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.

Use of virtual reality in port implantation to reduce perioperative anxiety and pain: protocol for a randomised controlled pilot trial at a single German university hospital (VIP-trial; DRKS00028508).

INTRODUCTION: Intravenous access port implantation is commonly performed under local anaesthesia, which offers advantages such as increased patient satisfaction and resource savings compared with general anaesthesia. However, patients may experience increased perioperative stress and anxiety in the operating room setting without general anaesthesia. Virtual reality (VR) distraction or hypnosis during surgery under local anaesthesia may help patients to auditorily and visually separate from their real environment and engage with a virtual environment through hypnorelaxing guidance. Previous studies suggested that VR hypnosedation may reduce the use of sedatives or general anaesthesia, and may offer additional benefits such as reducing postoperative pain and nausea, and promoting faster patient discharge. METHODS AND ANALYSIS: The VIP trial is a randomised controlled pilot trial comparing the usage of VR during port implantation with the current standard of care (local anaesthesia and analgosedation if needed). A total of 120 adult patients are included after screening for eligibility and obtaining informed consent. Patients are randomised preoperatively in a 1:1 ratio to the trial groups. The main outcomes are change of perioperative anxiety and pain. Further outcomes include patient satisfaction and tolerability, perioperative analgesia and sedation, occurrence of postoperative nausea, vomiting and VR sickness symptoms, surgeon's satisfaction, procedure duration, postoperative complications until postoperative day 30 and patient willingness to hypothetically undergo port implantation again under the same conditions. ETHICS AND DISSEMINATION: The VIP trial has been approved by the Ethics Committee of the Medical Faculty of Ulm University (reference number 03/22). If the intervention demonstrates that VR can effectively reduce perioperative anxiety and pain, it may become a novel standard of care to minimise the need for analgosedation or general anaesthesia in port implantation procedures and improve patient outcomes. The results will be submitted to a peer-reviewed journal in the field and will be presented at applicable conferences to ensure rigorous evaluation and access for the academic community. TRIAL REGISTRATION NUMBER: German Clinical Trials Register: DRKS00028508; registration date 15 March 2022; Universal Trial Number: U1111-1275-4995.

[Treatment concepts for hepatic echinococcosis]. / Therapiekonzepte bei hepatischer Echinokokkose.

The incidence of both cystic (CE) and alveolar echinococcosis (AE) is increasing in Germany. The CE can often be managed with drug treatment and interventional strategies. In contrast, AE shows characteristics of a malignant disease with a high morbidity and mortality. Benzimidazoles are potent drugs for both entities but with the necessity for a lifelong follow-up and the risk of side effects as well as progression under treatment. Therefore, the indications for surgical resection have to be carefully considered; however, the combination of drug treatment and surgery is the only curative approach. Recently, the use of minimally invasive surgery with reduced morbidity and mortality has justified surgical resection for a broader set of patients; however, minimally invasive surgery requires a high level of expertise and optimal perioperative planning. Therefore, treatment strategies, especially for AE require an individual stratified risk-benefit assessment in an interdisciplinary consensus.

Impact of perioperative steroid administration in patients undergoing elective liver resection: meta-analysis.

BACKGROUND: Perioperative steroid administration may improve postoperative outcomes in major abdominal surgery by reducing the systemic inflammatory response. The aim of this systematic review was to evaluate the impact of perioperative steroid administration on outcomes after elective liver resection. METHODS: PubMed, Cochrane Library, and Web of Science were systematically searched for randomized clinical trials (RCTs) comparing perioperative steroid administration with placebo, standard of care, or no steroids with respect to postoperative outcomes, particularly postoperative complications. Two independent reviewers critically appraised the studies and extracted data. Meta-analyses were performed using a random-effects model with ORs calculated for dichotomous outcomes and mean differences (MDs) for continuous outcomes. RESULTS: Ten RCTs comprising 930 patients were included. Perioperative steroid administration significantly reduced the overall postoperative complication rate (OR 0.61, 95 per cent c.i. 0.43 to 0.87; P = 0.006; I2 = 26 per cent). No significant differences were shown for individual complications. Several postoperative laboratory parameters were positively affected, like total serum bilirubin (MD -0.46; 95 per cent c.i. -0.74 to -0.18; P = 0.001; I2 = 80 per cent), interleukin 6 (MD -48.99; 95 per cent c.i. -60.72 to -37.27; P < 0.001; I2 = 0 per cent) and C-reactive protein (MD -5.20; 95 per cent c.i. -7.62 to -2.77; P < 0.001; I2 = 71 per cent). There were no signs of an increase in potential steroid-induced adverse events, namely infectious complications, thromboembolic events, or bleeding. CONCLUSIONS: Perioperative steroid administration significantly reduces the overall complication rate after elective liver resection without an increased risk of adverse effects.

