◽

Pancreatic Neuroendocrine Neoplasms

Purpose Emerging evidence suggests G3 pancreatic neuroendocrine neoplasms (pNENs) present heterogeneous morphology and biology. The 2017 WHO classification has introduced a new category of well-differentiated pancreatic neuroendocrine tumors (WD-pNETs) G3, compared with poorly differentiated pancreatic neuroendocrine carcinomas (PD-pNECs) G3. We aim to analysis the demographics and outcomes of patients with resectable 2017 WHO G3 pNENs to facilitate the distinction between two entities. Methods The multi-institutional retrospective cohort involving 57 surgically treated patients affected by 2017 WHO G3 pNENs were morphologically identified and clinically analyzed. Patients having WD-pNETs G3 and those having PD-pNECs G3 were compared. Results Thirty patients had WD-pNETs and 27 patients had PD-pNECs. The distributions of Ki-67 and mitotic count in patients with PD-pNECs or WD-pNETs showed remarkable disparities. ROC indicated cut-off value of Ki-67 was 45. PD-pNECs were more common in patients with elevated Ki-67 and mitotic count, advanced AJCC TNM stage, vascular invasion, regional lymph-node metastases, elevated NSE and decreased CgA levels compared with WD-pNETs (P < 0.05). The association between 2017 WHO G3 grade and TTR was statistically significant (P < 0.05). Univariate analysis indicated OS rates were associated with morphologic differentiation (WD-pNETs vs PD-pNECs), Ki-67, TNM staging, synchronous distant metastases, initial treatments, vascular invasion, regional lymph nodes metastases, mitotic count and age (P < 0.05). Multivariate analyses illustrated Ki-67, differentiation, TNM staging and vascular invasion were independent predictors (P < 0.05). Conclusions PD-pNECs G3 presented malignant biological behavior and dismal outcome compared with WD-pNETs G3. These findings challenge 2010 WHO classification and suggest the categorization can be improved by refined tumor grading.

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Loco-regional outcomes of a population-based cohort of rectal neuroendocrine tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.668 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 668-668

Author(s):

Erica S Tsang ◽

Yarrow Jean McConnell ◽

David F. Schaeffer ◽

Caroline Speers ◽

Hagen F. Kennecke

Keyword(s):

Surgical Resection ◽

Neuroendocrine Tumors ◽

Local Excision ◽

Univariate Analysis ◽

Local Relapse ◽

Population Based ◽

Mitotic Count ◽

Margin Status ◽

Ki 67 ◽

Pelvic Radiation

668 Background: Optimal management of rectal neuroendocrine tumors (NETs) is not well defined. We characterized the clinicopathologic features, loco-regional, and systemic management of a population-based cohort of rectal NETs. Methods: Patients diagnosed with rectal NETs from 1999-2011 were identified from British Columbia provincial databases. NETs were classified as G1 and G2 tumors with a Ki-67 ≤ 20% and/or mitotic count ≤ 20 per high power field. Results: Of 91 rectal NETs, median age was 58 (IQR 48-65) years and 35 (38%) were male. Median tumor size was 6 (IQR 4-8) mm. Median overall survival was 164.7 months, with 3 patients presenting with stage IV disease. Treatment included local excision (n = 79), surgical resection (n = 6), and pelvic radiation (n = 1; T3N1 tumor). Final margin status was positive in 17 (20%) cases. Local relapse occurred in 8 (9%) cases, and one relapse to bone 13 months after T3N1 tumor resection. Univariate analysis demonstrated an association between local relapse and T classification, Ki-67, mitotic count, grade, and perineural invasion (p< 0.01), but not N or M classification, or lymphovascular invasion. Local relapse was not associated with surgical management or margin status. Of 3 patients with metastatic disease, two received systemic management, with capecitabine and temozolomide. Conclusions: Rectal NETs generally presented with small, early tumors and were treated with local excision or surgical resection without pelvic radiation. [Table: see text]

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Is There a Need for New Classifications to Predict Prognosis in Gastroenteropancreatic Neuroendocrine Carcinomas?

