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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.

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.

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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. Twentythree 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.Luca Gianotti and Uberto Fumagalli Romario have equally contributed to first authorship.

BACKGROUNDMediastinal leakage (ML) is one of the most feared complications of esophagectomy. A standard strategy for its diagnosis and treatment has been difficult to establish because of the great variability in their incidence and mortality rates reported in the existing series.AIMTo assess the incidence, predictive factors, treatment, and associated mortality rate of mediastinal leakage using the standardized definition of mediastinal leaks recently proposed by the Esophagectomy Complications Consensus Group (ECCG).METHODSSeven Italian surgical centers (five high-volume, two low-volume) affiliated with the Italian Society for the Study of Esophageal Diseases designed and implemented a retrospective study including all esophagectomies (n = 501) with intrathoracic esophagogastric anastomosis performed from 2014 to 2017. Anastomotic MLs were defined according to the classification recently proposed by the ECCG.RESULTSFifty-nine cases of ML were recorded, yielding an overall incidence of 11.8% (95%CI: 9.1%-14.9%). The surgical approach significantly influenced the occurrence of ML: the proportion of leakage was 10.5% and 9% after open and hybrid esophagectomy (HE), respectively, and doubled (20%) after totally minimally invasive esophagectomy (TMIE) (P = 0.016). No other predictive factors were found. The 30- and 90-d overall mortality rates were 1.4% and 3.2%, respectively; the 30- and 90-d leak-related mortality rates were 5.1% and 10.2%, respectively; the 90-d mortality rates for TMIE and HE were 5.9% and 1.8%, respectively. Endoscopy was the first-line treatment in 49% of ML cases, with the need for retreatment in 17.2% of cases. Surgery was needed in 44.1% of ML cases. Endoscopic treatment had the lowest mortality rate (6.9%). Removal of the gastric tube with stoma formation was necessary in 8 (13.6%) cases.CONCLUSIONThe incidence of ML after esophagectomy was high mainly in the TMIE group. However, the general and specific (leak-related) mortality rates were low. Early treatment (surgical or endoscopic) of severe leaks is mandatory to limit related mortality.

A redo myotomy should be considered in patients who underwent myotomy for achalasia and presenting with recurrent dysphagia. Preliminary results using POEM indicate that the technique can be safely used in patients who have undergone previous surgical myotomy.

Achalasia is a neurodegenerative motility disorder of the esophagus; dysphagia, weight loss, chest pain, and regurgitation are its main symptoms. Surgical myotomy (HM) is considered the gold standard treatment. However, peroral endoscopic myotomy (POEM) seems to be a safe and effective alternative option. The aim of this study is to compare the safety and efficacy of these techniques. From March 2012 to June 2015, 74 patients with symptomatic primary achalasia underwent myotomy. The two groups were compared in terms of intraoperative and postoperative outcomes and Eckardt score at last follow-up. A morphofunctional comparison was also performed. Thirty-two myotomies were performed endoscopically (POEM group) and 42 were performed laparoscopically with a 180° anterior fundoplication (surgical myotomy [SM] group). Operative time was significantly shorter for the POEM group (63 [range: 32-114] vs. 76 minutes [54-152]; P = 0.0005). Myotomy was significantly longer for the POEM group (12 [range: 10-15] vs. 9 cm [range: 7-10]; P = 0.0001). Postoperative morbidity occurred in two patients (4.7%) in the SM group; no complications (P = not significant) were recorded for the POEM group. The median Eckardt score at last follow-up decreased for each group from 6 to 1 (P < 0.001). Morphological evaluation was performed for 20 patients and functional evaluation was performed in 18 patients of each group. Lower esophageal sphincter resting and relaxation pressures were significantly reduced in both groups (P < 0.001). Eight patients in the POEM group (40%) had esophagitis at endoscopy: 4 (20%) with Los Angeles (LA) grade A, 3 (15%) with LA grade B, and 1 patient with LA grade D (5%). Five patients in POEM group (28%) had a pathologic DeMeester score. In the SM group, one patient (5%) had esophagitis (P = 0.04; 95% CI) and 4 patients (22%) presented a pathological DeMeester score. Perioperative results for POEM and SM are similar. The absence of an antireflux wrap leads to an increased risk of reflux with consequent esophagitis. SM with an antireflux wrap could be a preferred choice when a long standing gastroesophageal reflux could potentially lead to a damage as, for example, in young patients.