Robotic Liver Surgery for Alveolar Echinococcosis: A Single-Centre Experience.

Alveolar echinococcosis (AE) is a rare disease caused by Echinococcosis multilocularis, which usually requires multidisciplinary management including surgery as the only curative approach. In recent years, minimally invasive strategies have been increasingly adopted for liver surgery. In particular, robotic surgery enables surgeons to perform even complex liver resections using a minimally invasive approach. However, there are only a few reports on robotic liver surgery for AE. Consecutive patients undergoing robotic liver surgery for AE were analysed based on the prospective database of the Interdisciplinary Robotic Centre of Ulm University Hospital. Between January 2021 and August 2022, a total of 16 patients with AE underwent robotic hepatectomy at our institution. Median age was 55.5 years (23−73), median body mass index (BMI) was 25.8 kg/m2 (20.2−36.8) and 12 patients (75%) were female. Anatomic resections were performed in 14 patients (87.5%), of which 4 patients (25%) underwent major hepatectomies (i.e., resection of >3 segments) including two right hemihepatectomies, one left hemihepatectomy and one extended right hemihepatectomy performed as associating liver partition with portal vein ligation staged (ALPPS) hepatectomy. There was no 90-day mortality, no postoperative bile leakage and no posthepatectomy haemorrhage. One patient developed posthepatectomy liver failure grade B after extended right hemihepatectomy using an ALPPS approach. One patient had to be converted to open surgery and developed an organ-space surgical site infection, for which he was re-admitted and underwent intravenous antibiotic therapy. Median length of postoperative hospital stay was 7 days (4−30). To our knowledge, this is the largest series of robotic liver surgeries for AE. The robotic approach seems safe with promising short-term outcomes in this selected cohort for both minor as well as major resections.

Pancreatic Cancer: Current Multimodality Treatment Options and the Future Impact of Molecular Biological Profiling.

Background: Pancreatic cancer (PDAC) - even if deemed resectable - has still a dismal prognosis and is the seventh leading cause of global cancer-related death with rising incidence worldwide. Summary: Surgical resection at best in combination with adjuvant systemic chemotherapy is the only potentially curative treatment. Surgical treatment has substantially improved over the last years with significantly reduced perioperative morbidity and mortality. Even when deemed radiologically resectable, the majority of PDAC is likely to have micrometastases, leaving most PDAC patients with an advanced stage. Recent 5-year overall survival was up to 46% in patients eligible for surgery with intensified adjuvant chemotherapy. Eligible for curative surgery are about one-third of the patients, and only 20% of these patients have the option for cure with surgery and adjuvant chemotherapy. Standards of care in treating PDAC patients include various mostly combinational chemotherapy approaches in the advanced and adjuvant setting. Moreover, first targeted therapies for individualizing treatment, e.g., specific subgroups like BRCA1/2 germline mutated patients, were established lately. Neoadjuvant concepts are currently part of research. This review focuses on current and future multimodal treatment options of PDAC and the impact of molecular profiling for individualizing treatment. Key Messages: State of the art in pancreatic cancer therapy is multimodal and includes novel strategies to allow molecular defined subgroup-specific treatment.

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.

[Multimodal, interdisciplinary therapeutic concepts for liver metastasized colorectal cancer]. / Hepatisch metastasiertes kolorektales Karzinom.

