Inga Rossion

Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial

BACKGROUND The ideal closure technique of the pancreas after distal pancreatectomy is unknown. We postulated that standardised closure with a stapler device would prevent pancreatic fistula more effectively than would a hand-sewn closure of the remnant. METHODS This multicentre, randomised, controlled, parallel group-sequential superiority trial was done in 21 European hospitals. Patients with diseases of the pancreatic body and tail undergoing distal pancreatectomy were eligible and were randomly assigned by central randomisation before operation to either stapler or hand-sewn closure of the pancreatic remnant. Surgical performance was assessed with intraoperative photo documentation. The primary endpoint was the combination of pancreatic fistula and death until postoperative day 7. Patients and outcome assessors were masked to group assignment. Interim and final analysis were by intention to treat in all patients in whom a left resection was done. This trial is registered, ISRCTN18452029. FINDINGS Between Nov 16, 2006, and July 3, 2009, 450 patients were randomly assigned to treatment groups (221 stapler; 229 hand-sewn closure), of whom 352 patients (177 stapler, 175 hand-sewn closure) were analysed. Pancreatic fistula rate or mortality did not differ between stapler (56 [32%] of 177) and hand-sewn closure (49 [28%] of 175; OR 0·84, 95% CI 0·53–1·33; p=0·56). One patient died within the fi rst 7 days after surgery in the hand-sewn group; no deaths occurred in the stapler group. Serious adverse events did not differ between groups. INTERPRETATION Stapler closure did not reduce the rate of pancreatic fistula compared with hand-sewn closure for distal pancreatectomy. New strategies, including innovative surgical techniques, need to be identified to reduce this adverse outcome. FUNDING German Federal Ministry of Education and Research.

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial.

Objectives:To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. Background:PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. Methods:A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. Results:From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. Conclusions:The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

Resection of the primary tumour versus no resection prior to systemic therapy in patients with colon cancer and synchronous unresectable metastases (UICC stage IV): SYNCHRONOUS - a randomised controlled multicentre trial (ISRCTN30964555)

BackgroundCurrently, it remains unclear, if patients with colon cancer and synchronous unresectable metastases who present without severe symptoms should undergo resection of the primary tumour prior to systemic chemotherapy. Resection of the primary tumour may be associated with significant morbidity and delays the beginning of chemotherapy. However, it may prevent local symptoms and may, moreover, prolong survival as has been demonstrated in patients with metastatic renal cell carcinoma. It is the aim of the present randomised controlled trial to evaluate the efficacy of primary tumour resection prior to systemic chemotherapy to prolong survival in patients with newly diagnosed colon cancer who are not amenable to curative therapy.Methods/designThe SYNCHRONOUS trial is a multicentre, randomised, controlled, superiority trial with a two-group parallel design. Colon cancer patients with synchronous unresectable metastases are eligible for inclusion. Exclusion criteria are primary tumour-related symptoms, inability to tolerate surgery and/or systemic chemotherapy and history of another primary cancer. Resection of the primary tumour as well as systemic chemotherapy is provided according to the standards of the participating institution. The primary endpoint is overall survival that is assessed with a minimum follow-up of 36 months. Furthermore, it is the objective of the trial to assess the safety of both treatment strategies as well as quality of life.DiscussionThe SYNCHRONOUS trial is a multicentre, randomised, controlled trial to assess the efficacy and safety of primary tumour resection before beginning of systemic chemotherapy in patients with metastatic colon cancer not amenable to curative therapy.Trial registrationISRCTN30964555

No Need for Routine Drainage After Pancreatic Head Resection: The Dual-center, Randomized, Controlled Pandra Trial (isrctn04937707).

