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.

Consensus on definition and severity grading of lymphatic complications after kidney transplantation.

BACKGROUND: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy. METHODS: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres. RESULTS: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention. CONCLUSION: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.

ANTECEDENTES: La incidencia de complicaciones linfáticas tras el trasplante renal (post-kidney-transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen. RESULTADOS: En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica. CONCLUSIÓN: Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.

Meta-analysis of recurrence pattern after resection for pancreatic cancer.

BACKGROUND: Initial recurrence mapping of resected pancreatic ductal adenocarcinoma (PDAC) could help in stratifying patient subpopulations for optimal postoperative follow-up. The aim of this systematic review and meta-analysis was to investigate the initial recurrence patterns of PDAC and to correlate them with clinicopathological factors. METHODS: MEDLINE and Web of Science databases were searched systematically for studies reporting first recurrence patterns after PDAC resection. Data were extracted from the studies selected for inclusion. Pooled odds ratios (ORs) and 95 per cent confidence intervals were calculated to determine the clinicopathological factors related to the recurrence sites. The weighted average of median overall survival was calculated. RESULTS: Eighty-nine studies with 17 313 patients undergoing PDAC resection were included. The weighted median rates of initial recurrence were 20·8 per cent for locoregional sites, 26·5 per cent for liver, 11·4 per cent for lung and 13·5 per cent for peritoneal dissemination. The weighted median overall survival times were 19·8 months for locoregional recurrence, 15·0 months for liver recurrence, 30·4 months for lung recurrence and 14·1 months for peritoneal dissemination. Meta-analysis revealed that R1 (direct) resection (OR 2·21, 95 per cent c.i. 1·12 to 4·35), perineural invasion (OR 5·19, 2·79 to 9·64) and positive peritoneal lavage cytology (OR 5·29, 3·03 to 9·25) were significantly associated with peritoneal dissemination as initial recurrence site. Low grade of tumour differentiation was significantly associated with liver recurrence (OR 4·15, 1·71 to 10·07). CONCLUSION: Risk factors for recurrence patterns after surgery could be considered for specific surveillance and treatments for patients with pancreatic cancer.

ANTECEDENTES: El mapeo del patrón de recidiva inicial tras la resección de un adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) podría ayudar a estratificar subpoblaciones de pacientes para un seguimiento postoperatorio óptimo. El objetivo de esta revisión sistemática con metaanálisis fue investigar los patrones de recidiva inicial de PDAC y correlacionarlos con factores clínico-patológicos. MÉTODOS: Se realizaron búsquedas sistemáticas en las bases de datos MEDLINE y Web of Science para seleccionar estudios que presentaran información sobre los patrones de recidiva inicial después de la resección del PDAC. Se extrajeron los datos de los estudios seleccionados para su inclusión en el metaanálisis. Se calcularon las razones de oportunidades agrupadas (pooled odds ratio, OR) y los i.c. del 95% para definir los factores clínico-patológicos relacionados con las localizaciones de la recidiva. Se estimó el promedio ponderado de la mediana de la supervivencia global. RESULTADOS: Se incluyeron 89 estudios con 17.313 pacientes a los que se realizó una resección por PDAC. Las tasas medias ponderadas de las localizaciones de la recidiva inicial fueron del 20,8% para la locorregional, 26,5% para las hepáticas, 11,4% para el pulmón y 13,5% para la diseminación peritoneal. La mediana ponderada de supervivencia global fue de 19,8 meses (locorregional), 15,0 meses (hígado), 30,4 meses (pulmón) y 14,1 meses (diseminación peritoneal). El metaanálisis demostró que la resección R1 (inicial) (OR 2,21, i.c. del 95% 1,12-4,35), la invasión perineural (OR 5,19; i.c. del 95% 2,79-9,64) y la positividad de la citología del lavado peritoneal (OR 5,29; i.c. del 95% 3,03-9,25) se asociaron significativamente con la diseminación peritoneal como localización de recidiva inicial. El bajo grado de diferenciación tumoral se asoció significativamente con la recidiva hepática (OR 4,15; i.c. del 95%: 1,71-10,07). CONCLUSIÓN: Se podrían tener en cuenta estos factores de riesgo de los patrones de recidiva tras la cirugía para realizar un seguimiento y tratamiento específicos en pacientes con cáncer de páncreas.

