Closed cannulation of subclavian vein vs open cut-down of cephalic vein for totally implantable venous access port (TIVAP) implantation: protocol for a systematic review and proportional meta-analysis of perioperative and postoperative complications

Background: Totally implantable venous access port (TIVAP) implantation is one of the most often performed operations in general surgery (over 100,000/year in Germany). The two main approaches for TIVAP placement are insertion into the cephalic vein through an open cut-down technique (OCD) or closed cannulation technique of the subclavian vein (CC) with Seldinger technique. Both procedures are performed with high success rates and very low complication frequencies. Because of the low incidence of complications, no single interventional trial is able to report a valid comparison of peri- and postoperative complication frequencies between both techniques. Therefore, the aim of this systematic review is to summarize evidence for peri- and postoperative complication rates in patients undergoing OCD or CC. Methods/Design: A systematic literature search will be conducted in The Cochrane Library, MEDLINE, and Embase to identify randomized controlled trials (RCTs), observational clinical studies (OCS), or case series (CS) reporting peri- and/or postoperative complications of at least one implantation technique. A priori defined data will be extracted from included studies, and methodological quality will be assessed. Event rates with their 95% confidence intervals will be derived taking into account the follow-up time per study by patient-months where appropriate. Pooled estimates of event rates with corresponding 95% confidence intervals will be calculated on the base of the Freeman-Tukey double arcsine transformation within a random effect model framework. Discussion: The findings of this systematic review with proportional meta-analysis will help to identify the procedure with the best benefit/risk ratio for TIVAP implantation. This may have influence on daily practice, and data may be implemented in treatment guidelines. Considering the impact of TIVAP implantation on patients’ well being together with its socioeconomic relevance, patients will benefit from evidence-based treatment and health-care costs may also be reduced. Systematic review registration PROSPERO CRD42013005180

Immediate tumor resection in patients with locally advanced gastroesophageal adenocarcinoma with nonresponse to chemotherapy after 4 weeks of treatment versus resection after completion of chemotherapy (OPTITREAT trial, DRKS00004668): study protocol for a randomized controlled pilot trial

Background: Neoadjuvant chemotherapy is a standard of care for patients with adenocarcinoma of the esophagus and stomach in Europe, but still only 20–40 % respond to therapy and the critical issue; how to treat nonresponding patients is still unclear. So far, there is no randomized trial evaluating the impact of early termination of neoadjuvant chemotherapy and immediate tumor resection in nonresponding patients with locally advanced gastroesophageal cancer on postoperative outcome. With this exploratory pilot trial, we want to get first estimates about the effect of discontinuation of chemotherapy with the aim to plan and conduct a further definitive trial. Methods/design: OPTITREAT is designed as a single-center, randomized controlled pilot trial with two parallel study groups. Four weeks after starting neoadjuvant chemotherapy in all patients, clinical response will be assessed by endoscopy and endosonographic ultrasound. Then, nonresponding patients (n = 84) will be randomized in a 1:1 ratio to intervention group with stopping chemotherapy and immediate tumor resection or control group with completion of chemotherapy before surgery. Outcome measures are overall survival, R0 resection rate, perioperative morbidity and mortality, histopathological response, and quality of life. Statistical analysis will be based on the intention-to-treat population. Due to the study design as an explorative pilot trial, no formal sample size calculation was performed. The planned total sample size of 120 patients is considered ethical and large enough to show the feasibility and safety of the concept. First data on differences between the study groups in the defined endpoints will also be generated. Discussion: Individualized therapy is of utmost interest in the treatment of locally advanced gastroesophageal adenocarcinoma as less than half of the patients show objective response to current chemotherapy regimens. The findings of the OPTITREAT trial will help to get first data about clinical response evaluation followed by immediate tumor resection in nonresponding patients after 4 weeks of neoadjuvant chemotherapy. Based on the results of this pilot study, a future confirmatory trial will be planned to prove efficacy and evaluate significance. Trial registration: German Clinical Trial Register number: DRKS0000466

Impact of preoperative patient education on the prevention of postoperative complications after major visceral surgery: the cluster randomized controlled PEDUCAT trial

