Prehabilitation in an Integrative Medicine Day Clinic for Patients Undergoing Neoadjuvant Treatment: Single-Center Feasibility Pilot Study.

BACKGROUND: Patients with cancer receiving neoadjuvant treatment prior to surgery are in a very stressful situation. Chemotherapy and radiation therapy put a strain on the quality of life and the pending surgery poses a relevant burden for many patients. Preparation of these patients for the intervention in terms of prehabilitation has great potential to reduce the burden of postoperative complications and may improve the clinical outcome. A prehabilitation approach also yields the possibility to address unmet patients' needs and to help them modify their lifestyle in a maintainable way. Therefore, a multimodal approach is mandatory during this critical period. OBJECTIVE: The aim of this study is to assess the feasibility of prehabilitation in an integrative medicine day clinic (PRIME-DC) prior to cancer surgery at a major university clinic. PRIME-DC is considered feasible if 80% of enrolled patients are willing and able to complete at least 6 out of the 8 weekly meetings, each lasting 6.5 hours, at such a clinic. Secondary end points aim to evaluate this multimodal program. METHODS: The PRIME-DC intervention combines mind-body medicine, exercise therapy, nutrition therapy, naturopathic counseling, and the application of a yarrow liver compress. Adult patients with cancer, with a primary tumor in the abdomen (including intraperitoneal cancer, stomach cancer, and extraperitoneal cancers such as pancreatic, bladder, rectal, esophageal, endometrial, ovarian, and cervical cancer) or the breast requiring a neoadjuvant oncological treatment setting are eligible to participate. The addressed cancer entities imply either an extensive surgical intervention with an expected need for prehabilitation (eg, abdominal surgery) or a neoadjuvant treatment of several months with a high burden of treatment-associated side effects (breast cancer). Adherence to the day clinic program is the primary end point being defined as presence during the day clinic session. Secondary end points are physical assessment and quality of life, together with a structured assessment of neoadjuvant treatment-associated side effects. Furthermore, to collect qualitative data voluntary participants of the day clinic will be interviewed in a semistructured way after completion of the day clinic program on each component of the study (mind-body intervention, exercise, nutrition, naturopathic counseling, and a yarrow liver compress). RESULTS: The procedures used in this study adhere to the tenets of the Declaration of Helsinki. As of February 2023, we enrolled 23 patients; the dominant cancer entity is breast cancer (18 enrolled patients). CONCLUSIONS: The presented protocol combines prehabilitation, lifestyle modification, naturopathic counseling, dietary assistance, and naturopathic treatment in an innovative and integrative way. TRIAL REGISTRATION: Deutsches Register Klinischer Studien German Clinical Trials Register DRKS00028126; https://drks.de/search/de/trial/DRKS00028126. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46765.

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.

Conventional partial pancreatoduodenectomy versus an extended pancreatoduodenectomy (triangle operation) for pancreatic head cancers-study protocol for the randomised controlled TRIANGLE trial.

BACKGROUND: Pancreatic ductal carcinoma (PDAC) is the fourth most frequent cause of cancer-related death in the Western world, and its incidence is rising. In patients that undergo curative resection, local recurrence (LR) is frequent. A recently described surgical technique of extended pancreatoduodenectomy (PD) termed the TRIANGLE operation has been proposed as a promising approach to reduce LR and improve disease-free survival in PDAC patients. METHODS: The TRIANGLE trial is a multicentre confirmatory randomised controlled superiority trial with two parallel study groups. A total of 270 patients with suspected or histologically confirmed pancreatic head cancer scheduled for PD will be included in the trial and randomly assigned to the intervention group (extended PD defined as Inoue level 3 dissection along the superior mesenteric and celiac artery as well as removal of all soft tissue in the so-called triangle between the celiac artery, the SMA and the mesenterico-portal axis) or the control group (conventional PD with lymphadenectomy and removal of soft tissue according to current guidelines). The primary endpoint of the trial will be the disease-free survival of patients. Other perioperative outcomes as well as oncological parameters and patient-reported outcomes will be analysed as secondary outcomes. DISCUSSION: Despite multimodal treatment, LR remains high and disease-free survival is limited following PD for PDAC. The TRIANGLE operation could address these shortcomings of conventional PD as indicated in several retrospective studies. However, this technique could be associated with more adverse events for patients including intractable diarrhoea. The TRIANGLE trial will close the evidence gap as well as offer a risk-benefit assessment of this more radical approach to PD. TRIAL REGISTRATION: German Clinical Trials Register DRKS00030576 (UTN U1111-1243-4412) 19th December 2022.

