Impact of spleen-preserving total gastrectomy on postoperative infectious complications and 5-year overall survival: systematic review and meta-analysis of contemporary randomized clinical trials.

Background: The role of splenectomy in proximal gastric cancer is still debated. The objective of the present meta-analysis was to provide more-robust evidence about the effect of spleen-preserving total gastrectomy on postoperative infectious complications, overall morbidity, and 5-year overall survival (os). Methods: PubMed, embase, and the Web of Science were consulted. Pooled effect measures were calculated using an inverse-variance weighted or Mantel-Haenszel in random effects meta-analysis. Heterogeneity was evaluated using I2 index and Cochran Q-test. Results: Three randomized controlled trials published between 2000 and 2018 were included. Overall, 451 patients (50.1%) underwent open total gastrectomy with spleen preservation and 448 (49.9%) underwent open total gastrectomy with splenectomy. The patients ranged in age from 24 to 78 years. No differences were found in the number of harvested lymph nodes (p = 0.317), the reoperation rate (p = 0.871), or hospital length of stay (p = 0.347). The estimated pooled risk ratios for infectious complications, overall morbidity, and mortality were 1.53 [95% confidence interval (ci): 1.09 to 2.14; p = 0.016], 1.51 (95% ci: 1.11 to 2.05; p = 0.008), and 1.23 (95% ci: 0.40 to 3.71; p = 0.719) respectively. The estimated pooled hazard ratio for 5-year os was 1.06 (95% ci: 0.78 to 1.45; p = 0.707). Conclusions: Spleen-preserving total gastrectomy should be considered in patients with curable gastric cancer because it is significantly associated with decreased postoperative infectious complications and overall morbidity, with no difference in the 5-year os. Those observations appear worthwhile for establishing better evidence-based treatment for gastric cancer.

Leukocytes as a reservoir of circulating oncogenic DNA and regulatory targets of tumor-derived extracellular vesicles.

Essentials Tumor-bearing mice were employed to follow oncogenic HRAS sequences in plasma, and blood cells. Cancer DNA accumulated in leukocytes above levels detected in exosomes, platelets and plasma. Extracellular vesicles and nucleosomes are required for uptake of tumor DNA by leukocytes. Uptake of tumor-derived extracellular vesicles by leukocytes triggers coagulant phenotype. SUMMARY: Background Tumor-derived extracellular vesicles (EVs) and free nucleosomes (NSs) carry into the circulation a wealth of cancer-specific, bioactive and poorly understood molecular cargoes, including genomic DNA (gDNA). Objective Here we investigated the distribution of extracellular oncogenic gDNA sequences (HRAS and HER2) in the circulation of tumor-bearing mice. Methods and Results Surprisingly, circulating leukocytes (WBCs), especially neutrophils, contained the highest levels of mutant gDNA, which exceeded the amount of this material recovered from soluble fractions of plasma, circulating EVs, platelets, red blood cells (RBCs) and peripheral organs, as quantified by digital droplet PCR (ddPCR). Tumor excision resulted in disappearance of the WBC-associated gDNA signal within 2-9 days, which is in line with the expected half-life of these cells. EVs and nucleosomes were essential for the uptake of tumor-derived extracellular DNA by neutrophil-like cells and impacted their phenotype. Indeed, the exposure of granulocytic HL-60 cells to EVs from HRAS-driven cancer cells resulted in a selective increase in tissue factor (TF) procoagulant activity and interleukin 8 (IL-8) production. The levels of circulating thrombin-antithrombin complexes (TAT) were markedly elevated in mice harboring HRAS-driven xenografts. Conclusions Myeloid cells may represent a hitherto unrecognized reservoir of cancer-derived, EV/NS-associated oncogenic gDNA in the circulation, and a possible novel platform for liquid biopsy in cancer. In addition, uptake of this material alters the phenotype of myeloid cells, induces procoagulant and proinflammatory activity and may contribute to systemic effects associated with cancer.