Systematic review of the quantity and quality of randomized clinical trials in pancreatic surgery.

BACKGROUND: RCTs are considered the reference standard in clinical research. However, surgical RCTs pose specific challenges and therefore numbers have been lower than those for randomized trials of medical interventions. In addition, surgical trials have often been associated with poor methodological quality. The objective of this study was to evaluate the evolution of quantity and quality of RCTs in pancreatic surgery and to identify evidence gaps. METHODS: PubMed, CENTRAL and Web of Science were searched systematically. Predefined data were extracted and organized in a database. Quantity and quality were compared for three intervals of the study period comprising more than three decades. Evidence maps were constructed to identify gaps in evidence. RESULTS: The search yielded 8210 results, of which 246 trials containing data on 26 154 patients were finally included. The number of RCTs per year increased continuously from a mean of 2·8, to 5·7 and up to 13·1 per year over the three intervals of the study. Most trials were conducted in Europe (46·3 per cent), followed by Asia (35·0 per cent) and North America (14·2 per cent). Overall, the quality of RCTs was moderate; however, with the exception of blinding, all domains of the Cochrane risk-of-bias tool improved significantly in the later part of the study. Evidence maps showed lack of evidence from RCTs for operations other than pancreatoduodenectomy and for specific diseases such as neuroendocrine neoplasms or intraductal papillary mucinous neoplasms. CONCLUSION: The quantity and quality of RCTs in pancreatic surgery have increased. Evidence mapping showed gaps for specific procedures and diseases, indicating priorities for future research.

Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy.

BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.

Meta-analysis of the prognostic role of perioperative platelet count in posthepatectomy liver failure and mortality.

BACKGROUND: Emerging evidence suggests that the perioperative platelet count (PLT) can predict posthepatectomy liver failure (PHLF). In this systematic review and meta-analysis, the impact of perioperative PLT on PHLF and mortality was evaluated. METHODS: MEDLINE and Web of Science databases were searched systematically for relevant literature up to January 2018. All studies comparing PHLF or mortality in patients with a low versus high perioperative PLT were included. Study quality was assessed using methodological index for non-randomized studies (MINORS) criteria. Meta-analyses were performed using Mantel-Haenszel tests with a random-effects model, and presented as odds ratios (ORs) with 95 per cent confidence intervals. RESULTS: Thirteen studies containing 5260 patients were included in the meta-analysis. Two different cut-off values for PLT were used: 150 and 100/nl. Patients with a perioperative PLT below 150/nl had higher PHLF (4 studies, 817 patients; OR 4·79, 95 per cent c.i. 2·89 to 7·94) and mortality (4 studies, 3307 patients; OR 3·78, 1·48 to 9·62) rates than patients with a perioperative PLT of 150/nl or more. Similarly, patients with a PLT below 100/nl had a significantly higher risk of PHLF (4 studies, 949 patients; OR 4·65, 2·60 to 8·31) and higher mortality rates (7 studies, 3487 patients; OR 6·35, 2·99 to 13·47) than patients with a PLT of 100/nl or greater. CONCLUSION: A low perioperative PLT correlates with higher PHLF and mortality rates after hepatectomy.

Validation of at least 1 mm as cut-off for resection margins for pancreatic adenocarcinoma of the body and tail.

