Table. Pathological Features and Molecular Profile of Early-Onset Colorectal Cancer Pathological features Molecular profile Poor differentiation Microsatellite stability Mucinous tumors More likely to exhibit LINE-1 hypomethylation and TP53 sequence variations Signet-ring morphology Less frequently harbor KRAS, BRAF V600E, and APC sequence variations Perineural/venous invasion Promoter methylation of CpG islands Abbreviations: APC, adenomatous polyposis coli; BRAF, B-Raf; KRAS, K-Ras; LINE-1, long interspersed nuclear elements; TP53, tumor protein 53.

Objective: To define “best possible” outcomes for secondary bariatric surgery (BS). Background: Management of poor response and of long-term complications after BS is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. Methods: Out of 44,884 BS performed in 18 high-volume centers from 4 continents between 06/2013-05/2019, 5,349 (12%) secondary BS cases were identified. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of centers. Benchmark cases had no previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, thromboembolic events, BMI> 50 kg/m2 or age> 65 years. Results: The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8 ± 10 years, 8.4 ± 5.3 years after primary BS, with a BMI 35.2 ± 7 kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.6% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.37) and after conversional/reversal or revisional procedures with gastrointestinal suture/stapling (OR 1.84). Benchmark cutoffs for conversional BS were ≤4.5% re-intervention, ≤8.3% re-operation 90-days postoperatively. At 2-years (IQR 1–3) 15.6% of benchmark patients required a reoperation. Conclusion: Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

Objective Management of poor response and of long-term complications after bariatric surgery (BS) is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. Benchmarking uses best performance in a given field as reference point for improvement. Our aim was to define ‘‘best possible’’ outcomes for elective secondary BS. Methods The establishment of benchmarks in secondary BS followed a standardized methodology, based on recommendations of a Delphi consensus panel of experts. This multicenter study analyzed patients undergoing elective secondary BS in 18 high-volume centers on 4 continents from 06/2013 to 05/2019. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers. Benchmark cases had no: previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI>50kg/m2 or age>65 years. Descriptive statistics, multivariate logistic regression and data visualization were performed using the R software. Results Out of 44’884 elective bariatric procedures performed in the participating centers, 5’328 secondary BS cases were identified. The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8±10 years, 8.4±5.3 years after primary BS, with a body mass index 35.2±7kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.57% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.36) and after conversional or revisional procedures with gastrointestinal suture/stapling (OR 1.7). Benchmark cutoffs at 90-days postoperatively were ≤5.8% re-intervention and ≤8.8% re-operation rate. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. Conclusion Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

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Background The molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status. Methods Anonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I–III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated. Results A total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively). Conclusion Patients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers.