The effect of prophylactic mesh implantation on the development of incisional hernias in patients with elevated BMI: a systematic review and meta-analysis.

BACKGROUND: Incisional hernia is a common complication after midline laparotomy. In certain risk profiles incidences can reach up to 70%. Large RCTs showed a positive effect of prophylactic mesh reinforcement (PMR) in high-risk populations. OBJECTIVES: The aim was to evaluate the effect of prophylactic mesh reinforcement on incisional hernia reduction in obese patients after midline laparotomies. METHODS: Following the PRISMA guidelines, a systematic literature search in Medline, Web of Science and CENTRAL was conducted. RCTs investigating PMR in patients with a BMI ≥ 27 reporting incisional hernia as primary outcome were included. Study quality was assessed using the Cochrane risk-of-bias tool and certainty of evidence was rated according to the GRADE Working Group grading of evidence. A random-effects model was used for the meta-analysis. Secondary outcomes included postoperative complications. RESULTS: Out of 2298 articles found by a systematic literature search, five RCTs with 1136 patients were included. There was no significant difference in the incidence of incisional hernia when comparing PMR with primary suture (odds ratio (OR) 0.59, 95% CI 0.34-1.01, p = 0.06, GRADE: low). Meta-analyses of seroma formation (OR 1.62, 95% CI 0.72-3.65; p = 0.24, GRADE: low) and surgical site infections (OR 1.52, 95% CI 0.72-3.22, p = 0.28, GRADE: moderate) showed no significant differences as well as subgroup analyses for BMI ≥ 40 and length of stay. CONCLUSIONS: We did not observe a significant reduction of the incidence of incisional hernia with prophylactic mesh reinforcement used in patients with elevated BMI. These results stand in contrast to the current recommendation for hernia prevention in obese patients.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Learning Curves in Open, Laparoscopic, and Robotic Pancreatic Surgery: A Systematic Review and Proposal of a Standardization.

Objective: To depict and analyze learning curves for open, laparoscopic, and robotic pancreatoduodenectomy (PD) and distal pancreatectomy (DP). Background: Formal training is recommended for safe introduction of pancreatic surgery but definitions of learning curves vary and have not been standardized. Methods: A systematic search on PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in pancreatic surgery. Primary outcome was the number needed to reach the learning curve as defined by the included studies. Secondary outcomes included endpoints defining learning curves, methods of analysis (statistical/arbitrary), and classification of learning phases. Results: Out of 1115 articles, 66 studies with 14,206 patients were included. Thirty-five studies (53%) based the learning curve analysis on statistical calculations. Most often used parameters to define learning curves were operative time (n = 51), blood loss (n = 17), and complications (n = 10). The number of procedures to surpass a first phase of learning curve was 30 (20-50) for open PD, 39 (11-60) for laparoscopic PD, 25 (8-100) for robotic PD (P = 0.521), 16 (3-17) for laparoscopic DP, and 15 (5-37) for robotic DP (P = 0.914). In a three-phase model, intraoperative parameters improved earlier (first to second phase: operating time -15%, blood loss -29%) whereas postoperative parameters improved later (second to third phase: complications -46%, postoperative pancreatic fistula -48%). Studies with higher sample sizes showed higher numbers of procedures needed to overcome the learning curve (rho = 0.64, P < 0.001). Conclusions: This study summarizes learning curves for open-, laparoscopic-, and robotic pancreatic surgery with different definitions, analysis methods, and confounding factors. A standardized reporting of learning curves and definition of phases (competency, proficiency, mastery) is desirable and proposed.

Impact of discontinuing contact precautions and enforcement of basic hygiene measures on nosocomial vancomycin-resistant Enterococcus faecium transmission.

OBJECTIVES: Vancomycin-resistant Enterococcus faecium (VREfm) has emerged as a pathogen of major concern for public health. Although definitive evidence is lacking, contact precautions have been a crucial element in infection prevention and control (IPC) strategies designed to limit nosocomial VRE transmission. This study investigated the effect of discontinuing contact precautions while enforcing basic hygiene measures, including hand hygiene, environmental cleaning and antiseptic body washing, for patients with VRE in intensive care units (ICUs) on the prevention of nosocomial VRE transmission causing bacteraemia. METHODS: Contact precautions were discontinued in January 2018. In total, 96 VREfm isolates from 61 patients with VREfm bacteraemia and/or colonization hospitalized in eight ICUs in a tertiary care hospital in 2016 and 2019 in were characterized by whole-genome sequencing. VRE transmission was investigated using patient movement data and admission screening for reliable identification of nosocomial acquisition. RESULTS: Discontinuation of contact precautions did not increase VREfm transmission events (eight in 2016 vs one in 2019). While the rate of endogenous VREfm was similar in both years (38% vs 31%), the number of non-colonized patients prior to VREfm bacteraemia was 16 (16/29, 55%) in 2019, which was significantly higher than in 2016 (8/32, 25%). The mean incidence density for VREfm bacteraemia was similar for both years (0.26 vs 0.31 per 1000 patient-days in 2016 and 2019, respectively). CONCLUSION: Discontinuation of contact precautions while enforcing basic hygiene measures did not lead to an increase in nosocomial bloodstream infection rates due to VREfm transmission in a hyperendemic ICU setting.

