Mesenteric sparing approach for advanced nodal extent in small intestinal neuroendocrine tumors. Is there a limit to the vascular resection in order to avoid creating a short small bowel syndrome? An anatomic research study.

PURPOSE: By selectively perfusing the first three jejunal arteries (JA), we aim to assess the individual perfusion length of small bowel (SB) and its impact on nodal resection in stage III-up small-intestinal neuroendocrine tumors (SI-NET). METHODS: Our anatomical research protocol implies a midline laparotomy and three measures of the SB length. We then perform a classical anterior approach of the superior mesenteric vessels. We carry on with the complete dissection and checking of the superior mesenteric artery (SMA) in order to identify the first three JA. Then we selectively perfuse each artery with colored latex solutions and measure the length of small bowel perfused respectively. RESULTS: We conducted our protocol on six cadaveric subjects. Mean(SD) SB length was 413(5.7), 535(13.2), 485(15), 353(25.1), 730(17.3) and 525(16° cm respectively from subject one to six. Most JA originated from the left side of the SMA. The first JA originated from its posterior wall in two subjects. Mean(SD) distance of origin of the first three JA was 4.6(1.3)cm, 6(1.1)cm and 7.1(0.9)cm respectively. Mean(SD) diameter of SMA was 10.8(3.3)mm. Mean diameter of the three first JA was 4(1.4)mm, 4(1.5)mm and 5(1.2)mm respectively. Mean(SD) SB length perfused by first and second JA was 224(14.9)cm, 175(8.6)cm, 238.3(7.6)cm, 84.3(5.1)cm, 233.3(5.8)cm and 218.3(10.4)cm respectively from subject one to six. CONCLUSION: We observed a trend suggesting that the first and second JA may sustain a SB length beyond the viable 1.5 m limit, implying the feasibility of stage III-up SI-NET resection with just two JA.

Phenotypic characterisation of SMAD4 variant carriers.

BACKGROUND: Both hereditary haemorrhagic telangiectasia (HHT) and juvenile polyposis syndrome (JPS) are known to be caused by SMAD4 pathogenic variants, with overlapping symptoms for both disorders in some patients. Additional connective tissue disorders have also been reported. Here, we describe carriers of SMAD4 variants followed in an HHT reference centre to further delineate the phenotype. METHODS: Observational study based on data collected from the Clinical Investigation for the Rendu-Osler Cohort database. RESULTS: Thirty-three participants from 15 families, out of 1114 patients with HHT, had an SMAD4 variant (3%).Regarding HHT, 26 out of 33 participants (88%) had a definite clinical diagnosis based on Curaçao criteria. Complication frequencies were as follows: epistaxis (n=27/33, 82%), cutaneous telangiectases (n=19/33, 58%), pulmonary arteriovenous malformations (n=17/32, 53%), hepatic arteriovenous malformations (AVMs) (n=7/18, 39%), digestive angiodysplasia (n=13/22, 59%). No cerebral AVMs were diagnosed.Regarding juvenile polyposis, 25 out of 31 participants (81%) met the criteria defined by Jass et al for juvenile polyposis syndrome. Seven patients (21%) had a prophylactic gastrectomy due to an extensive gastric polyposis incompatible with endoscopic follow-up, and four patients (13%) developed a digestive cancer.Regarding connective tissue disorders, 20 (61%) had at least one symptom, and 4 (15%) participants who underwent echocardiography had an aortic dilation. CONCLUSION: We describe a large cohort of SMAD4 variant carriers in the context of HHT. Digestive complications are frequent, early and diffuse, justifying endoscopy every 2 years. The HHT phenotype, associating pulmonary and hepatic AVMs, warrants systematic screening. Connective tissue disorders broaden the phenotype associated with SMAD4 gene variants and justify systematic cardiac ultrasound and skeletal complications screening.

Neuropilin 2 and soluble neuropilin 2 in neuroendocrine neoplasms.