Prophylactic effect of retromuscular mesh placement during loop ileostomy closure on incisional hernia incidence-a multicentre randomised patient- and observer-blind trial (P.E.L.I.O.N trial).

BACKGROUND: Incisional hernia is a frequent complication following loop ileostomy reversal. Incisional hernias are associated with morbidity, loss of health-related quality of life and costs and warrant the investigation of prophylactic measures. Prophylactic mesh implantation at the time of surgical stoma reversal has shown to be a promising and safe method to prevent incisional hernias in this setting. However, the efficacy of this method has not yet been investigated in a large multicentre randomised-controlled trial (RCT) with adequate external validity. The P.E.L.I.O.N. trial will evaluate the efficacy of prophylactic mesh reinforcement after loop ileostomy closure in decreasing the rate of incisional hernia versus standard closure alone. METHODS: P.E.L.I.O.N. is a multicentre, patient- and observer-blind RCT. Patients undergoing loop ileostomy closure will undergo intraoperative 1:1 randomisation into either abdominal wall closure with a continuous slowly absorbable suture in small-stitch technique without mesh reinforcement (control group) or abdominal wall closure with an additional reinforcement with a retromuscular non-absorbable, macro-pore (pore size ≥ 1000 µm or effective porosity >0%) light-weight monofilament or mixed structure mesh. A total of 304 patients (152 per group) will need to be randomised in the study. Based on inclusion and exclusion criteria, 1,014 patients are expected to be screened for eligibility in order to recruit the necessary number of patients. The primary endpoint will be the frequency of incision hernias within 24 months according to the European Hernia Society definition. Secondary endpoints will be the frequency of surgical site occurrences (including surgical site infections, wound seromas and hematomas, and enterocutaneous fistulas), postoperative pain, the number of revision surgeries and health-related quality of life. Safety will be assessed by measuring postoperative complications ≥ grade 3 according to the Dindo-Clavien classification. DISCUSSION: Depending on the results of the P.E.L.I.O.N. trial, prophylactic mesh implantation could become the new standard for loop ileostomy reversal. TRIAL REGISTRATION: DRKS00027921, U1111-1273-4657.

Top 10 research priorities in colorectal cancer: results from the Colorectal Cancer Priority-Setting Partnership.

BACKGROUND: Colorectal cancer (CRC) is the third most frequent cause of cancer death in the word. Which aspects of research into CRC should be accorded the highest priority remains unclear, because relevant stakeholders, such as patients, nurses, and physicians, played hardly any part in the development of research projects. The goal in forming the CRC Priority-Setting Partnership (PSP) was to bring all relevant stakeholders together to identify and prioritize unresolved research questions regarding the diagnosis, treatment, and follow-up of CRC. METHODS: The CRC PSP worked in cooperation with the British James Lind Alliance. An initial nationwide survey was conducted, and evidence uncertainties were collected, categorized, summarized, and compared with available evidence from the literature. The as-yet unresolved questions were (provisionally) ranked in a second national wide survey, and at a concluding consensus workshop all stakeholders came together to finalize the rankings in a nominal group process and compile a top 10 list. RESULTS: In the first survey (34% patients, 51% healthcare professionals, 15% unknown), 1102 submissions were made. After exclusion of duplicates and previously resolved questions, 66 topics were then ranked in the second survey (56% patients, 39% healthcare professionals, 5% unknown). This interim ranking process revealed distinct differences between relatives and healthcare professionals. The final top 10 list compiled at the consensus workshop covers a wide area of research topics. CONCLUSION: All relevant stakeholders in the CRC PSP worked together to identify and prioritize the top 10 evidence uncertainties. The results give researchers and funding bodies the opportunity to address the most patient-relevant research projects. It is the first detailed description of a PSP in Germany, and the first PSP on CRC care worldwide.

