ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors

Falconi, Massimo; Eriksson, Barbro; Kaltsas, Gregory; Bartsch, Detlef K.; Capdevila, Jaume; Caplin, Martyn; Kos–Kudła, Beata; Kwekkeboom, Dik J.; Rindi, Guido; Klöppel, Günter; Reed, Nicholas; Kianmanesh, Réza; Jensen, Robert T.

doi:10.1159/000443171

Cited by 1,152 publications

(1,403 citation statements)

References 208 publications

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“…In selected patients, NET may be treated with limited resection or even managed conservatively, for example due to co-morbidities or presumable low risk of progressive disease [6]. Tumour grade was previously considered as a supplementary tool to predict presence of regional lymph node metastases [43,44,45].…”

Section: Ki67 LI Is Imperfect Predictor Of Regional Lymph Node Metastmentioning

confidence: 99%

“…What is more important, it is critical for establishing the diagnosis of pancreatic NEC, which in current WHO guidelines is based on assessment of proliferation rate in NEN and independent largely from consideration of morphological picture. As clinical management of NET and NEC is different [6,65], to distinguish between these entities is the most important aspect in diagnostics of neuroendocrine neoplasms [11].…”

Section: Significance Of Ki67 LI In Pancreatic Nenmentioning

confidence: 99%

“…Ki67 LI may be used for selection of particular types of treatment and for surveillance programmes [6,7], for example for a choice -surgery vs. surveillance for small non-functioning NET [6], treatment selection in advanced disease [7,70], or length of intervals between assessments during follow-up [6]. Ki67 LI may also serve as a potential predictor of response to chemotherapy [71], radioembolization or chemoembolization [72] in non-operable NEN.…”

Section: Significance Of Ki67 LI In Pancreatic Nenmentioning

confidence: 99%

“…Assessment of Ki67 labeling index (LI) is now a routine procedure for pancreatic NEN [1,4,5]. Ki67 LI is the most important molecular biomarker used for optimizing clinical management of patients with NEN of the pancreas [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Guidelines for Ki67 LI scoring in gastro-enteropancreatic NEN were published (as detailed in Supplementary Information (SI) - Table S1) [1,4,5,6,11,[29][30][31]. According to the World Health Organization (WHO) 2010 guidelines, grading of gastro-entero-pancreatic neuroendocrine neoplasms includes documentation of mitotic count and Ki67 LI [1].…”

Section: Introductionmentioning

confidence: 99%

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Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Liszka¹

2016

pjp

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Reporting of Ki67 labeling index (LI) is a routine in diagnostics of neuroendocrine neoplasms of the pancreas. The aim of the study was to examine whether heterogeneity of Ki67 LI distribution in primary tumoral tissue influences precision of reporting of Ki67 LI and Ki67-LI-based grade, both established in adherence to WHO 2010 guidelines. Seventy-one samples of neuroendocrine tumours (NET) and 6 samples of neuroendocrine carcinomas (NEC) of the pancreas were taken for manual counting of Ki67 LI in 25 portions of 100 cells (2500 cells in total) in 3 hot spots an in a single area of lower proliferation rate (cold spot) in each case. Both NET and NEC showed Ki67 LI heterogeneity within primary tumour. Almost 20% of NET showed higher grade when 500 cells rather than 2000 cells were counted in hot spot area. Suboptimal choice of hot spot resulted in under-grading of approximately 20% of NET. Cold spots were constantly present in NET. Heterogeneity of Ki67 LI was also present in NEC, but it virtually never resulted in under-grading. Concept and methodology of Ki67 LI counting in neuroendocrine neoplasms of the pancreas requires clarification. Efforts aiming to improve precision of assessment of Ki67 LI are needed.

