K. Roberts

Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review.

BACKGROUND A post-operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality. METHOD An electronic search was performed of Medline (1946-2014) and EMBASE (1996-2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool. RESULTS Six eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre-operatively whereas 1 score included intra-operative and two studies post-operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16-50). CONCLUSION These scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed.

Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial

Introduction The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres. Methods and analysis Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters—bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion—will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival. Ethics and dissemination The protocol was approved by the National Research Ethics Service (London—Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. Trial registration number NCT02740608; Pre-results.

Evaluation of the current guidelines for resection of hepatocellular carcinoma using the Appraisal of Guidelines for Research and Evaluation II instrument

BACKGROUND & AIMS Numerous guidelines for the management of hepatocellular carcinoma (HCC) have been developed. The Appraisal of Guidelines for Research & Evaluation (AGREE II) is the only validated instrument to assess the methodological quality of guidelines. We aim to appraise the methodological quality of existing guidelines for the resection of HCC using the AGREE II instrument. METHODS Cochrane, Medline, Google Scholar and Embase were searched using both PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and free text. The assessment of the included clinical practice guidelines and consensuses were performed using the AGREE II instrument, version 2013. Guidelines with a score ⩾80% for the overall appraisal item were considered as applicable without modifications. RESULTS Literature searches identified 22 clinical practice guidelines. Five out of 22 guidelines passed the 70% mark on overall assessment, 11 out of 22 had shortcomings on indications, contraindications, side effects, key recommendations, technical aspects, transparency and health economics. Ten of 22 scored below the 50% mark showing that the guideline had low methodological and overall quality. Only 3/22 clinical practice guidelines were considered applicable without modifications. CONCLUSIONS The methodological quality of guidelines for the surgical management of HCC is generally poor. Future guideline development should be informed by the use of the AGREE II instrument. Guidelines based upon high quality evidence could improve stratification of patients and individualized treatment strategies. Lay summary: The methodology of clinical practice guidelines for resection for hepatocellular carcinoma (HCC) evaluated with the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument is generally poor. However, there are some clinical practice guidelines that are based upon higher quality evidence and can form the framework within which patients with HCC can be selected for surgical resection. Future guideline development should be informed by the use of the AGREE II instrument.

Pancreatico-psoas fistula: a rare complication of acute pancreatitis

The authors present a case of post endoscopic retrograde cholangio-pancreatography acute pancreatitis complicated by a pancreatico-psoas fistula, as well as reviewing similar previously published cases. The patient had a fluctuating clinical course over 4 months, developing multiple life-threatening complications including portal vein thrombosis, gastrointestinal bleeding, aspiration pneumonia and acute kidney injury on a background of chronic kidney disease. The authors followed the long-held surgical principle of draining sepsis and avoiding surgical intervention. The fistula dried up with conservative management and time also allowed portal venous collateral formation with resolution of his ascites.

Survival following right lobe split graft, living- and deceased-donor liver transplantation in adult patients: a systematic review and network meta-analysis

Graft and patient survival outcomes following split liver transplantation (SLT), living‐donor liver transplantation (LDLT) and deceased‐donor liver transplantation (DDLT) were estimated using Bayesian network meta‐analysis. Databases were searched for relevant articles over the previous 20 years (MEDLINE, Embase, Cochrane Library and Google Scholar). Systematic review, pairwise meta‐analysis and Bayesian network meta‐analysis were performed. Pairwise meta‐analysis demonstrated that there were no significant differences in graft and patient survival outcomes. Consequently, Bayesian network meta‐analysis demonstrated no significant differences in 1‐, 3‐ and 5‐year graft and patient survival between the three alternative liver transplantations. No discrepancies were demonstrated after comparisons of direct and indirect evidence of 1‐, 3‐ and 5‐year patient and graft survival of the three node‐split models namely SLT, LDLT and DDLT. The 1‐, 3‐ and 5‐year graft and patient survival of the SLT and LDLT cohorts compared to the DDLT cohort demonstrated no significant differences. The direct and indirect evidence of this study can serve as comparator for future studies.