Protocol of a prospective study investigating the association of PAncreatic parenchymal RISk factors with postoperative pancreatic fistula after partial pancreaticoduodenectomy (PARIS trial).

INTRODUCTION: Partial pancreatoduodenectomy (PD) is the treatment of choice for many malignant and benign diseases of the pancreatic head. Postoperative complication rates of up to 40% are regularly reported. One of the most common and potentially life-threatening complication is the postoperative pancreatic fistula (POPF). Parenchymal risk factors like main pancreatic duct diameter or texture of the pancreatic gland have already been identified in retrospective studies. The aim of this study is to evaluate the diagnostic value of parenchymal risk factors on POPF in a prospective manner. METHODS AND ANALYSIS: All patients scheduled for elective PD at the Department of General, Visceral and Transplantation Surgery of the University of Heidelberg will be screened for eligibility. As diagnostic factors, diameter and texture of the pancreatic gland as well as radiological and histopathological features will be recorded. Furthermore, the new four class risk classification system by the International Study Group of Pancreatic Surgery (ISGPS) will be recorded. The postoperative course will be monitored prospectively. The primary endpoint will be the association of the main pancreatic duct size and the texture of the pancreatic gland on POPF according to the updated ISGPS definition. The diagnostic value of the above-mentioned factors for POPF will be evaluated in a univariable and multivariable analysis. ETHICS AND DISSEMINATION: PARIS is a monocentric, prospective, diagnostic study to evaluate the association of parenchymal risk factors and the development of POPF approved by the Ethics Committee of the medical faculty of Heidelberg University (S-344/2019). Results will be available in 2022 and will be published at national and international meetings. With this knowledge, the intraoperative and perioperative decision-making process could be eased and improve the individual outcome of patient. TRIAL REGISTRATION NUMBER: DRKS00017184.

Protocol for a randomised controlled trial to compare postoperative complications between minimally invasive and open DIStal PAnCreaTectomy (DISPACT-2 trial).

INTRODUCTION: In recent years, minimally invasive distal pancreatectomy (MIDP) has been used with increasing frequency to accelerate patient recovery. Distal pancreatectomy has an overall morbidity rate of 30%-40%. The known advantages of minimally invasive techniques must be rigorously compared with those of open surgery before they can be completely implemented into clinical practice. METHODS AND ANALYSIS: DISPACT-2 is a multicentre randomised controlled trial comparing minimally invasive (conventional laparoscopic or robotic assisted) with open distal pancreatic resection in patients undergoing elective surgery for benign as well as malign diseases of the pancreatic body and tail. After screening for eligibility and obtaining informed consent, a total of 294 adult patients will be preoperatively randomised in a 1:1 ratio. The primary hypothesis is that MIDP is non-inferior to open distal pancreatectomy in terms of postoperative mortality and morbidity expressed as the Comprehensive Complication Index (CCI) within 3 months after index operation, with a non-inferiority margin of 7.5 CCI points. Secondary endpoints include pancreas-specific complications, oncological safety and patient reported outcomes. Follow-up for each individual patient will be 2 years. ETHICS AND DISSEMINATION: The DISPACT-2 trial has been approved by the Ethics Committee of the medical faculty of Heidelberg University (S-693/2017). Results of the primary endpoint will be available in 2024 and will be published at national and international meetings. Full results will be made available in an open access, peer-reviewed journal. The website www.dispact.de contains up-to-date information regarding the trial. TRIAL REGISTRATION NUMBER: DRKS00014011.

Evaluation of robotic versus open partial pancreatoduodenectomy-study protocol for a randomised controlled pilot trial (EUROPA, DRKS00020407).

