Optimal lymph node dissection for gastric cancer: a narrative review.

The management of gastric cancer has long been debated, particularly the extent of lymph node (LN) dissection required during curative surgery. LN invasion stands out as the most critical prognostic factor in gastric cancer. Historically, Japanese academic societies were the pioneers in defining a classification system for regional gastric LN stations, numbering them from 1 to 16. This classification was later used to differentiate between different types of LN dissection, such as D1, D2 and D3. However, these definitions were often considered too complex to be universally adopted, resulting in wide variations in recommendations from one country to another and making it difficult to compare published studies. In addition, the optimal extent of LN dissection remains uncertain, with initially recommended dissections being extensive but associated with significant morbidity without a clear survival benefit. The aim of this review is to make a case for extending LN dissection based on the existing literature, which includes a comprehensive examination of the current definitions of lymphadenectomy and an analysis of the results of all randomised controlled trials evaluating morbidity, mortality and long-term survival associated with different types of LN dissection. Finally, we provide a summary of the various recommendations issued by organizations such as the Japanese Gastric Research Association, the National Comprehensive Cancer Network, the European Society for Medical Oncology, and the French National Thesaurus of Digestive Oncology.

Outcomes Associated With Esophageal Perforation Management: Results From a French Nationwide Population-based Cohort Study.

OBJECTIVE: To evaluate outcomes associated with esophageal perforation (EP) management at a national level and determine predictive factors of 90-day mortality (90dM), failure-to-rescue (FTR), and major morbidity (MM, Clavien-Dindo 3-4). BACKGROUND: EP remains a challenging clinical emergency. Previous population-based studies showed rates of 90dM up to 38.8% but were outdated or small-sized. METHODS: Data from patients admitted to hospitals with EP were extracted from the French medico-administrative database (2012-2021). Etiology, management strategies, and short and long-term outcomes were analyzed. A cutoff value of the annual EP management caseload affecting FTR was determined using the "Chi-squared Automatic Interaction Detector" method. Random effects logistic regression model was performed to assess independent predictors of 90dM, FTR, and MM. RESULTS: Among 4765 patients with EP, 90dM and FTR rates were 28.0% and 19.4%, respectively. Both remained stable during the study period. EP was spontaneous in 68.2%, due to esophageal cancer in 19.7%, iatrogenic postendoscopy in 7.3%, and due to foreign body ingestion in 4.7%. Primary management consisted of surgery (n = 1447,30.4%), endoscopy (n = 590,12.4%), isolated drainage (n = 336,7.0%), and conservative management (n = 2392,50.2%). After multivariate analysis, besides age and comorbidity, esophageal cancer was predictive of both 90dM and FTR. An annual threshold of ≥8 EP managed annually was associated with a reduced 90dM and FTR rate. In France, only some university hospitals fulfilled this condition. Furthermore, primary surgery was associated with a lower 90dDM and FTR rate despite an increase in MM. CONCLUSIONS: We provide evidence for the referral of EP to high-volume centers with multidisciplinary expertise. Surgery remains an effective treatment for EP.

Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network: A Multicentric Retrospective Study.

OBJECTIVE: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM). BACKGROUND: Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative. METHODS: A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression. RESULTS: A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25). CONCLUSIONS: Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.