Background: The prevention of postoperative complications is of prime importance after complex elective abdominal operations. Preoperative patient education may prevent postoperative complications and improve patients’ wellbeing, but evidence for its efficacy is poor. The aims of the PEDUCAT trial were (a) to assess the impact of preoperative patient education on postoperative complications and patient-reported outcomes in patients scheduled for elective complex visceral surgery and (b) to evaluate the feasibility of cluster randomization in this setting. Methods: Adult patients (age ≥ 18 years) scheduled for elective major visceral surgery were randomly assigned in clusters to attend a preoperative education seminar or to the control group receiving the department’s standard care. Outcome measures were the postoperative complications pneumonia, deep vein thrombosis (DVT), pulmonary embolism, burst abdomen, and in-hospital fall, together with patient-reported outcomes (postoperative pain, anxiety and depression, patient satisfaction, quality of life), length of hospital stay (LOS), and postoperative mortality within 30 days after the index operation. Statistical analysis was primarily by intention to treat. Results: In total 244 patients (60 clusters) were finally included (intervention group 138 patients; control group 106 patients). Allocation of hospital wards instead of individual patients facilitated study conduct and reduced confusion about group assignment. In the intervention and control groups respectively, pneumonia occurred in 7.4% versus 8.3% (p = 0.807), pulmonary embolism in 1.6% versus 1.0% (p = 0.707), burst abdomen in 4.2% versus 1.0% (p = 0.165), and in-hospital falls in 0.0% versus 4.2% of patients (p = 0.024). DVT did not occur in any of the patients. Mortality rates (1.4% versus 1.9%, p = 0.790) and LOS (14.2 (+/− 12.0) days versus 16.1 (+/− 15.0) days, p = 0.285) were also similar in the intervention and control groups. Conclusions: Cluster randomization was feasible in the setting of preoperative patient education and reduced the risk of contamination effects. The results of this trial indicate good postoperative outcomes in patients undergoing major visceral surgery without superiority of preoperative patient education compared to standard patient care at a high-volume center. However, preoperative patient education is a helpful instrument not only for teaching patients but also for training the nursing staff. Trial registration: German Clinical Trials Registry, DRKS00004226 . Registered on 23 October 2012. Registered 8 days after the first enrollment

Pylorus Resection Does Not Reduce Delayed Gastric Emptying After Partial Pancreatoduodenectomy A Blinded Randomized Controlled Trial (PROPP Study, DRKS00004191)

Objectives: The aim of this study was to investigate the effect of pylorus resection on postoperative delayed gastric emptying (DGE) after partial pancreatoduodenectomy (PD). Background: PD is the standard treatment for tumors of the pancreatic head. Preservation of the pylorus has been widely accepted as standard procedure. DGE is a common complication causing impaired oral intake, prolonged hospital stay, and postponed further treatment. Recently, pylorus resection has been shown to reduce DGE. Methods:Patients undergoing PD for any indication at the University of Heidelberg were randomized to either PD with pylorus preservation (PP) or PD with pylorus resection and complete stomach preservation (PR). The primary endpoint was DGE within 30 days according to the International Study Group of Pancreatic Surgery definition. Results: Ninety-five patients were randomized to PP and 93 patients to PR. There were no baseline imbalances between the groups. Overall, 53 of 188 patients (28.2%) developed a DGE (grade: A 15.5%;B 8.8%;C 3.3%). In the PP group 24 of 95 patients (25.3%) and in the PR group 29 of 93 patients (31.2%) developed DGE (odds ratio 1.534, 95% confidence interval 0.788 to 2.987;P = 0.208). Higher BMI, indigestion, and intraabdominal major complications were significant risk factors for DGE. Conclusions: In this randomized controlled trial, pylorus resection during PD did not reduce the incidence or severity of DGE. The development of DGE seems to be multifactorial rather than attributable to pyloric dysfunction alone. Pylorus preservation should therefore remain the standard of care in PD.Trial Registration:German Clinical Trials Register DRKS0000419

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer : An International Multicenter Cohort Study

Background. Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS.Methods. This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression.Results. The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS.Conclusions. This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.Peer reviewe

Response to: Surgical approach for totally implantable venous access port: a full strategy to avoid the percutaneous approach complications

Purpose!#!The publication activity of 38 German general/visceral surgery university departments, documented by first or last authorship from staff surgeons (chief and consultants), was evaluated.!##!Methods!#!The observation period extended from 2007 to 2017 and all PubMed-listed publications were considered. Impact factor (IF) was evaluated through the publishing journal's 5-year IF in 2016, as was the IF for each individual publication. Ranking was expressed in quartiles.!##!Results!#!The staff surgeons of the 38 departments comprised 442 surgeons, of which only 351 (79.4%) were active as first or last authors. Four thousand six hundred and ninety-nine publications published in 702 journals were recorded. The four leading departments in publication number published as much as the last 20 departments (1330 vs. 1336 publications, respectively). The mean of the first (most active) department quartile was 19.6 publications, the second 15.4, the third 11.0, and the last quartile 7.6 per publishing surgeon. The total cumulative impact factor was 14,130. When examining the mean number of publications per publishing surgeons per the 10 year period, the mean of the first quartile was 57.9 cumulative IF, the second 45.0, the third 29.5, and the fourth quartile 17.1. With 352 (7.5%) publications, the most frequently used journal was Chirurg, followed by Langenbeck's Archives of Surgery with 274 (5.8%) publications. Pancreas-related topics led in terms of publication number and IF generated per individual publication.!##!Conclusion!#!A significant difference in publication performance of individual departments was apparent that cannot be explained by staff number. This indicates that there are as yet unknown factors responsible for minor publication activity in many university departments