BACKGROUND: Partial pancreatoduodenectomy (PD) is the indicated surgical procedure for a wide range of benign and malignant diseases of the pancreatic head and distal bile duct and offers the only potential cure for pancreatic head cancer. The current gold standard, open PD (OPD) performed via laparotomy, is associated with morbidity in around 40% of cases, even at specialised centres. Robotic PD (RPD) might offer a viable alternative to OPD and has been shown to be feasible. Encouraging perioperative results have been reported for RPD in a number of small, non-randomised studies. However, since those studies showed a considerable risk of bias, a thorough comparison of RPD with OPD is warranted. METHODS: The EUROPA (EvalUation of RObotic partial PAncreatoduodenectomy) trial is designed as a randomised controlled unblinded exploratory surgical trial with two parallel study groups. A total of 80 patients scheduled for elective PD will be randomised after giving written informed consent. Patients with borderline or non-resectable carcinoma of the pancreatic head as defined by the National Comprehensive Cancer Network guidelines, distant metastases or an American Society of Anaesthesiologists (ASA) score > III will be excluded. The experimental intervention, RPD, will be compared with the control intervention, OPD. An intraoperative dropout of approximately eight patients per group is expected because they may receive another type of surgical procedure than planned. Overall, 64 patients need to be analysed. The primary endpoint of the trial is overall postoperative morbidity within 90 days after index operation, measured using the Comprehensive Complication Index (CCI). The secondary endpoints include the feasibility of recruitment and assessment of clinical, oncological and safety parameters and quality of life and cost-effectiveness. DISCUSSION: The EUROPA trial is the first randomised controlled trial comparing RPD with OPD. Differences in postoperative morbidity will be evaluated to design a future multicentre confirmatory efficacy trial. TRIAL REGISTRATION: German Clinical Trial Register DRKS00020407 . Registered on 9 March 2020.

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.

Postoperative complications and mobilisation following major abdominal surgery with vs. without fitness tracker-based feedback (EXPELLIARMUS): study protocol for a student-led multicentre randomised controlled trial (CHIR-Net SIGMA study group).

BACKGROUND: Postoperative complications following major abdominal surgery are frequent despite progress in surgical technique and perioperative care. Early and enhanced postoperative mobilisation has been advocated to reduce postoperative complications, but it is still unknown whether it can independently improve outcomes after major surgery. Fitness trackers (FTs) are a promising tool to improve postoperative mobilisation, but their effect on postoperative complications and recovery has not been investigated in clinical trials. METHODS: This is a multicentre randomised controlled trial with two parallel study groups evaluating the efficacy of an enhanced and early mobilisation protocol in combination with FT-based feedback in patients undergoing elective major abdominal surgery. Participants are randomly assigned (1:1) to either the experimental group, which receives daily step goals and a FT giving feedback about daily steps, or the control group, which is mobilised according to hospital standards. The control group also receives a FT, however with a blackened screen; thus no FT-based feedback is possible. Randomisation will be stratified by type of surgery (laparoscopic vs. open). The primary endpoint of the study is postoperative morbidity within 30 days measured via the Comprehensive Complication Index. Secondary endpoints include number of steps as well as a set of functional, morbidity and safety parameters. A total of 348 patients will be recruited in 15 German centres. The study will be conducted and organised by the student-led German Clinical Trial Network SIGMA. DISCUSSION: Our study aims at investigating whether the implementation of a simple mobilisation protocol in combination with FT-based feedback can reduce postoperative morbidity in patients undergoing major abdominal surgery. If so, FTs would offer a cost-effective intervention to enhance postoperative mobilisation and improve patient outcomes. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (DRKS, German Clinical Trials Register): DRKS00016755, UTN U1111-1228-3320. Registered on 06.03.2019.

[Design and Evaluation of a Clinical Investigator Training for Student-lead Prospective Multicentre Clinical Trials: a CHIR-Net SIGMA Research-based Learning Project]. / Design und Evaluation eines Prüf-Studierenden-Kurses für studentische prospektive Multicenterstudien ­ ein CHIR-Net-SIGMA-Projekt zum forschenden Lernen.

