AIMTo investigate the neoadjuvant chemotherapy (NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODSWe proceeded to a review of the literature with PubMed, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials (RCTs) comparing NAC followed by surgery (NAC + S) with surgery alone (SA) for gastric cancer (GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association (JGCA) performed in both arms, disease-specific (DSS) and disease-free survival (DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment.RESULTSWe identified a total of 16 randomized controlled trials comparing NAC + S (n = 1089) with SA (n = 973) published in the period from January 1993 - March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node (LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. In the third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the “Study Treatment” protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction (EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients’ populations are even higher than the survival rates reported after NAC followed by incomplete surgery.CONCLUSIONNAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicine-related demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended (D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.

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 use-fulness 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.

Introduction: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach. Materials and methods: This was a retrospective cohort study of patients with mid-transverse colon cancer treated with a segmental colon resection or an extended hemicolectomy (right or left) between 2006 and 2016 in 28 high-volume (more than 70 procedures/year) Italian referral centers for colorectal surgery.Results: The study included 1529 patients, 388 of whom underwent a segmental resection while 1141 underwent an extended resection. A higher number of complications has been reported in the segmental group than in the extended group (30.1% versus 23.6%; p 0.010). In 42 cases the main complication was the anastomotic leak (4.4% versus 2.2%; p 0.020). Recovery outcomes also showed statistical differences: time to first flatus (p 0.014), time to first mobilization (p 0.040), and overall hospital stay (p < 0.001) were significantly shorter in the extended group. Even if overall survival were similar between the groups (95.1% versus 97%; p 0.384), 3-year disease-free survival worsened after segmental resection (78.1% versus 86.2%; p 0.001). Conclusions: According to our results, an extended right colon resection for TCC seems to be surgically safer and more oncologically valid.

BACKGROUND: Global experience with splenic flexure cancer is limited because of its low incidence. Both limited (segmental) and extended resections are performed, because agreement on which is the adequate procedure has not been reached. OBJECTIVE: The purpose of this study was to investigate whether segmental resection is as safe and effective as extended resection. DESIGN: This nationwide retrospective cohort study included all consecutive resections of splenic flecure cancer between January 2006 and December 2016 using data from the National Colorectal Cancer Network of the Italian Society of Surgical Oncology following the guidelines set out in the STROBE statement. SETTING: Data were obtained for 31 Italian Referral Centers for Colorectal Surgery. PATIENTS: A total of 1304 patients were submitted to resection of the splenic flexure (n = 791, 60.7%) or extended procedures (extended right and left colectomies; n = 513, 39.3%). MAIN OUTCOME MEASURES: We evaluated Clavien-Dindo ≥3 postoperative complications and oncological (number of lymph nodes removed, length of free proximal and distal margins, rate of R0 resections) and survival outcomes. RESULTS: The 2 arms were well balanced in regard to sex, BMI, ASA and Eastern Cooperative Oncology Group scores, and disease stage. Limited resection was performed more frequently using a minimally invasive approach (62.1% vs 50.9%, p < 0.001) and with shorter operation times than extended procedures (165 vs 189 minutes, p < 0.001), but the same Clavien-Dindo ≥3 postoperative complications (6.44% vs 6.43%, p = 0.99), 30-day mortality (0.63% vs 0.38%), oncological outcomes, and survival rates (5-year overall survival 0.84 vs 0.83, 5-year progression-free survival 0.85 vs 0.84). LIMITATIONS: There are limitations inherent to the retrospective nature of the study and a potential lack of consistency in treatment across centers over time. Indications as to why a specific operation was chosen were based mostly on surgeons’ beliefs. CONCLUSIONS: Segmental resection is a safe and effective treatment option for cancer of the splenic flexure. See Video Abstract at http://links.lww.com/DCR/B307. LA RESECCIÓN DE COLON SEGMENTARIA ES UNA OPCIÓN DE TRATAMIENTO SEGURA Y EFICAZ PARA EL CÁNCER DE COLON DE LA FLEXIÓN ESPLÉNICA: UN ESTUDIO RETROSPECTIVO A NIVEL NACIONAL DE LA SOCIEDAD ITALIANA DE ONCOLOGÍA QUIRÚRGICA - GRUPO COLABORATIVO RED DE CÁNCER COLORRECTAL ANTECEDENTES: La experiencia global con el cáncer de flexión esplénica es limitada debido a su baja incidencia. Se realizan resecciones limitadas (segmentarias) y extendidas, ya que no se ha llegado a un acuerdo sobre cuál es el procedimiento adecuado. OBJETIVO: El propósito de este estudio fue investigar si la resección segmentaria es tan segura y efectiva como la resección extendida. DISEÑO: Este estudio de cohorte retrospectivo a nivel nacional incluyó todas las resecciones consecutivas de cáncer de flecura esplénica entre enero de 2006 y diciembre de 2016 utilizando datos de la Red Nacional de Cáncer Colorrectal de la Sociedad Italiana de Oncología Quirúrgica siguiendo las pautas establecidas en la declaración STROBE. ENTORNO CLINICO: Se obtuvieron datos para 31 centros de referencia italianos para cirugía colorrectal. PACIENTES: Un total de 1304 pacientes fueron sometidos a resección de la flexión esplénica (n = 791, 60.7%) o procedimientos extendidos (colectomías extendidas derecha e izquierda; n = 513, 39.3%). PRINCIPALES MEDIDAS DE VALORACION: Evaluamos Clavien-Dindo ≥3 complicaciones postoperatorias y oncológicas (número de ganglios linfáticos extirpados, longitud de márgenes proximales y distales libres, tasa de resecciones R0) y resultados de supervivencia. RESULTADOS: Los dos brazos estaban bien equilibrados en cuanto a sexo, IMC, ASA y puntajes ECOG, y etapa de la enfermedad. La resección limitada se realizó con mayor frecuencia utilizando un enfoque mínimamente invasivo (62.1% versus 50,9%, p < 0.001) y con tiempos de operación más cortos que los procedimientos extendidos (165 min versus 189 min, p <0.001), pero el mismo Clavien-Dindo ≥3 complicaciones postoperatorias (6,44% versus 6,43%, p = 0.99), mortalidad a los 30 días (0,63% versus 0,38%), resultados oncológicos y tasas de supervivencia (5-y OS 0,84 versus 0,83, 5-PFS 0,85 versus 0,84). LIMITACIONES: Existen limitaciones inherentes a la naturaleza retrospectiva del estudio y una posible falta de consistencia en el tratamiento entre centros a lo largo del tiempo. Las indicaciones de por qué se eligió una operación específica se basaron principalmente en crieterios de los cirujanos. CONCLUSIONES: La resección segmentaria es una opción de tratamiento segura y efectiva para el cáncer de la flexión esplénica. Consulte Video Resumen en http://links.lww.com/DCR/B307. (Traducción—Dr. Adrian Ortega)

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.