Neuropilin 2 (NRP2), a transmembrane non-tyrosine kinase receptor, has been described as a potential critical player in the tumourigenesis of several solid cancers and particularly in neuroendocrine neoplasms (NENs). A soluble form of NRP2 (sNRP2) has been previously described and corresponds to a truncated splice isoform. Its prognostic value has never been studied in NEN. NRP2 expression was studied by immunochemistry on tissue microarrays (n = 437) and on circulating tumour cells (CTCs, n = 5 patients with neuroendocrine carcinoma, NEC). We described the levels of sNRP2 in 229 patients with NEN using the ELISA method to identify the factors associated with sNRP2 levels and to evaluate its prognostic role; 90 blood donors represented the healthy control group. NRP2 was found in 97% of neuroendocrine tumours (396/410) and in 74% of NEC (20/27). NRP2 was also expressed in CTC of all the studied patients. The receiver operating characteristic (ROC) analysis showed that sNRP2 had a weak capacity to discriminate between NEN patients and healthy controls (area under curve (AUC) = 0.601, P = 0.053). Abnormal sNRP2 levels were associated with inflammatory syndrome, bone and peritoneal metastases, and abnormal chromogranin A levels. Patients with high sNRP2 levels (sNRP2Q3-Q4) had significantly poorer overall survival in multivariate analysis (HR 0.16, 95% CI (0.04-0.67), P = 0.015). In conclusion, the present study found that sNRP2 and NRP2 could represent a new prognostic biomarker and a therapeutic target, respectively, particularly in aggressive NEN.

Operating room organization and surgical performance: a systematic review.

BACKGROUND: Organizational factors may influence surgical outcomes, regardless of extensively studied factors such as patient preoperative risk and surgical complexity. This study was designed to explore how operating room organization determines surgical performance and to identify gaps in the literature that necessitate further investigation. METHODS: We conducted a systematic review according to PRISMA guidelines to identify original studies in Pubmed and Scopus from January 1, 2000 to December 31, 2019. Studies evaluating the association between five determinants (team composition, stability, teamwork, work scheduling, disturbing elements) and three outcomes (operative time, patient safety, costs) were included. Methodology was assessed based on criteria such as multicentric investigation, accurate population description, and study design. RESULTS: Out of 2625 studies, 76 met inclusion criteria. Of these, 34 (44.7%) investigated surgical team composition, 15 (19.7%) team stability, 11 (14.5%) teamwork, 9 (11.8%) scheduling, and 7 (9.2%) examined the occurrence of disturbing elements in the operating room. The participation of surgical residents appeared to impact patient outcomes. Employing specialized and stable teams in dedicated operating rooms showed improvements in outcomes. Optimization of teamwork reduced operative time, while poor teamwork increased morbidity and costs. Disturbances and communication failures in the operating room negatively affected operative time and surgical safety. CONCLUSION: While limited, existing scientific evidence suggests that operating room staffing and environment significantly influences patient outcomes. Prioritizing further research on these organizational drivers is key to enhancing surgical performance.

The Need for Centralization for Small Intestinal Neuroendocrine Tumor Surgery: A Cohort Study from the GTE-Endocan-RENATEN Network, the CentralChirSINET Study.

BACKGROUND: The concept of surgical centralization is becoming more and more accepted for specific surgical procedures. OBJECTIVE: The aim of this study was to evaluate the relationship between procedure volume and the outcomes of surgical small intestine (SI) neuroendocrine tumor (NET) resections. METHODS: We conducted a retrospective national study that included patients who underwent SI-NET resection between 2019 and 2021. A high-volume center (hvC) was defined as a center that performed more than five SI-NET resections per year. The quality of the surgical resections was evaluated between hvCs and low-volume centers (lvCs) by comparing the number of resected lymph nodes (LNs) as the primary endpoint. RESULTS: A total of 157 patients underwent surgery in 33 centers: 90 patients in four hvCs and 67 patients in 29 lvCs. Laparotomy was more often performed in hvCs (85.6% vs. 59.7%; p < 0.001), as was right hemicolectomy (64.4% vs. 38.8%; p < 0.001), whereas limited ileocolic resection was performed in 18% of patients in lvCs versus none in hvCs. A bi-digital palpation of the entire SI length (95.6% vs. 34.3%, p < 0.001), a cholecystectomy (93.3% vs. 14.9%; p < 0.001), and a mesenteric mass resection (70% vs. 35.8%; p < 0.001) were more often performed in hvCs. The proportion of patients with ≥8 LNs resected was significantly higher (96.3% vs. 65.1%; p < 0.001) in hvCs compared with lvCs, as was the proportion of patients with ≥12 LNs resected (87.8% vs. 52.4%). Furthermore, the number of patients with multiple SI-NETs was higher in the hvC group compared with the lvC group (43.3% vs. 25.4%), as were the number of tumors in those patients (median of 7 vs. 2; p < 0.001). CONCLUSIONS: Optimal SI-NET resection was significantly more often performed in hvCs. Centralization of surgical care of SI-NETs is recommended.

