Radio-Guided Surgery with a New-Generation ß-Probe for Radiolabeled Somatostatin Analog, in Patients with Small Intestinal Neuroendocrine Tumors.

BACKGROUND: Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs. OBJECTIVE: We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a ß-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives. METHODS: This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at 68Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a ß-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported. RESULTS: The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12-41 µSv). CONCLUSION: This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel ß-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs. CLINICAL TRIALS REGISTRATION: 68Ga-DOTATOC Radio-Guided Surgery with ß-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic. CLINICALTRIALS: gov/ct2/show/NCT05448157 ].

Biological and targeting differences between the rare KRAS A146T and canonical KRAS mutants in gastric cancer models.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related death worldwide, with a poor prognosis for patients with advanced disease. Since the oncogenic role of KRAS mutants has been poorly investigated in GC, this study aims to biochemically and biologically characterize different KRAS-mutated models and unravel differences among KRAS mutants in response to therapy. METHODS: Taking advantage of a proprietary, molecularly annotated platform of more than 200 GC PDXs (patient-derived xenografts), we identified KRAS-mutated PDXs, from which primary cell lines were established. The different mutants were challenged with KRAS downstream inhibitors in in vitro and in vivo experiments. RESULTS: Cells expressing the rare KRAS A146T mutant showed lower RAS-GTP levels compared to those bearing the canonical G12/13D mutations. Nevertheless, all the KRAS-mutated cells displayed KRAS addiction. Surprisingly, even if the GEF SOS1 is considered critical for the activation of KRAS A146T mutants, its abrogation did not significantly affect cell viability. From the pharmacologic point of view, Trametinib monotherapy was more effective in A146T than in G12D-mutated models, suggesting a vulnerability to MEK inhibition. However, in the presence of mutations in the PI3K pathway, more frequently co-occurrent in A146T models, the association of Trametinib and the AKT inhibitor MK-2206 was required to optimize the response. CONCLUSION: A deeper genomic and biological characterization of KRAS mutants might sustain the development of more efficient and long-lasting therapeutic options for patients harbouring KRAS-driven GC.

Diagnosis and staging of small intestinal neuroendocrine tumors with CT enterography and PET with Gallium-68: preoperative risk stratification protocol.

PURPOSE: Pre-operative diagnosis and staging of small intestine neuroendocrine tumors (SI-NETs) remain sub-optimal, with open palpation during surgery still considered the gold standard. This limits a standardized implementation of minimally invasive surgery (MIS). The aim of this single-center retrospective study was to assess a tailored diagnostic work-up to identify candidates at low risk of undetected disease who may benefit from MIS. METHODS: Patients diagnosed with SI-NETs between 2013 and 2022 who underwent contrast-enhanced computed tomography enterography (CTE) and Ga68-DOTATOC-positron emission tomography-CT (68 Ga DOTATATE PET/CT) preoperatively and subsequently underwent open surgical resection were included. Imaging studies were reassessed by two radiologists. Combined use of CTE and 68 Ga DOTATATE PET/CT in determining primary lesion disease burden (number of lesions) and LN disease stage (distal and proximal relative to superior mesenteric vessels) was assessed, using surgical reports and pathology as gold standard. RESULTS: Overall, 56 patients were included. Sensitivity of CTE and 68 Ga DOTATATE PET/CT for at least one primary SI-NET was 100% and 94%, respectively. In the presence of concordance between studies, combined use of CTE and 68 Ga DOTATATE PET/CT for detection of single primary tumors improved specificity to 89% (n = 25/28) with a positive predictive value of 87.5% (n = 21/24). Distal LN disease was identified in 89.2% of cases (n = 33/37). The association of single lesion and distal LN disease was found pre-operatively in 32% of patients (n = 18). CONCLUSION: Combined use of CTE and 68 Ga DOTATATE PET/CT enables identifying low-risk surgical candidates (single SI-NET lesions with distal LN disease).

End-to-side circular stapled versus side-to-side linear stapled intrathoracic esophagogastric anastomosis following minimally invasive Ivor-Lewis esophagectomy: comparison of short-term outcomes.