BACKGROUND: The definition of resection margin (R) status in pancreatic cancer is under debate. Although a margin of at least 1 mm is an independent predictor of survival after resection for pancreatic head cancer, its relevance to pancreatic body and tail cancers remains unclear. This study aimed to validate R status based on a 1-mm tumour-free margin as a prognostic factor for resected adenocarcinoma involving the pancreatic body and tail. METHODS: Patients who underwent distal or total pancreatectomy for adenocarcinomas of the pancreatic body and tail between January 2006 and December 2014 were identified from a prospective database. Resection margins were evaluated using a predefined cut-off of 1 mm. Rates of R0, R1 with invasion within 1 mm of the margin (R1 less than 1 mm), and R1 with direct invasion of the resection margin (R1 direct) were determined, and overall survival in each group assessed by Kaplan-Meier analysis. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. RESULTS: R0 resection was achieved in 107 (23·5 per cent) and R1 in 348 (76·5 per cent) of 455 patients. Among R1 resections, invasion within 1 mm of the margin was found in 104 (22·9 per cent) and direct invasion in 244 (53·6 per cent). The R0 rate was 28·9 per cent after distal and 18·6 per cent after total pancreatectomy. In the total cohort, median survival times for patients with R0, R1 (less than 1 mm) and R1 (direct) status were 62·4, 24·6 and 17·2 months respectively, with 5-year survival rates of 52·6, 16·8 and 13·0 per cent (P < 0·001). In patients who received adjuvant chemotherapy, respective median survival times were 68·6, 32·8 and 21·4 months, with 5-year survival rates of 56, 22 and 16·0 per cent (P < 0·001). In multivariable analysis, R status was independently associated with survival. CONCLUSION: A cut-off of at least 1 mm for evaluation of resection margins is an independent determinant of survival after resection of adenocarcinomas of the pancreatic body and tail.

Meta-analysis of delayed gastric emptying after pylorus-preserving versus pylorus-resecting pancreatoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pylorus-preserving pancreatoduodenectomy. Recent studies have suggested that resection of the pylorus is associated with decreased rates of DGE. However, superiority of pylorus-resecting pancreatoduodenectomy was not shown in a recent RCT. This meta-analysis summarized evidence of the effectiveness and safety of pylorus-preserving compared with pylorus-resecting pancreatoduodenectomy. METHODS: RCTs and non-randomized studies comparing outcomes of pylorus-preserving and pylorus-resecting pancreatoduodenectomy were searched systematically in MEDLINE, Web of Science and CENTRAL. Random-effects meta-analyses were performed and the results presented as weighted odds ratios (ORs) or mean differences with their corresponding 95 per cent confidence intervals. Subgroup analyses were performed to account for interstudy heterogeneity between RCTs and non-randomized studies. RESULTS: Three RCTs and eight non-randomized studies with a total of 992 patients were included. Quantitative synthesis across all studies showed superiority for pylorus-resecting pancreatoduodenectomy regarding DGE (OR 2·71, 95 per cent c.i. 1·48 to 4·96; P = 0·001) and length of hospital stay (mean difference 3·26 (95 per cent c.i. -1·04 to 5·48) days; P = 0·004). Subgroup analyses including only RCTs showed no significant statistical differences between the two procedures regarding DGE, and for all other effectiveness and safety measures. CONCLUSION: Pylorus-resecting pancreatoduodenectomy is not superior to pylorus-preserving pancreatoduodenectomy for reducing DGE or other relevant complications.

Comparison of chlorhexidine-isopropanol with isopropanol skin antisepsis for prevention of surgical-site infection after abdominal surgery.

