Aim: Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage.Methods: The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient‐, disease‐, treatment‐ and postoperative outcome‐related factors on anastomotic leak after univariable and multivariable analysis was measured.Results: A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30‐day leak‐related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection.Conclusions: While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high‐risk patients eligible for protective stoma construction.

Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?

Gastric cancer is the world's third leading cause of cancer mortality. In spite of significant therapeutic improvements, the clinical outcome for patients with advanced gastric cancer is poor; thus, the identification and validation of novel targets is extremely important from a clinical point of view. We generated a wide, multilevel platform of gastric cancer models, comprising 100 patient-derived xenografts (PDX), primary cell lines, and organoids. Samples were classified according to their histology, microsatellite stability, Epstein–Barr virus status, and molecular profile. This PDX platform is the widest in an academic institution, and it includes all the gastric cancer histologic and molecular types identified by The Cancer Genome Atlas. PDX histopathologic features were consistent with those of patients' primary tumors and were maintained throughout passages in mice. Factors modulating grafting rate were histology, TNM stage, copy number gain of tyrosine kinases/KRAS genes, and microsatellite stability status. PDX and PDX-derived cells/organoids demonstrated potential usefulness to study targeted therapy response. Finally, PDX transcriptomic analysis identified a cancer cell–intrinsic microsatellite instability (MSI) signature, which was efficiently exported to gastric cancer, allowing the identification, among microsatellite stable (MSS) patients, of a subset of MSI-like tumors with common molecular aspects and significant better prognosis. In conclusion, we generated a wide gastric cancer PDX platform, whose exploitation will help identify and validate novel “druggable” targets and optimize therapeutic strategies. Moreover, transcriptomic analysis of gastric cancer PDXs allowed the identification of a cancer cell–intrinsic MSI signature, recognizing a subset of MSS patients with MSI transcriptional traits, endowed with better prognosis. Significance: This study reports a multilevel platform of gastric cancer PDXs and identifies a MSI gastric signature that could contribute to the advancement of precision medicine in gastric cancer.

Incidence and treatment of mediastinal leakage after esophagectomy: Insights from the multicenter study on mediastinal leaks