The impact of synchronous liver resection on the risk of anastomotic leakage following elective colorectal resection. A propensity score match analysis on behalf of the iCral study group.

INTRODUCTION: how best to manage patients with colorectal cancer and synchronous liver metastasis is still controversial, with specific concerns of increased risk of postoperative complications following combined resection. We aimed at analyzing the influence of combined liver resection on the risk of anastomotic leak (AL) following colorectal resection. METHODS: we reviewed the iCral prospectively maintained database to compare the relative risk of AL of patients undergoing colorectal resection for cancer to that of patients receiving simultaneous liver and colorectal resection for cancer with isolated hepatic metastases. The incidence of AL was the primary outcome of the analysis. Perioperative details and postoperative complications were also appraised. RESULTS: out of a total of 996 patients who underwent colorectal resection for cancer, 206 receiving isolated colorectal resection were compared with a matched group of 53 patients undergoing simultaneous liver and colorectal resection. Combined surgery had greater operative time and resulted in longer postoperative hospitalization compared to colorectal resection alone. The proportion of overall morbidity following combined resection was significantly higher than after isolated colorectal resection (56.6% vs. 37.9%, p = 0.021). Overall, the two groups of patients did not differ neither on the rate of major postoperative complications, nor in terms of AL (9.4% vs. 6.3%, p = 0.381). At specific multivariate analysis, the duration of surgery was the only risk factor independently associated with the likelihood of AL. CONCLUSIONS: combining hepatic with colorectal resection for the treatment of synchronous liver metastasis from colorectal cancer does not increase significantly the incidence of AL.

Complications and mortality in a cohort of patients undergoing emergency and elective surgery with perioperative SARS-CoV-2 infection: an Italian multicenter study. Teachings of Phase 1 to be brought in Phase 2 pandemic.

Since the beginning of the pandemic due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its related disease, coronavirus disease 2019 (COVID-19), several articles reported negative outcomes in surgery of infected patients. Aim of this study is to report results of patients with COVID-19-positive swab, in the perioperative period after surgery. Data of COVID-19-positive patients undergoing emergent or oncological surgery, were collected in a retrospective, multicenter study, which involved 20 Italian institutions. Collected parameters were age, sex, body mass index, COVID-19-related symptoms, patients' comorbidities, surgical procedure, personal protection equipment (PPE) used in operating rooms, rate of postoperative infection among healthcare staff and complications, within 30-postoperative days. 68 patients, who underwent surgery, resulted COVID-19-positive in the perioperative period. Symptomatic patients were 63 (92.5%). Fever was the main symptom in 36 (52.9%) patients, followed by dyspnoea (26.5%) and cough (13.2%). We recorded 22 (32%) intensive care unit admissions, 23 (33.8%) postoperative pulmonary complications and 15 (22%) acute respiratory distress syndromes. As regards the ten postoperative deaths (14.7%), 6 cases were related to surgical complications. One surgeon, one scrub nurse and two circulating nurses were infected after surgery due to the lack of specific PPE. We reported less surgery-related pulmonary complications and mortality in Sars-CoV-2-infected patients, than in literature. Emergent and oncological surgery should not be postponed, but it is mandatory to use full PPE, and to adopt preoperative screenings and strategies that mitigate the detrimental effect of pulmonary complications, mostly responsible for mortality.

Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer.

PURPOSE: To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain (CNG) or an activating truncation within a deoxyadenosine tract element (DATE) in the promoter region of the MET ligand HGF. PATIENTS AND METHODS: A single-institution cohort of 230 patients with stage II/III gastric cancer was studied. Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction. Quantitative polymerase chain reaction (qPCR) for MET CNG and sequencing for HGF DATE truncation (< 25 deoxyadenosines instead of 30) were used. Results were analyzed for association with disease-free survival (DFS) and overall survival (OS). To assess the reliability of the qPCR measurement, a random sample of cases was reanalyzed using an alternative assay (fluorescent in situ hybridization [FISH]) with calculation of the intracorrelation coefficient (ICC). RESULTS: In 216 assessable patients, MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients (10%) and 30 patients (13%), respectively. Patients with MET CNG five or more copies (MET-positive) showed significantly worse prognosis with multivariate hazard ratio (HR) of 3.02 (95% CI, 1.71 to 5.33; P < .001) for DFS and multivariate HR of 2.91 (95% CI, 1.65 to 5.11; P < .001) for OS. The agreement between qPCR and FISH was high, with ICC = 0.9% (95% CI, 0.81% to 0.95%; the closer the ICC is to 1, the greater is the agreement). HGF-truncated DATE did not show relevant prognostic effect. CONCLUSION: In this study, qPCR revealed approximately 10% of white patients with gastric cancer harboring MET CNG of five or more copies. This marker was significantly associated with unfavorable prognosis. This information is relevant to the current clinical development of anti-MET compounds.

Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer.

