Multifactorial mitigation strategy to reduce clinically relevant pancreatic fistula in high-risk pancreatojejunostomy following pancreaticoduodenectomy.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is the most dreadful complication of pancreaticoduodenectomy (PD) and previous literature focused on technical modifications of pancreatic remnant reconstruction. We developed a multifactorial mitigation strategy (MS) and the aim of the study is to assess its clinical impact in patients at high-risk of POPF. METHODS: All patients candidate to PD between 2012 and 2018 were considered. Only patients with a high Fistula Risk Score (FRS 7-10) were included. Patients undergoing MS were compared to patients receiving Standard Strategy (SS). Clinical outcomes were compared between the two groups. Multivariate hierarchical logistic regression analyses were performed to detect independent predictors of POPF. RESULTS: Out of 212 patients, 33 were finally included in MS Group and 29 in SS Group. POPF rate was significantly lower in MS Group (12.1% vs 44.8%, p = 0.005). Delayed gastric emptying, postoperative pancreatitis, complications and hospital stay were also significantly lower in MS Group. Hierarchical logistic regression analyses showed that Body Mass Index (OR = 1.196, p = 0.036) and MS (OR = 0.187, p = 0.032) were independently associated with POPF. CONCLUSION: A multifactorial MS can be helpful to reduce POPF rate in patients with high FRS following PD. Personalized approach for vulnerable patients should be investigated in the future.

Clinical impact of preoperative tumour contact with superior mesenteric-portal vein in patients with resectable pancreatic head cancer.

INTRODUCTION: The NCCN classification of resectability in pancreatic head cancer does not consider preoperative radiological tumour ≤ 180° contact with portal vein/superior mesenteric vein (PV/SMV) as a negative prognostic feature. The aim of this study is to evaluate whether this factor is associated with higher rate of incomplete resection and poorer survival. METHODS: All patients considered for pancreatic resection between 2012 and 2017 at two Spanish referral centres were included. Patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC) according to NCCN classification were excluded. Preoperative CT scans were reviewed by dedicated radiologists to identify radiologic tumour contact with PV/SMV. RESULTS: Out of 302, 71 patients were finally included in this study. Twenty-two (31%) patients showed tumour-PV/SMV contact (group 1) and 49 (69%) did not show any contact (group 2). Patients in group 1 showed a statistically significantly higher rate of R1 and R1-direct margins compared with group 2 (95 vs 28% and 77 vs 10%) and lower median survival (24 vs 41 months, p = 0.02). Preoperative contact with PV/SMV, lymph node metastases, R1-direct margin and NO adjuvant chemotherapy were significantly associated with disease-specific survival at multivariate analysis. CONCLUSION: Preoperative radiological tumour contact with PV/SMV in patients with NCCN resectable PDAC is associated with high rate of pathologic positive margins following surgery and poorer survival.

Does the Artery-first Approach Improve the Rate of R0 Resection in Pancreatoduodenectomy?: A Multicenter, Randomized, Controlled Trial.

OBJECTIVE: To compare the rates of R0 resection in pancreatoduodenectomy (PD) for pancreatic and periampullary malignant tumors by means of standard (ST-PD) versus artery-first approach (AFA-PD). BACKGROUND: Standardized histological examination of PD specimens has shown that most pancreatic resections thought to be R0 resections are R1. "Artery-first approach" is a surgical technique characterized by meticulous dissection of arterial planes and clearing of retropancreatic tissue in an attempt to achieve a higher rate of R0. To date, studies comparing AFA-PD versus ST-PD are retrospective cohort or case-control studies. METHODS: A multicenter, randomized, controlled trial was conducted in 10 University Hospitals (NCT02803814, ClinicalTrials.gov). Eligible patients were those who presented with pancreatic head adenocarcinoma and periampullary tumors (ampulloma, distal cholangiocarcinoma, duodenal adenocarcinoma). Assignment to each group (ST-PD or AFA-PD) was randomized by blocks and stratified by centers. The primary end-point was the rate of tumor-free resection margins (R0); secondary end-points were postoperative complications and mortality. RESULTS: One hundred seventy-nine patients were assessed for eligibility and 176 randomized. After exclusions, the final analysis included 75 ST-PD and 78 AFA-PD. R0 resection rates were 77.3% (95% CI: 68.4-87.4) with ST-PD and 67.9% (95% CI: 58.3-79.1) with AFA-PD, P=0.194. There were no significant differences in postoperative complication rates, overall 73.3% versus 67.9%, and perioperative mortality 4% versus 6.4%. CONCLUSIONS: Despite theoretical oncological advantages associated with AFA-PD and evidence coming from low-level studies, this multicenter, randomized, controlled trial has found no difference neither in R0 resection rates nor in postoperative complications in patients undergoing ST-PD versus AFA-PD for pancreatic head adenocarcinoma and other periampullary tumors.