Management strategies of anastomotic ulcer after gastric bypass and risk factors of recurrence.

BACKGROUND: Marginal ulcers (MU) after gastric bypass are a challenging problem. The first-line treatment is a medical therapy with eviction of risk factors but is sometimes insufficient. The management strategies of intractable ulcers are still not clearly defined. The aim of our study was to analyse the risk factors for recurrence, the management strategies used and their efficiencies. METHODS: Based on a retrospective analysis of all MU managed in our tertiary care centre of bariatric surgery during the last 14 years, a descriptive analysis of the cohort, the management strategies and their efficiency were analysed. A logistic regression was done to identify the independent associated risk factors of intractable ulcer. RESULTS: Fifty-six patients matched inclusion criteria: 30 were referred to us (13 Roux-en-Y Gastric Bypass-RYGB and 17 One Anastomosis Gastric Bypass-OAGB), 26 were operated on in our institution (24 RYGB and 2 OAGB). 11 patients had a complicated inaugural MU requiring an interventional procedure in emergency: 7 perforations, 4 haemorrhages. The majority of MU were treated medically as a first-line therapy (n = 45; 80.4%). 32 MU recurred: 20 patients required surgery as a 2nd line therapy, 6 were operated on as a 3rd line therapy and 1 had a surgery as a 5th line therapy. The OAGB was the only risk factor of recurrence (p = 0.018). We found that the Surgical management was significantly more frequent for patients with a OAGB (84% versus 35% for RYGB, p = 0.001); the most performed surgical procedure was a conversion of OAGB to RYGB (n = 11, 37.9%). CONCLUSION: Surgery was required for a large number of MU especially in case of recurrence, but recurrence can still occur after the surgery. The OAGB was the only risk factor of recurrence identified and conversion to RYGB seemed to be effective for the healing.

Management of neuroendocrine neoplasms: conformity with guidelines in and outside a center of excellence.

Purpose: To improve neuroendocrine neoplasm (NEN) management, the European Neuroendocrine Tumor Society (ENETS) recognised 62 Centers of Excellence (CoE). This retrospective study compares conformity of patients' initial management within vs outside an ENETS CoE with clinical practice guidelines (CPGs). Methods: Patients diagnosed with a NEN between August 2018 and July 2020 and presented in the Lyon-CoE Multidisciplinary Tumour Board (MDT) were included. Factors potentially associated with the conformity of initial management (work-up and first treatment) to CPG underwent univariate and multivariate analyses. Results: Among the 615 included patients, 170 (27.6%) were initially managed in the CoE and 445 (72.4%) were only presented at the CoE-MDT. Patients in the CoE group more often had intestinal or pancreatic primaries, metastatic disease (61.8% vs 33%), hereditary syndrome, and a functioning tumour. Work-up conformity was 37.1% in the CoE (vs 29.9%, P = 0.09); this was 95.8% for the first treatment (vs 88.7%, P = 0.01). After multivariate analysis, CPG conformity was significantly higher for patients managed in the CoE, for younger patients, for those having a grade 1-2 tumour, and a genetic syndrome. Pancreatic and small intestinal (SI) NET surgeries performed in the CoE had a higher splenic preservation rate during left pancreatectomy, better detection of multiple tumours in SI surgeries, and higher number of resected lymph nodes. Conclusions: Given the widespread observance of CPG, not all patients require management in the CoE. Referral should be considered for more complex cases such as metastatic diseases, G2 tumours, or carcinoid syndromes. Finally, we should encourage the centralization of NET surgery.

18F-DOPA PET/CT at the Forefront of Initial or Presurgical Evaluation of Small-Intestine Neuroendocrine Tumors.

