Results of robotic liver surgery in association with IWATE criteria - the first 100 cases.

BACKGROUND: Aim of the current study was to present the results of the implementation phase of a robotic liver surgery program and to assess the validity of the IWATE difficulty score in predicting difficulty and postoperative complications in robotic liver surgery. METHODS: Based on the prospective database of the Interdisciplinary Robotic Center of Ulm University Hospital, the first 100 robotic liver surgeries were identified and analyzed. Perioperative parameters (duration of surgery and blood loss) and postoperative parameters including morbidity, mortality, and length of hospital stay were assessed and the results were compared between different IWATE difficulty categories. RESULTS: From November 2020 until January 2023, 100 robotic liver surgeries were performed (41 female, 59 male; median age 60.6 years, median BMI 25.9 kg/m2). Median duration of surgery was 180 min (IQR: 128.7), and median blood loss was 300 ml (IQR: 550). Ninety-day mortality was 2%, and overall morbidity was 21%, with major complications occurring in 13% of patients (≥ grade 3 according to Clavien/Dindo). A clinically relevant postoperative biliary leakage was observed in 3 patients. Posthepatectomy liver failure occurred in 7% (4 Grade A, 3 Grade B). Duration of surgery (p < 0.001), blood loss (p < 0.001), CCI (p = 0.004), overall morbidity (p = 0.004), and length of hospital stay (p < 0.001) were significantly increased in the IWATE 'expert' category compared to lower categories. DISCUSSION: Robotic surgery offers a minimally invasive approach for liver surgery with favorable clinical outcomes, even in the implementation phase. In the current study the IWATE difficulty score had the ability to predict both difficulty of surgery as well as postoperative outcomes when assessing the complexity of robotic liver surgery. Therefore, the role of the IWATE score in predicting these outcomes highlights its importance as a tool in surgical planning and decision-making.

Antecolic versus retrocolic reconstruction after partial pancreaticoduodenectomy.

BACKGROUND: Pancreatic cancer remains one of the five leading causes of cancer deaths in industrialised nations. For adenocarcinomas in the head of the gland and premalignant lesions, partial pancreaticoduodenectomy represents the standard treatment for resectable tumours. The gastro- or duodenojejunostomy after partial pancreaticoduodenectomy can be reestablished via either an antecolic or retrocolic route. The debate about the more favourable technique for bowel reconstruction is ongoing. OBJECTIVES: To compare the effectiveness and safety of antecolic and retrocolic gastro- or duodenojejunostomy after partial pancreaticoduodenectomy. SEARCH METHODS: In this updated version, we conducted a systematic literature search up to 6 July 2021 to identify all randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library 2021, Issue 6, MEDLINE (1946 to 6 July 2021), and Embase (1974 to 6 July 2021). We applied no language restrictions. We handsearched reference lists of identified trials to identify further relevant trials, and searched the trial registries clinicaltrials.govand World Health Organization International Clinical Trials Registry Platform for ongoing trials. SELECTION CRITERIA: We considered all RCTs comparing antecolic with retrocolic reconstruction of bowel continuity after partial pancreaticoduodenectomy for any given indication to be eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the identified references and extracted data from the included trials. The same two review authors independently assessed risk of bias of included trials, according to standard Cochrane methodology. We used a random-effects model to pool the results of the individual trials in a meta-analysis. We used odds ratios (OR) to compare binary outcomes and mean differences (MD) for continuous outcomes. MAIN RESULTS: Of a total of 287 citations identified by the systematic literature search, we included eight randomised controlled trials (reported in 11 publications), with a total of 818 participants. There was high risk of bias in all of the trials in regard to blinding of participants and/or outcome assessors and unclear risk for selective reporting in six of the trials. There was little or no difference in the frequency of delayed gastric emptying (OR 0.67; 95% confidence interval (CI) 0.41 to 1.09; eight trials, 818 participants, low-certainty evidence) with relevant heterogeneity between trials (I2=40%). There was little or no difference in postoperative mortality (risk difference (RD) -0.00; 95% CI -0.02 to 0.01; eight trials, 818 participants, high-certainty evidence); postoperative pancreatic fistula (OR 1.01; 95% CI 0.73 to 1.40; eight trials, 818 participants, low-certainty evidence); postoperative haemorrhage (OR 0.87; 95% CI 0.47 to 1.59; six trials, 742 participants, low-certainty evidence); intra-abdominal abscess (OR 1.11; 95% CI 0.71 to 1.74; seven trials, 788 participants, low-certainty evidence); bile leakage (OR 0.82; 95% CI 0.35 to 1.91; seven trials, 606 participants, low-certainty evidence); reoperation rate (OR 0.68; 95% CI 0.34 to 1.36; five trials, 682 participants, low-certainty evidence); and length of hospital stay (MD -0.21; 95% CI -1.41 to 0.99; eight trials, 818 participants, low-certainty evidence). Only one trial reported quality of life, on a subgroup of 73 participants, also without a relevant difference between the two groups at any time point. The overall certainty of the evidence was low to moderate, due to some degree of heterogeneity, inconsistency and risk of bias in the included trials. AUTHORS' CONCLUSIONS: There was low- to moderate-certainty evidence suggesting that antecolic reconstruction after partial pancreaticoduodenectomy results in little to no difference in morbidity, mortality, length of hospital stay, or quality of life. Due to heterogeneity in definitions of the endpoints between trials, and differences in postoperative management, future research should be based on clearly defined endpoints and standardised perioperative management, to potentially elucidate differences between these two procedures. Novel strategies should be evaluated for prophylaxis and treatment of common complications, such as delayed gastric emptying.