Conflicts of interest in randomised controlled surgical trials: systematic review and qualitative and quantitative analysis

Conflicts of interest may lead to biased trial designs and unbalanced interpretation of study results. We aimed to evaluate the reporting of potential conflicts of interest in full publications of surgical randomised controlled trials (RCTs). A systematic literature search was performed in CENTRAL, MEDLINE and EMBASE (1985–2014) to find all surgical RCTs of medical devices and perioperative pharmacological or nutritional interventions. The information on conflicts of interest was evaluated both quantitatively and qualitatively, and the development of stated conflicts over time was studied. Of 7934 articles, 444 met the inclusion criteria. In 93 of 444 trials (20.9%), conflicts of interest were disclosed. In half of the cases, the information provided was insufficient to permit conclusions regarding possible influence on the trials. Information about conflicts of interest has increased continuously during the last decades (1985–1994: 0%, 1995–2004: 2.8% and 2005–2014: 33.0%; p<0.001). Among the 115 industry-funded trials, industry participation was considered as a potential conflict of interest in 24 cases (20.9%). Over the past three decades, only every 10th trial has provided appropriate information on conflicts of interest. However, transparency is crucial for the reliability of evidence-based medicine. There is an urgent need for the full disclosure of all conflicts of interest in surgical publishing and for transparency regarding cooperation between academia and industry

Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce postoperative pancreatic fistula after distal pancreatectomy: the PREBOTPilot trial

Introduction Postoperative pancreatic fistula (POPF) is still the most frequently occurring and clinically relevant complication after distal pancreatectomy (DP). Preoperative endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi represents an innovative approach to prevent POPF. The aim of this project (PREBOTPilot) is to generate the first randomised controlled trial data on the safety, feasibility and efficacy of preoperative endoscopic BTX injection into the sphincter of Oddi to prevent clinically relevant POPF following DP.Methods and analysis PREBOTPilot is an investigator-initiated, single-centre, randomised, controlled, open-label, phase II clinical trial with two parallel study groups and an exploratory study design. 60 patients scheduled for DP will be randomised to intervention and control group. In the intervention group, patients will undergo preoperative endoscopic injection of BTX into the sphincter of Oddi, whereas in the control group no preoperative endoscopy will be performed. The combined primary endpoint is the occurrence of clinically relevant POPF and/or death within 30 days after DP. The secondary endpoints comprise further postoperative outcome parameters and quality of life up to 3 months after DP as well as safety and feasibility of the procedure. Statistical analysis is based on the modified intention-to-treat population, excluding patients without status post DP. For safety analysis, rates of adverse events (AEs) and serious AEs will be calculated with 95% CIs for group comparisons.Ethics, funding and dissemination PREBOTPilot has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4043654) and the Ethics Committee of Heidelberg University (reference number AFmo-523/2019). This trial is supported by the German Federal Ministry of Education and Research (BMBF). The results of the trial will be presented at national and international conferences and published in a peer-reviewed journal.Trial registration number DRKS00020401

Prospective trial to evaluate the prognostic value of different nutritional assessment scores for survival in pancreatic ductal adenocarcinoma (NURIMAS Pancreas SURVIVAL)

Abstract Background Malnutrition is associated with poor survival in pancreatic cancer patients. Nutritional scores show great heterogeneity diagnosing malnutrition. The aim of this study was to find the score best suitable to identify patients with malnutrition related to worse survival after surgery for pancreatic ductal adenocarcinoma (PDAC). This study represents a follow‐up study to the prospective NURIMAS Pancreas trial that evaluated short term impact of nutritional score results after surgery. Methods Risk of malnutrition was evaluated preoperatively using 12 nutritional assessment scores. Patients were followed‐up prospectively for at least 3 years. Patients at risk for malnutrition were compared with those not at risk according to each score using Kaplan–Meier survival statistics. Results A total of 116 patients receiving a PDAC resection in curative intent were included. Malnutrition according to the Subjective Global Assessment score (SGA), the Short Nutritional Assessment Questionnaire (SNAQ), and the INSYST2 score was associated with worse overall survival (SGA: at‐risk: 392 days; not at‐risk: 942 days; P = 0.001; SNAQ: at‐risk: 508 days; not at‐risk: 971 days; P = 0.027; INSYST2: at‐risk: 538 days; not at risk: 1068; P = 0.049). In the multivariate analysis, SGA (hazard ratio of death 2.16, 95% confidence interval 1.34–3.47, P = 0.002) was associated with worse overall survival. Conclusions Malnutrition as defined by the Subjective Global Assessment is independently associated with worse survival in resected PDAC patients. The SGA should be used to stratify PDAC patients in clinical studies. Severely malnourished patients according to the SGA profit from intensified nutritional therapy should be evaluated in a randomized controlled trial