Our objective was to compare the respective value of 68Ga-DOTATOC and 18F-DOPA PET/CT for initial staging or presurgical work-up of patients with small-intestine neuroendocrine tumors (SiNETs). Methods: This was a retrospective, multicenter, noninterventional investigation involving 53 non-surgically treated SiNET patients who underwent both 68Ga-DOTATOC and 18F-DOPA PET/CT within a 6-mo interval without surgical intervention or therapeutic change between the 2 PET/CT studies. Percentage detection rate was calculated according to per-region and per-lesion analyses. Sensitivity for primary tumor detection was assessed in 37 surgically treated patients, taking surgical results (76 SiNETs) as the diagnostic gold standard. Results: 68Ga-DOTATOC PET/CT and 18F-DOPA PET/CT individually identified at least 1 primary SiNET in 92% (34/37) of the patients. Intestinal tumor multifocality was confirmed by histology in 8 patients. 68Ga-DOTATOC and 18F-DOPA PET/CT were concordantly positive for tumor multifocality in 5 patients, discordantly positive in 2 patients, and concordantly negative in 1 patient. The detection rate for subdiaphragmatic nodal metastases on per-region-based analysis was 91% and 98% for 68Ga-DOTATOC and 18F-DOPA PET/CT, respectively (P = 0.18). 18F-DOPA PET/CT detected a higher number of abnormal subdiaphragmatic nodes (P = 0.009). Regarding mesenteric nodes only, 18F-DOPA PET/CT detected more positive regions (P = 0.005) and nodal lesions (P = 0.003) than 68Ga-DOTATOC PET/CT, including nodes at the origin of mesenteric vessels. For detection of distant metastases, 68Ga-DOTATOC and 18F-DOPA PET/CT performed equally well on a per-region-based analysis. As compared with 68Ga-DOTATOC, 18F-DOPA PET/CT detected more hepatic (P < 0.001), peritoneal (P < 0.001), and lung metastases (P < 0.001). Conclusion: 18F-DOPA PET/CT detected more lesions than 68Ga-DOTATOC PET/CT in the studied patients. The respective roles of the two should be discussed in terms of disease staging and treatment selection.

Digestive perforations related to endoscopy procedures: a local management charter based on local evidence and experts' opinion.

Background and study aims Perforations are a known adverse event of endoscopy procedures; a proposal for appropriate management should be available in each center as recommended by the European Society of Gastrointestinal Endoscopy. The objective of this study was to establish a charter for the management of endoscopic perforations, based on local evidence. Patients and methods Patients were included if they experienced partial or complete perforation during an endoscopic procedure between 2008 and 2018 (retrospectively until 2016, then prospectively). Perforations (size, location, closure) and management (imagery, antibiotics, surgery) were analyzed. Using these results, a panel of experts was asked to propose a consensual management charter. Results A total of 105 patients were included. Perforations occurred mainly during therapeutic procedures (91, 86.7%). Of the perforations, 78 (74.3 %) were diagnosed immediately and managed during the procedure; 69 of 78 (88.5 %) were successfully closed. Closures were more effective during therapeutic procedures (60 of 66, 90.9 %) than during diagnostic procedures (9 of 12, 75.0 %, P  = 0.06). Endoscopic closure was effective for 37 of 38 perforations (97.4 %) < 0.5 cm, and for 26 of 34 perforations (76.5 %) ≥ 0.5 cm ( P  < 0.05). For perforations < 0.5 cm, systematic computed tomography (CT) scan, antibiotics, or surgical evaluation did not improve the outcome. Four of 105 deaths (3.8 %) occurred after perforation, one of which was attributable to the perforation itself. Conclusions Detection and closure of perforations during endoscopic procedure had a better outcome compared to delayed perforations; perforations < 0.5 cm had a very good prognosis and CT scan, surgeon evaluation, or antibiotics are probably not necessary when the endoscopic closure is confidently performed. This work led to proposal of a local management charter.

Concept of reintervention with thorough lymphadenectomy after suboptimal resection of small-intestine neuroendocrine neoplasms: A multicentre preliminary study.