Factors of Early Recurrence After Resection for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Two-thirds of patients undergoing liver resection for intrahepatic cholangiocarcinoma experience recurrence after surgery. Our aim was to identify factors associated with early recurrence after resection for intrahepatic cholangiocarcinoma. METHODS: Patients with intrahepatic cholangiocarcinoma undergoing curative intent resection (complete resection and lymphadenectomy) were included in two centers between 2005 and 2021 and were divided into three groups: early recurrence (< 12 months after resection), delayed recurrence (> 12 months), and no recurrence. Patients experiencing early (< 90 days) postoperative mortality were excluded. RESULTS: Among 120 included patients, 44 (36.7%) experienced early recurrence, 24 (20.0%) experienced delayed recurrence, and 52 (43.3%) did not experience recurrence after a median follow-up of 59 months (IQR: 26-113). The median recurrence-free survival was 16 months (95% CI: 9.6-22.4). Median overall survival was 55 months (95% CI: 45.7-64.3), while it was 25 months for patients with early recurrence (p < 0.001). Patients with early recurrence had significantly larger tumors (59.1% of tumors > 70 mm in early vs. 58.3% in delayed vs. 26.9% in no recurrence group, p = 0.002), multiple lesions (65.9% vs. 29.2% vs. 11.5%, p < 0.001), and positive lymph nodes (N +) (38.6% vs. 37.5% vs. 11.5%, p = 0.005). In multivariable analysis, presence of multiple lesions (OR: 9.324; 95% CI: 3.051-28.489; p < 0.001) and positive lymph nodes (OR: 3.307. 95% CI: 1.001-11.011. p = 0.05) were associated with early recurrence. CONCLUSION: Early recurrence after curative resection of intrahepatic cholangiocarcinoma is frequent and is associated with the presence of multiple lesions and positive lymph nodes, raising the question of surgery's futility in this context.

Colibactin-positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer.

Colibactin-producing E. coli (CoPEC) are frequently detected in colorectal cancer (CRC) and exhibit procarcinogenic properties. Because increasing evidence show the role of immune environment and especially of antitumor T-cells in CRC development, we investigated the impact of CoPEC on these cells in human CRC and in the APCMin/+ mice colon. T-cell density was evaluated by immunohistochemistry in human tumors known for their CoPEC status. APCmin/+ mice were chronically infected with a CoPEC strain (11G5). Immune cells (neutrophils and T-cell populations) were then quantified by immunofluorescent staining of the colon. The quantification of lymphoid populations was also performed in the mesenteric lymph nodes (MLNs). Here, we show that the colonization of CRC patients by CoPEC is associated with a decrease of tumor-infiltrating T lymphocytes (CD3+ T-cells). Similarly, we demonstrated, in mice, that CoPEC chronic infection decreases CD3+ and CD8+ T-cells and increases colonic inflammation. In addition, we noticed a significant decrease in antitumor T-cells in the MLNs of CoPEC-infected mice compared to that of controls. Moreover, we show that CoPEC infection decreases the antimouse PD-1 immunotherapy efficacy in MC38 tumor model. Our findings suggest that CoPEC could promote a procarcinogenic immune environment through impairment of antitumor T-cell response, leading to tumoral resistance to immunotherapy. CoPEC could thus be a new biomarker predicting the anti-PD-1 response in CRC.

Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Elderly: Is It Reasonable? A Meta-Analysis.

BACKGROUND: Whether cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is safe and worthwhile for elderly patients remains unclear. This meta-analysis of outcomes after CRS plus HIPEC for the elderly aimed to generate a higher level of evidence and precise indications for these patients. METHODS: A systematic literature search for studies reporting postoperative outcomes after CRS plus HIPEC for elderly patients was performed in the MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Knowledge Conference Proceedings Citation Index-Science, and Google Scholar databases. The included studies evaluated the overall 30-day postoperative morbidity, 90-day postoperative mortality, grade 3 or higher postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay. RESULTS: The inclusion criteria were met by 13 retrospective studies involving 2544 patients. Considering only comparative studies, the 90-day postoperative mortality was significantly increased for elderly patients [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27-0.88; I 2 = 79%]. The 30-day grade 3 or higher postoperative morbidity was increased in the patients 70 years of age or older (14.5%; 95% CI 8.1-24.4 vs. 32.3%; 95% CI 22.4-44.0%; p = 0.004; I 2 = 85%). The overall 30-day postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay were not affected by age. CONCLUSIONS: Treatment of the elderly with CRS plus HIPEC was associated with increased severe postoperative morbidity and mortality. However, these conclusions should be weighted given the existence of major biases in the included studies. Age alone probably would not be a formal contraindication, but frailty should be taken into account. Further prospective studies are needed.

