ERAS Protocol Applied to Oncological Colorectal Mini-invasive Surgery Reduces the Surgical Stress Response and Improves Long-term Cancer-specific Survival.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are known to reduce postoperative complications and improve short-term outcomes by minimizing the surgical stress response (SSR). Retrospective reviews of large cohorts suggest that they may also have an impact on long-term oncological outcomes. In 2016, Mari et al published a randomized trial on ERAS protocol and the impact on the SSR; they found that IL-6 was less expressed in patients who undergo laparoscopic colorectal surgery within an ERAS protocol compared with controls. The aim of the present study is to report the long-term oncological outcomes of patients enrolled 5 years after the conclusion of the study. METHODS: Patients enrolled had received the indication for major colorectal surgery, aged between 18 and 80 years, with American Society of Anesthesiologists (ASA) grades I to III, autonomous for mobilization and walking, eligible for laparoscopic technique. In total, 140 patients were enrolled and randomized into 2 groups of 70 patients each. Among these patients, 52 in the ERAS group (EG) and 53 in the Standard group (SG) had colorectal cancer. For them, a 5-year oncological follow-up according to the NCCN 16 guidelines was planned. IL-6, C-reactive protein, prolactine, white blood cell count, albumin, and prealbumin were compared between oncological patients in the EG and in the SG. RESULTS: EG showed lower IL-6 on postoperative day 1 (21.2±9.1 vs. 40.3 ±11.3; P <0.05) and on day 5 (14.9±6.2 vs. 38.7±8.9; P <0.05), lower C-reactive protein on day 1 (48.3±15.7 vs. 89.4±20.3; P <0.05) and on day 5 (38.3±11.4 vs. 74.3±19.7; P <0.05), and lower pre-albumine on day 5 (18.9±7.2 vs. 12.3±6.9; P <0.05) compared with SG. Median oncological follow-up was 57 months [46.5 to 60]. There was no statistically significant difference in overall survival (log rank=0.195) and disease-free survival (Log rank=0.089) between groups. Cancer-specific survival was significantly better (log rank=0.038) in the EG compared with patients in the SG. CONCLUSIONS: ERAS protocol applied to colorectal laparoscopic surgery for cancer is able to minimize the SSR. As a possible result, cancer-specific survival seems to be improved in patients within enhanced protocols. However, even though there may be an association between an excess of SSR and worse oncological outcomes, the favorable effect of ERAS protocols toward better overall and disease-free survival is yet to be demonstrated.

Distant free air is not a contraindication for definitive laparoscopic treatment of acute perforated diverticulitis: a multi-center experience.

The paradigm of emergency laparotomy with sigmoid resection and protective stoma has been challenged for perforated diverticular disease (PDD) with free extraluminal air. Early clinical stabilization could lead to interval laparoscopic resection without stoma within 2 weeks from perforation. Patients admitted for acute diverticulitis underwent abdominal computed tomography (CT) scan. When free air was seen, endoluminal enema was administred. All patients underwent assessement of clinical stability. In unstable patients, upfront emergency surgery was performed. Stable patients underwent a conservative management consisting in fasting, central line intravenous fluids, antibiotic therapy, pain management, O2 therapy and percutaneous radiological drainage when indicated. In successful conservative management early interval surgery was planned within 15 days. Early delayed definitive laparoscopic treatment (EDDLT) was defined as laparoscopic resection of the affected colon without ostomy. A total of 235 patients were admitted to the emergency department for PDD. Among these, 142 had pericolic free air and were excluded from the study. Ninety-three had distant free air. Thirty-seven were hemodynamically unstable and underwent upfront surgery. Fifty-six patients showed a clinical stability and started on EDDLT. EDDLT was successfully performed in 36 patients (64.3%). In 20 patients (35.7%) EDDLT was unsuccessful. At multivariate analysis, distant CT extravasation of endoluminal contrast was independently associated with unsuccessful EDDLT (OR 2.1, CI 0.94-5.32). Patients with distant extraluminal free air after PDD may be treated with early delayed surgery after intensive medical therapy. Distant spread of endoluminal contrast at CT was a risk factor for unsuccessful EDDLT often indicating fecal peritonitis.

Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses.