BACKGROUND: Scientific skills are not sufficiently taught during medical training, neither in medical school nor during postgraduate education. This results in a lack of clinician scientists. In order to counter this problem, the surgical study network (CHIR-Net) founded SIGMA (Student-initiated German Medical Audit). This paper describes the development, performance and evaluation of a Clinical Investigator Training (CIT) aiming to qualify students to autonomously conduct clinical trials. MATERIAL AND METHODS: Based on the Kern cycle, a curriculum was developed, composed of three parts: online tutorials, a workshop and a follow-up period. The educational objectives were defined according to Bloom's taxonomy of knowledge. The learning objectives were based on the requirements of the "Network of Coordinating Centers for Clinical Trials" and the German Medical Association as well as content relevant to clinical studies. A wide range of educational instruments and assessments were used. By including all relevant professional groups involved in clinical trials, an interconnected working environment for students was generated. The increase in knowledge was assessed by a multiple-choice pre/post exam. The satisfaction of participants was analysed by a 5-point Likert scale, on which 5 indicated full approval. RESULTS: The first SIGMA CIT was realised in 2018; the workshop took place in Heidelberg in February. Thirty-two medical students from thirteen different centres participated. On average, 53.8 ± 8.3% of questions were answered correctly in the pre-test, compared with 71.2 ± 7.2% in the post-test (p < 0.0001). The maximal individual improvement was 30%; the lowest difference compared to the pre-test was 5%. Subjective evaluation results were positive with an average result of 4.63 ± 0.34 on a 5-point Likert scale. CONCLUSION: It is feasible to teach medical students the fundamentals of clinical trials. A compact Clinical Investigator Training using modern principles of teaching is able to prepare students for an autonomous performance of clinical trials.

Hernia reduction following laparotomy using small stitch abdominal wall closure with and without mesh augmentation (the HULC trial): study protocol for a randomized controlled trial.

BACKGROUND: Incisional hernias are among the most frequent complications following abdominal surgery and cause substantial morbidity, impaired health-related quality of life and costs. Despite improvements in abdominal wall closure techniques, the risk for developing an incisional hernia is reported to be between 10 and 30% following midline laparotomies. There have been two recent innovations with promising results to reduce hernia risks, namely the small stitches technique and the placement of a prophylactic mesh. So far, these two techniques have not been evaluated in combination. METHODS: The HULC trial is a multicentre, randomized controlled, observer- and patient-blinded surgical effectiveness trial with two parallel study groups. A total of 812 patients scheduled for elective abdominal surgery via a midline laparotomy will be randomized in 12 centres after informed consent. Patients will be randomly assigned to the control group receiving closure of the midline incision with a slowly absorbable monofilament suture in the small stitches technique or to the intervention group, who will receive a small stitches closure followed by augmentation with a light-weight polypropylene mesh in the onlay technique. The primary endpoint will be the occurrence of incisional hernias, as defined by the European Hernia Society, within 24 months after surgery. Further perioperative parameters, as well as patient-reported outcomes, will be analysed as secondary outcomes. DISCUSSION: The HULC trial will address the yet unanswered question of whether a combination of small stitched fascial closure and onlay mesh augmentation after elective midline laparotomies reduces the risk of incisional hernias. The HULC trial marks the logical and innovative next step in the development of a safe abdominal closure technique. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00017517. Registered on 24th June 2019.

Prospective multicentre cohort study of patient-reported outcomes and complications following major abdominal neoplastic surgery (PATRONUS) - study protocol for a CHIR-Net student-initiated German medical audit study (CHIR-Net SIGMA study).