BACKGROUND: Prevention of surgical-site infection (SSI) has received increasing attention. Clinical trials have focused on the role of skin antisepsis in preventing SSI. The benefit of combining antiseptic chlorhexidine with alcohol has not been compared with alcohol-based skin preparation alone in a prospective controlled clinical trial. METHODS: Between August and October 2014, patients undergoing abdominal surgery received preoperative skin antisepsis with 70 per cent isopropanol (PA). Those treated between November 2014 and January 2015 received 2 per cent chlorhexidine with 70 per cent isopropanol (CA). The primary endpoint was SSI on postoperative day (POD) 10, which was evaluated using univariable analysis, and a multivariable logistic regression model correcting for known independent risk factors for SSI. The study protocol was published in the German Registry of Clinical Studies (DRKS00011174). RESULTS: In total, 500 patients undergoing elective midline laparotomy were included (CA 221, PA 279). The incidence of superficial and deep SSIs was significantly different on POD 10: 14 of 212 (6·6 per cent) among those treated with CA and 32 of 260 (12·3 per cent) in those who received PA (P = 0·038). In the multivariable analysis, skin antisepsis with CA was an independent factor for reduced incidence of SSI on POD 10 (P = 0·034). CONCLUSION: This study showed a benefit of adding chlorhexidine to alcohol for skin antisepsis in reducing early SSI compared with alcohol alone.

Randomized clinical trial of stapler hepatectomy versus LigaSure™ transection in elective hepatic resection.

BACKGROUND: Previous studies have demonstrated stapler hepatectomy and use of various energy devices to be safe alternatives to the clamp-crushing technique in elective hepatic resection. In this randomized trial, the effectiveness and safety of stapler hepatectomy were compared with those of parenchymal transection with the LigaSure™ vessel sealing system. METHOD: Patients scheduled for elective liver resection at two tertiary-care centres were randomized during surgery to stapler hepatectomy or transection with the LigaSure™ device. Total intraoperative blood loss was the primary efficacy endpoint. Transection time, duration of operation, perioperative complications and length of hospital stay were recorded as secondary endpoints. RESULTS: A total of 138 patients were analysed, 69 in the LigaSure™ and 69 in the stapler hepatectomy group. Baseline characteristics were well balanced between the groups. Mean intraoperative blood loss was significantly higher in the LigaSure™ group than the stapler hepatectomy group: 1101 (95 per cent c.i. 915 to 1287) versus 961 (752 to 1170) ml (P = 0·028). The parenchymal transection time was significantly shorter in the stapler group (P = 0·005), as was the total duration of operation (P = 0·027). Surgical morbidity did not differ between the groups, nor did the grade of complications. CONCLUSION: Stapler hepatectomy was associated with reduced blood loss and a shorter duration of operation than the LigaSure™ device for parenchymal transection in elective partial hepatectomy. Registration number: NCT01858987 (http://www.clinicaltrials.gov).

Network meta-analysis of topical haemostatic agents in thyroid surgery.

BACKGROUND: The objective of this study was to investigate the potential benefit of local haemostatic agents for the prevention of postoperative bleeding after thyroidectomy. METHODS: A systematic literature search was performed, and RCTs involving adult patients who underwent thyroid surgery using either active (AHA) or passive (PHA) haemostatic agents were included in the review. The main outcome was the rate of cervical haematoma that required reoperation. A Bayesian random-effects model was used for network meta-analysis with minimally informative prior distributions. RESULTS: Thirteen RCTs were included. The rate of cervical haematoma requiring reoperation ranged from 0 to 9·1 per cent, and was not reduced by haemostatic agents: AHA versus control (odds ratio (OR) 1·53, 95 per cent credibility interval 0·21 to 10·77); PHA versus control (OR 2·74, 0·41 to 16·62) and AHA versus PHA (OR 1·77, 0·12 to 25·06). No difference was observed in the time required for drain removal, duration of hospital stay, and the rate of postoperative hypocalcaemia or recurrent nerve palsy. AHA led to a significantly lower total postoperative blood loss and reduced operating time in comparison with both the control and PHA groups. CONCLUSION: The general use of local haemostatic agents has not been shown to reduce the rate of clinically relevant bleeding.

Staging of pancreatic cancer based on the number of positive lymph nodes.

