Prognostic Factors in Pancreatic Endocrine Neoplasms: An Analysis of 136 Cases With a Proposal for Low-Grade and Intermediate-Grade Groups

Hochwald, Steven N.; Zee, Sui Y.; Conlon, Kevin C.; Colleoni, Roberto; Louie, Otway; Brennan, Murray F.; Klimstra, David S.

doi:10.1200/jco.2002.10.030

Cited by 367 publications

(270 citation statements)

References 14 publications

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“…Radiological evidence of liver involvement alone was not significant for survival (P ¼ 0.960). Contrary to what reported for localised NETs in previous studies, we could not demonstrate an impact of age and sex on prognosis (Janson et al, 1997;Hochwald et al, 2002).…”

Section: Discussioncontrasting

confidence: 99%

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The prognostic role of WHO classification, urinary 5-hydroxyindoleacetic acid and liver function tests in metastatic neuroendocrine carcinomas of the gastroenteropancreatic tract

et al. 2007

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The World Health Organisation (WHO) classification (2000) is widely used to classify neuroendocrine carcinomas (NECs), yet its prognostic value needs to be confirmed. In this study, patients with metastatic NECs (n ¼ 119) were classified according to WHO guidelines into well differentiated and poorly differentiated (WDNECs and PDNECs). Histological differentiation based on WHO criteria had the highest impact on overall survival (OS) (PDNECs : WDNECs hazard ratio (HR) ¼ 4.02, P ¼ 0.02); however, PDNECs represented only a small percentage of patients (8%). In a WDNEC-restricted analysis, abnormal liver function tests (LFTs) and elevated urinary 5-hydroxyindoleacetic acid (u5HIAA) were independent prognostic factors for survival (HR ¼ 2.65, P ¼ 0.006 and HR ¼ 2.51, P ¼ 0.003, respectively) and were used to create a WDNEC-specific prognostic model (low risk ¼ both normal, intermediate risk ¼ one of them abnormal, high risk ¼ both abnormal). Low-risk WDNECs had the most favourable prognosis (median OS, mOS 8.1 years), which was significantly better compared to both intermediate-risk and high-risk WDNECs (mOS 3.2 and 1.4 years, with P ¼ 0.01 and Po0.001, respectively). High-risk WDNECs displayed the shortest OS (1.3 years), which was similar to that of PDNECs (P ¼ 0.572). This analysis supports the prognostic value of WHO classification for metastatic NECs arising from the gastroenteropancreatic tract; however, risk stratification using readily available u5HIAA and LFTs may be necessary for the heterogeneous group of WDNECs.

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Section: Discussioncontrasting

confidence: 99%

“…Five-year OS for patients with metastatic NETs has been reported ranging from 26 to 73% in previous large series, showing a rather variable survival that needs to be further stratified (Eriksson et al, 1990;Madeira et al, 1998;Hochwald et al, 2002;Modlin et al, 2003).…”

Section: Discussionmentioning

confidence: 95%

The prognostic role of WHO classification, urinary 5-hydroxyindoleacetic acid and liver function tests in metastatic neuroendocrine carcinomas of the gastroenteropancreatic tract

et al. 2007

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“…21,22 The functional status of pancreatic neuroendocrine tumors was determined according to clinical and serologic findings at presentation. Neuroendocrine tumors from the gastrointestinal tract and lung were also classified using WHO criteria.…”