Comparison of endoscopic vacuum therapy versus endoscopic stenting for esophageal leaks: systematic review and meta-analysis.

Esophageal leaks remain a life-threatening postoperative complication of esophagectomy. Currently, self-expanding metal stents (SEMS) represent the endoscopic mainstay of treatment. Recently, endoscopic vacuum therapy (EVT) has emerged and shown promising results in these patients. We conducted an electronic systematic search using MEDLINE databases (PubMed, EMBASE, and Web of Science) looking for studies comparing EVT and SEMS for the treatment of esophageal leak and/or perforation. Four studies including 163 patients matched the inclusion criteria. Esophageal leak closure rate is significantly higher with EVT than SEMS [pooled odds ratio 5.51 (95% CI 2.11-14.88; P < 0.001)]. Additionally, EVT has a shorter treatment duration [pooled mean difference -9.0 days (95% CI 16.6-1.4; P = 0.021)], lower major complication (P = 0.011), and in-hospital mortality (P = 0.002) rate compared to SEMS. EVT for esophageal leak is feasible and safe. It has the potential to become the new gold standard in the endoscopic treatment of esophageal leaks and perforations. However, further comparative studies with SEMS are needed to strengthen the current evidence.

Esophagectomy in patients with liver cirrhosis: a systematic review and Bayesian meta-analysis.

INTRODUCTION: Patients with esophageal carcinoma and concomitant liver cirrhosis carry a high operative risk and may be denied esophagectomy. We performed a systematic review of the literature and meta-analysis to investigate postoperative outcomes in these patients. METHODS: Studies reporting outcomes after esophagectomy in patients with liver cirrhosis were searched in Medline, Embase, Cochrane Library, ISI Web of Science, and Scopus until June 2017, matching the terms "liver cirrhosis", "esophageal neoplasm" and/or "esophageal surgery". Extracted data included study characteristics, demographic and clinical patient characteristics, type of surgical procedure, and postoperative outcomes. A systematic review and Bayesian meta-analysis were performed. RESULTS: Five observational, retrospective and single-arm studies with a total of 157 patients were included. The main cause of death was liver failure followed by pneumonia/sepsis and anastomotic leak. Ascites and pleural effusion were the most frequent postoperative complications (pooled rates 36% and 34%, respectively). The pooled morbidity rate was 74% (95% HPD=46-81%) while the pooled mortality was 18% (95% HPD=17-27%). Study heterogeneity (τ2) was low, ranging from 0.046 to 0.080. An incidental diagnosis of liver cirrhosis was reported in 15.6% of patients in one series. Five-year survival was similar between cirrhotic and non-cirrhotic patients but was statistically significantly higher in patients with MELD score<10. CONCLUSIONS: Sound scientific evidence with regard to efficacy and outcomes of esophagectomy in patients with concomitant liver cirrhosis is lacking. There is a need to properly select these frail patients to reduce postoperative morbidity and mortality rates.

Crura augmentation with Bio-A® mesh for laparoscopic repair of hiatal hernia: single-institution experience with 100 consecutive patients.