The Journal of Tepecik Education and Research Hospital ◽

10.5222/terh.2021.29200 ◽

2021 ◽

Author(s):

Emel Tekin ◽

Arzu Avcı ◽

Neşe Ekinci

Keyword(s):

Survival Rates ◽

Case Series ◽

Threshold Value ◽

World Health ◽

Proliferation Index ◽

Neuroendocrine Neoplasms ◽

Ki 67 ◽

Significant Difference ◽

Who 2010 Classification ◽

Health Organization

Objective: Neuroendocrine neoplasms (NEN) are frequently located in the lung and gastroenteropancreatic (GEP) system organs. Neuroendocrine carcinoma (NEC) constitutes 5% of GEP NENs and has a very high malignancy potential. In this study, it is aimed to determine a new threshold value in addition to the 20% Ki-67 proliferation index that was specified as a threshold value for predicting survival in patients with grade (G) 3 tumors according to World Health Organization (WHO) 2010 classification. Method: Demographic, clinicopathologic features and survival rates of 34 patients diagnosed with GEP NEC between 2008-2015 in İzmir Katip Celebi University Atatürk Training and Research Hospital Medical Pathology Clinic were evaluated retrospectively. Results: Most of the 34 (76.5%) cases were male and the average age was 63.9 years. Median survival rates were 15, and 7 months in patients with Ki-67 indexes of ≤65% and >65%, respectively (p=0.232). Conclusion: Recent studies have shown heterogeneity of high-grade NENs, identified as NEC and foreseen their subdivision into biological subgroups. The researchers suggest that the NECs should be divided into two categories as patients with Ki-67 indexes of 20-55% and >55%. In our study, the most significant difference in survival rates was observed when 65% was selected as threshold value for Ki-67 index which supports the results of other studies in the literature. Since the number of our cases is limited and it is a single-center study, the findings obtained needs to be further investigated in studies with greater number of case series.

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Clinicopathological features and prognostic factors of colorectal neuroendocrine neoplasms.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.572 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 572-572

Author(s):

Mengjie Jiang ◽

Hanguang Hu ◽

Ying Yuan

Keyword(s):

Prognostic Factors ◽

Tumor Size ◽

Cox Regression ◽

Survival Rates ◽

Delayed Diagnosis ◽

Tumor Location ◽

Neuroendocrine Neoplasms ◽

Clinicopathological Feature ◽

Ki 67 ◽

Pathological Classification

572 Background: Limited research is available regarding colorectal neuroendocrine neoplasms (NENs), especially in China. The prognostic factors of colorectal NENs remain controversial. Methods: A total of 68 patients with colorectal NENs were studied retrospectively. Clinical characteristics and prognosis between colonic and rectal NENs were compared. The Kaplan-Meier method and Cox regression models were used to evaluate the capacity of various factors to predict the outcome. Results: Of the 68 colorectal NENs patients, 43 (63.2%) had rectal NENs, and 25 (36.8%) had colonic NENs. Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size ( P < 0.0001) and distant metastasis ( P < 0.0001). Colonic NENs had a worse prognosis ( P= 0.027), with 5-year overall survival rates of 66.7% vs. 88.1% compared with rectal NENs. Neuroendocrine tumors, neuroendocrine carcinomas and mixed adenoendocrine carcinomaswere noted in 61.8%, 23.5% and 14.7% of patients, respectively. According to the available data (n = 49), Ki-67 index values were ≤ 2% in 27 (39.7%) patients, ranged from 3 to 20% in 6 patients (8.8%) and were > 20% in 16 patients (23.5%). Multivariate analyses revealed that tumor location was not an independent prognostic factor ( P= 0.081), but tumor size ( P= 0.037) and pathological classification ( P= 0.012) were independent prognostic factors. Conclusions: Significant differences in clinicopathological feature and outcome exist between colonic and rectal NENs. Multivariate analysis indicated that tumor size and pathological classification were associated with the prognosis. However, tumor location was not an independent factor. The worse outcome of colonic NENs observed in clinical practice might be due not only to the biological differences, but also to larger tumor size in colonic NENs caused by the delayed diagnosis.

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A comparison of Ki-67 and mitotic count as prognostic markers for metastatic pancreatic and midgut neuroendocrine neoplasms

British Journal of Cancer ◽

10.1038/bjc.2013.156 ◽

2013 ◽

Vol 108 (9) ◽

pp. 1838-1845 ◽

Cited By ~ 79

Author(s):

M S Khan ◽

T V Luong ◽

J Watkins ◽

C Toumpanakis ◽

M E Caplin ◽

...

Keyword(s):

Prognostic Markers ◽

Mitotic Count ◽

Neuroendocrine Neoplasms ◽

Ki 67

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Clinical and Prognostic Value of PET/CT Imaging with Combination of 68Ga-DOTATATE and 18F-FDG in Gastroenteropancreatic Neuroendocrine Neoplasms

Contrast Media & Molecular Imaging ◽

10.1155/2018/2340389 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 14

Author(s):

Panpan Zhang ◽

Jiangyuan Yu ◽

Jie Li ◽

Lin Shen ◽

Nan Li ◽

...