Section: Study Groupmentioning

confidence: 99%

PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma

et al. 2011

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PAX (paired box) genes encode a family of transcription factors that regulate organogenesis in a variety of organs. Very little is known about the role of PAX8 in endocrine cell development and the expression of PAX8 in neuroendocrine tumors. The purpose of this study was to analyze PAX8 immunohistochemical expression in gastroenteropancreatic and pulmonary well-differentiated neuroendocrine tumors to determine whether PAX8 can reliably distinguish pancreatic neuroendocrine tumors from neuroendocrine tumors of other anatomic sites and other pancreatic non-ductal neoplasms. In total, 221 well-differentiated neuroendocrine tumors were evaluated: 174 primary neuroendocrine tumors (66 pancreatic, 31 ileal, 21 pulmonary, 20 gastric, 17 rectal, 11 appendiceal, and 8 duodenal) and 47 neuroendocrine tumors metastatic to the liver (31 pancreatic, 11 ileal, 2 pulmonary, 2 duodenal, and 1 rectal). Fifteen solid-pseudopapillary neoplasms and six acinar cell carcinomas of the pancreas were also evaluated. PAX8 was positive in 49/66 (74%) primary pancreatic neuroendocrine tumors. PAX8 expression did not correlate with World Health Organization categorization, grade, size, functional status, or the presence of liver or lymph node metastasis. PAX8 expression was identified in 0/31 (0%) ileal, 0/21 (0%) pulmonary, 2/20 (10%) gastric, 5/17 (29%) rectal, 1/11 (9%) appendiceal, and 6/8 (75%) duodenal neuroendocrine tumors. PAX8 was positive in 4/15 (27%) solid-pseudopapillary neoplasms of the pancreas, whereas all acinar cell carcinomas (0/6) lacked immunoreactivity. Among liver metastases, only pancreatic neuroendocrine tumors (20/31, 65%) were PAX8 positive, whereas no cases of ileal (0/11), pulmonary (0/2), duodenal (0/2), and rectal (0/1) neuroendocrine tumor metastases were PAX8 positive. PAX8 is expressed in primary and metastatic pancreatic well-differentiated neuroendocrine tumors, and its expression can reliably distinguish pancreatic from ileal and pulmonary well-differentiated neuroendocrine tumors. Duodenal neuroendocrine tumors and a subset of rectal, gastric, and appendiceal neuroendocrine tumors may also express PAX8. PAX8 expression can distinguish pancreatic neuroendocrine tumors from acinar cell carcinomas, but its utility in distinguishing neuroendocrine tumors from solid-pseudopapillary neoplasms is limited.

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“…In the case of pancreatectomy for benign tumors, the benefits of preventing insulinopenic diabetes by autologous islet transplantation have to be balanced against the oncological risk of transplanting tumor cells. The presence of a single tumor, demonstration of the benign nature of the tumor on frozen sections [low mitotic activity and absence of necrosis (9), no vascular or perineural invasion] and complete removal render a symptomatic recurrence of the insulinoma unlikely (10). We present the case reports and metabolic studies of two patients who underwent islet autotransplantation after an 80% left pancreatectomy for insulinoma.…”

Section: Introductionmentioning

confidence: 98%

Islet Autotransplantation After Left Pancreatectomy for Non-Enucleable Insulinoma

Oberholzer¹,

Máthé²,

Bucher³

et al. 2003

American Journal of Transplantation

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Insulinoma is a rare, almost always benign endocrine tumor of the pancreas, clinically characterized by hyperinsulinemic, hypoglycemic episodes. Surgical excision is the therapy of choice, which may lead to postpancreatectomy diabetes mellitus in the case of extensive pancreatic resection.We present the cases and the metabolic follow up of two patients, 81 and 73 years old, with insulinoma localized close to the main duct in the pancreatic neck. Both patients underwent an 80% left pancreatectomy, avoiding a pancreatico-enteric anastomosis. In order to prevent postpancreatectomy diabetes, the islets from the tumor-free part of the resected pancreas were isolated and injected via a right colic vein into the portal system. After a follow up of 6 and 3 years respectively, both patients remained insulin-independent without any dietary restrictions. Fasting and glucagon-stimulated C-peptide-levels and glycosylated hemoglobin remained within normal range. There were no signs of recurrent insulinoma. Liver biopsy performed in one patient at 1 year after autotransplantation, showed intact, insulin-producing islets within the portal spaces.In conclusion, autologous islet transplantation can preserve the insulin secretory reserve after extended left pancreatectomy for the treatment of benign tumors in the pancreatic neck.

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Prognostic Factors in Pancreatic Endocrine Neoplasms: An Analysis of 136 Cases With a Proposal for Low-Grade and Intermediate-Grade Groups

Cited by 367 publications

References 14 publications

The prognostic role of WHO classification, urinary 5-hydroxyindoleacetic acid and liver function tests in metastatic neuroendocrine carcinomas of the gastroenteropancreatic tract

The prognostic role of WHO classification, urinary 5-hydroxyindoleacetic acid and liver function tests in metastatic neuroendocrine carcinomas of the gastroenteropancreatic tract

PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma

Islet Autotransplantation After Left Pancreatectomy for Non-Enucleable Insulinoma

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