[Evidence-based medicine in surgical practice - locating clinical studies and systematic reviews by searching the Medline database]. / Evidenzbasierte Medizin in der chirurgischen Praxis - Die Literatursuche nach klinischen Studien und systematischen Übersichtsarbeiten in der Datenbank Medline.

BACKGROUND: Every day approximately 75 clinical trials and 11 systematic reviews are published in the health-care intervention and medical field. Due to this growing number of publications it is a challenge for every practicing clinician to keep track with the latest research. The implementation of new and effective diagnostic and therapeutic interventions into daily clinical routine may thus be delayed. Conversely, ineffective or even harmful interventions might still be in use. Decision-making in evidence-based medicine (EBM) requires consideration of the most recent high quality evidence. Randomised controlled trials (RCTs) are regarded as the "gold standard" to prove the efficacy of surgical interventions in patient-oriented research. Systematic reviews combine results from RCTs by summarising single RCTs which answer a particular clinical question. Some basic knowledge in systematic literature searching is required and helpful for detecting relevant publications. MATERIAL AND METHODS: This article shows various possibilities for locating clinical studies and systematic reviews in the database Medline on the basis of illustrative step-by-step instructions. RESULTS AND CONCLUSION. Depending on the aim and topic of the literature search, the time required for the task may vary. In routine practice, a systematic literature search is unrealistic in most cases. Clinicians in need of a quick update of current evidence on a certain clinical topic may make use of up-to-date systematic reviews. During a systematic literature search, different approaches and strategies might be necessary.

Randomised clinical trial: a 1-week, double-blind, placebo-controlled study of pancreatin 25 000 Ph. Eur. minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) often occurs following pancreatic surgery. AIM: To demonstrate the superior efficacy of pancreatin 25 000 minimicrospheres (Creon 25000 MMS; 9-15 capsules/day) over placebo in treating PEI after pancreatic resection. METHODS: A 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study with a 1-year, open-label extension (OLE). Subjects ≥18 years old with PEI after pancreatic resection, defined as baseline coefficient of fat absorption (CFA) <80%, were randomised to oral pancreatin or placebo (9-15 capsules/day: 3 with main meals, 2 with snacks). In the OLE, all subjects received pancreatin. The primary efficacy measure was least squares mean CFA change from baseline to end of double-blind treatment (ancova). RESULTS: All 58 subjects randomised (32 pancreatin, 26 placebo) completed double-blind treatment and entered the OLE; 51 completed the OLE. The least squares mean CFA change in the double-blind phase was significantly greater with pancreatin vs. placebo: 21.4% (95% CI: 13.7, 29.2) vs. -4.2% (-12.8, 4.5); difference 25.6% (13.9, 37.3), P < 0.001. The mean ± s.d. CFA increased from 53.6 ± 20.6% at baseline to 78.4 ± 20.7% at OLE end (P < 0.001). Treatment-emergent adverse events occurred in 37.5% subjects on pancreatin and 26.9% on placebo during double-blind treatment, with flatulence being the most common (pancreatin 12.5%, placebo 7.7%). Only two subjects discontinued due to treatment-emergent adverse events, both during the OLE. CONCLUSIONS: This study demonstrates superior efficacy of pancreatin 25 000 over placebo in patients with PEI after pancreatic surgery, measured by change in CFA. Pancreatin was generally well tolerated at the high dose administered (EudraCT registration number: 2005-004854-29).

[Evidence-based antibiotic prophylaxis in general and visceral surgery]. / Evidenzbasierte Antibiotikaprophylaxe in der Allgemein- und Viszeralchirurgie.

The use of prophylactic perioperative antibiotic therapy if indicated could successfully and safely prevent surgical wound infections. The current guidelines (S1) for prophylactic perioperative antibiotic therapy of the Study Group of the Scientific Medical Associations (AWMF) of 2004 was replaced by a recommendation of the study group of the Paul-Ehrlich-Gesellschaft for Chemotherapy (PEG) in 2010. This recommendation includes recent research data from 2000 to 2008. Indications and choice of antibiotic agent depend on specific risk factors of the patient and the operation performed. The aim of this article is to describe the current recommendations of the PEG for general and visceral surgery.

[Impact of clinical trials for surgery]. / Bedeutung klinischer Studien für die Chirurgie.