PURPOSE: The search for the optimal procedure for creation of a safe gastroesophageal intrathoracic anastomosis with a lower risk of leakage in totally minimally invasive Ivor-Lewis esophagectomy (TMIIL) is ongoing. In the present study, we compared the outcomes of end-to-side (with circular stapler [CS]) and side-to-side (with linear stapler [LS]) techniques for intrathoracic anastomosis during TMIIL performed in 2 European high-volume centers for upper gastrointestinal surgery. A propensity score method was used to compare the CS and LS groups. METHODS: We retrospectively evaluated patients with lower esophageal cancer or Siewert type 1 or 2 esophagogastric junction carcinoma who underwent a planned TMIIL esophagectomy, performed from January 2017 to September 2020. The anastomosis was created by a semi-mechanical technique using a LS in one center and by a mechanical technique using a CS in the other center. General features, operative techniques, pathology data, and short-term outcomes were analyzed. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. The primary endpoint of the study was the rate of anastomotic leakage in the two groups. Secondary endpoints included rates of anastomotic stricture and overall postoperative complications. RESULTS: Considering the whole population, 256 patients were included; of those, 220 received the anastomosis with a circular stapler (CS group), and 36 received the anastomosis with a linear stapler (LS group). No significant differences by group in terms of sex, age, American Society of Anesthesiologists physical status classification, and type of neoplasm were showed. The rate of anastomotic leakage did not differ in the two groups (9.6% CS vs. 5.6% LS, p = 0.438), as well as the rate of anastomotic stricture in the 3-month follow-up (0.9% CS vs. 2.8% LS, p = 0.367). The rate of chyle leakage and of pulmonary, cardiac, and infective complications was not significantly different in the groups. After propensity score matching, 72 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups. CONCLUSIONS: The results of our study suggest that both techniques for esophagogastric anastomosis during TMIIL are feasible, safe, and effective, with comparable rates of postoperative anastomotic leakage and stricture.

Is Re-introducing Major Open and Minimally Invasive Surgery during COVID-19 Safe for Patients and Healthcare Workers? An International, Multi-centre Cohort Study in the Field of Oesophago-gastric Surgery.

INTRODUCTION: The COVID-19 pandemic has resulted in unparalleled changes to patient care, including the suspension of cancer surgery. Concerns regarding COVID-19-related risks to patients and healthcare workers with the re-introduction of major complex minimally invasive and open surgery have been raised. This study examines the COVID-19 related risks to patients and healthcare workers following the re-introduction of major oesophago-gastric (EG) surgery. PATIENTS AND METHODS: This was an international, multi-centre, observational study of consecutive patients treated by open and minimally invasive oesophagectomy and gastrectomy for malignant or benign disease. Patients were recruited from nine European centres serving regions with a high population incidence of COVID-19 between 1 May and 1 July 2020. The primary endpoint was 30-day COVID-19-related mortality. All staff involved in the operative care of patients were invited to complete a health-related survey to assess the incidence of COVID-19 in this group. RESULTS: In total, 158 patients were included in the study (71 oesophagectomy, 82 gastrectomy). Overall, 87 patients (57%) underwent MIS (59 oesophagectomy, 28 gastrectomy). A total of 403 staff were eligible for inclusion, of whom 313 (78%) completed the health survey. Approaches to mitigate against the risks of COVID-19 for patients and staff varied amongst centres. No patients developed COVID-19 in the post-operative period. Two healthcare workers developed self-limiting COVID-19. CONCLUSIONS: Precautions to minimise the risk of COVID-19 infection have enabled the safe re-introduction of minimally invasive and open EG surgery for both patients and staff. Further studies are necessary to determine the minimum requirements for mitigations against COVID-19.

Multidimensional Prognostic Index (MPI) score has the major impact on outcome prediction in elderly surgical patients with colorectal cancer: The FRAGIS study.