How does the application of surgical components in enhanced recovery programs for colorectal surgery change over time?

BACKGROUND: Enhanced recovery programs (ERP) improve post-operative outcomes in proportion to how fully they are implemented. Maintaining an optimal level of application of all the ER components is thus essential. Our aim was to assess the sustainability of ER surgical components 2 years after their first implementation. METHOD: Patients undergoing elective colorectal resections were included in a prospective database. To retrospectively analyze compliance with ERP over a period of 24 months, the following components were considered: colonic preparation, surgical approach, nasogastric tube omission and absence of abdominal drainage. RESULTS: 2565 patients with a mean age of 63.6 ± 14.4 years from 63 colorectal centers were included. There were 1853 (72.2%) colectomies and 558 (21.7%) rectal resections. The median duration of hospital stay was 5 days [Interquartiles 4-8]. Overall morbidity was 21.9%, surgical morbidity was 8.1%, including 2.8% anastomotic fistulae. Overall, the ERP component most often applied with was postoperative nasogastric tube omission (93.6%), followed by laparoscopic approach (81.7%), absence of drainage (74.9%), and colonic preparation omission (67.3%). Implementation of surgical components significantly decreased over time: less laparoscopy (from 86.8% to 76.6%, p < 0.001), less drain omission (from 88.7% to 72%, p < 0.001), less nasogastric tube omission (from 100% to 93.4%, p = 0.002) and less colonic preparation omission (from 73.6% to 65.6%, p = 0.01). CONCLUSION: This large-scale study found that implementation of surgical components in ERP decreased over time. Further efforts are needed to sustain compliance with ERP and surgical teams should focus on repeated audits.

Does intraoperative closed-suction drainage influence the rate of pancreatic fistula after pancreaticoduodenectomy?

BACKGROUND: Although drainage of pancreatic anastomoses after pancreaticoduodenectomy (PD) is still debated, it remains recommended, especially in patients with a high risk of post-operative pancreatic fistula (POPF). Modalities of drainage of pancreatic anastomoses, especially the use of passive (PAD) or closed-suction (CSD) drains, and their impact on surgical outcomes, have been poorly studied. The aim was to compare CSD versus PAD on surgical outcomes after PD. METHODS: Retrospective analysis of 197 consecutive patients who underwent a standardized PD at two tertiary centers between March 2012 and April 2015. Patients with PAD (n = 132) or CSD (n = 65) were compared. RESULTS: There was no significant difference in terms of 30-day overall and severe post-operative morbidity, post-operative hemorrhage, post-operative intra-abdominal fluid collections, 90-day post-operative mortality and mean length of hospital stay. The rate of POPF was significantly increased in the CSD group (47.7% vs. 32.6%; p = 0.04). CSD was associated with an increase of grade A POPF (21.5% vs. 8.3%; p = 0.03), while clinically relevant POPF were not impacted. In patients with grade A POPF, the rate of undrained intra-abdominal fluid collections was increased in the PAD group (46.1% vs. 21.4%; p = 0.18). After multivariate analysis, CSD was an independent factor associated with an increased rate of POPF (OR = 2.43; p = 0.012). CONCLUSIONS: There was no strongly relevant difference in terms of surgical outcomes between PAD or CSD of pancreatic anastomoses after PD, but CSD may help to decrease the rate of undrained post-operative intra-abdominal collections in some patients. Further randomized, multi-institutional studies are needed.

Lymphovenous anastomosis for recurrent swelling syndrome and chylous effusion due to cervical thoracic duct cyst.

Thoracic duct (TD) cyst is an uncommon abnormality that can be manifested as a cervical swelling. Pathogenesis includes congenital or degenerative weakness of the wall of the TD and obstruction of the lymphoid flow. Diagnosis is crucial to eliminate malignant disease or vein thrombosis and can be established by imaging and needle aspiration. We report a case of recurrent cervical swelling with spontaneous chylothorax and chyloperitoneum. A TD cyst with a terminal obstruction of the TD was diagnosed on lymphangiography. Treatment by microsurgical lymphovenous anastomosis was successful, and the patient was free of symptom 3 years later.

Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study.

BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

Esophageal cancer - French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR).

INTRODUCTION: This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022. RESULTS: EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.

Probiotics/Synbiotics to Reduce Infectious Complications after Colorectal Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

AIM: The aims of this systematic review and meta-analysis were to assess to what extent probiotics/synbiotics reduce infectious complications after colorectal surgery and whether probiotics or synbiotics should be considered as perioperative measures preventing or reducing infectious complications after CRS and should be included in enhanced recovery programmes (ERP). Secondary aims were to answer practical questions precisely on the best formulation and the type and timing of probiotics or synbiotics in CRS. METHOD: This systematic review and quantitative meta-analysis were conducted in accordance with PRISMA 2020 guidelines. Inclusion criteria were randomised trials comparing perioperative probiotics/synbiotics with a placebo or standard care in elective colorectal surgery. Exclusion criteria were non-randomised trials. Overall infectious complications and surgical site infections (SSIs including both deep abdominal infections and wound (skin or under the skin) infections) were the primary outcomes. Secondary outcomes were pulmonary and urinary infections, wound infections, and anastomotic leaks. The databases consulted were Medline, Cochrane Database of Systematic Reviews, Scopus, and Clinical Trials Register. Risk of bias was assessed according to the GRADE approach. The analysis calculated the random effects estimates risk ratio (RR) for each outcome. RESULTS: 21 trials were included; 15 evaluated probiotics, and 6 evaluated synbiotics. There were significantly fewer infectious complications (risk ratio (RR) 0.59 [0.47-0.75], I2 = 15%) and fewer SSI (RR 0.70 [0.52-0.95], I2 = 0%) in the probiotic or synbiotic group. There were also significantly fewer pulmonary infections (RR 0.35 [0.20-0.63]) and urinary infections RR 0.41 [0.19-0.87]) as opposed to anastomotic leaks (RR 0.83 [0.47-1.48]) and wound infections (RR 0.74 [0.53-1.03]). Sensitivity analyses showed no significant difference between probiotics and synbiotics in reducing postoperative infections (RR 0.55 [0.42-0.73] versus RR 0.69 [0.42-1.13], p = 0.46). CONCLUSIONS: Based on the finding of this study, probiotics/synbiotics reduce infectious complications after colorectal surgery. The effect size was more pronounced for pulmonary and urinary infections. From a practical aspect, some of the questions related to formulations and duration of probiotics or synbiotics need to be answered before including them definitively in enhanced recovery after colorectal surgery programmes.

The Role of Magnetic Resonance Imaging in the Management of Esophageal Cancer.

Esophageal cancer (EC) is the eighth more frequent cancer worldwide, with a poor prognosis. Initial staging is critical to decide on the best individual treatment approach. Current modalities for the assessment of EC are irradiating techniques, such as computed tomography (CT) and positron emission tomography/CT, or invasive techniques, such as digestive endoscopy and endoscopic ultrasound. Magnetic resonance imaging (MRI) is a non-invasive and non-irradiating imaging technique that provides high degrees of soft tissue contrast, with good depiction of the esophageal wall and the esophagogastric junction. Various sequences of MRI have shown good performance in initial tumor and lymph node staging in EC. Diffusion-weighted MRI has also demonstrated capabilities in the evaluation of tumor response to chemoradiotherapy. To date, there is not enough data to consider whole body MRI as a routine investigation for the detection of initial metastases or for prediction of distant recurrence. This narrative review summarizes the current knowledge on MRI for the management of EC.

Imaging of postoperative complications following Ivor-Lewis esophagectomy.