Objective: This dual-center, randomized, controlled, noninferiority trial aimed to prove that omission of drains does not increase reintervention rates after pancreatic surgery. Background: There is considerable uncertainty regarding intra-abdominal drainage after pancreatoduodenectomy. Methods: Patients undergoing pancreatic head resection with pancreaticojejunal anastomosis were randomized to intra-abdominal drainage versus no drainage. Primary endpoint was overall reintervention rate (relaparotomy or radiologic intervention). Secondary endpoints were clinically relevant pancreatic fistula (grade B/C), mortality, morbidity, and hospital stay. The planned sample size was 188 patients per group. Results: A total of 438 patients were randomized. Forty-three patients (9.8%) were excluded because no pancreatic anastomosis was performed, and 395 patients (202 drain, 193 no-drain) were analyzed. Reintervention rates were not inferior in the no-drain group (drain 21.3%, no-drain 16.6%; P = 0.0004). Overall in-hospital mortality (3.0%) was the same in both groups (drain 3.0%, no-drain 3.1%; P = 0.936). Overall surgical morbidity (41.8%) was comparable (P = 0.741). Clinically relevant pancreatic fistula (grade B/C: drain 11.9%, no-drain 5.7%; P = 0.030) and fistula-associated complications (drain 26.4%; no drain 13.0%; P = 0.0008) were significantly reduced in the no-drain group. Operation time (P = 0.093), postoperative hemorrhage (P = 0.174), intra-abdominal abscess formation (P = 0.199), biliary leakage (P = 0.382), delayed gastric emptying (P = 0.062), burst abdomen (P = 0.480), wound infection (P = 0.758), and hospital stay (P = 0.487) did not show significant differences. Conclusions: Omission of drains was not inferior to intra-abdominal drainage in terms of postoperative reintervention and superior in terms of clinically relevant pancreatic fistula rate and fistula-associated complications. There is no need for routine prophylactic drainage after pancreatic resection with pancreaticojejunal anastomosis.

Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID): protocol for a randomized clinical multi-center trial

AbstractBackgroundFractures of the distal radius represent the most common fracture in elderly patients, and often indicate the onset of symptomatic osteoporosis. A variety of treatment options is available, including closed reduction and plaster casting, K-wire-stabilization, external fixation and open reduction and internal fixation (ORIF) with volar locked plating. The latter is widely promoted by clinicians and hardware manufacturers. Closed reduction and cast stabilization for six weeks is a simple, convenient, and ubiquitously available intervention. In contrast, ORIF requires hospitalization, but allows for functional rehabilitation.Given the lack of randomized controlled trials, it remains unclear whether ORIF leads to better functional outcomes one year after injury than closed reduction and casting.Methods/DesignORCHID (Open reduction and internal fixation versus casting for highly comminuted intra-articular fractures of the distal radius) is a pragmatic, randomized, multi-center, clinical trial with two parallel treatment arms. It is planned to include 504 patients in 15 participating centers throughout Germany over a three-year period. Patients are allocated by a central web-based randomization tool.The primary objective is to determine differences in the Short Form 36 (SF-36) Physical Component Score (PCS) between volar locked plating and closed reduction and casting of intraarticular, comminuted distal radius fractures in patients > 65 years of age one year after the fracture. Secondary outcomes include differences in other SF-36 dimensions, the EuroQol-5D questionnaire, the Disability of the Arm, Shoulder, and Hand (DASH) instrument. Also, the range of motion in the affected wrist, activities of daily living, complications (including secondary ORIF and revision surgery), as well as serious adverse events will be assessed. Data obtained during the trial will be used for later health-economic evaluations. The trial architecture involves a central statistical unit, an independent monitoring institute, and a data safety monitoring board. Following approval by the institutional review boards of all participating centers, conduct and reporting will strictly adhere to national and international rules, regulations, and recommendations (e.g., Good Clinical Practice, data safety laws, and EQUATOR/CONSORT proposals)DiscussionTo our knowledge, ORCHID is the first multicenter RCT designed to assess quality of life and functional outcomes following operative treatment compared to conservative treatment of complex, intra-articular fractures of the distal radius in elderly patients. The results are expected to influence future treatment recommendations and policies on an international level.Trial registrationISRCTN: ISRCTN76120052 Registration date: 31.07.2008; Randomization of first patient: 15.09.2008

Perioperative management in distal pancreatectomy: results of a survey in 23 European participating centres of the DISPACT trial and a review of literature