Systematic reviews in surgery-recommendations from the Study Center of the German Society of Surgery.

BACKGROUND: Systematic reviews are an important tool of evidence-based surgery. Surgical systematic reviews and trials, however, require a special methodological approach. PURPOSE: This article provides recommendations for conducting state-of-the-art systematic reviews in surgery with or without meta-analysis. CONCLUSIONS: For systematic reviews in surgery, MEDLINE (via PubMed), Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) should be searched. Critical appraisal is at the core of every surgical systematic review, with information on blinding, industry involvement, surgical experience, and standardisation of surgical technique holding special importance. Due to clinical heterogeneity among surgical trials, the random-effects model should be used as a default. In the experience of the Study Center of the German Society of Surgery, adherence to these recommendations yields high-quality surgical systematic reviews.

Meta-analysis of primary open versus closed cannulation strategy for totally implantable venous access port implantation.

BACKGROUND: There is still no reference standard for the implantation of totally implantable venous access ports (TIVAPs). A recently published multicentre randomised controlled trial (RCT) revealed a significantly greater risk of pneumothorax after closed cannulation than after an open strategy. The aim of this meta-analysis was to provide an update of the available evidence for the safety and effectiveness of primary open versus closed cannulation strategy. METHODS: RCTs comparing outcomes of open cut-down of the cephalic vein and closed cannulation of the subclavian vein were sought systematically in MEDLINE, Web of Science and CENTRAL. The primary outcome was the occurrence of pneumothorax. A beta-binominal model was applied to combine the respective outcomes, and results are presented as odds ratios (OR) with 95% confidence interval (CI). RESULTS: Six RCTs with a total of 1831 patients were included in final analysis. Meta-analysis showed statistically significant superiority of the open cut-down technique regarding pneumothorax (OR 0.308, 95% CI 0.122 to 0.776), but a statistically significant higher failure of the primary technique for the open cut-down technique than for closed cannulation (OR 2.364, 95% CI 1.051 to 5.315). There were no significant differences between the two procedures regarding other morbidity endpoints. CONCLUSION: This meta-analysis shows a general superiority of open cut-down of the cephalic vein over closed cannulation of the subclavian vein regarding the occurrence of pneumothorax. Open cut-down should be the first-line approach for TIVAP implantation. Closed cannulation should be performed with ultrasound as second-line procedure if the open technique fails. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013005180.

Primary Open Versus Closed Implantation Strategy for Totally Implantable Venous Access Ports: The Multicentre Randomized Controlled PORTAS-3 Trial (DRKS 00004900).