Postoperative imaging plays a key role in the identification of complications after Ivor-Lewis esophagectomy (ILE). Careful analysis of imaging examinations can help identify the cause of the presenting symptoms and the mechanism of the complication. The complex surgical procedure used in ILE results in anatomical changes that make imaging interpretation challenging for many radiologists. The purpose of this review was to make radiologists more familiar with the imaging findings of normal anatomical changes and those of complications following ILE to enable accurate evaluation of patients with an altered postoperative course. Anastomotic leak, gastric conduit necrosis and pleuropulmonary complications are the most serious complications after ILE. Computed tomography used in conjunction with oral administration of contrast material is the preferred diagnostic tool, although it conveys limited sensitivity for the diagnosis of anastomotic fistula. In combination with early endoscopic assessment, it can also help early recognition of complications and appropriate therapeutic management.

Gut Microbiota as Potential Biomarker and/or Therapeutic Target to Improve the Management of Cancer: Focus on Colibactin-Producing Escherichia coli in Colorectal Cancer.

The gut microbiota is crucial for physiological development and immunological homeostasis. Alterations of this microbial community called dysbiosis, have been associated with cancers such colorectal cancers (CRC). The pro-carcinogenic potential of this dysbiotic microbiota has been demonstrated in the colon. Recently the role of the microbiota in the efficacy of anti-tumor therapeutic strategies has been described in digestive cancers and in other cancers (e.g., melanoma and sarcoma). Different bacterial species seem to be implicated in these mechanisms: F. nucleatum, B. fragilis, and colibactin-associated E. coli (CoPEC). CoPEC bacteria are prevalent in the colonic mucosa of patients with CRC and they promote colorectal carcinogenesis in susceptible mouse models of CRC. In this review, we report preclinical and clinical data that suggest that CoPEC could be a new factor predictive of poor outcomes that could be used to improve cancer management. Moreover, we describe the possibility of using these bacteria as new therapeutic targets.

Prognostic value of a combination of innovative factors (gut microbiota, sarcopenia, obesity, metabolic syndrome) to predict surgical/oncologic outcomes following surgery for sporadic colorectal cancer: a prospective cohort study protocol (METABIOTE).

INTRODUCTION: Colorectal cancer (CRC) is still associated with poor prognosis, especially in patients with advanced disease. Development of new prognostic tools replacing or supplementing those routinely used is definitely needed, with the aim to optimise and personalise treatment strategies. Gut microbiota composition and body composition profile (obesity, sarcopenia and metabolic syndrome) have recently been reported separately as new relevant prognostic factors for postoperative surgical and oncologic outcomes following CRC surgery. However interactions that exist between these factors have been poorly studied. The purpose of this translational prospective cohort study (METABIOTE) is to investigate potential interactions between gut microbiota, body composition profile and postoperative outcomes and recurrence in patients undergoing surgery for non-metastatic sporadic CRC. METHODS AND ANALYSIS: This single-centre project aims to prospectively enrol 300 consecutive patients undergoing surgery for non-metastatic sporadic CRC at the University Hospital of Clermont-Ferrand, France for the identification of specific microbial signatures (from tumour, colonic mucosa and stools samples) associated with particular metabolic profiles that could impact postoperative morbidity and oncologic outcomes, using microbiological, molecular and imaging approaches. The primary outcome is the 5-year overall survival (OS). Other outcomes are 5-year CRC-related OS, 5-year disease-free survival, 30-day postoperative morbidity, 90-day postoperative mortality and length of hospital stay. ETHICS AND DISSEMINATION: This study protocol was reviewed and approved by an independent French regional review board (n°2018-A00352-53, 'Comité de Protection des Personnes Ile de France VII' on 4 July 2018, declared to the competent French authority ('Agence Nationale de Sécurité du Médicament et des produits de santé', France), and registered on the Clinical Trials web-based platform (NCT03843905). Oral and written informed consent will be obtained from each included patient. Study results will be reported to the scientific community at conferences and in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT03843905..

Enteral versus parenteral nutrition in the conservative treatment of upper gastrointestinal fistula after surgery: a multicenter, randomized, parallel-group, open-label, phase III study (NUTRILEAK study).

BACKGROUND: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. METHODS/DESIGN: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. DISCUSSION: The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.