Digestive Neuroendocrine Neoplasms (NEN): French Intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, GTE, RENATEN, TENPATH, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR)

Mestier, Louis de; Lepage, Côme; Baudin, Éric; Coriat, Romain; Courbon, F.; Couvelard, Anne; Cao, Christine Do; Frampas, É.; Gaujoux, Sébastien; Gincul, Rodica; Goudet, P.; Lombard‐Bohas, Catherine; Poncet, Gilles; Smith, Denis; Ruszniewski, Philippe; Lecomte, Thierry; Bouché, Olivier; Walter, Thomas; Cadiot, Guillaume

doi:10.1016/j.dld.2020.02.011

Cited by 95 publications

(142 citation statements)

References 130 publications

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“…The third one is 18F-2-fluorodeoxyglucose (FDG-PET) which mainly has a prognostic value high FDG uptake which is correlated with worse survival even in well-differentiated NETs such as SI-NETs. The results of FDG-PET and SSTRI can be combined to perform metabolic grading [24][25][26]. Metabolic grading has been reported to be better than the Ki67 proliferation index to predict tumor aggressiveness in SI-NET of any grade, by providing a whole-body evaluation of tumor aggressiveness and reducing the sampling bias.…”

Section: Preoperative Imagingmentioning

confidence: 99%

“…perform metabolic grading [24][25][26]. Metabolic grading has been reported to be better than the Ki67 proliferation index to predict tumor aggressiveness in SI-NET of any grade, by providing a wholebody evaluation of tumor aggressiveness and reducing the sampling bias.…”

Section: Mlnm Imagingmentioning

confidence: 99%

“…Whatever the efficacy of octreotide regarding carcinoid crisis, it does not seem deleterious, as no increased rate of anastomotic leakage has been reported despite the octreotide-induced decrease of visceral perfusion. Consequently, octreotide prophylaxis must be included within the perioperative management protocol at a rate ranging from 100-500 mcg/h, even more so if risk factors are present [15,25]. Despite this preparation, anesthesiologists must be ready to face a carcinoid crisis by prompt usage of octreotide bolus but also vasopressor drugs (such as vasopressin and phenylephrine) in order to limit the duration of hypotension, which could lead to postoperative morbidity.…”

Section: Prevention and Management Of The Carcinoid Crisismentioning

confidence: 99%

“…In order to limit those risks, patients should be referred to specialized centers [68], but an oncologic resection may not be possible in an emergency context. In this case, the procedure should focus on the life-threatening condition, and consider a limited resection of the diseased intestine to avoid subsequent difficult reoperation [25]. Thereafter, a re-intervention for oncological purposes should be planned if the first emergency surgery was non-optimal R2 resection, fewer than eight resected lymph nodes, absent of entire small bowel palpation, carcinomatosis, and positive postoperative imaging [25].…”

Section: Emergency Surgerymentioning

confidence: 99%

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Surgery and Perioperative Management in Small Intestinal Neuroendocrine Tumors

Deguelte¹,

Perrier²,

Hammoutene³

et al. 2020

JCM

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Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to advanced stage at diagnosis, or palliative intent. Surgeons must be informed about the specific surgical management of SI-NETs according to their hormonal secretion, their usual dissemination at the time of diagnosis and the need for bowel-preserving surgery to avoid short bowel syndrome. The aim of this paper is to review the surgical indications and techniques, and perioperative and postoperative management of SI-NETs.

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Section: Preoperative Imagingmentioning

confidence: 99%

Section: Mlnm Imagingmentioning

confidence: 99%

Section: Prevention and Management Of The Carcinoid Crisismentioning

confidence: 99%

Section: Emergency Surgerymentioning

confidence: 99%

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Surgery and Perioperative Management in Small Intestinal Neuroendocrine Tumors

Deguelte¹,

Perrier²,

Hammoutene³

et al. 2020

JCM

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“…In these patients, therapeutic options include somatostatin analogs, cytotoxic or targeted agents, liver-directed therapies and peptide-radionuclide receptor therapy (Frilling et al 2014, Pavel et al 2016. No clear recommendation exist regarding therapeutic sequences, given the lack of predictive biomarkers or trials comparing these treatments (Walter et al 2012, Frilling et al 2014, Pavel et al 2016, de Mestier et al 2020a. Chemotherapy remains a therapeutic cornerstone as it can benefit to patients with aggressive tumors (i.e.…”