Keyword(s):

Prognostic Value ◽

Clinicopathological Characteristics ◽

Neuroendocrine Neoplasms ◽

Ki 67 ◽

Gastroenteropancreatic Neuroendocrine Neoplasms ◽

Pet Ct ◽

Group A ◽

Well Differentiated ◽

Group B ◽

Fdg Pet Ct

Background. To evaluate the clinical and prognostic value of PET/CT with combination of 68Ga-DOTATATE and 18F-FDG in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Method. 83 patients of GEP-NENs who underwent 68Ga-DOTATATE and 18F-FDG PET/CT were enrolled between June 2013 and December 2016. Well-differentiated (WD) NETs are divided into group A (Ki-67 < 10%) and group B (Ki-67 ≥ 10%), and poorly differentiated (PD) NECs are defined as group C. The relationship between PET/CT results and clinicopathological characteristics was retrospectively investigated. Result. For groups A/B/C, the sensitivities of 68Ga-DOTATATE and 18F-FDG were 78.8%/83.3%/37.5% and 52.0%/72.2%/100.0%. A negative correlation between Ki-67 and SUVmax of 68Ga-DOTATATE (R = −0.415; P ≤ 0.001) was observed, while a positive correlation was noted between Ki-67 and SUVmax of 18F-FDG (R = 0.683; P ≤ 0.001). 62.5% (5/8) of patients showed significantly more lesions in the bone if 68Ga-DOTATATE was used, and 22.7% (5/22) of patients showed more lymph node metastases if 18F-FDG was used. Conclusions. The sensitivity of dual tracers was correlated with cell differentiation, and a correlation between Ki-67 and both SUVmax of PET-CTs could be observed. 68Ga-DOTATATE is suggested for WD-NET and 18F-FDG is probably suitable for patients with Ki-67 ≥ 10%.

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Primary squamous cell carcinoma of the ampulla of Vater: management and review of the literature

BMJ Case Reports ◽

10.1136/bcr-2020-236477 ◽

2021 ◽

Vol 14 (1) ◽

pp. e236477

Author(s):

Subhash Soni ◽

Poonam Elhence ◽

Vaibhav Kumar Varshney ◽

Sunita Suman

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Survival Rates ◽

Ampulla Of Vater ◽

Metallic Stent ◽

Biological Behaviour ◽

Curative Intent ◽

Term Survival ◽

History Of

Squamous cell carcinoma (SCC) of the ampulla of Vater is a rare pathology and only few cases are reported in the literature. With limited experience of primary SCC in the ampulla of Vater, its biological behaviour, prognosis and long-term survival rates are not well known. A 38-year-old woman presented with a history of painless progressive jaundice for which self-expending metallic stent was placed 3 years back. She was evaluated and initially diagnosed as probably periampullary adenocarcinoma. She underwent pancreaticoduodenectomy and histopathology with immunohistochemistry was suggestive of SCC of ampulla of Vater. She received adjuvant chemotherapy and doing well with no recurrence after 1 year of follow-up. In conclusion, SCC of the ampulla is an unusual pathology that should be kept as a differential diagnosis for periampullary tumours. Surgical treatment with curative intent should be performed whenever feasible even in the setting of bulky tumour to improve the outcome.

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Expression and clinical significance of miR-3615 in hepatocellular carcinoma

Journal of International Medical Research ◽

10.1177/0300060520981547 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052098154

Author(s):

Xin Yuan ◽

Yize Zhang ◽

Zujiang Yu

Keyword(s):

Hepatocellular Carcinoma ◽

Survival Curve ◽

Clinicopathological Characteristics ◽

The Cancer Genome Atlas ◽

Prognostic Information ◽

Ki 67 ◽

Tissue Samples ◽

Expression Levels ◽

Kaplan Meier ◽

Serum Alpha Fetoprotein

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.

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Mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder: a case report

Surgical Case Reports ◽

10.1186/s40792-021-01152-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Tatsuki Ishikawa ◽

Katsunori Nakano ◽

Masafumi Osaka ◽

Kenichi Aratani ◽

Kadotani Yayoi ◽

...

Keyword(s):

System Analysis ◽

Cancer Control ◽

Staging System ◽

Neuroendocrine Neoplasms ◽

Ki 67 ◽

Regional Lymph Nodes ◽

Abdominal Ultrasonography ◽

Case Presentation ◽

History Of ◽

Lymph Nodes Dissection

Abstract Background Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare. Case presentation We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy. Conclusions GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient.

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