BACKGROUND: One of the most important aspects of designing a clinical trial is selecting appropriate outcomes. Patient-reported outcomes (PROs) can provide a personal assessment of the burden and impact of a malignant disease and its treatment. PROs comprise a wide range of outcomes including basic clinical symptom scores and complex metrics such as health-related quality of life (HRQoL). There is limited data on how postoperative complications following cancer surgery affect symptoms and HRQoL. For this reason the primary aim of the PATRONUS study is to investigate how perioperative complications affect cancer-related symptoms and HRQoL in patients undergoing abdominal cancer surgery. The PATRONUS study is designed and will be initiated and conducted by medical students under the direct supervision of clinician scientists based on the concept of inquiry-based learning. METHODS: PATRONUS is a non-interventional prospective multicentre cohort study. Patients undergoing elective oncological abdominal surgery will be recruited at regional centres of the clinical network of the German Surgical Society (CHIR-Net) and associated hospitals. A core set of 12 cancer associated symptoms will be assessed via the PRO version of the Common Terminology Criteria for Adverse Events. The cancer-specific HRQoL will be measured via the computerised adaptive testing version of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. PROs will be measured eight times over a period of six months. The short-term clinical outcome measure is the rate of postoperative complications (grade II to V) within 30 days according to the Clavien-Dindo classification. The long-term clinical outcome is overall survival within six months postoperative. DISCUSSION: PATRONUS will provide essential insights into the patients' assessment of their well-being and quality of life in direct relation to clinical outcome parameters following abdominal cancer surgery. Furthermore, PATRONUS will investigate the feasibility of multicentre student-led clinical research. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00013035 (registered on October 26, 2017). Universal Trial Number (UTN): U1111-1202-8863.

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.

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).

Intravenous versus epidural analgesia to reduce the incidence of gastrointestinal complications after elective pancreatoduodenectomy (the PAKMAN trial, DRKS 00007784): study protocol for a randomized controlled trial.

BACKGROUND: Despite substantial improvements in surgical and anesthesiological practices leading to decreased mortality of less than 5 % at high-volume centers, pancreatic surgery is still associated with high morbidity rates of up to 50 %. Attention is increasingly directed toward the optimization of perioperative management to reduce complications and enhance postoperative recovery. Currently, two different strategies for postoperative pain management after pancreatoduodenectomy are being routinely used: patient-controlled intravenous analgesia and thoracic epidural analgesia. Evidence is lacking to assess which strategy entails fewer postoperative complications. METHODS/DESIGN: The PAKMAN trial is designed as an adaptive, pragmatic, randomized, controlled, multicenter, open-label, superiority trial with two parallel study groups. A total of 370 patients scheduled for elective pancreatoduodenectomy will be randomized after giving written informed consent, and 278 patients are needed for analysis. Patients with chronic pancreatitis, severe chronic obstructive pulmonary disease (COPD), American Society of Anesthesiologists (ASA) physical status classification ≥ IV, or chronic pain syndrome will be excluded. The group A intervention includes intraoperative general anesthesia and postoperative patient-controlled intravenous analgesia; the group B intervention comprises combined intraoperative general anesthesia and epidural analgesia with postoperative epidural analgesia. The primary endpoint of this trial is a composite of the gastrointestinal complications (delayed gastric emptying, pancreatic fistula, biliary leak, gastrointestinal bleeding, and postoperative ileus) up to postoperative day 30. The aim is to investigate whether the frequency of gastrointestinal complications following pancreatoduodenectomy can be reduced by 15 % using postoperative, patient-controlled intravenous analgesia compared with epidural analgesia. DISCUSSION: Several previous studies investigating the two different strategies for postoperative pain management have mainly focused on their effectiveness in pain control. However, the PAKMAN trial is the first to compare them with regard to their impact on the surgical endpoint "postoperative gastrointestinal complications" after pancreatoduodenectomy. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00007784.

Nutritional Risk in Major Abdominal Surgery: Protocol of a Prospective Observational Trial to Evaluate the Prognostic Value of Different Nutritional Scores in Pancreatic Surgery.

BACKGROUND: The influence of patients' preoperative nutritional status on their clinical outcome has already been proven. Therefore, patients with malnutrition are in need of additional therapeutic efforts. However, for pancreatic surgery, evidence suggesting the adequacy of existing nutritional assessment scores to estimate malnutrition associated with postoperative outcome is limited. OBJECTIVE: The aim of the observational trial "Nutritional Risk in Major Abdominal Surgery (NURIMAS) Pancreas" is to prospectively assess and analyze different nutritional assessment scores for their prognostic value on postoperative complications in patients undergoing pancreatic surgery. METHODS: All patients scheduled to receive elective pancreatic surgery at the University Hospital of Heidelberg will be screened for eligibility. Preoperatively, 12 nutritional assessment scores will be collected and patients will be assigned either at risk or not at risk for malnutrition. The postoperative course will be followed prospectively and complications according to the Clavien-Dindo classification will be recorded. The prognostic value for complications will be evaluated for every score in a univariable and multivariable analysis corrected for known risk factors in pancreatic surgery. RESULTS: Final data analysis is expected to be available during Spring 2016. CONCLUSIONS: The NURIMAS Pancreas trial is a monocentric, prospective, observational trial aiming to find the most predictive clinical nutritional assessment score for postoperative complications. Using the results of this protocol as a knowledge base, it is possible to conduct nutritional risk-guided intervention trials to prevent postoperative complications in the pancreatic surgical population. TRIAL REGISTRATION: germanctr.de: DRKS00006340; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00006340 (Archived by WebCite at http://www.webcitation.org/6bzXWSRYZ).