We investigated the clinical significance of tumour-infiltrating FOXP3-positive regulatory T cells (Tregs) in radically resected (R0) gastric cancer. From a single-institution database, tumors of 110 patients who underwent R0 resection for stage II-III disease were studied for FOXP3-positive Tregs by immunohistochemistry. The observed median number of FOXP3-positive Tregs was used as the cut-point in analyses (<6 versus >or=6 count). Tregs were significantly higher in gastric carcinomas than in normal tissue (P = 0.0001). Tregs count >or=6 was significantly associated with vascular/lymphatic/perineural invasion (VELIPI) in the tumour (P = 0.03). Multivariate analysis showed association between adverse relapse-free survival and grading 3, stage III, VELIPI and Tregs count >or=6 (P = 0.02). Adverse overall survival was associated with grading 3, stage III, VELIPI and Tregs count >or=6 (P = 0.006). FOXP3-positive Tregs may be a novel marker for identifying high-risk gastric cancer patients. Present findings deserve additional investigation as Tregs may also represent an innovative therapeutic target.

Estrogens maintain bile duct mass and reduce apoptosis after biliodigestive anastomosis in bile duct ligated rats.

BACKGROUND/AIMS: Disapperacence of bile ducts (ductopenia) represents the terminal, common stage of human cholangiopathies, and estrogens exert a major role in stimulating cholangiocyte proliferation. We thus evaluated whether estrogen administration protect from the bile duct loss induced by the biliary-digestive diversion in bile duct ligated (BDL) rats. METHODS: After 3 weeks of BDL, rats were subjected to biliary-digestive diversion and treated with daily injections of 17beta-estradiol or a control solution. RESULTS: Both after 7 and 14 days from the biliary-digestive diversion a marked increase of the number of apoptotic cholangiocytes was observed. In contrast, 17beta-estradiol significantly reduced cholangiocyte apoptosis. 17beta-estradiol also prevented the biliary-digestive diversion-induced loss of PCNA-positive cholangiocytes and of the bile duct mass. Biliary-digestive diversion determined a marked reduction of ERK1/2 phopsphorylation in cholangiocytes that was reversed by the administration of 17beta-estradiol. CONCLUSIONS: This study indicates that estrogens prevent the increase of cholangiocyte apoptosis and loss of cholangiocyte proliferation induced by the biliary-digestive diversion in the BDL rat. In parallel, 17beta-estradiol also enhanced ERK1/2 phosphorylation, which is instead strongly reduced by the biliary-digestive diversion. These novel findings suggest that estrogens could prevent the evolution of cholangiopathies toward ductopenia.

Cecropin B enhances betalactams activities in experimental rat models of gram-negative septic shock.

OBJECTIVE: To investigate the efficacy of imipenem, piperacillin combined with cecropin B in the prevention of lethality in 2 rat models of septic shock. Main outcome measures were bacterial growth in blood and intra-abdominal fluid, endotoxin and TNF-alpha concentrations in plasma, and lethality. BACKGROUND: Sepsis remains a serious clinical problem despite intense efforts to improve survival. It is a major cause of morbidity and mortality in hospitalized patients. The primary cause of Gram-negative shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of Gram-negative bacteria. METHODS: Adult male Wistar rats were given (1). an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 LPS or (2). 2 x 1010 CFU of E. coli ATCC 25922. All animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg cecropin B, 20 mg/kg imipenem, and 120 mg/kg piperacillin alone and combined with 1 mg/kg cecropin B. Each group included 20 animals. RESULTS All compounds reduced the lethality when compared with controls. Piperacillin and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. On the other hand, each betalactam determined an increase of plasma endotoxin and TNF-alpha concentration. Combination between cecropin B and betalactams showed to be the most effective treatment in reducing all variables measured. CONCLUSION: Cecropin B enhances betalactams activities in Gram-negative sepic shock rat models.

Therapeutic efficacy of the magainin analogue MSI-78 in different intra-abdominal sepsis rat models.

OBJECTIVES: This study was designed to investigate the antimicrobial and anti-endotoxin activity of MSI-78, a synthetic cationic peptide analogue of magainin 2. METHODS: The in vitro antimicrobial activity of MSI-78 was investigated against the commercially available quality control strain Escherichia coli ATCC 25922. In addition, three rat models of septic shock were investigated: (i) rats were injected intraperitoneally with 1 mg Escherichia coli 0111:B4 LPS; (ii) rats were given an intraperitoneal injection of 2 x 10(10) cfu of Escherichia coli ATCC 25922; (iii) intra-abdominal sepsis was induced via caecal ligation and puncture. All animals were randomized to receive after 360 min intravenously isotonic sodium chloride solution, 1 mg/kg MSI-78, or 60 mg/kg piperacillin. Main outcome measures were: abdominal exudate and plasma bacterial growth, plasma endotoxin and tumour necrosis factor alpha (TNF-alpha) concentrations, and lethality. RESULTS: Our in vitro data showed that MSI-78 possesses a strong activity against Escherichia coli. The in vivo studies showed that all compounds reduced the lethality when compared to controls. MSI-78 showed a slightly higher antimicrobial activity than piperacillin and achieved a substantial decrease in endotoxin and TNF-alpha plasma concentrations than the beta-lactam. CONCLUSIONS: Because of its strong double anti-endotoxin and antimicrobial activities MSI-78 could be an interesting compound for Gram-negative septic shock treatment.

Temporin A soaking in combination with intraperitoneal linezolid prevents vascular graft infection in a subcutaneous rat pouch model of infection with Staphylococcus epidermidis with intermediate resistance to glycopeptides.

The efficacy of linezolid and temporin A in the prevention of prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides was investigated in a subcutaneous rat pouch model. Linezolid and temporin A, alone or combined, greatly reduced the bacterial numbers compared to the effect with control drugs.