Complete surgical resection is the only hope to cure small intestine neuroendocrine neoplasms (SiNENs). However, inadequate lymphadenectomy or entire small bowel palpation for multiple primary tumours renders at least 20% of resections suboptimal. This study was undertaken to investigate reintervention outcomes after initial suboptimal resections (ISORs), and agreement between residual tumour identification on interval imaging and during reintervention. This retrospective, multicentre study included all patients undergoing reintervention within 18 months post ISOR. Disease-free survival (DFS) was defined as the time from reintervention resection date to recurrence or any-cause of death. The kappa coefficient assessed agreement rates between suspected residual tumour on interval imaging and its presence at reintervention. A total of 21 patients underwent reintervention for nonmetastatic SiNENs (median follow-up 2.3 [IQR 0.6-3.75] years). Residual tumour, suspected in 17/21 (81%) patients based on interval imaging, was found in 20/21 (95%) during reintervention. Interval imaging-intraoperative detection agreement was fair for residual primary tumours (kappa = 0.28, 95% CI: 0.05-0.62; p = .09) and residual lymph node metastases (kappa = 0.17, 95% CI: 0.28-0.62; p = .45). Reintervention achieved complete tumour clearance in 16/21 (76%) patients, among whom 5/16 (31%) developed liver metastases during follow-up. Median DFS was 70.6 months (IQR 39.7-not reached). Reintervention post-ISOR can obtain tumour clearance and prolonged remission. It should be systematically discussed after suspected ISOR, even when postoperative imaging does not find any residual tumour. To maximize detection of potentially resectable residual disease, imaging modalities after "curative" surgery should be redefined.

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for small bowel neuroendocrine tumors with peritoneal metastasis.

BACKGROUND: Up to 20% of patients with small-bowel neuroendocrine tumors (SB-NETs) may present with peritoneal carcinomatosis (PM). Surgical cytoreduction (CRS) has been proposed as an adequate management as it confers a survival benefit in selected patients. The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to CRS in this context may be an option but data on its added benefits is lacking. METHODS: A search was performed in the prospective multicenter international collaborative database of the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working groups, and patients who underwent a surgical treatment (CRS or CRS with HIPEC) for a SB-NET with PM were identified and compared. RESULTS: Between 2002 and 2016, a total of 67 patients were identified as having a CRS for SB-NET, with 36 receiving HIPEC during surgery. Median postoperative follow-up was 34 months. The peritoneal cancer index (PCI) and the completeness of cytoreduction score (CCR-score) were higher in the CRS-HIPEC group. More grade III-IV complications occurred in this group as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Despite a tendency toward a better progression/recurrence-free survival in patients receiving HIPEC, no significant differences were noted between the CRS and CRS-HIPEC groups in terms of postoperative recurrence. CONCLUSIONS: HIPEC does not seem to provide additional benefits in terms of postoperative evolution and survival in patients with SB-NET undergoing CRS. It is associated with higher morbidity. It may possibly lead to an improved recurrence-free survival, but further reports are required to confirm this assumption.

Association of Hospital Bed Turnover With Patient Outcomes in Digestive Surgery.

To determine the influence of hospital bed turnover rate (BTR) on the occurrence of complications following minor or major digestive surgery. Background: Performance improvement in surgery aims at increasing productivity while preventing complications. It is unknown whether this relationship can be influenced by the complexity of surgery. Methods: A nationwide retrospective cohort study was conducted, based on generalized estimating equation modeling to determine the effect of hospital BTR on surgical outcomes, adjusting for patient mix and clustering within 631 public and private French hospitals. All patients who underwent minor or major digestive surgery between January 1, 2013 and December 31, 2018 were included. Hospital BTR was defined as the annual number of stays per bed for digestive surgery and categorized into tertiles. The primary endpoint was a composite measurement of events occurring within 30 days after surgery: inpatient death, extended intensive care unit (ICU) admission, and reoperation. Results: Rate of adverse events was 2.51% in low BTR hospitals versus 2.25% in high BTR hospitals for minor surgery, and 16.79% versus 16.83% for major surgery. Patients who underwent minor surgery in high BTR hospitals experienced lower complications (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.81-0.97; P = 0.009), mortality (OR, 0.87; 95% CI, 0.78-0.98, P = 0.02), ICU admission (OR, 0.83; 95% CI, 0.70-0.99; P = 0.03), and reoperation (OR, 0.91; 95% CI, 0.85-0.97; P = 0.002) compared to those in low BTR hospitals. Such differences were not consistently observed among patients admitted for major surgery. Conclusions: High turnover of patients in beds is beneficial for minor procedures, but questionable for major surgeries.

Principles of Surgical Management of Small Intestinal NET.

INTRODUCTION: Small-intestinal neuroendocrine tumors (siNETs) account for 25% of gastroenteropancreatic NETs. Multiple siNETs appear to develop in a limited segment of the small bowel (SB), 89% of them being located in the ileum, most often within 100 cm of the ileocecal valve (ICV). According to the European Neuroendocrine Tumor Society (ENETS) and the American Joint Committee on Cancer (AJCC), all localized siNETs should be considered for radical surgical resection with adequate lymphadenectomy irrespective of the absence of lymphadenopathy or mesenteric involvement. Surgical management of siNETs: The preoperative workout should include a precise evaluation of past medical and surgical history, focusing on the symptoms of carcinoid syndrome (flush, diarrhea, and cardiac failure). Morphological evaluation should include a CT scan including a thin-slice arterial CT, a PET/CT with 68 Ga, and a hepatic MRI in cases of suspected metastasis. Levels of 24 h urinary 5-hydroxyindoleacetic acid are needed. Regarding surgery, the limiting component is the number of free jejunal branches allowing a resection without risk of short small bowel syndrome. The laparoscopic approach has been poorly studied, and open laparotomy remains the gold standard to explore the abdominal cavity and entirely palpate the small bowel through bidigital palpation and compression. An extensive lymphadenectomy is required. A prophylactic cholecystectomy should be performed. In case of emergency surgery, current recommendations are not definitive. However, there is expert agreement that it is not reasonable to initiate resection of the mesenteric mass without comprehensive workup and mapping. CONCLUSION: The surgery of siNETs is in constant evolution. The challenge lies in the ability to propose a resection without imposing short small bowel syndrome on the patients. The oncological benefits supported in the literature led to recent changes in the recommendations of academic societies. The next steps remain the dissemination of reproducible quality criteria to perform these procedures.

Prophylactic colectomy and rectal preservation in FAP: systematic endoscopic follow-up and adenoma destruction changes natural history of polyposis.

Background and study aims Prophylactic surgery of familial adenomatous polyposis (FAP) includes total colectomy with ileorectal anastomosis (IRA) to proctocolectomy with ileoanal anastomosis (IAA). Surgical guidelines rely on studies without systematic endoscopic follow-up and treatment. Our aim was to report our experience based on a different approach: therapeutic follow-up, comparing in this setting IRA and IAA in terms of oncological safety and quality of life. Patients and methods Between January 1965 and November 2015, all patients who underwent prophylactic surgery for FAP with therapeutic endoscopic follow-up in Lyon University hospital: systematic endoscopic treatment of adenomas, were retrospectively and prospectively (since 2011) included. Results A total of 296 patients were analyzed: 92 had proctocolectomy with IAA (31.1 %), 197 total colectomy with IRA (66.5 %), and seven abdominoperineal resections (2.4 %). Median follow-up was 17.1 years (range, 0-38.1). Incidence of secondary cancer (IR vs. IAA) was 6.1 % vs. 1.1 % ( P  = 0.06; 95 %CI 0.001-0.36). The 15-year cancer-free and overall survival (IR vs. IAA) were 99.5 % vs 100 % ( P  = 0.09) and 98.9 % vs. 98.8 % ( P  = 0.82), respectively. Postoperative morbidity occurred in 44 patients: 29 (14.7 %) in the IRA and 15 (16.3 %) in the IAA group ( P  = 0.72). The mean number of stools per day in the respective groups were 4.4 (2.5) vs. 5.5 (2.6) ( P  = 0.001). Fecal incontinence occurred in 14 patients (7.1 %) in the IRA vs. 16 (17.4 %) in the IAA group ( P  = 0.03). Conclusions A combination of therapeutic endoscopic treatment and extended rectal preservation appears to be a safe alternative to ileoanal J-pouch anastomosis.

Unifocal versus Multiple Ileal Neuroendocrine Tumors Location: An Embryological Origin.