Section: Introductionmentioning

confidence: 99%

Critical appraisal of MGMT in digestive NET treated with alkylating agents

Mestier

Couvelard

Blažević

et al. 2020

Endocrine-Related Cancer

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The efficacy of alkylating agents (temozolomide, dacarbazine, streptozotocin) in patients with advanced neuroendocrine tumors (NETs) has been well documented, especially in pancreatic NETs. Alkylating agents transfer methyl adducts on DNA bases. Among them, O6-methylguanine accounts for many of their cytotoxic effects and can be repaired by the O6-methylguanine-methyltransferase (MGMT). However, whether the tumor MGMT status could be a reliable biomarker of efficacy of alkylating agents in NETs is still a matter of debate. Herein, we sought to provide a critical appraisal of the role of the MGMT status in NETs. After reviewing the molecular mechanisms of repair of DNA damage induced by alkylating agents, we aimed to comprehensively review the methods of determination of the MGMT status and its impact on prognosis, prediction of response and progression-free survival in patients with advanced digestive NETs treated by alkylating agents. About half of pancreatic NETs are MGMT-deficient, as determined by impaired tumor MGMT expression or by MGMT promoter methylation. Overall, while published studies are heterogeneous and mostly limited in size, they advocate that MGMT deficiency may be a relevant biomarker for increased objective response rate, prolonged progression-fee survival and overall survival in patients with advanced NETs treated by alkylating agents. While these data require confirmation in prospective controlled studies, future research should focus on the standardization of MGMT status assessment. Additional mechanisms of repair of DNA damages induced by alkylating agents should be explored in order to identify biomarkers complementary to MGMT, and targets for potential antitumor synergy such as PARP.

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Molecular deciphering of primary liver neuroendocrine neoplasms confirms their distinct existence with foregut‐like profile

Mestier

Nicolle

Poté

et al. 2022

The Journal of Pathology

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Isolated hepatic localizations of neuroendocrine tumors (NETs) are generally considered as metastatic NETs of unknown primary but could correspond to primary hepatic NETs (PHNETs), a poorly explored entity. We aimed to describe the clinicopathological and molecular features of PHNETs and compare them with other primary NETs. We assembled a retrospective cohort of patients managed for hepatic localization of NET without extra‐hepatic primary tumor after exhaustive clinical, imaging, and immunohistochemical characterization. We performed whole‐exome sequencing with mutational and copy number analysis. Transcriptomic profiles were compared with pancreatic (n = 31), small‐bowel (n = 22), and lung (n = 15) NETs using principal component analysis, unsupervised clustering, and gene set enrichment analysis. Among 27 screened patients, 16 had PHNET (solitary tumor in 63%, median size 11 cm, G2 NETs in 81%) following clinical and pathological review. DNA analyses showed ‘foregut‐like’ genomic profiles with frequent alterations in pathways of Fanconi DNA repair (75%), histone modifiers (58%), adherens junctions (58%), and cell cycle control (50%). The most frequently involved genes were KMT2A (58%), ATM (42%), CDH1, CDKN2C, FANCF, and MEN1 (33% each). Transcriptomic analyses showed that PHNETs clustered closer to foregut (pancreatic, lung) NETs than to midgut (small‐bowel) NETs, while remaining a distinct entity with a specific profile. Assessment of potentially predictive biomarkers suggested efficacy of treatments usually active in foregut NETs. In conclusion, PHNETs display a foregut‐like molecular profile distinct from other types of NETs, with recurrent molecular alterations. Upon exhaustive work‐up to exclude an unrecognized primary tumor, PHNETs should not be considered metastatic NETs from an unknown primary. © 2022 The Pathological Society of Great Britain and Ireland.

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Digestive Neuroendocrine Neoplasms (NEN): French Intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, GTE, RENATEN, TENPATH, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR)

Cited by 95 publications

References 130 publications

Surgery and Perioperative Management in Small Intestinal Neuroendocrine Tumors

Surgery and Perioperative Management in Small Intestinal Neuroendocrine Tumors

Critical appraisal of MGMT in digestive NET treated with alkylating agents

Molecular deciphering of primary liver neuroendocrine neoplasms confirms their distinct existence with foregut‐like profile

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