BACKGROUND: The International Study Group on Pancreatic Surgery has stated that at least 12 lymph nodes should be evaluated for staging of pancreatic cancer. The aim of this population-based study was to evaluate whether the number of positive lymph nodes refines staging. METHODS: Patients who underwent pancreatectomy for stage I-II pancreatic cancer between 2004 and 2012 were identified from the Surveillance, Epidemiology, and End Results database. The predictive value of the number of positive lymph nodes for survival was assessed by generalized receiver operating characteristic (ROC) curve analysis and propensity score-adjusted Cox regression analysis. RESULTS: Some 5036 patients were included, with a median of 18 (i.q.r. 15-24) lymph nodes examined. Positive lymph nodes were found in 3555 patients (70·6 per cent). The median duration of follow-up was 15 (i.q.r. 8-28) months. ROC curve analysis revealed that two positive lymph nodes best discriminated overall survival. Patients with one or two positive lymph nodes (pN1a) and those with three or more positive lymph nodes (pN1b) had an increased risk of overall mortality compared with patients who were node-negative (pN0): hazard ratio (HR) 1·47 (95 per cent c.i. 1·33 to 1·64) and HR 2·01 (1·82 to 2·22) respectively. These findings were confirmed by propensity score-adjusted Cox regression analysis. The 5-year overall survival rates were 39·8 (95 per cent c.i. 36·5 to 43·3) per cent for patients with pN0, 21·0 (18·6 to 23·6) per cent for those with pN1a and 11·4 (9·9 to 13·3) per cent for patients with pN1b disease. CONCLUSION: The number of positive lymph nodes in the resection specimen is a prognostic factor in patients with pancreatic cancer.

Meta-analysis of prophylactic abdominal drainage in pancreatic surgery.

BACKGROUND: Intra-abdominal drains are frequently used after pancreatic surgery whereas their benefit in other gastrointestinal operations has been questioned. The objective of this meta-analysis was to compare abdominal drainage with no drainage after pancreatic surgery. METHODS: PubMed, the Cochrane Library and Web of Science electronic databases were searched systematically to identify RCTs comparing abdominal drainage with no drainage after pancreatic surgery. Two independent reviewers critically appraised the studies and extracted data. Meta-analyses were performed using a random-effects model. Odds ratios (ORs) were calculated to aggregate dichotomous outcomes, and weighted mean differences for continuous outcomes. Summary effect measures were presented together with their 95 per cent confidence intervals. RESULTS: Some 711 patients from three RCTs were included. The 30-day mortality rate was 2·0 per cent in the drain group versus 3·4 per cent after no drainage (OR 0·68, 95 per cent c.i. 0·26 to 1·79; P = 0·43). The morbidity rate was 65·6 per cent in the drain group and 62·0 per cent in the no-drain group (OR 1·17, 0·86 to 1·60; P = 0·31). Clinically relevant pancreatic fistulas were seen in 11·5 per cent of patients in the drain group and 9·5 per cent in the no-drain group. Reinterventions, intra-abdominal abscesses and duration of hospital stay also showed no significant difference between the two groups. CONCLUSION: Pancreatic resection with, or without abdominal drainage results in similar rates of mortality, morbidity and reintervention.

Meta-analysis of hybrid natural-orifice transluminal endoscopic surgery versus laparoscopic surgery.

