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

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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Treatment and outcomes of neuroendocrine malignancies (NEMs) of the rectum.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.594 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 594-594

Author(s):

Erica Tsang ◽

Caroline Speers ◽

Hagen F. Kennecke

Keyword(s):

Surgical Resection ◽

Local Excision ◽

Early Stage ◽

Univariate Analysis ◽

Mitotic Count ◽

Stage I ◽

High Power Field ◽

Early Stage Disease ◽

Pelvic Radiation ◽

Distant Relapse

594 Background: NEMs of the rectum are rare and standard therapy is not well defined. We sought to characterize the clinicopathologic features, locoregional, and systemic management of a series of rectal NEMs and correlated these with outcomes. Methods: Patients referred to the BC Cancer Agency with rectal NEMs between 2005-2011 were included. Well-differentiated tumors with a Ki67 ≤20% and/or mitotic count ≤ 20 per high power field were classified as neuroendocrine tumors (NETs) while poorly differentiated tumors with higher Ki67 and/or mitotic count were classified as neuroendocrine carcinomas (NECs). Results: Of 28 NEMs, 18 (64%) NETs, and 9 (36%) NECs were identified with a median age of 56 and 59, respectively. Of 15 patients with stage I-III NETs, 13 underwent local excision, 2 had a surgical resection and none received pelvic radiation. Univariate analysis demonstrated an association between tumor size (< 1cm, 1-2 cm, > 2cm) and T stage (χ2 = 10.7, p = 0.03). One of 15 NETs developed distant relapse 8.9 months after surgical resection of a T1bN1 tumor. Of 9 NECs, only 2 presented with stage I-III tumors and were treated with radiation (1) or surgery (1). One patient developed distant relapse 4.8 months after radiation. Among all NEMs, liver was the most common site of metastasis (n = 10) followed by bone (n = 3). Median overall survival was 46.5 and 4.8 months for NETs and NECs (p < 0.01), respectively. Conclusions: Rectal NEMs comprise a rare subgroup of rectal tumors and may be classified as NETs or NECs. NETs generally present with early stage disease and are associated with good outcomes with local excision and without pelvic radiation. Rectal NECs frequently present with advanced disease and are associated with poor outcomes.

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Small Neuroendocrine Tumors of the Whole Gastrointestinal Tract Performed Endoscopic or Surgical Resections Also Show Positive for Lymphovascular Invasion

Digestion ◽

10.1159/000517282 ◽

2021 ◽

pp. 1-8

Author(s):

Haruna Miyashita ◽

Takuji Yamasaki ◽

Yoshihiro Akita ◽

Yoshitaka Ando ◽

Yuki Maruyama ◽

...

Keyword(s):

Surgical Resection ◽

Neuroendocrine Tumors ◽

Tumor Size ◽

Lymphovascular Invasion ◽

Distant Metastases ◽

High Rate ◽

Ki 67 ◽

Primary Endpoints ◽

Invasion Impact ◽

Prognostic Stratification

Background and Aims: In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. Methods: We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. Results: Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases <5 mm, with a lymphovascular invasion rate of 8.7% for those 5–10 mm. Lymphovascular invasion ≤10% required a tumor size ≤8 mm, and lymphovascular invasion ≤5% required a tumor size ≤6 mm. A cutoff of 6 mm was identified, which yielded a sensitivity of 79% and a specificity of 63%. Even small GI-NETs grade 1 of the whole GI tract also showed positive for lymphovascular invasion. Conclusions: GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.

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Surgical Management of Advanced Adrenocortical Carcinoma: A 21-year Population-based Analysis

The American Surgeon ◽

10.1177/000313481307901033 ◽

2013 ◽

Vol 79 (10) ◽

pp. 1115-1118 ◽

Cited By ~ 19

Author(s):

Thuy B. Tran ◽

Douglas Liou ◽

Vijay G. Menon ◽

Nicholas N. Nissen

Keyword(s):