BACKGROUND: The potential utility of both non-absorbable and absorbable meshes to reinforce the esophageal hiatus and prevent recurrent hernia has been investigated in observational studies and a few randomized clinical trials. Use of absorbable mesh has been associated with lesser side-effects, but the long-term safety and effectiveness are still debated. This rather scanty clinical evidence is due to heterogeneity and bias regarding the type of mesh and operation used, the modalities of follow-up, and the reporting of objective results. OBJECTIVES: The aim of the study was to assess safety, quality of life, and recurrence-free probability after laparoscopic repair of hiatal hernia reinforced with a synthetic absorbable mesh. METHODS: Observational, retrospective, single-center cohort study. All patients with hiatal hernia who underwent laparoscopic crura repair using a biosynthetic mesh (Gore Bio A® tissue reinforcement, Flagstaff, AZ) were included. Pre- and post-operative symptoms were assessed with the GERD-HRQL questionnaire. Objective follow-up consisted of upper gastrointestinal endoscopy and barium swallow study. RESULTS: From September 2011 to March 2016, a total of 100 patients underwent hiatal hernia repair using a Bio-A® mesh. All surgical procedures were completed laparoscopically. Postoperative morbidity rate was 10%. All patients had a minimum follow-up of 6 months, and the median follow-up was 30 (IQR = 22) months. No mesh-related complications occurred. The incidence of recurrent hernia ≥2 cm was 9%, and eight of the nine patients had a preoperative type III hernia. The median GERD-HRQL score was significantly reduced after operation (p < 0.001). The recurrence-free probability at 1 and 5 years was, respectively, 0.99 (CI 0.97-1.00) and 0.84 (CI 0.74-0.97), and no reoperation was required. No association was found between age, BMI, hernia size, previously failed surgical repairs and hernia recurrence. CONCLUSIONS: The use of a synthetic absorbable mesh to reinforce the esophageal hiatus is safe and appears to be effective and durable over a medium-term follow-up.

Coagulation and angiogenic gene expression profiles are defined by molecular subgroups of medulloblastoma: evidence for growth factor-thrombin cross-talk.

BACKGROUND: The coagulation system becomes activated during progression and therapy of high-grade brain tumors. Triggering tissue factor (F3/TF) and thrombin receptors (F2R/PAR-1) may influence the vascular tumor microenvironment and angiogenesis irrespective of clinically apparent thrombosis. These processes are poorly understood in medulloblastoma (MB), in which diverse oncogenic pathways define at least four molecular disease subtypes (WNT, SHH, Group 3 and Group 4). We asked whether there is a link between molecular subtype and the network of vascular regulators expressed in MB. METHODS: Using R2 microarray analysis and visualization platform, we mined MB datasets for differential expression of vascular (coagulation and angiogenesis)-related genes, and explored their link to known oncogenic drivers. We evaluated the functional significance of this link in DAOY cells in vitro following growth factor and thrombin stimulation. RESULTS: The coagulome and angiome differ across MB subtypes. F3/TF and F2R/PAR-1 mRNA expression are upregulated in SHH tumors and correlate with higher levels of hepatocyte growth factor receptor (MET). Cultured DAOY (MB) cells exhibit an up-regulation of F3/TF and F2R/PAR-1 following combined SHH and MET ligand (HGF) treatment. These factors cooperate with thrombin, impacting the profile of vascular regulators, including interleukin 1ß (IL1B) and chondromodulin 1 (LECT1). CONCLUSIONS: Coagulation pathway sensors (F3/TF, F2R/PAR-1) are expressed in MB in a subtype-specific manner, and may be functionally linked to SHH and MET circuitry. Thus coagulation system perturbations may elicit subtype/context-specific changes in vascular and cellular responses in MB.

Vertical banded gastroplasty modifies plasma ghrelin secretion in obese patients.

BACKGROUND: Restrictive bariatric surgery causes weight loss through substantial decline of appetite with satiety after meals. Reduction of plasma ghrelin levels after Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding could contribute to these effects, although contradictory results have been reported. The only restrictive operation still not yet investigated is vertical banded gastroplasty (VBG). We studied the effects of VBG on basal plasma ghrelin levels and meal-mediated inhibition. METHODS: 12 morbidly obese patients, 11 female and 1 male, were studied before and after VBG, when the BMI fell by 20%. The control group consisted of 6 lean volunteers. Active ghrelin was determined by RIA after overnight fasting and after the administration of a liquid meal. RESULTS: Obese patients preoperatively had significantly lower basal plasma ghrelin levels than lean volunteers, and the meal did not inhibit ghrelin secretion. After VBG and 20% BMI loss, basal plasma ghrelin levels increased and the reduction caused by a meal recovered. CONCLUSIONS: Weight loss caused by VBG is associated with higher plasma ghrelin levels in obese patients. The operation restores the normal adaptation of the A- cells of the stomach to a meal.