The rate of false-positive diagnosis of colorectal liver metastases in patients undergoing resection with the development of a novel, externally validated risk score

Background: Diagnostic error in patients undergoing resection of colorectal liver metastases (CRLM) is unusual but exposes patients to unnecessary risks associated with treatment. The primary aim of this study was to determine the rate of and risk factors for a false‐positive diagnosis of colorectal liver metastases in patients undergoing hepatic resection. The secondary aim was to develop and validate a risk score to predict a false‐positive diagnosis. Methods: Patients were identified from prospectively maintained databases. Patients who underwent a first liver resection for presumed colorectal liver metastases were divided into 2 groups: CRLMPOS (colorectal liver metastases present on histology or appearance of complete pathologic response to preoperative chemotherapy) and CRLMNEG (all others). Univariable analysis and multivariable binary logistic regression were used to identify risk factors for CRLMNEG. Risk scores were developed for CRLMNEG both with and without the use of preoperative carcinoembryonic antigen and were validated on an external cohort. Results: 3.1% of patients in both test and validation cohorts were CRLMNEG (39/1,252 and 59/1,900, respectively). CRLMNEG patients had fewer (P=.006) and smaller lesions (P < .001) with lower serum levels of carcinoembryonic antigen (P < .001), T (P=.031) and N (P < .001) and a lower Dukes’ stage of the primary (P < .001). The risk score performed well (area under the receiver operating characteristic curve 0.869; standard error=0.030; P < .001) with reasonable performance on validation (area under receiver operating characteristic curve 0.743; standard error=0.058; P < .001]). Conclusion: A false‐positive diagnosis of colorectal liver metastases affected the same proportion of patients in 2 unrelated cohorts. This study identified risk factors for false‐positive diagnosis with development of a novel risk score supported by external validation.

Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems

BACKGROUND Pancreatic neuroendocrine tumors (PNETs) display wide heterogeneity with highly variable prognosis. This study aimed to identify variables related to survival after surgical resection of PNET. METHODS A total of 143 patients were identified from a prospectively maintained database. Patient characteristics were analyzed and prognostic factors for overall survival and progression-free survival were evaluated. The WHO, ENETS and AJCC scoring systems were applied to the cohort, and their ability to predict patient outcomes were compared. RESULTS Multivariate analysis found that female gender, lymph node metastases and increasing WHO 2010 grade to be independently associated with reduced overall survival (P < 0.05). Patients requiring multi-visceral resection or debulking surgery found to be associated with shortest survival. ROC analysis found the ENETS and AJCC scoring systems to be similarly predictive of 5-year overall survival. Modified Ki67 significantly improved its accuracy in predicting 5-year overall survival (AUROC: 0.699 vs 0.605; P < 0.01). CONCLUSIONS Multi-visceral or debulking surgery is associated with poor outcomes. There seems to be no significant difference between enucleation and anatomical segmental resection. Available scoring systems have reasonable accuracy in stratifying disease severity, with no system identified as being superior. Prognostic stratification with modified grading systems needs further validation before applied in clinical practice.

Right lobe split liver graft versus whole liver transplantation: A systematic review by updated traditional and cumulative meta-analysis

INTRODUCTION Advancements in surgical techniques and experience of donor-recipient pairing has led to a wider use of right split liver grafts in adults. An update meta-analysis was conducted to compare right split liver graft (RSLG) and whole liver transplantation (WLT) using traditional and cumulative approaches. METHODS Databases were searched for relevant articles over the previous 20 years (MEDLINE, Embase, Cochrane Library, and Google Scholar). Meta-analyses were performed using both fixed and random effects models. Patient and graft survival were obtained using the inverse variance hazard ratio method. RESULTS Donors were significantly younger in the RSLG group than in the WLT group (MD = -12.06 [-16.29 to -7.83]; P < .001). In addition, the model for end-stage liver disease (MELD) score was significantly lower in the RSLG group than in the WLT group (MD = -2.45 [-4.61 to -.28]; P = .03). However, cold ischaemia time was significantly longer by 1 h in the RSLG group than in the WLT group (MD = 57 [20.63-92.73]; P = .002). Overall biliary, vascular, and outflow tract complications and hepatic artery thrombosis were significantly lower in the WLT group than in the RSLG group (odds ratio [OR] = 1.75 [1.35-2.27], P < .001; OR = 1.91 [1.37-2.65], P = .006; Peto OR = 1.83 [1.19-2.82], P = .006; and Peto OR = 2.07 [1.39-3.10], P = .004, respectively). However, no difference in patient and graft survival was noted between the two cohorts. CONCLUSIONS Although the RSLG group had a higher postoperative complication rate than the WLT group, equal patient and graft survival benefits were observed.