BACKGROUND: This study aims (I) to evaluate whether the Multidimensional Prognostic Index (MPI) score is associated with postoperative outcomes and (II) to develop a prognostic model for individual complication-risk prediction following colorectal cancer (CRC) surgery. METHOD: This is a prospective multicentric cohort study. Consecutive ≥75-year-old candidates for elective CRC surgery were enrolled from October 2017 to August 2019. Patients underwent standardized preoperative geriatric assessment including the MPI. Patients with MPI score > 0.33 were classified as frail. Logistic regression models were employed to evaluate variables associated with major postoperative complications and mortality, using 10-fold cross-validated LASSO (least absolute shrinkage and selection operator) for model selection. RESULTS: In all, 104 patients were included, 34 (33%) had MPI score > 0.33. Major postoperative complications occurred in 52% of frail versus 16% of fit (MPI score ≤ 0.33) patients (p < .01). Both 30-day (9% vs. 0%; p = .033) and 90-day mortality (18% vs. 1%; p < .01) were higher among frail patients. In multivariate analysis, MPI score was associated with adverse outcomes. A final postoperative complication predictive model was created, including MPI score, gait-speed test, ASA (American Society of Anesthesiology) score, surgical approach, and stoma creation. CONCLUSION: MPI score is strongly associated with postoperative major complications in CRC elderly patients and it is a primary component of an individual prediction model.

Open versus minimally invasive total gastrectomy after neoadjuvant chemotherapy: results of a European randomized trial.

BACKGROUND: Surgical resection with adequate lymphadenectomy is regarded the only curative option for gastric cancer. Regarding minimally invasive techniques, mainly Asian studies showed comparable oncological and short-term postoperative outcomes. The incidence of gastric cancer is lower in the Western population and patients often present with more advanced stages of disease. Therefore, the reproducibility of these Asian results in the Western population remains to be investigated. METHODS: A randomized trial was performed in thirteen hospitals in Europe. Patients with an indication for total gastrectomy who received neoadjuvant chemotherapy were eligible for inclusion and randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG). Primary outcome was oncological safety, measured as the number of resected lymph nodes and radicality. Secondary outcomes were postoperative complications, recovery and 1-year survival. RESULTS: Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. The mean number of resected lymph nodes was 43.4 ± 17.3 in OTG and 41.7 ± 16.1 in MITG (p = 0.612). Forty-eight patients in the OTG group had a R0 resection and 44 patients in the MITG group (p = 0.617). One-year survival was 90.4% in OTG and 85.5% in MITG (p = 0.701). No significant differences were found regarding postoperative complications and recovery. CONCLUSION: These findings provide evidence that MITG after neoadjuvant therapy is not inferior regarding oncological quality of resection in comparison to OTG in Western patients with resectable gastric cancer. In addition, no differences in postoperative complications and recovery were seen.

Impact of COVID-19 outbreak on esophageal cancer surgery in Northern Italy: lessons learned from a multicentric snapshot.

Coronavirus Disease-19 (COVID-19) outbreak has significantly burdened healthcare systems worldwide, leading to reorganization of healthcare services and reallocation of resources. The Italian Society for Study of Esophageal Diseases (SISME) conducted a national survey to evaluate changes in esophageal cancer management in a region severely struck by COVID-19 pandemic. A web-based questionnaire (26 items) was sent to 12 SISME units. Short-term outcomes of esophageal resections performed during the lockdown were compared with those achieved in the same period of 2019. Six (50%) centers had significant restrictions in their activity. However, overall number of resections did not decrease compared to 2019, while a higher rate of open esophageal resections was observed (40 vs. 21.7%; P = 0.034). Surgery was delayed in 24 (36.9%) patients in 6 (50%) centers, mostly due to shortage of anesthesiologists, and occupation of intensive care unit beds from intubated COVID-19 patients. Indications for neoadjuvant chemo (radio) therapy were extended in 14% of patients. Separate COVID-19 hospital pathways were active in 11 (91.7%) units. COVID-19 screening protocols included nasopharyngeal swab in 91.7%, chest computed tomography scan in 8.3% and selective use of lung ultrasound in 75% of units. Postoperative interstitial pneumonia occurred in 1 (1.5%) patient. Recovery from COVID-19 pandemic was characterized by screening of patients in all units, and follow-up outpatient visits in only 33% of units. This survey shows that clinical strategies differed considerably among the 12 SISME centers. Evidence-based guidelines are needed to support the surgical esophageal community and to standardize clinical practice in case of further pandemics.

Incidence and Grading of Complications After Gastrectomy for Cancer Using the GASTRODATA Registry: A European Retrospective Observational Study.