OBJECTIVES: PORTAS-3 was designed to compare the frequency of pneumothorax or haemothorax in a primary open versus closed strategy for port implantation. BACKGROUND DATA: The implantation strategy for totally implantable venous access ports with the optimal benefit/risk ratio remains unclear. METHODS: PORTAS-3 was a multicentre, randomized, controlled, parallel-group superiority trial. Adult patients with oncological disease scheduled for elective port implantation were randomized to a primary open or closed strategy. Primary endpoint was the rate of pneumothorax or haemothorax. Assuming a difference of 2.5% between the 2 groups, a sample size of 1154 patients was needed to prove superiority of the open group. A logistic regression model after the intention-to-treat principle was applied for analysis of the primary endpoint. RESULTS: Between November 9, 2014 and September 5, 2016, 1205 patients were randomized. Of these, 1159 (open n = 583; closed n = 576) were finally analyzed. The rate of pneumothorax or haemothorax was significantly reduced with the open strategy [odds ratio 0.27, 95% confidence interval (CI) 0.09-0.88; P = 0.029]. Operation time was shorter for the closed strategy. Primary success rates, tolerability, morbidity, dose rate of radiation, and 30-day mortality did not differ significantly between the groups. CONCLUSION: A primary open strategy by cut-down of the cephalic vein, if necessary enhanced by a modified Seldinger technique, reduces the frequency of pneumothorax or haemothorax after central venous port implantation significantly compared with a closed strategy by primary puncture of the subclavian vein without routine sonographic guidance. Therefore, open surgical cut-down should be the reference standard for port implantation in comparable cohorts. TRIAL REGISTRATION: German Clinical Trials Register DRKS 00004900.

Randomised-controlled feasibility trial on abdominal wall closure techniques in patients undergoing relaparotomy (ReLap study; DRKS00013001).

BACKGROUND: Patients undergoing relaparotomy are generally underrepresented in clinical trials, despite how common the procedure is in clinical practice. Specifically, techniques for re-do abdominal wall closure have never been evaluated in a randomised-controlled trial. The aim of this trial was to identify the optimal abdominal wall closure technique in patients undergoing relaparotomy. METHODS: In this monocentric, randomised feasibility trial, patients scheduled for elective relaparotomy were randomised to abdominal wall closure with either the small stitches technique, using Monomax® 2-0, or the large stitches technique, using PDS II® 1 loop. Patients' postoperative courses were followed for 1 year after the index operation. Effectiveness and safety outcomes were compared at a level of significance of 5% between the two techniques. RESULTS: A total of 100 out of 131 patients (76.3%) were evenly randomised to the small stitches and large stitches groups. The time for abdominal wall closure did not differ between the two techniques (small stitches 27.5 ± 9.5 min versus large stitches 25.3 ± 12.4 min; p = 0.334). The overall comprehensive complication index was 14.4 ± 15.5 in the small stitches group and 19.9 ± 23.4 in the large stitches group (p = 0.168). Specifically, rates of surgical site infection (small stitches 30.0% versus large stitches 36.0%; p = 0.524) and burst abdomen (small stitches 4.0% versus large stitches 0.0%; p = 0.495) did not differ. After 1 year, incisional hernia rate was 7.5% in the small stitches group and 10.0% in the large stitches group (p > 0.999). DISCUSSION: Both abdominal wall closure techniques investigated in this trial were feasible in relaparotomy patients. This exploratory trial revealed no noticeable difference in the effectiveness or safety of the small stitches technique with Monomax® 2-0 versus the large stitches technique with PDS II® 1 loop. Therefore, surgeons should stay with their preferred suture technique in relaparotomy patients. TRIAL REGISTRATION: Deutsches Register Klinischer Studien ( www.germanctr.de ): DRKS00013001.

Evidence-based recommendations for blinding in surgical trials.

RATIONALE: Blinding reduces performance and detection bias in randomized controlled trials (RCT). There is evidence that lack of blinding leads to overestimation of treatment effects in pharmacological trials. Since surgical trials use interventions with a physical component, blinding is often complicated. The aim of this study was to analyze, in general and abdominal surgery RCT, the status of blinding, the potential for blinding, and the influence of blinding on outcomes. METHODS: A systematic search of the literature in CENTRAL, MEDLINE, and Web of Science was conducted to identify RCT with a surgical intervention, starting in 1996, the year when the first CONSORT statement was published. Information on general study characteristics and blinding methods was extracted. The presence or absence of blinding of the study contributors-patients, surgeons, data collectors, outcome assessors, and data analysts-was analyzed. The association of blinding with the trial outcome was investigated for every study contributor. RESULTS: Out of 29,119 articles, 378 RCT were included in the analysis. These investigated a total of 62,522 patients, of whom 15,025 were blinded (24.0%). Contributors could have been blinded in far more trials, as the potential for blinding measures ranged from 69% for outcome assessors to 98% for data analysts. If blinding of surgeons would have been possible but had not been performed, this was associated with more significant trial outcomes (OR 13.670; 95% CI 1.308 to 142.840; p = 0.0289). DISCUSSION: The potential of blinding, an important quality measure in surgical RCT, has not been exhausted. This study summarizes the existing evidence on blinding in surgical trials and gives evidence-based recommendations for the use of blinding in future surgical trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2015:CRD42015026837.

Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial.

BACKGROUND: There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. METHODS: This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. FINDINGS: Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. INTERPRETATION: No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. FUNDING: German Research Foundation (DFG).

Evaluation of Open and Minimally Invasive Adrenalectomy: A Systematic Review and Network Meta-analysis.

BACKGROUND: Adrenalectomy can be performed via open and various minimally invasive approaches. The aim of this systematic review was to summarize the current evidence on surgical techniques of adrenalectomy. METHODS: Systematic literature searches (MEDLINE, EMBASE, Web of Science, Cochrane Library) were conducted to identify randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing at least two surgical procedures for adrenalectomy. Statistical analyses were performed, and meta-analyses were conducted. Furthermore, an indirect comparison of RCTs and a network meta-analysis of CCTs were carried out for each outcome. RESULTS: Twenty-six trials (1710 patients) were included. Postoperative complication rates did not show differences for open and minimally invasive techniques. Operation time was significantly shorter for open adrenalectomy than for the robotic approach (p < 0.001). No differences were found between laparoscopic and robotic approaches. Network meta-analysis showed open adrenalectomy to be the fastest technique. Blood loss was significantly reduced in the robotic arm compared with open and laparoscopic adrenalectomy (p = 0.01). Length of hospital stay (LOS) was significantly lower after conventional laparoscopy than open adrenalectomy in CCTs (p < 0.001). Furthermore, both retroperitoneoscopic (p < 0.001) and robotic access (p < 0.001) led to another significant reduction of LOS compared with conventional laparoscopy. This difference was not consistent in RCTs. Network meta-analysis revealed the lowest LOS after retroperitoneoscopic adrenalectomy. CONCLUSION: Minimally invasive adrenalectomy is safe and should be preferred over open adrenalectomy due to shorter LOS, lower blood loss, and equivalent complication rates. The retroperitoneoscopic access features the shortest LOS and operating time. Further high-quality RCTs are warranted, especially to compare the posterior retroperitoneoscopic and the transperitoneal robotic approach.

Predictive value of mucinous histology in colon cancer: a population-based, propensity score matched analysis.

BACKGROUND: This investigation aimed to assess whether mucinous histology impacts overall (OS) and cancer-specific survival (CSS) in colon cancer. METHODS: Colon cancer patients who underwent surgery between 2004 and 2011 were identified in the Surveillance, Epidemiology, and End Results database. OS and CSS were assessed using Cox regression and propensity score methods. RESULTS: Out of 121 628 patients, 12 863 (10.6%) had a mucinous histology. Five-year OS and CSS for mucinous adenocarcinoma were 54.4% (95% CI: 53.4-55.5%) and 66.5% (95% CI: 65.5-67.5%) compared with 60.2% (95% CI: 59.8-60.5%) and 71.9% (95% CI: 71.5-72.2%) for non-mucinous adenocarcinoma (P<0.001). This survival disadvantage disappeared in multivariable analyses (hazard ratio (HR)=1.02, 95% CI: 0.99-1.05, P=0.269 and HR=1.03, 95% CI: 0.99-1.06, P=0.169), and after propensity score matching (OS: HR=0.99, 95% CI: 0.93-1.04, P=0.606 and CSS: HR=0.99, 95% CI:0.92-1.06, P=0.783). CONCLUSIONS: In this population-based investigation, a mucinous histology did not negatively impact survival. Hence, the present study does not provide evidence to change treatment strategies in patients with mucinous adenocarcinoma of the colon.

Prognostic Relevance of Mucinous Subtype in a Population-based Propensity Score Analysis of 40,083 Rectal Cancer Patients.