INTRODUCTION: Small-intestinal neuroendocrine tumors (SI-NET) are situated preferentially within the ileum. The aim was to describe a potential difference in location between unifocal and multiple ileal-NET. PATIENTS AND METHODS: Between December 2010 and December 2019, all consecutive patients who underwent resection in our European Neuroendocrine Tumor Society Center of Excellence, of at least 1 non-duodenal SI-NET, were retrospectively included. The main objective was to prove that multiple ileal-NET were mostly located on the left side of the superior mesenteric artery (SMA) axis (defined as 40 cm from the ileocecal valve), and unifocal ones on the right side. RESULTS: Ninety-four patients were included, 6 with unifocal jejunal-NET located 35 cm (range, 10-60) from the duodenojejunal angle (DJA), 44 (47%) with unifocal ileal-NET and 44 (47%) with multiple ileal-NET. The median number of tumors in multiple ileal-NET was 7 (range, 2-95), within a median small bowel segment of 105 cm (10-240). The median length between the proximal tumor and the DJA was 428 cm (300-635) and 540 cm (350-725) for the distal one; 40 (91%) of them were located on the left side of the SMA axis. In contrast, unifocal ileal-NET were located at a median distance of 577 cm (305-820) from the DJA (p < 0.001, compared to multiple ileal-NET); 30 (68%) of them were on the right side of the SMA axis (p < 0.001). CONCLUSION: Multiple ileal-NET are mostly located on the left side of the SMA axis. Further studies are warranted to explore the embryological origin of unifocal versus multiple ileal-NET.

Third bariatric procedure for insufficient weight loss or weight regain: how far should we go?

BACKGROUND: Revisional procedures in bariatric surgery are increasing with several debated failure risk factors, such as super obesity and old age. No study has yet evaluated the outcomes and risks of a third bariatric procedure indicated for weight loss failure or weight regain. OBJECTIVES: To assess failure risks of a third bariatric procedure according to Reinhold's criteria (percentage excess weight loss [%EWL] ≤50% and/or body mass index [BMI] ≥35 kg/m2). SETTING: A university-affiliated tertiary care center, France. METHODS: From 2009 to 2019, clinical data and weight loss results of patients who benefited from 3 bariatric procedures for weight loss failure or weight regain were collected prospectively and analyzed using a binary logistic regression. Weight loss failure was defined according to Reinhold's criteria. RESULTS: Among 1401 bariatric procedures performed, 336 patients benefited from 2 or more procedures, and 45 had a third surgery. Eleven patients that were reoperated on because of malnutrition or gastroesophageal reflux disease were excluded from the final analysis. Among 34 patients with 3 procedures because of weight loss failure or regain, mean BMI was 48.3 ± 8.3 kg/m2, and mean age was 30 ± 10.7 years. Three out of 34 patients (9%) presented a severe complication (Dindo-Clavien IIIb) and 2 (6%) had a minor one. Achieving Reinhold's weight loss criteria after the second bariatric procedure was a significant predictor of success of the third procedure (ß = 2.9 ± 1.3 S.E.). CONCLUSION: Not reaching Reinhold's criteria after a second bariatric procedure was identified as a significant risk factor of failure of a third procedure. A third surgery should be carefully discussed especially in case of primary failure of previous procedures.

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).

INTRODUCTION: This document is a summary of the French Intergroup guidelines regarding the management of digestive neuroendocrine neoplasms (NEN) published in February 2020 (www.tncd.org). METHODS: All French medical societies involved in the management of NEN took part in this work. Recommendations were graded into four categories (A, B, C or D), according to the level of evidence found in the literature until May 2019. RESULTS: The management of NEN is challenging because of their heterogeneity and the increasing complexity of diagnostic and therapeutic procedures. Pathological analysis is required for their diagnostic and prognostic characterization, which mainly relies on differentiation, grade and stage. The two main emergency situations are functioning syndromes and poorly-differentiated carcinoma. Chromogranin A is the main biochemical marker of NET, although of limited clinical interest. Initial characterization relies on morphological and isotopic imaging. The treatment of localized NET relies on watchful follow-up and local or surgical resection depending on its supposed aggressiveness. Treatment options for metastatic disease include surgery, somatostatin analogues, chemotherapy, targeted therapies, organ-driven locoregional therapies and peptide-receptor radionuclide therapy. As specific predictive factors of treatment efficacy are yet to be identified and head-to-head comparisons have not or only rarely been performed, the therapeutic strategy currently depends on prognostic factors. Cumulative toxicity and the impact of treatment on quality of life must be considered since survival is relatively long in most patients with NET. CONCLUSION: These guidelines are proposed to achieve the most beneficial therapeutic strategy in clinical practice as the therapeutic landscape of NEN is becoming ever more complex. These recommendations are permanently being reviewed.