About half of all patients with colorectal carcinoma (CRC) develop metastases mainly in the liver during the course of their disease. Metastatic disease is associated with a low 5-year overall survival rate of only 5-7 %, particularly when there is no possibility of local treatment. However, if there is an opportunity to resect the metastases, especially isolated liver metastases, the chance of long-term survival is approximately 15-27 % after both primary resection or secondary resection after neoadjuvant pretreatment. Overall, long-term survival of patients with metastatic CRC has improved significantly in recent years due to a combination of modern systemic therapies, advanced liver surgery and local ablative procedures.Of note, for the vast majority of patients, metastatic resection does not mean cure, but a significant prolongation of overall survival with a good quality of life. Chemotherapy-free intervals after metastasis resection maintain quality of life and can help to reduce toxicity.In this review, we would like to present the "toolbox" for the multidisciplinary treatment of metastatic CRC and give recommendations how the individual modalities should be optimally used, considering tumor-specific characteristics and patient preferences.

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

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.

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.

Evidence Map of Pancreatic Surgery-A living systematic review with meta-analyses by the International Study Group of Pancreatic Surgery (ISGPS).

BACKGROUND: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates. RESULTS: Out of 30,860 articles reviewed, 328 randomized controlled trials on 35,600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%-2%) for partial pancreatoduodenectomy and <1% (99% confidence interval: 0%-1%) for distal pancreatectomy. The benchmark for overall complications was 53% (99%confidence interval: 46%-61%) for partial pancreatoduodenectomy and 59% (99% confidence interval: 44%-80%) for distal pancreatectomy. CONCLUSION: The International Study Group of Pancreatic Surgery Evidence Map of Pancreatic Surgery, which is freely accessible via www.evidencemap.surgery and as a mobile phone app, provides a regularly updated overview of the available literature displayed in an intuitive fashion. Clinical decision making and evidence-based patient information are supported by the primary data provided, as well as by living meta-analyses. Researchers can use the systematic literature search and processed data for their own projects, and funding bodies can base their research priorities on evidence gaps that the map uncovers.

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.

Ghost ileostomy versus conventional loop ileostomy in patients undergoing low anterior resection for rectal cancer (DRKS00013997): protocol for a randomised controlled trial.

INTRODUCTION: Anastomotic leakage is the most important complication in colorectal surgery occurring in up to 20% after low anterior rectal resection. Therefore, a diverting ileostomy is usually created during low anterior resection to protect the anastomosis or rather to diminish the consequences in case of anastomotic leakage. The so-called virtual or ghost ileostomy is a pre-stage ostomy that can be easily exteriorised, if anastomotic leakage is suspected, in order to avoid the severe consequences of anastomotic leakage. On the other hand, an actual ileostomy can be avoided in patients, who do not develop anastomotic leakage. METHODS AND ANALYSIS: The GHOST trial is a randomised controlled pilot trial comparing ghost ileostomy with conventional loop ileostomy in patients undergoing low anterior resection with total mesorectal excision for rectal cancer. After screening for eligibility and obtaining informed consent, a total of 60 adult patients are included in the trial. Patients are intraoperatively randomised to the trial groups in a 1:1 ratio after assuring that none of the intraoperative exclusion criteria are present. The main outcome parameter is the comprehensive complication index as a measure of safety. Further outcomes include specific complications, stoma-related complications, complications of ileostomy closure, frequency of transformation of ghost ileostomy into conventional ileostomy, frequency of terminal ostomy creation, proportion of patients with an ostomy at 6 months after index surgery, anorectal function (Wexner score) and quality of life assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Follow-up for each individual patient will be 6 months. ETHICS AND DISSEMINATION: The GHOST trial has been approved by the Medical Ethics Committee of Heidelberg University (reference number S-694/2017). If the intervention proves to be safe, loop ileostomy could be spared in a large proportion of patients, thus also avoiding stoma-related complications and a second operation (ileostomy closure) with its inherent complications in these patients. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS00013997); Universal Trial Number: U1111-1208-9742.

Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial.