BACKGROUND: The prognostic relevance of mucinous histology in colorectal cancer remains unclear, especially for rectal neoplasms. The objective of this study was to evaluate if mucinous subtype has a relevant impact on overall survival (OS) and cancer-specific survival (CSS) of patients with adenocarcinomas of the rectum. METHODS: On the basis of the data set of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute of the United States, patients with rectal cancer between 2004 and 2011 were identified. Risk-adjusted Cox regression analysis and propensity score methods were used to assess OS and CSS. RESULTS: In total, 40,083 patients with stage I-IV rectal cancer, of whom 2483 (6.2 %) had mucinous histology, were included in this study. In unadjusted analysis, the 5-year OS and CSS for patients with a mucinous adenocarcinoma was 54.3 % [95 % confidence interval (CI) 52.0-56.7] and 61.4 % (95 % CI 59.1-63.9) compared to 66.4 % (95 % CI 65.8-67.0) and 74.5 % (95 % CI 73.9-75.1) for patients with nonmucinous adenocarcinoma (P < 0.001). The survival disadvantage persisting in risk-adjusted Cox proportional hazard regression analysis [hazard ratio (HR) 1.23, 95 % CI 1.15-1.31, P < 0.001 and 1.25, 95 % CI 1.16-1.35, P < 0.001) disappeared after propensity score matching (OS: HR = 0.96, 95 % CI 0.76-1.21, P = 0.722; CSS: HR 1.06, 95 % CI 0.80-1.40, P = 0.693). CONCLUSIONS: This population-based, propensity score matched analysis shows that mucinous histology itself does not constrain survival in rectal cancer patients. Therefore, treatment decisions should not be different according to mucinous histology.

Incisional Hernia Rates After Laparoscopic or Open Abdominal Surgery-A Systematic Review and Meta-Analysis.

BACKGROUND: Incisional hernias are one of the most common long-term complications associated with open abdominal surgery. The aim of this review and meta-analysis was to systematically assess laparoscopic versus open abdominal surgery as a general surgical strategy in all available indications in terms of incisional hernia occurrence. METHODS: A systematic literature search was performed to identify randomized controlled trials comparing incisional hernia rates after laparoscopic versus open abdominal surgery in all indications. Random effects meta-analyses were calculated and presented as risk differences (RD) with their corresponding 95 % confidence intervals (CI). RESULTS: 24 trials (3490 patients) were included. Incisional hernias were significantly reduced in the laparoscopic group (RD -0.06, 95 % CI [-0.09, -0.03], p = 0.0002, I (2) = 75). The advantage of the laparoscopic procedure persisted in the subgroup of total-laparoscopic interventions (RD -0.14, 95 % CI [-0.22, -0.06], p = 0.001, I (2) = 87 %), whereas laparoscopically assisted procedures did not show a significant reduction of incisional hernias compared to open surgery (RD -0.01, 95 % CI [-0.03, 0.01], p = 0.31, I (2) = 35 %). Wound infections were significantly reduced in the laparoscopic group (RD -0.06, 95 % CI [-0.09, -0.03], p < 0.0001, I (2) = 35 %); overall postoperative morbidity was comparable in both groups (RD -0.06, 95 % CI [-0.13, 0.00], p = 0.06; I (2) = 64 %). Open abdominal surgery showed a significantly longer hospital stay compared to laparoscopy (RD -1.92, 95 % CI [-2.67, -1.17], p < 0.00001, I (2) = 87 %). At short-term follow-up, quality of life was in favor of laparoscopy. CONCLUSIONS: Incisional hernias are less frequent using the total-laparoscopic approach instead of open abdominal surgery. Whenever possible, the less traumatic access should be chosen.

Antecolic versus retrocolic reconstruction after partial pancreaticoduodenectomy.