Technical advances in surgery for pancreatic cancer.

BACKGROUND: Multimodal treatment concepts enhance options for surgery in locally advanced pancreatic ductal adenocarcinoma (PDAC). This review provides an overview of technical advances to facilitate curative-intent resection in PDAC. METHODS: A review of the literature addressing current technical advances in surgery for PDAC was performed, and current state-of-the-art surgical techniques summarized. RESULTS: Artery-first and uncinate-first approaches, dissection of the anatomical triangle between the coeliac and superior mesenteric arteries and the portomesenteric vein, and radical antegrade modular pancreatosplenectomy were introduced to enhance the completeness of resection and reduce the risk of local recurrence. Elaborated techniques for resection and reconstruction of the mesenteric-portal vein axis and a venous bypass graft-first approach frequently allow resection of PDAC with venous involvement, even in patients with portal venous congestion and cavernous transformation. Arterial involvement does not preclude surgical resection per se, but may become surgically manageable with recent techniques of arterial divestment or arterial resection following neoadjuvant treatment. CONCLUSION: Advanced techniques of surgical resection and vessel reconstruction provide a toolkit for curative-intent surgery in borderline resectable and locally advanced PDAC. Effects of these surgical approaches on overall survival remain to be proven with high-level clinical evidence.

Impaired autophagy increases susceptibility to endotoxin-induced chronic pancreatitis.

Chronic pancreatitis (CP) is associated with elevated plasma levels of bacterial lipopolysaccharide (LPS) and we have demonstrated reduced acinar cell autophagy in human CP tissue. Therefore, we investigated the role of autophagy in experimental endotoxin-induced pancreatic injury and aimed to identify LPS in human CP tissue. Pancreatic Atg7-deficient mice were injected with a single sub-lethal dose of LPS. Expression of autophagy, apoptosis, necroptosis, and inflammatory markers was determined 3 and 24 h later utilizing immunoblotting and immunofluorescence. The presence of LPS in pancreatic tissue from mice and from patients and healthy controls was determined using immunohistochemistry, immunoblots, and chromogenic assay. Mice lacking pancreatic autophagy exhibited local signs of inflammation and were particularly sensitive to the toxic effect of LPS injection as compared to control mice. In response to LPS, Atg7Δpan mice exhibited enhanced vacuolization of pancreatic acinar cells, increase in TLR4 expression coupled to enhanced expression of NF-κΒ, JNK, and pro-inflammatory cytokines by acinar cells and enhanced infiltration by myeloid cells (but not Atg7F/F controls). Cell death was enhanced in Atg7Δpan pancreata, but only necroptosis and trypsin activation was further amplified following LPS injection along with elevated pancreatic LPS. The presence of LPS was identified in the pancreata from all 14 CP patients examined but was absent in the pancreata from all 10 normal controls. Altogether, these results support a potential role for metabolic endotoxemia in the pathogenesis of CP. Moreover, the evidence also supports the notion that autophagy plays a major cytoprotective and anti-inflammatory role in the pancreas, and blunting metabolic endotoxemia-induced CP.

[Surgery of pancreatic cancer: techniques to avoid local recurrence]. / Chirurgie des Pankreaskarzinoms: Techniken zur Vermeidung des Lokalrezidivs.

BACKGROUND: In addition to the prognostically important systemic recurrence, a high rate of local recurrence is a relevant problem of pancreatic cancer surgery. Improvement of local control is a requirement for surgical resection as a prerequisite for a potentially curative treatment. OBJECTIVES: Summary of the current evidence on frequency, relevance, and risk factors of local recurrence. Presentation of strategies for reduction of local recurrence with a special focus on surgical resection techniques. MATERIAL AND METHODS: Analysis and appraisal of currently available scientific literature on the topic. RESULTS AND CONCLUSION: Local recurrences occur as the first manifestation of tumor recurrence in 20-50% of patients after resection of pancreatic cancer. The considerable variations of reported local recurrence rates depend on the quality of surgery, regimens of (neo)adjuvant therapy as well as the design of surveillance and duration of follow-up. An R1 status is an important risk factor for local recurrence highlighting the relevance of a local radical resection. The majority of local recurrences consist of perivascular and lymph node recurrences. Therefore, lymphadenectomy, radical dissection directly at the celiac and mesenteric vessels including resection of the periarterial nerve plexus and vascular resection are starting points for improving surgical resection techniques. The safety and efficacy of radical resection techniques in the context of multimodal treatment of pancreatic cancer have to be further evaluated in prospective studies.