OBJECTIVE: Utilizing a standardized dataset based on a newly developed list of 27 univocally defined complications, this study analyzed data to assess the incidence and grading of complications and evaluate outcomes associated with gastrectomy for cancer in Europe. SUMMARY BACKGROUND DATA: The absence of a standardized system for recording gastrectomy-associated complications makes it difficult to compare results from different hospitals and countries. METHODS: Using a secure online platform (www.gastrodata.org), referral centers for gastric cancer in 11 European countries belonging to the Gastrectomy Complications Consensus Group recorded clinical, oncological, and surgical data, and outcome measures at hospital discharge and at 30 and 90 days postoperatively. This retrospective observational study included all consecutive resections over a 2-year period. RESULTS: A total of 1349 gastrectomies performed between January 2017 and December 2018 were entered into the database. Neoadjuvant chemotherapy was administered to 577 patients (42.8%). Total (46.1%) and subtotal (46.4%) gastrectomy were the predominant resections. D2 or D2+ lymphadenectomy was performed in almost 80% of operations. The overall complications' incidence was 29.8%; 402 patients developed 625 complications, with the most frequent being nonsurgical infections (23%), anastomotic leak (9.8%), other postoperative abnormal fluid from drainage and/or abdominal collections (9.3%), pleural effusion (8.3%), postoperative bleeding (5.6%), and other major complications requiring invasive treatment (5.6%). The median Clavien-Dindo score and Comprehensive Complications Index were IIIa and 26.2, respectively. In-hospital, 30-day, and 90-day mortality were 3.2%, 3.6%, and 4.5%, respectively. CONCLUSIONS: The use of a standardized platform to collect European data on perioperative complications revealed that gastrectomy for gastric cancer is still associated with heavy morbidity and mortality. Actions are needed to limit the incidence of, and to effectively treat, the most frequent and most lethal complications.

Intraoperative use of fluorescence with indocyanine green reduces anastomotic leak rates in rectal cancer surgery: an individual participant data analysis.

BACKGROUND: Fluorescence imaging by means of Indocyanine green (ICG) has been applied to intraoperatively determine the perfusion of the anastomosis. The purpose of this Individual Participant Database meta-analysis was to assess the effectiveness in decreasing the incidence of anastomotic leak (AL) after rectal cancer surgery. METHODS: We searched PubMed, Embase, Cochrane Library and ClinicalTrial.gov, EU Clinical Trials and ISRCTN registries on September 1st, 2019. We considered eligible those studies comparing the assessment of anastomotic perfusion during rectal cancer surgery by intraoperative use of ICG fluorescence compared with standard practice. We defined as primary outcome the incidence of AL at 30 days after surgery. The studies were assessed for quality by means of the ROBINS-I and the Cochrane risk tools. We calculated odds ratios (ORs) using the Individual patient data analysis, restricted to rectal lesions, according to original treatment allocation. RESULTS: The review of the literature and international registries produced 15 published studies and 5 ongoing trials, for 9 of which the authors accepted to share individual participant data. 314 patients from two randomized trials, 452 from three prospective series and 564 from 4 non-randomized studies were included. Fluorescence imaging significantly reduced the incidence of AL (OR 0.341; 95% CI 0.220-0.530; p < 0.001), independent of age, gender, BMI, tumour and anastomotic distance from the anal verge and neoadjuvant therapy. Also, overall morbidity and reintervention rate were positively influenced by the use of ICG. CONCLUSIONS: The incidence of AL may be reduced when ICG fluorescence imaging is used to assess the perfusion of a colorectal anastomosis. Limitations relate to the consistent number of non-randomized studies included and their heterogeneity in defining and assessing AL. Ongoing large randomized studies will help to determine the exact role of routine ICG fluorescence imaging may decrease the incidence of AL in surgery for rectal cancer.

Preoperative monocyte-to-lymphocyte ratio predicts recurrence in gastrointestinal stromal tumors.