BACKGROUND: Hybrid natural-orifice transluminal endoscopic surgery (NOTES), combining access through a natural orifice with small-sized abdominal trocars, aims to reduce pain and enhance recovery. The objective of this systematic review and meta-analysis was to compare pain and morbidity in hybrid NOTES and standard laparoscopy. METHODS: A systematic literature search was performed to identify RCTs and non-RCTs comparing hybrid NOTES and standard laparoscopy. The main outcome was pain on postoperative day (POD) 1. Secondary outcomes were pain during the further postsurgical course, rescue analgesia, complications, and satisfaction with the cosmetic result. The results of meta-analysis in a random-effects model were presented as odds ratio (ORs) or standard mean differences (MDs) with 95 per cent confidence intervals. RESULTS: Six RCTs and 21 non-randomized trials including 2186 patients were identified. In hybrid NOTES the score on the numerical pain scale was lower on POD 1 (-0·75, 95 per cent c.i. -1·09 to -0·42; P = 0·001) and on POD 2-4 (-0·58, -0·91 to -0·26; P < 0·001) than that for standard laparoscopy. The need for rescue analgesia was reduced in hybrid NOTES (OR 0·36, 0·24 to 0·54; P < 0·001). The reduction in complications found for hybrid NOTES compared with standard laparoscopy (OR 0·52, 0·38 to 0·71; P < 0·001) was not significant when only RCTs were considered (OR 0·83, 0·43 to 1·60; P = 0·570). The score for cosmetic satisfaction was higher after NOTES (MD 1·14, 0·57 to 1·71; P < 0·001). CONCLUSION: Hybrid NOTES reduces postoperative pain and is associated with greater cosmetic satisfaction in selected patients.

Incidence, risk factors and clinical implications of chyle leak after pancreatic surgery.

BACKGROUND: Chyle leak is a well known but poorly characterized complication after pancreatic surgery. Available data on incidence, risk factors and clinical significance of chyle leak are highly heterogeneous. METHODS: For this cohort study all patients who underwent pancreatic surgery between January 2008 and December 2012 were identified from a prospective database. Chyle leak was defined as any drainage output with triglyceride content of 110 mg/dl or more. Risk factors for chyle leak were assessed by univariable and multivariable analyses. The clinical relevance of chyle leak was evaluated using hospital stay and resolution by 14 days for short-term outcome and overall survival for long-term outcome. RESULTS: Chyle leak developed in 346 (10·4 per cent) of 3324 patients. Pre-existing diabetes, resection for malignancy, distal pancreatectomy, duration of surgery 180 min or longer, and concomitant pancreatic fistula or abscess were independent risk factors for chyle leak. Both isolated chyle leak and coincidental chyle leak (with other intra-abdominal complications) were associated with prolonged hospital stay. Some 178 (87·7 per cent) of 203 isolated chyle leaks and 90 (70·3 per cent) of 128 coincidental chyle leaks resolved with conservative management within 14 days. Initial and maximum drainage volumes were associated with duration of hospital stay and success of therapy by 14 days. Impact on survival was restricted to chyle leaks that persisted at 14 days in patients with cancer undergoing palliative surgery. CONCLUSION: Chyle leak is a relevant complication, with an incidence of more than 10 per cent after pancreatic surgery, and has a major impact on hospital stay. Drainage volume is associated with hospital stay and success of therapy.

Prospective trial to evaluate the prognostic value of different nutritional assessment scores in pancreatic surgery (NURIMAS Pancreas).

BACKGROUND: Preoperative nutritional status has an impact on patients' clinical outcome. For pancreatic surgery, however, it is unclear which nutritional assessment scores adequately assess malnutrition associated with postoperative outcome. METHODS: Patients scheduled for elective pancreatic surgery at the University of Heidelberg were screened for eligibility. Twelve nutritional assessment scores were calculated before operation, and patients were categorized as either at risk or not at risk for malnutrition by each score. The postoperative course was monitored prospectively by assessors blinded to the nutritional status. The primary endpoint was major complications evaluated for each score in a multivariable analysis corrected for known risk factors in pancreatic surgery. RESULTS: Overall, 279 patients were analysed. A major complication occurred in 61 patients (21·9 per cent). The proportion of malnourished patients differed greatly among the scores, from 1·1 per cent (Nutritional Risk Index) to 79·6 per cent (Nutritional Risk Classification). In the multivariable analysis, only raised amylase level in drainage fluid on postoperative day 1 (odds ratio (OR) 4·91, 95 per cent c.i. 1·10 to 21·84; P = 0·037) and age (OR 1·05, 1·02 to 1·09; P = 0·005) were significantly associated with major complications; none of the scores was associated with, or predicted, postoperative complications. CONCLUSION: None of the nutritional assessment scores defined malnutrition relevant to complications after pancreatic surgery and these scores may thus be abandoned.