BACKGROUND: Pancreatic cancer remains one of the five leading causes of cancer deaths in industrialized nations. For adenocarcinomas in the head of the gland and premalignant lesions, partial pancreaticoduodenectomy represents the standard treatment for resectable tumours. The gastro- or duodenojejunostomy after partial pancreaticoduodenectomy can be reestablished via either an antecolic or a retrocolic route. The debate about the more favourable technique for bowel reconstruction is ongoing. OBJECTIVES: To compare the effectiveness and safety of antecolic and retrocolic gastro- or duodenojejunostomy after partial pancreaticoduodenectomy. SEARCH METHODS: We conducted a systematic literature search on 29 September 2015 to identify all randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library 2015, issue 9, MEDLINE (1946 to September 2015), and EMBASE (1974 to September 2015). We applied no language restrictions. We handsearched reference lists of identified trials to identify further relevant trials, and searched the trial registry clinicaltrials.gov for ongoing trials. SELECTION CRITERIA: We considered all randomised controlled trials that compared antecolic versus retrocolic reconstruction of bowel continuity after partial pancreaticoduodenectomy for any given indication to be eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the identified references and extracted data from the included trials. The same two review authors independently assessed risk of bias of included trials, according to standard Cochrane methodology. We used a random-effects model to pool the results of the individual trials in a meta-analysis. We used odds ratios to compare binary outcomes and mean differences for continuous outcomes. MAIN RESULTS: Of a total of 216 citations identified by the systematic literature search, we included six randomised controlled trials (reported in nine publications), with a total of 576 participants. We identified a moderate heterogeneity of methodological quality and risk of bias of the included trials. None of the pooled results for our main outcomes of interest showed significant differences: delayed gastric emptying (OR 0.60; 95% CI 0.31 to 1.18; P = 0.14), mortality (RD -0.01; 95% CI -0.03 to 0.02; P = 0.72), postoperative pancreatic fistula (OR 0.98; 95% CI 0.65 to 1.47; P = 0.92), postoperative haemorrhage (OR 0.79; 95% CI 0.38 to 1.65; P = 0.53), intra-abdominal abscess (OR 0.93; 95% CI 0.52 to 1.67; P = 0.82), bile leakage (OR 0.89; 95% CI 0.36 to 2.15; P = 0.79), reoperation rate (OR 0.59; 95% CI 0.27 to 1.31; P = 0.20), and length of hospital stay (MD -0.67; 95%CI -2.85 to 1.51; P = 0.55). Furthermore, the perioperative outcomes duration of operation, intraoperative blood loss and time to NGT removal showed no relevant differences. Only one trial reported quality of life, on a subgroup of participants, also without a significant difference between the two groups at any time point. The overall quality of the evidence was only low to moderate, due to heterogeneity, some inconsistency and risk of bias in the included trials. AUTHORS' CONCLUSIONS: There was low to moderate quality evidence suggesting no significant differences in morbidity, mortality, length of hospital stay, or quality of life between antecolic and retrocolic reconstruction routes for gastro- or duodenojejunostomy. Due to heterogeneity in definitions of the endpoints between trials, and differences in postoperative management, future research should be based on clearly defined endpoints and standardised perioperative management, to potentially elucidate differences between these two procedures. Novel strategies should be evaluated for prophylaxis and treatment of common complications, such as delayed gastric emptying.

Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma.

BACKGROUND: Pancreatic cancer is the fourth-leading cause of cancer death for both, men and women. The standard treatment for resectable tumours consists of a classic Whipple (CW) operation or a pylorus-preserving pancreaticoduodenectomy (PPW). It is unclear which of these procedures is more favourable in terms of survival, postoperative mortality, complications, and quality of life. OBJECTIVES: The objective of this systematic review was to compare the effectiveness of CW and PPW techniques for surgical treatment of cancer of the pancreatic head and the periampullary region. SEARCH METHODS: We conducted searches on 28 March 2006, 11 January 2011, 9 January 2014, and 18 August 2015 to identify all randomised controlled trials (RCTs), while applying no language restrictions. We searched the following electronic databases on 18 August 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE) from the Cochrane Library (2015, Issue 8); MEDLINE (1946 to August 2015); and EMBASE (1980 to August 2015). We also searched abstracts from Digestive Disease Week and United European Gastroenterology Week (1995 to 2010); we did not update this part of the search for the 2014 and 2015 updates because the prior searches did not contribute any additional information. We identified two additional trials through the updated search in 2015. SELECTION CRITERIA: RCTs comparing CW versus PPW including participants with periampullary or pancreatic carcinoma. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials. We used a random-effects model for pooling data. We compared binary outcomes using odds ratios (ORs), pooled continuous outcomes using mean differences (MDs), and used hazard ratios (HRs) for meta-analysis of survival. Two review authors independently evaluated the methodological quality and risk of bias of included trials according to the standards of The Cochrane Collaboration. MAIN RESULTS: We included eight RCTs with a total of 512 participants. Our critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. Postoperative mortality (OR 0.64, 95% confidence interval (CI) 0.26 to 1.54; P = 0.32), overall survival (HR 0.84, 95% CI 0.61 to 1.16; P = 0.29), and morbidity showed no significant differences, except of delayed gastric emptying, which significantly favoured CW (OR 3.03, 95% CI 1.05 to 8.70; P = 0.04). Furthermore, we noted that operating time (MD -45.22 minutes, 95% CI -74.67 to -15.78; P = 0.003), intraoperative blood loss (MD -0.32 L, 95% CI -0.62 to -0.03; P = 0.03), and red blood cell transfusion (MD -0.47 units, 95% CI -0.86 to -0.07; P = 0.02) were significantly reduced in the PPW group. All significant results were associated with low-quality evidence based on GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. AUTHORS' CONCLUSIONS: Current evidence suggests no relevant differences in mortality, morbidity, and survival between the two operations. However, some perioperative outcome measures significantly favour the PPW procedure. Given obvious clinical and methodological heterogeneity, future high-quality RCTs of complex surgical interventions based on well-defined outcome parameters are required.