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Section: Ki67 LI Is Imperfect Predictor Of Regional Lymph Node Metastmentioning

confidence: 99%

Section: Significance Of Ki67 LI In Pancreatic Nenmentioning

confidence: 99%

Section: Significance Of Ki67 LI In Pancreatic Nenmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Liszka¹

2016

pjp

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Evaluation of Survival Following Surgical Resection for Small Nonfunctional Pancreatic Neuroendocrine Tumors

et al. 2023

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ImportanceThe number of patients with small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is increasing. However, the role of surgery for small NF-PanNETs remains unclear.ObjectiveTo evaluate the association between surgical resection for NF-PanNETs measuring 2 cm or smaller and survival.Design, Setting, and ParticipantsThis cohort study used data from the National Cancer Database and included patients with NF-pancreatic neuroendocrine neoplasms who were diagnosed between January 1, 2004, and December 31, 2017. Patients with small NF-PanNETs were divided into 2 groups: group 1a (tumor size, ≤1 cm) and group 1b (tumor size, 1.1-2.0 cm). Patients without information on tumor size, overall survival, and surgical resection were excluded. Data analysis was performed in June 2022.ExposuresPatients with vs without surgical resection.Main Outcomes and MeasuresThe primary outcome was overall survival of patients in group 1a or group 1b who underwent surgical resection compared with those who did not, which was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Interactions between preoperative factors and surgical resection were analyzed with a multivariable Cox proportional hazards regression model.ResultsOf the 10 504 patients with localized NF-PanNETs identified, 4641 were analyzed. These patients had a mean (SD) age of 60.5 (12.7) years and included 2338 males (50.4%). The median (IQR) follow-up time was 47.1 (28.2-71.6) months. In total, 1278 patients were in group 1a and 3363 patients were in group 1b. The surgical resection rates were 82.0% in group 1a and 87.0% in group 1b. After adjustment for preoperative factors, surgical resection was associated with longer survival for patients in group 1b (hazard ratio [HR], 0.58; 95% CI, 0.42-0.80; P &lt; .001) but not for patients in group 1a (HR, 0.68; 95% CI, 0.41-1.11; P = .12). In group 1b, interaction analysis found that age of 64 years or younger, absence of comorbidities, treatment at academic institutions, and distal pancreatic tumors were factors associated with increased survival after surgical resection.Conclusions and RelevanceFindings of this study support an association between surgical resection and increased survival in select patients with NF-PanNETs measuring 1.1 to 2.0 cm who were younger than 65 years, had no comorbidities, received treatment at academic institutions, and had tumors of the distal pancreas. Future investigations of surgical resection for small NF-PanNETs that include the Ki-67 index are warranted to validate these findings.

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Follow-up Recommendations for Completely Resected Gastroenteropancreatic Neuroendocrine Tumors

et al. 2018

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There is no consensus on optimal follow-up for completely resected gastroenteropancreatic neuroendocrine tumors. Published guidelines for follow-up are complex and emphasize closer surveillance in the first 3 years after resection. Neuroendocrine tumors have a different pattern and timescale of recurrence, and thus require more practical and tailored follow-up. The Commonwealth Neuroendocrine Tumour Collaboration convened an international multidisciplinary expert panel, in collaboration with the North American Neuroendocrine Tumor Society, to create patient-centered follow-up recommendations for completely resected gastroenteropancreatic neuroendocrine tumors. This panel used the RAND/UCLA (University of California, Los Angeles) Appropriateness Method to generate recommendations. A large international survey was conducted outlining current the surveillance practice of neuroendocrine tumor practitioners and shortcomings of the current guidelines. A systematic review of available data to date was supplemented by recurrence data from 2 large patient series. The resultant guidelines suggest follow-up for at least 10 years for fully resected small-bowel and pancreatic neuroendocrine tumors and also identify clinical situations in which no follow-up is required. These recommendations stratify follow-up strategies based on evidence-based prognostic factors that allow for a more individualized patient-centered approach to this complex and heterogeneous malignant neoplasm.

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ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors

Cited by 1,152 publications

References 208 publications

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Evaluation of Survival Following Surgical Resection for Small Nonfunctional Pancreatic Neuroendocrine Tumors

Follow-up Recommendations for Completely Resected Gastroenteropancreatic Neuroendocrine Tumors

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