INTRODUCTION: Pancreatic cancer is the fourth-leading cause of cancer-related death in developed countries. Despite advances in systemic chemotherapy, the mainstay of curative therapy for non-metastatic disease is surgical resection. However, the perioperative period is characterised by stress and inflammatory reactions that can contribute to metastatic spread and disease recurrence. Catecholamines and prostaglandins play a crucial role in these reactions. Therefore, a drug repurposing of betablockers and cyclooxygenase inhibitors seems reasonable to attenuate tumour-associated inflammation by inhibiting psychological, surgical and inflammatory stress responses. This may cause a relevant antitumourigenic and antimetastatic effect during the perioperative period, a window for cancer-directed therapy that is currently largely unexploited. METHODS AND ANALYSIS: This is a prospective, single-centre, two-arm randomised, patient and observer blinded, placebo-controlled, phase-II trial evaluating safety and feasibility of combined perioperative treatment with propranolol and etodolac in adult patients with non-metastatic cancer of the pancreatic head undergoing elective pancreatoduodenectomy. 100 patients fulfilling the eligibility criteria will be randomised to perioperative treatment for 25 days perioperatively with a combination of propranolol and etodolac or placebo. Primary outcome of interest will be safety in terms of serious adverse events and reactions within 3 months. Furthermore, adherence to trial medication will be assessed as feasibility outcomes. Preliminary efficacy data will be evaluated for the purpose of power calculation for a potential subsequent phase-III trial. The clinical trial is accompanied by a translational study investigating the mechanisms of action of the combined therapy on a molecular basis. ETHICS AND DISSEMINATION: The PROSPER-trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4042875) and the Ethics Committee of the Medical Faculty of the University of Heidelberg (reference number AFmo-385/2018). The final trial results will be published in a peer-reviewed journal and will be presented at appropriate national and international conferences. TRIAL REGISTRATION NUMBERS: DRKS00014054; EudraCT number: 2018-000415-25.

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.

Randomized Trial of Pylorus-Preserving vs. Pylorus-Resecting Pancreatoduodenectomy: Long-Term Morbidity and Quality of Life.

BACKGROUND: The randomized controlled PROPP trial (DKRS00004191) showed that pylorus-resecting pancreatoduodenectomy (PR) is not superior to the pylorus-preserving procedure (PP) in terms of perioperative outcome, specifically in reduction of delayed gastric emptying. Non-superiority of PR was also confirmed in a recent meta-analysis of randomized controlled trials. However, long-term data on morbidity and quality of life after PP compared to PR are sparse. The aim of this study was to investigate long-term outcomes of patients included in the PROPP trial. METHODS: Between February 2013 and June 2016, a total of 188 patients underwent PD and were intraoperatively randomized to either preservation or resection of the pylorus (95 vs. 93 patients). For long-term follow-up, morbidity and quality of life (EORTC QLQ-C30/PAN26) were monitored until January 1, 2018. Statistical analysis was performed on an intention-to-treat basis. RESULTS: The mean duration of follow-up was 34.3 (± 11.3) months. Sixty-three of the 188 patients had died (PP n = 33, PR n = 30), 29 patients were lost to follow-up (PP n = 17, PR n = 12), and the remaining 96 patients were included in long-term follow-up (PP n = 45, PR n = 51). There was no difference between PP and PR patients regarding endocrine and exocrine pancreatic function, receipt of adjuvant/palliative chemotherapy, cancer recurrence, and other relevant characteristics. Late cholangitis occurred significantly more often in patients following pylorus resection (P = 0.042). Reoperations, readmissions to hospital, and quality of life scores except pain were comparable between the two study groups. CONCLUSIONS: Similar to short-term results, long-term follow-up showed no significant differences between pylorus resection compared to pylorus preservation.

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.

The emerging field of pancreatic tissue engineering: A systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells.

A bioartificial endocrine pancreas is proposed as a future alternative to current treatment options. Patients with insulin-secretion deficiency might benefit. This is the first systematic review that provides an overview of scaffold materials and techniques for insulin-secreting cells or cells to be differentiated into insulin-secreting cells. An electronic literature survey was conducted in PubMed/MEDLINE and Web of Science, limited to the past 10 years. A total of 197 articles investigating 60 different materials met the inclusion criteria. The extracted data on materials, cell types, study design, and transplantation sites were plotted into two evidence gap maps. Integral parts of the tissue engineering network such as fabrication technique, extracellular matrix, vascularization, immunoprotection, suitable transplantation sites, and the use of stem cells are highlighted. This systematic review provides an evidence-based structure for future studies. Accumulating evidence shows that scaffold-based tissue engineering can enhance the viability and function or differentiation of insulin-secreting cells both in vitro and in vivo.