Surgical Resection ◽

Adrenocortical Carcinoma ◽

Univariate Analysis ◽

Survival Rates ◽

Stage Iv ◽

Population Based ◽

Stage Iii ◽

Dismal Prognosis ◽

Advanced Stages ◽

The Impact

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis. When diagnosed in advanced stages of the disease, the outcomes of surgical resection are not well understood. The objective of this study is to determine the impact of surgery in patients with advanced ACC. Using the Surveillance, Epidemiology and End Results database, we identified patients diagnosed with Stage III and IVACC between 1988 and 2009. A total of 320 patients with Stage III and IV disease were included in our analysis. In patients treated with surgical resection, the Stage III 1- and 5-year survival rates were 77 and 40 per cent, respectively, whereas the Stage IV 1- and 5-year survival rates were 54 and 27.6 per cent, respectively. Patients treated without surgery had poor survival at 1 year for both Stage III (13%) and Stage IV (16%) ( P < 0.01 compared with the surgical groups). Lymph node dissection was performed in 26 per cent of the patients with advanced ACC and was associated with improved survival in univariate analysis of Stage IV patients. Overall, our results indicate that favorable survival outcomes can be achieved even in patients with Stage III and IV disease and surgery should be considered in patients with advanced ACC.

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Pancreatic neuroendocrine tumors: Single institution review over 10 years.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15183 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15183-e15183

Author(s):

Aakanksha Asija ◽

Stacey Milan ◽

Anthony Prestipino ◽

Charles Yeo ◽

Madhavan V. Pillai

Keyword(s):

Surgical Resection ◽

Median Survival ◽

Neuroendocrine Tumors ◽

Univariate Analysis ◽

Stage Iv ◽

Tnm Staging ◽

The Body ◽

Stage I ◽

University Hospital ◽

Pancreatic Neuroendocrine Tumors

e15183 Background: Pancreatic neuroendocrine tumors(pNET) are rare tumors accounting for less than 5% of pancreatic cancer. They are functionally and biologically heterogeneous and have not been studied in great detail until recently. Methods: We conducted a retrospective review of 79 consecutive patients with pNET diagnosed and treated at Thomas Jefferson University Hospital between the years of 2000 and 2010. Results: Of the 79 patients whose records were reviewed, 32 were male and 47 were female. Median age at diagnosis was 61 years. Two cases were associated with MEN1 syndrome. Primary tumor arose in the head, body and tail of the pancreas in 15, 10 and 26 patients, resp. In 6 patients, the tumor was multifocal. The neuroendocrine tumor was accompanied by pancreatic adenocarcinoma in 1 patient and intraductal papillary mucinous neoplasm in 3. In 10 patients, distant metastasis was detected, involving liver only. Tumor was functional in 9 patients: 5 insulinoma, 2 gastrinoma,1 glucagonoma and 1 VIPoma. As per TNM staging, 28, 22 and 10 patients were Stage I, II and III, and IV at diagnosis. Treatment by surgical resection was undertaken in 54 patients. In 21 patients, the tumor was discovered incidentally; 21 patients presented with abdominal pain. Other symptoms were irregular bowel movements, weight loss and jaundice. 51 of the 79 (64.5%) patients were alive at last follow up. On univariate analysis, median survival for females was 137 months vs 114 months for male. Median survival for patients with functional tumors was similar to those with nonfunctioning tumors (118 and 115 months, resp). Median survival for patients with Stage I, II, and III and Stage IV patients were 234,112 and 40 months resp. Median survival for patients who underwent surgical resection was 130 months vs those who did not (30 months). Conclusions: Majority of pNET were located in the body and tail of pancreas; an area requiring thorough scrutiny with special imaging studies for diagnosis. Only a minority of patients presented with liver metastasis(12%) and a smaller number showed hormonal activity (11%). Prognosis improved markedly in patients who underwent surgical resection. Therefore, whenever appropriate, surgical resection should be the treatment of choice in patients with pNET.

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Prognosis following surgical resection versus local excision of stage pT1 colorectal cancer: A population-based cohort study

The Surgeon ◽

10.1016/j.surge.2019.06.004 ◽

2020 ◽

Vol 18 (2) ◽

pp. 65-74

Author(s):

Rachael McBride ◽

Blanaid M. Hicks ◽

Helen G. Coleman ◽

Maurice B. Loughrey ◽

Anna T. Gavin ◽

...

Keyword(s):

Colorectal Cancer ◽

Cohort Study ◽

Surgical Resection ◽

Local Excision ◽

Population Based

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

10.21203/rs.3.rs-1151806/v1 ◽

2022 ◽

Author(s):

Young Mok Park ◽

Hyung Il Seo ◽

Byeong Gwan Noh ◽

Suk Kim ◽

Seung Baek Hong ◽

...