Effectiveness of Tachosil(®) in the prevention of postoperative pancreatic fistula after distal pancreatectomy: a systematic review and meta-analysis.

PURPOSE: Postoperative pancreatic fistula (POPF) is a frequent and clinically relevant problem after distal pancreatectomy. A variety of methods have been tested in the attempt to prevent POPF, most of them without convincing results. METHODS: A systematic literature search was conducted in PubMed, Embase and the Cochrane Library to identify clinical studies comparing pancreatic stump closure with the addition of Tachosil(®) to conventional stump closure. The identified studies were critically appraised, and meta-analyses were performed using a random-effects model. Dichotomous data were pooled using odds ratios, and weighted mean differences were calculated for continuous outcomes, together with the corresponding 95 % confidence intervals. RESULTS: Four studies (two randomised controlled trials and two retrospective clinical studies) reporting data from 738 patients were included in the meta-analysis. Overall POPF, clinically-relevant POPF, mortality, reoperations, intraoperative blood loss and length of hospital stay did not differ significantly between conventional closure and additional covering of the pancreatic stump with Tachosil(®). A sensitivity analysis of only randomised controlled trials confirmed the results. CONCLUSIONS: The application of Tachosil(®) to the pancreatic stump after distal pancreatectomy is a safe procedure but provides no relevant benefit in terms of POPF, mortality, reoperation rate, blood loss or length of hospital stay. Future research should concentrate on novel methods of pancreatic stump closure to prevent POPF after distal pancreatectomy.

Stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy.

BACKGROUND: Resections of the pancreatic body and tail reaching to the left of the superior mesenteric vein are defined as distal pancreatectomy. Most distal pancreatectomies are elective treatments for chronic pancreatitis, benign or malignant diseases, and they have high morbidity rates of up to 40%. Pancreatic fistula formation is the main source of postoperative morbidity, associated with numerous further complications. Researchers have proposed several surgical resection and closure techniques of the pancreatic remnant in an attempt to reduce these complications. The two most common techniques are scalpel resection followed by hand-sewn closure of the pancreatic remnant and stapler resection and closure. OBJECTIVES: To compare the rates of pancreatic fistula in people undergoing distal pancreatectomy using scalpel resection followed by hand-sewn closure of the pancreatic remnant versus stapler resection and closure. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biosis and Science Citation Index from database inception to October 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy (irrespective of language or publication status). DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion and extracted the data. Taking into consideration the clinical heterogeneity between the trials (e.g. different endpoint definitions), we analysed data using a random-effects model with Review Manager (RevMan), calculating risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: In two eligible trials, a total of 381 participants underwent distal pancreatic resection and were randomised to closure of the pancreatic remnant either with stapler (n = 191) or scalpel resection followed by hand-sewn closure (n = 190). One was a single centre pilot RCT and the other was a multicentre blinded RCT. The single centre pilot RCT evaluated 69 participants in five intervention arms (stapler, hand-sewn, fibrin glue, mesh and pancreaticojejunostomy), although we only assessed the stapler and hand-sewn closure groups (14 and 15 participants, respectively). The multicentre RCT had two interventional arms: stapler (n = 177) and hand-sewn closure (n = 175). The rate of postoperative pancreatic fistula was the main outcome, and it occurred in 79 of 190 participants in the hand-sewn group compared to 65 of 191 participants in the stapler group. Neither the individual trials nor the meta-analysis showed a significant difference between resection techniques (RR 0.90; 95% CI 0.55 to 1.45; P = 0.66). In the same way, postoperative mortality and operation time did not differ significantly. The single centre RCT had an unclear risk of bias in the randomisation, allocation and both blinding domains. However, the much larger multicentre RCT had a low risk of bias in all domains. Due to the small number of events and the wide confidence intervals that cannot exclude clinically important benefit or harm with stapler versus hand-sewn closure, there is a serious possibility of imprecision, making the overall quality of evidence moderate. AUTHORS' CONCLUSIONS: The quality of evidence is moderate and mainly based on the high weight of the results of one multicentre RCT. Unfortunately, there are no other completed RCTs on this topic except for one relevant ongoing trial. Neither stapler nor scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy showed any benefit compared to the other method in terms of postoperative pancreatic fistula, overall postoperative mortality or operation time. Currently, the choice of closure is left up to the preference of the individual surgeon and the anatomical characteristics of the patient. Another (non-European) multicentre trial (e.g. with an equality or non-inferiority design) would help to corroborate the findings of this meta-analysis. Future trials assessing novel methods of stump closure should compare them either with stapler or hand-sewn closure as a control group to ensure comparability of results.