BackgroundConcomitant treatment in addition to intervention may influence the primary outcome, especially in complex interventions such as surgical trials. Evidence-based standards for perioperative care after distal pancreatectomy, however, have been rarely defined. This studys objective was therefore to identify and analyse the current basis of evidence for perioperative management in distal pancreatectomy.MethodsA standardised questionnaire was sent to 23 European centres recruiting patients for a randomized controlled trial (RCT) on open distal pancreatectomy that would compare suture versus stapler closure of the pancreatic remnant (DISPACT trial, ISRCTN 18452029). Perioperative strategies (e.g., bowel preparation, pain management, administration of antibiotics, abdominal incision, drainages, nasogastric tubes, somatostatin, mobilisation and feeding regimens) were assessed. Moreover, a systematic literature search in the Medline database was performed and retrieved meta-analyses and RCTs were reviewed.ResultsAll 23 centres returned the questionnaire. Consensus for thoracic epidural catheters (TECs), pain treatment and transverse incisions was found, as well as strong consensus for the placement of intra-abdominal drainages and perioperative single-shot antibiotics. Also, there was consensus that bowel preparation, somatostatin application, postoperative nasogastric tubes and intravenous feeding might not be beneficial. The literature search identified 16 meta-analyses and 19 RCTs demonstrating that bowel preparation, somatostatin therapy and nasogastric tubes can be omitted. Early mobilisation, feeding and TECs seem to be beneficial for patients. The value of drainages remains unclear.ConclusionMost perioperative standards within the centres participating in the DISPACT trial are in accordance with current available evidence. The need for drainages requires further investigation.Trial registrationClinical trial registration: ISRCTN 18452029

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).

Pancreatogastrostomy versus pancreatojejunostomy for RECOnstruction after partial PANCreatoduodenectomy (RECOPANC): study protocol of a randomized controlled trial UTN U1111-1117-9588

BackgroundPancreatoduodenectomy is one of the most complex abdominal operations, usually performed for tumors of the periampullary region and chronic pancreatitis. Leakage of pancreatic juice from the pancreatoenteric anastomosis, called postoperative pancreatic fistula, is the most prominent postoperative complication. Retrospective studies show a significant reduction of fistula rates with pancreatogastrostomy as compared to pancreatojejunostomy, the most frequently employed method of pancreatoenterostomy. Most single-center prospective trials, however, have not validated this finding. A large multicenter trial is needed for clarification.Methods/designRECOPANC is a prospective, randomized, controlled multicenter trial with two treatment arms, pancreatogastrostomy versus pancreatojejunostomy. The trial hypothesis is that postoperative pancreatic fistula rate is lower after pancreatogastrostomy when compared to pancreatojejunostomy. Fourteen academic centers for pancreatic surgery will participate to allocate 360 patients to the trial. The duration of the entire trial is four years including prearrangement and analyses.DiscussionPostoperative pancreatic fistula is the main reason for clinically important postoperative morbidity after pancreatoduodenectomy. The primary goal of the chosen reconstruction technique for pancreatoenteric anastomosis is to minimize postoperative fistula rate. A randomized trial performed at multiple high-volume centers for pancreatic surgery is the best opportunity to investigate one of the most crucial issues in pancreatic surgery.Trial registrationGerman Clinical Trials Register DRKS00000767 (2011/03/23), FSI 2011/05/31. Universal Trial Number U1111-1117-9588.

Klinische Studien außerhalb des Arzneimittelgesetzes

Proof of safety and effectiveness of surgical procedures follows the same scientific principles as for drugs. Control of bias and chance when evaluating new operations has to be considered and should generally be followed using randomized controlled trials (RCT). The expenditure for study design, execution and analysis can be substantial due to specific characteristics of surgical treatments. The largest challenges represent the maintenance of comparable treatment and assessment within and between the study groups of a RCT, such as, blinding of surgeons, learning curves, standardization of procedures, and monitoring interventions to ensure execution according to protocol. This evaluation is made even more difficult due to lack of broadly accepted definitions of surgically relevant endpoints in daily practice and research. Since 2004, new methods and procedures are being tested to demonstrate the feasibility of surgical RCTs through a grant program for surgical clinical trial centers in Germany. In six surgical trial centers, a number of surgical RCTs have been designed and conducted. The first results of high-quality surgical RCTs are described.

Hand-suture versus stapling for closure of loop ileostomy: HASTA-Trial: a study rationale and design for a randomized controlled trial

BackgroundColorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet.Methods/DesignA study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer.The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol.DiscussionAim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for closure of loop ileostomy in patients with rectal cancer.Trial registrationGerman Clinical Trial Register Number: DRKS00000040