Keyword(s):

Univariate Analysis ◽

Survival Rates ◽

Ampulla Of Vater ◽

Clinicopathological Characteristics ◽

Mitotic Count ◽

Neuroendocrine Neoplasms ◽

Clinical Report ◽

Ki 67 ◽

Poorly Differentiated Neuroendocrine Carcinoma ◽

Staging Systems

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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Grade Assignment by Ki-67 Proliferative Index, Mitotic Count, and Phosphohistone H3 Count in Surgically Resected Gastrointestinal and Pancreatic Neuroendocrine Tumors

Pancreas ◽

10.1097/mpa.0000000000000923 ◽

2017 ◽

Vol 46 (10) ◽

pp. 1359-1365 ◽

Cited By ~ 1

Author(s):

Claire E. Murphy ◽

Kinsey A. McCormick ◽

Veena Shankaran ◽

Deepti M. Reddi ◽

Paul E. Swanson ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Mitotic Count ◽

Pancreatic Neuroendocrine Tumors ◽

Proliferative Index ◽

Ki 67 ◽

Phosphohistone H3 ◽

Grade Assignment

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The Influence of Tumor Stage on the Prognostic Value of Ki-67 Index and Mitotic Count in Small Intestinal Neuroendocrine Tumors

The American Journal of Surgical Pathology ◽

10.1097/pas.0000000000000968 ◽

2018 ◽

Vol 42 (2) ◽

pp. 247-255 ◽

Cited By ~ 7

Author(s):

Yu Sun ◽

Christine Lohse ◽

Thomas Smyrk ◽

Timothy Hobday ◽

Trynda Kroneman ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Prognostic Value ◽

Tumor Stage ◽

Mitotic Count ◽

Ki 67 ◽

Small Intestinal

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Efficacy and Prognostic Factors for Y-90 Radioembolization (Y-90) in Metastatic Neuroendocrine Tumors with Liver Metastases

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2020/5104082 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Erica S. Tsang ◽

Jonathan M. Loree ◽

Janine M. Davies ◽

Sharlene Gill ◽

David Liu ◽

...

Keyword(s):

Liver Metastases ◽

Neuroendocrine Tumors ◽

Performance Status ◽

Population Based ◽

Somatostatin Analogue ◽

Ecog Performance Status ◽

Ki 67 ◽

Well Differentiated ◽

Grade 3 ◽

Metastatic Liver

Background. Yttrium-90 (Y-90) can be an effective liver-directed therapy for patients with metastatic neuroendocrine tumors (NETs), but population-based data are limited. We characterized the use of Y-90 in NET patients and identified factors associated with response. Methods. We identified 49 patients with metastatic liver-dominant NETs across BC Cancer’s six regional centres who received Y-90 between June 2011 and January 2017 in British Columbia, Canada. Baseline characteristics, radiographic responses, and outcomes were summarized. Results. Of the 49 patients who received Y-90, the median age was 56 years (range 21–78), 49% were male, and 94% had an ECOG performance status of 0–1. The primary location of the NET included pancreas (31%), small bowel (41%), large bowel (6%), unknown (14%), and others (12%). 69% of these patients had liver metastases alone, and tumors were graded as G1 (61%), G2 (25%), G3 (2%), and unknown (12%). Prior therapies included surgery (63%), local ablative therapy (25%), somatostatin analogue (69%), and systemic therapy (35%). The median Y-90 dose was 2.2 GBq (range 0.8–3.6), as SIR-spheres (69%) or TheraSpheres (29%). Median time to Y-90 from diagnosis of metastases measured 1.54 years. 88% received segmental Y-90, with 1 (69%), 2 (29%), and 3 (2%) treatments. Y-90 resulted in partial response (53%), stable disease (33%), and progressive disease (12%). Y-90 was well-tolerated, with infrequent grade 3-4 biochemical toxicities (2%) and grade 3 abdominal pain (6%). Longer overall survival (OS) was associated with resection of primary tumor, well-differentiated histology, and low Ki-67. Median OS was 27.2 months (95% CI 8.0–46.5).Conclusions. In our population-based cohort, Y-90 was well-tolerated in patients with metastatic liver-dominant NETs. Prior surgical resection was an important predictor of OS.

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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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