Laparoscopic versus open distal pancreatectomy for pancreatic adenocarcinoma: a systematic review and meta-analysis

Abstract Objectives: To compare the effectiveness, safety and oncologic adequacy of laparoscopic and open distal pancreatectomy (ODP) for pancreatic adenocarcinoma. Methods: A systematic literature search was performed using EMBASE, Medline, the Cochrane library, and Google Scholar. Meta-analyses were performed using both fixed-effect and random-effect models. A cumulative meta-analysis was performed to track the accumulation of evidence. The power that a new trial of specified samples would give to the present meta-analysis was estimated with simulation-based sample size calculation. Results: Patients who underwent laparoscopic distal pancreatectomy (LDP) had significantly smaller tumours [mean difference (MD) = −0.49 (−0.83 to −0.14), p = 0.005], less estimated blood loss [MD = −157.27 (−281.63 to −32.91), p = 0.01], and shorter average hospital stay by two days [MD = −2.35 (−3.1 to −1.59), p < .001] than those who underwent ODP. No significant differences in feasibility, effectiveness, and safety were noted. Cumulative meta-analysis demonstrated that the results were not dominated by a particular study. A new trial with 350 patients in each arm will give a maximum power of 48% to the present meta-analysis. Conclusions: LDP for pancreatic adenocarcinoma provides similar clinical and oncologic outcomes with shorter hospital stay by two days compared to ODP. However, underpowered sample size and smaller tumour size may have influenced the results of laparoscopic surgery. Therefore, an adequately powered randomized controlled trial is needed to shed further light on the appropriateness of this approach.

Pancreatoduodenectomy for periampullary cancer and biliary obstruction: impact of a pathway to avoid preoperative biliary drainage

Abstract Background Randomised trials have shown that preoperative biliary drainage (PBD) causes more harm than a straight to surgery approach for patients with jaundice and periampullary malignancy. However, it remains standard practice in many centres for jaundiced patients to undergo PBD. The aim of this study was to review the impact of a pathway to avoid PBD before pancreatoduodenectomy on clinical outcomes. Methods A pathway to avoid PBD was implemented at the start of the study period (August, 2015). A dedicated nurse specialist and surgeon visited each referring trust to raise awareness of the pathway. Inclusion criteria were patients with resectable periampullary cancers and jaundice; patients were selected for surgery without PBD if they had not undergone PBD before referral and bilirubin concentration did not exceed 450 μmol/L. Time from initial CT scan to referral to multidisciplinay team discussion to specialist clinic and surgery were recorded. Findings Over 12 months, 61 and 32 patients underwent pancreatoduodenectomy with and without PBD, respectively. 58 patients in the PBD group (95%) had undergone PBD before referral. There was no difference in demographic data or tumour types between the two groups. The duration of key intervals from referral to surgery were all shorter in the no PBD group than in the PBD group (median total duration 16 days [IQR 8–39] vs 65 [9–181], p vs 46/61, p=0·009) and venous resection (10/31 vs 4/46, p=0·014) in the no PBD group than in the PBD group. The sensitivity of initial staging CT for correctly staging resectable locally advanced disease was 91% and 50% in the no PBD and PBD groups, respectively (p=0·042). The accuracy of the initial CT scan to define locally advanced resectable disease was worse in the PBD group, presumably related to the difference in time between CT and surgery. Furthermore, average costs of treatment between presentation and surgery were £3178 cheaper in the no PBD group. Interpretation Early surgery to avoid PBD is possible within the National Health Service. By reducing the time to surgery more patients undergo potentially curative surgery and costs of treatment are reduced. An understanding about why surgery without PBD is not done routinely is needed, as is the development of strategies to support its more widespread practice. Funding Pancreatic Cancer UK.