Effect of delayed CNI-based immunosuppression with Advagraf® on liver function after MELD-based liver transplantation [IMUTECT].

BACKGROUND: MELD-based allocation for liver transplantation follows the "sickest-patient-first" strategy. The latter patients present with both, decreased immune competence and poor kidney function which is further impaired by immunosuppressants. METHODS/DESIGN: In this prospective observational study, 50 patients with de novo low-dose standard Advagraf®-based immunosuppression consisting of Advagraf®, Mycophenolat-mofetil and Corticosteroids after liver transplantation will be evaluated. Advagraf® trough levels of 7-10 µg/l will be reached at the end of the first postoperative week. Immunostatus, infectious complications, graft and kidney function are compared between patients with a pretransplant calculated MELD-score of ≤20 and >20. Each group comprises of 25 consecutive patients. Prior to liver transplantation and on the postoperative days 1, 3 and 7, the patients' graft function (LiMAx test) will be evaluated. On the postoperative days 3, 5 and 7 the patients' immune status will be evaluated by the measurement of their monocytic HLA-DR status.Infectious complications (CMV-reactivation, wound infection, urinary tract infection, and pneumonia), graft- and kidney function will be analysed on day 0, within the first week, and 1, 3, 6, 9 and 12 months after liver transplantation. DISCUSSION: This study was designed to assess the effect of a standard low-dose Calcineurin inhibitor-based immunosuppression regime with Advagraf® on the rate of infectious complications, graft and renal function after liver transplantation. TRIAL REGISTRATION: The trial is registered at "Clinical Trials" (http://www.clinicaltrials.gov), NCT01781195.

Pylorus resection or pylorus preservation in partial pancreatico-duodenectomy (PROPP study): study protocol for a randomized controlled trial.

BACKGROUND: Partial pancreatico-duodenectomy (PD) is the standard treatment for tumors of the pancreatic head. Today, preservation of the pylorus has been widely accepted as the surgical standard in this procedure. A common postoperative complication is the occurrence of delayed gastric emptying (DGE), which causes impairment of oral intake andpatients' quality of life, prolongation of hospital stay and delay of further treatment (for example adjuvant chemotherapy). In a small number of two retrospective and one randomized studies, a modification by resection of the pylorus with preservation of the stomach has shown to reduce DGE incidence. The aim of the present study is to investigate the effect of pylorus resection on postoperative DGE in PD. METHODS/DESIGN: Patients undergoing elective PD for any indication equal or older than 18 years and who have given informed consent will be included. Patients will be randomized to either PD with pylorus preservation or PD with pylorus resection and complete stomach preservation. Sample size (n = 89 patients per group) is calculated on an assumed difference in DGE incidence of 20%. Primary study endpoint is DGE within 30 days; secondary endpoints are operation time, blood loss, morbidity, mortality, hospital stay and quality of life (QoL). DISCUSSION: DGE is a relevant clinical problem following PD with a great impact on patients' recovery, length of hospital stay, QoL and consecutive adjuvant therapies. As there is no causal therapy, prevention of DGE is essential to improve outcome. The technical modification of pylorus resection may offer a simple and effective method for this purpose. The present study is designed to increase the existing body of evidence and potentially change the future standard surgical procedure of PD. TRIAL REGISTRATION: German Clinical Trials Register DRKS00004191.