Enzymatic mediastinitis as a fearsome complication of pancreatic necrosectomy.

Several types of thoracic complications can be associated with severe acute pancreatitis. Some are very common, such as pleural effusion, whilst some others are very rare although life threatening, such as enzymatic mediastinitis (EM). Only a few cases of EM (when related to acute pancreatitis) have been described in the literature. Here we describe the case of a 76-year-old female who developed acute respiratory failure and atrial fibrillation during the postoperative period after an open pancreatic necrosectomy, due to an EM episode. The mediastinal collection was drained by thoracotomy, following an improvement of the patient's general condition. This is the first case of EM following surgical management for acute necrotizing pancreatitis. EM is a rare but life threatening complication that usually requires surgery.

Factors associated with mortality in patients with infected pancreatic necrosis: the "surgery effect".

Severe acute pancreatitis complicated by infection is associated with high mortality. Invasive treatment is indicated in the presence of infected (suspected) pancreatic and/or peripancreatic necrosis (IPN) in the absence of response to intensive medical support. Step-up approach (SUA) has been demonstrated to lower complication rate compared to upfront open surgery. However, this approach has not been associated with lower mortality, and no factors have been studied that could help to identify the high risk patients. In this study, we aimed to analyse those factors associated with mortality following the invasive treatment of IPN, focusing on the role of surgical necrosectomy. A retrospective and observational study based on a multicentre prospective database was conducted. The database was coordinated by the Hospital General Universitario de Alicante, Spain and the Spanish Association of Pancreatology. Demographics, clinical data, and laboratory and imaging findings were collected. Atlanta 2012 criteria were considered to classify acute necrotizing pancreatitis and for the definition of IPN. Step-up approach was used in all centres with the intention of avoiding surgery whenever possible. Surgical necrosectomy was performed by open approach. From January 2013 to October 2014, a total of 1655 patients with the diagnosis of acute pancreatitis were included in our database. 1081 were recruited for the final analysis. Out of them, 205 (19%) were classified into acute necrotizing pancreatitis. 77 (8.3%) patients underwent invasive treatment of INP and were included in our study. Overall mortality was 29.9%. Upfront endoscopic or percutaneous drainage was performed in 60 (77.9%) patients and mortality was 26.6%. Out of 60, 22 (36.6%) patients subsequently received rescue surgery; mortality in rescue surgery group was 18.3%. Upfront surgery was carried out in 17 (22.1%) patients; mortality in this group was 41%. At univariate analysis, surgical necrosectomy, extrapancreatic infection, immunosuppression and de-novo haemodialysis were associated with mortality. At multivariate analysis, only surgical necrosectomy was significantly associated with mortality (p = 0.002 OR 3.89). Surgical approach for IPN is associated with high mortality rate. However, these data should be interpreted with caution, since we are not able to assess whether this occurs due to the need of surgery as the only resort when the other approaches are not feasible or fail.

How to close the pancreatic stump and the role of sealants.

Postoperative pancreatic fistula (POPF) is the most common and also the most threatening complication following distal pancreatectomy. For this reason, morbidity and mortality of this operation remain still high. Over the last two decades, many different studies have been performed aiming to reduce the rate and the severity of POPF. However, effective treatments to prevent or avoid clinically relevant pancreatic fistula are still unclear. In this review, we discuss the current evidence on such a relevant topic.

Enzymatic mediastinitis as a fearsome complication of pancreatic necrosectomy

Several types of thoracic complications can be associated with severe acute pancreatitis. Some are very common, such as pleural effusion, whilst some others are very rare although life threatening, such as enzymatic mediastinitis (EM). Only a few cases of EM (when related to acute pancreatitis) have been described in the literature. Here we describe the case of a 76-year-old female who developed acute respiratory failure and atrial fibrillation during the postoperative period after an open pancreatic necrosectomy, due to an EM episode. The mediastinal collection was drained by thoracotomy, following an improvement of the patient's general condition. This is the first case of EM following surgical management for acute necrotizing pancreatitis. EM is a rare but life threatening complication that usually requires surgery

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