Palliative resection of the primary tumor in 442 metastasized neuroendocrine tumors of the pancreas: a population-based, propensity score-matched survival analysis.

PURPOSE: There is an ongoing debate on whether palliative removal of the primary tumor may result in a survival benefit for patients with incurable stage IV pancreatic neuroendocrine tumors (P-NET). The objective of this study was to assess whether palliative resection of the primary tumor in patients with incurable stage IV P-NET has an impact on survival. METHODS: Patients with stage IV P-NET registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2011 were identified. Those undergoing resection of metastases were excluded. Overall and cancer-specific survival of patients who did and did not undergo resection of their primary tumor were compared by means of risk-adjusted Cox proportional hazard regression analysis and propensity score-matched analysis. RESULTS: A total of 442 stage IV P-NET patients were identified, of whom 75 (17.0 %) underwent palliative primary tumor resection. The latter showed a significant benefit in both overall survival (hazard ratio [HR] of death = 0.41, 95 % confidence interval [CI] 0.25-0.66, p < 0.001) and cancer-specific survival (HR of death = 0.41, 95 % CI 0.25-0.67, p < 0.001) in unadjusted multivariate Cox regression analysis; the benefit persisted after propensity score adjustment. CONCLUSIONS: This population-based analysis of stage IV P-NET patients provides compelling evidence that palliative resection of the primary tumor is associated with significant survival benefit. Thus, the recent recommendations judging resection of the primary as inadvisable and the accompanying trend towards fewer palliative resections of the primary tumor have to be contested.

Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma.

Background Pancreatic cancer is the fourth leading cause of cancer death for men and the fifth for women. The standard treatment for resectable tumours consists of a classic Whipple (CW) operation or a pylorus-preserving pancreaticoduodenectomy (PPW). It is unclear which of these procedures is more favourable in terms of survival, mortality, complications and quality of life.Objectives The objective of this systematic review is to compare the effectiveness of CW and PPW techniques for surgical treatment of cancer of the pancreatic head and the periampullary region.Search methods We conducted searches on 28 March 2006, 11 January 2011 and 9 January 2014 to identify all randomised controlled trials (RCTs),while applying no language restrictions. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects(DARE) from The Cochrane Library (2013, Issue 4); MEDLINE (1946 to January 2014); and EMBASE (1980 to January 2014). We also searched abstracts from Digestive Disease Week and United European Gastroenterology Week (1995 to 2010). We identified no additional studies upon updating the systematic review in 2014.Selection criteria We considered RCTs comparing CW versus PPW to be eligible if they included study participants with periampullary or pancreatic carcinoma. Data collection and analysis Two review authors independently extracted data from the included studies. We used a random-effects model for pooling data. We compared binary outcomes using odds ratios (ORs), pooled continuous outcomes using mean differences (MDs) and used hazard ratios (HRs) for meta-analysis of survival. Two review authors independently evaluated the methodological quality and risk of bias of included studies according to the standards of The Cochrane Collaboration.Main results We included six RCTs with a total of 465 participants. Our critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. In-hospital mortality (OR 0.49, 95% confidence interval (CI) 0.17 to 1.40; P value 0.18), overall survival (HR 0.84, 95% CI 0.61 to 1.16; P value 0.29) and morbidity showed no significant differences. However, we noted that operating time (MD -68.26 minutes, 95% CI -105.70 to -30.83; P value 0.0004) and intraoperative blood loss (MD -0.76 mL, 95%CI -0.96 to -0.56; P value < 0.00001) were significantly reduced in the PPW group. All significant results are associated with low quality of evidence as determined on the basis of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria.Authors' conclusions No evidence suggests relevant differences in mortality, morbidity and survival between the two operations. Given obvious clinical and methodological heterogeneity, future research must be undertaken to perform high-quality randomised controlled trials of complex surgical interventions on the basis of well-defined outcome parameters.