BACKGROUND AND OBJECTIVES: Several inflammation markers were found to have a prognostic value in cancer. We investigated the significance of preoperative white cell ratios in determining gastrointestinal stromal tumors (GISTs) outcome. METHODS: Clinicopathological features of patients who underwent surgery for GIST were reviewed. The following peripheral blood inflammation markers were calculated: neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-white blood cell ratio (NWR), lymphocyte-white cell ratio (LWR), monocyte-white cell ratio (MWR), and platelet-white cell ratio (PWR). RESULTS: We analyzed 127 patients. Three- and five-year disease-free survival (DFS) were 89.7% and 86.9%, respectively. The univariate analysis selected tumor diameter (P = 0.003), gastric location ( P = 0.024), cell type ( P = 0.024), mitosis ( P < 0.001), MLR ( P = 0.014), NLR ( P = 0.016), and PLR ( P = 0.001) as the factors associated to DFS. The independent prognostic factors for DFS were mitosis ( P = 0.001), NLR ( P = 0.015), MLR ( P = 0.015), and PLR ( P = 0.031), with MLR showing the highest statistical significance and hazard ratio (HR) value. MLR, NLR, and PLR were the only prognostic factors in the subgroup of patients with moderate to high Miettinen's risk class. A high value of MLR was associated with reduced DFS. CONCLUSION: MLR, NLR, and PLR are independent prognostic factors for DFS in GISTs. We first demonstrated the role of MLR as a predictor of recurrence in GIST. Its inclusion into clinical management may improve the recurrence estimation.

International consensus on a complications list after gastrectomy for cancer.

BACKGROUND: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. METHODS: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. RESULTS: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. CONCLUSION: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.

Association Between Compliance to an Enhanced Recovery Protocol and Outcome After Elective Surgery for Gastric Cancer. Results from a Western Population-Based Prospective Multicenter Study.

BACKGROUND: The association between compliance to an enhanced recovery protocol (ERAS) and outcome after surgery for gastric cancer has been poorly investigated, particularly in Western patients. The aim of the study was to evaluate whether the rate of adherence to the ERAS program was correlated with outcome and time of discharge. METHODS: A prospective, observational, multicenter study was designed to be performed at Italian referral centers for gastric surgery. The protocol was discussed and approved by the Italian Research Group on Gastric Cancer. Twenty-three ERAS domains were applied. A multivariate logistic regression was used to assess the association between ERAS compliance and overall and major complication rates. The Poisson regression model (measured as mean ratios) was used to assess the association of ERAS compliance rate and length of stay (LOS). RESULTS: Eight centers participated and 290 subjects with a median age of 73 years were enrolled. The overall rates of adherence to pre-, intra-, and postoperative ERAS items were 69.8%, 60.3%, and 82.5%, respectively. At the multivariate model, there was an association between overall rate of morbidity and an overall ERAS compliance rate greater than 70% (OR 0.413; 95% CI 0.235-0.7240; P 0.002). A similar association was found for major complications (OR 0.328; 95% CI 0.151-0.709; P 0.005). The Poisson regression showed that in patients with ERAS compliance rate >70%, LOS was reduced of approximately 20% (mean ratio 0.812; 95% CI 0.694-0.950; P 0.009). CONCLUSIONS: These results suggest a moderate compliance to an ERAS program and a significant association between adherence and outcomes.

Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications.

BACKGROUND: HER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma. METHODS: HER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri- or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC. RESULTS: Eighteen of 101 patients (17.8 %) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 %). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 % CI 0.22-0.99), P = 0.046] and overall survival [HR = 0.33 (95 % CI 0.13-0.83), P < 0.018], independent of clinical-pathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 % of pairs, while this rate increased up to 27.2 % when diagnostic biopsies and paired surgical samples were compared. CONCLUSIONS: HER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2.

Multi-port versus single-port cholecystectomy: results of a multi-centre, randomised controlled trial (MUSIC trial).

BACKGROUND: Single-port laparoscopic surgery as an alternative to conventional laparoscopic cholecystectomy for benign disease has not yet been accepted as a standard procedure. The aim of the multi-port versus single-port cholecystectomy trial was to compare morbidity rates after single-access (SPC) and standard laparoscopy (MPC). METHODS: This non-inferiority phase 3 trial was conducted at 20 hospital surgical departments in six countries. At each centre, patients were randomly assigned to undergo either SPC or MPC. The primary outcome was overall morbidity within 60 days after surgery. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov (NCT01104727). RESULTS: The study was conducted between April 2011 and May 2015. A total of 600 patients were randomly assigned to receive either SPC (n = 297) or MPC (n = 303) and were eligible for data analysis. Postsurgical complications within 60 days were recorded in 13 patients (4.7 %) in the SPC group and in 16 (6.1 %) in the MPC group (P = 0.468); however, single-access procedures took longer [70 min (range 25-265) vs. 55 min (range 22-185); P < 0.001]. There were no significant differences in hospital length of stay or pain VAS scores between the two groups. An incisional hernia developed within 1 year in six patients in the SPC group and in three in the MPC group (P = 0.331). Patients were more satisfied with aesthetic results after SPC, whereas surgeons rated the aesthetic results higher after MPC. No difference in quality of life scores, as measured by the gastrointestinal quality of life index at 60 days after surgery, was observed between the two groups. CONCLUSIONS: In selected patients undergoing cholecystectomy for benign gallbladder disease, SPC is non-inferior to MPC in terms of safety but it entails a longer operative time. Possible concerns about a higher risk of incisional hernia following SPC do not appear to be justified. Patient satisfaction with aesthetic results was greater after SPC than after MPC.