Meta-analysis of immunonutrition in major abdominal surgery.

BACKGROUND: The objective of this study was to evaluate the potential benefits of immunonutrition in major abdominal surgery with special regard to subgroups and influence of bias. METHODS: A systematic literature search from January 1985 to July 2015 was performed in MEDLINE, Embase and CENTRAL. Only RCTs investigating immunonutrition in major abdominal surgery were included. Outcomes evaluated were mortality, overall complications, infectious complications and length of hospital stay. The influence of different domains of bias was evaluated in sensitivity analyses. Evidence was rated according to the GRADE Working Group grading of evidence. RESULTS: A total of 83 RCTs with 7116 patients were included. Mortality was not altered by immunonutrition. Taking all trials into account, immunonutrition reduced overall complications (odds ratio (OR) 0·79, 95 per cent c.i. 0·66 to 0·94; P = 0·01), infectious complications (OR 0·58, 0·51 to 0·66; P < 0·001) and shortened hospital stay (mean difference -1·79 (95 per cent c.i. -2·39 to -1·19) days; P < 0·001) compared with control groups. However, these effects vanished after excluding trials at high and unclear risk of bias. Publication bias seemed to be present for infectious complications (P = 0·002). Non-industry-funded trials reported no positive effects for overall complications (OR 1·13, 0·88 to 1·46; P = 0·34), whereas those funded by industry reported large effects (OR 0·66, 0·48 to 0·91; P = 0·01). CONCLUSION: Immunonutrition after major abdominal surgery did not seem to alter mortality (GRADE: high quality of evidence). Immunonutrition reduced overall complications, infectious complications and shortened hospital stay (GRADE: low to moderate). The existence of bias lowers confidence in the evidence (GRADE approach).

Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer.

BACKGROUND: In the recent International Study Group of Pancreatic Surgery (ISGPS) consensus on extended pancreatectomy, several issues on perioperative outcome and long-term survival remained unclear. Robust data on outcomes are sparse. The present study aimed to assess the outcome of extended pancreatectomy for borderline resectable and locally advanced pancreatic cancer. METHODS: A consecutive series of patients with primary pancreatic adenocarcinoma undergoing extended pancreatectomies, as defined by the new ISGPS consensus, were compared with patients who had a standard pancreatectomy. Univariable and multivariable analysis was performed to identify risk factors for perioperative mortality and characteristics associated with survival. Long-term outcome was assessed by means of Kaplan-Meier analysis. RESULTS: The 611 patients who had an extended pancreatectomy had significantly greater surgical morbidity than the 1217 patients who underwent a standard resection (42·7 versus 34·2 per cent respectively), and higher 30-day mortality (4·3 versus 1·8 per cent) and in-hospital mortality (7·5 versus 3·6 per cent) rates. Operating time of 300 min or more, extended total pancreatectomy, and ASA fitness grade of III or IV were associated with increased in-hospital mortality in multivariable analysis, whereas resections involving the colon, portal vein or arteries were not. Median survival and 5-year overall survival rate were reduced in patients having extended pancreatectomy compared with those undergoing a standard resection (16·1 versus 23·6 months, and 11·3 versus 20·6 per cent, respectively). Older age, G3/4 tumours, two or more positive lymph nodes, macroscopic positive resection margins, duration of surgery of 420 min or above, and blood loss of 1000 ml or more were independently associated with decreased overall survival. CONCLUSION: Extended resections are associated with increased perioperative morbidity and mortality, particularly when extended total pancreatectomy is performed. Favourable long-term outcome is achieved in some patients.