Myeloproliferative neoplasms (MPNs) are the most frequent underlying causes of splanchnic vein thromboses (SVTs). MPN patients with SVTs (MPN-SVT) often have a unique presentation including younger age, female predominance, and low Janus kinase 2 (JAK2) mutation allele burden. This study aimed at identifying risk factors for adverse hematologic outcomes in MPN-SVT patients. We performed a retrospective study of a fully characterized cohort of MPN-SVT patients. The primary outcome was the incidence of evolution to myelofibrosis, acute leukemia, or death. Eighty patients were included in the testing cohort. Median follow-up was 11 years. Most of the patients were women with a mean age of 42 years and a diagnosis of polycythemia vera. The primary outcome was met in 13% of the patients and was associated with a JAK2V617F allele burden ≥50% (odds ratio [OR], 14.7) and presence of additional mutations in genes affecting chromatin/spliceosome (OR, 9). We identified high-risk patients (29% of the cohort) as those harboring at least 1 molecular risk factor: JAK2-mutant allele burden ≥50%, presence of chromatin/spliceosome/TP53 mutation. High-risk patients had worse event-free survival (81% vs 100%; P = .001) and overall survival at 10 years (89% vs 100%; P = .01) than low-risk patients. These results were confirmed in an independent validation cohort of 30 MPN-SVT patients. In conclusion, molecular profiling identified MPN-SVT patients with dismal outcome. In this high-risk population, a disease-modifying therapy should be taken into consideration to minimize the probability of transformation.

AHR gene-dioxin interactions and birthweight in the Seveso Second Generation Health Study.

Background: 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is proposed to interfere with fetal growth via altered activity of the aryl hydrocarbon receptor (protein: AHR; gene: AHR) pathway which regulates diverse biological and developmental processes including xenobiotic metabolism. Genetic variation in AHR is an important driver of susceptibility to low birthweight in children exposed to prenatal smoking, but less is known about these genetic interactions with TCDD, AHR's most potent xenobiotic ligand. Methods: The Seveso Women's Health Study (SWHS), initiated in 1996, is a cohort of 981 Italian women exposed to TCDD from an industrial explosion in July 1976. We measured TCDD concentrations in maternal serum collected close to the time of the accident. In 2008 and 2014, we followed up the SWHS cohort and collected data on birth outcomes of SWHS women with post-accident pregnancies. We genotyped 19 single nucleotide polymorphisms (SNPs) in AHR among the 574 SWHS mothers. Results: Among 901 singleton births, neither SNPs nor TCDD exposure alone were significantly associated with birthweight. However, we found six individual SNPs in AHR which adversely modified the association between maternal TCDD and birthweight, implicating gene-environment interaction. We saw an even stronger susceptibility to TCDD due to interaction when we examined the joint contribution of these SNPs in a risk allele score. These SNPs were all located in noncoding regions of AHR, particularly in proximity to the promoter. Conclusions: This is the first study to demonstrate that genetic variation across the maternal AHR gene may shape fetal susceptibilities to TCDD exposure.

Intracorporeal Anastomosis Reduces Surgical Stress Response in Laparoscopic Right Hemicolectomy: A Prospective Randomized Trial.

Total laparoscopic right hemicolectomy is a procedure that involves an intracorporeal anastomosis. This approach may reduce tissue injury resulting in a significant lower surgical stress response (SSR) compared with the same procedure performed with an extracorporeal anastomosis. The purpose of this study was to compare the SSR level between 2 groups of patients undergoing laparoscopic right hemicolectomy with intracorporeal or extracorporeal anastomosis. From June 2015 to December 2016, 60 patients were enrolled and randomized. Interleukin-6, C-reactive protein, procalcitonin, white blood cell count, cortisol, prolactin, prealbumin, albumin, triglycerides, and transferrin were analyzed preoperatively and at 1, 3, and 5 days postoperatively. Interleukin-6 and C-reactive protein levels were significantly lower in the intracorporeal group on days 1, 3, and 5 postoperatively compared with the extracorporeal group. Gastrointestinal recovery was significantly earlier in the intracorporeal group. The intracorporeal anastomosis in laparoscopic right hemicolectomy reduces SSR, which may play a role in bowel recovery.