Roux-en-Y with or without jejunal J-pouch reconstruction after total gastrectomy for gastric cancer: systematic review and meta-analysis of long-term functional outcomes.

BACKGROUND: Increased survival of patients undergoing total gastrectomy for gastric cancer has prompted several efforts to improve long-term postgastrectomy syndrome (PGS) outcomes. Whether a J-pouch (JP) reconstruction may be more beneficial than a standard Roux-en-Y (RY) is controversial. METHODS: A systematic review with meta-analysis was conducted, including studies reporting long-term outcomes of patients treated with total gastrectomy and JP vs RY esophagojejunostomy for gastric adenocarcinoma. A literature search was performed on PubMed, Scopus, and Google Scholar. Primary endpoints were symptom control, weight loss, eating capacity (EC), and quality of life (QoL) with at least 6 months of follow-up. Safety endpoints were explored. RESULTS: Overall, 892 patients were included from 15 studies (6 randomized controlled trials [RCTs] and 9 non-RCTs): 452 (50.7%) in the JP group and 440 (49.3%) in the RY group. Compared with RY, JP showed a significantly lower rate of dumping syndrome (13.8% vs 26.9%, odds ratio [OR], 0.29; 95% confidence interval [CI], 0.14-0.58; P < .001; I2 = 22%) and heartburn symptoms (20.4% vs 39.0%; OR, 0.29; 95% CI, 0.14-0.64; P = .002; I2 = 0%). Reflux (OR, 0.61; 95% CI, 0.28-1.32; P = .21; I2 = 42%) and epigastric fullness (OR, 0.60; 95% CI, 0.18-2.05; P = .41; I2 = 69%) were similar in both groups. Weight loss and EC were similar between the groups. QoL outcome seemed to be burdened by bias. There was no difference in morbidity, mortality, and anastomotic leak rate between groups. Operative time was significantly longer for JP than for RY (271.9 vs 251.6 minutes, respectively; mean difference, 21.55; 95% CI, 4.64-38.47; P = .01; I2 = 96%). CONCLUSION: JP reconstruction after total gastrectomy for gastric cancer is as safe as RY and may provide an advantage in postgastrectomy dumping syndrome and heartburn symptoms.

Differences in the molecular organisation of tumours along the colon are linked to interactions within the tumour ecosystem.

Tumours exhibit significant heterogeneity in their molecular profiles across patients, largely influenced by the tissue of origin, where certain driver gene mutations are predominantly associated with specific cancer types. Here, we unveil an additional layer of complexity: some cancer types display anatomic location-specific mutation profiles akin to tissue-specificity. To better understand this phenomenon, we concentrate on colon cancer. While prior studies have noted changes of the frequency of molecular alterations along the colon, the underlying reasons and whether those changes occur rather gradual or are distinct between the left and right colon, remain unclear. Developing and leveraging stringent statistical models on molecular data from 522 colorectal tumours from The Cancer Genome Atlas, we reveal disparities in molecular properties between the left and right colon affecting many genes. Interestingly, alterations in genes responsive to environmental cues and properties of the tumour ecosystem, including metabolites which we quantify in a cohort of 27 colorectal cancer patients, exhibit continuous trends along the colon. Employing network methodologies, we uncover close interactions between metabolites and genes, including drivers of colon cancer, showing continuous abundance or alteration profiles. This underscores how anatomic biases in the composition and interactions within the tumour ecosystem help explaining gradients of carcinogenesis along the colon.