Clinical trials play a key role in patient care, academic education and research in surgery. Without valid studies the practice of evidence-based medicine is limited. Surgery is supported through funding by the German Ministry of Education and Research to establish an infrastructure for clinical trials. So far seven universities have worked together in a network since 2007 and successfully obtained funding for six large randomized trials from a program existing since 2004. Until now 2,249 patients have been randomized within 11 trials and 910 patients have been treated at local hospitals without academic responsibilities. An increase in the interest in clinical trials in daily practice has resulted through the certification of hospitals for special treatment that specifies that at least 5% of all patients are included in clinical trials.

[Which abdominal incisions predispose for incisional hernias?]. / Welche Zugänge prädisponieren für Narbenhernien?

Incisional hernias are the most common long-term complication after laparotomy with a cumulative incidence up to 20%. Generally all injuries to the integrity of the abdominal wall can result in the development of an incisional hernia. Midline and transverse incisions cause similar hernia rates. By selection of a sufficient closure technique and appropriate suture material as well as taking appropriate accompanying treatment (antibiotic prophylaxis) and risk factors into consideration, surgery can reduce surgical site infections, wound dehiscence and incisional hernias. Results from randomized controlled trials have not yet demonstrated a superiority of laparoscope-assisted procedures compared to laparotomy for the prevention of incisional hernias. Access through natural orifices and removal of specimens through the same approach (NOTES) may prevent incisional hernias completely. The approach to the abdominal cavity has to be chosen according to the underlying disease of the patient, the anatomical conditions and further circumstances (e.g. urgency, extensibility, preservation of function of the abdominal wall and safety).

[Survival, mortality and quality of life after pylorus-preserving or classical Whipple operation. A systematic review with meta-analysis]. / Uberleben, Mortalität und Lebensqualität nach pyloruserhaltender oder klassischer Whipple-Operation. Systematische Ubersichtsarbeit mit Metaanalyse.

BACKGROUND: Two surgical procedures are mainly performed for the treatment of pancreatic head cancer and periampullary carcinoma: the classical Whipple operation and the pylorus-preserving Whipple operation. METHODS: This manuscript represents an extension of a systematic review and meta-analysis previously published in the Annals of Surgery. A systematic literature search was performed in MEDLINE, EMBASE and the Cochrane Library (central) to identify randomized controlled trials (RCTs) and observational studies. A meta-analysis based on a random-effects model was performed for the hazard ratios (HR) of survival and the odds ratios (OR) of postoperative mortality. The results of the different studies on quality of life (QoL) could not be summarized quantitatively in a meta-analysis and were therefore summarized qualitatively. Subgroup analyses were performed by study type, RCTs, prospective cohort studies (PSs), retrospective cohort studies (RSs), study quality and tumor localization (pancreatic head cancer versus periampullary carcinoma). RESULTS: The systematic literature search retrieved 4,503 studies of which 4,460 did not fulfill the inclusion criteria. The remaining 43 studies (6 RCTs, 12 PSs and 25 RSs) representing 3,893 patients were finally included in the review. There was neither a significant survival difference for patients with pancreatic head cancer in the pooled estimate of the RCTs (HR 0.80; 95% CI 0.53-1.22; p=0.16) nor in the pooled estimate of the PSs (HR 0.84; 95% CI 0.7-1.0; p=0.95) or the RSs (HR 0.84; 95% CI 0.7-1.01; p=0.21). Survival of patients with periampullary carcinoma was not significantly different in the RCTs (HR 1.02; 95% CI 0.49-2.13; p=0.3), the PSs (HR 1.26; 95% CI 0.46-3.42; p=0.65) or the RSs (HR 0.86; 95% CI 0.6-1.24; p=0.33). Postoperative mortality was not significantly different after both types of operations (RCTs: HR 0.49; 95% CI 0.17-1.4; p=0.18; PSs: HR 0.63; 95% CI 0.34-1.18; p=0.15; RSs: HR 0.7; 95% CI 0.37-1.31; p=0.27). QoL was reported as either the same in both groups or in favor of the pylorus-preserving Whipple operation. CONCLUSIONS: Mortality, survival and QoL were not significantly different between the classical Whipple and the pylorus-preserving Whipple operations. Given the poor quality of the underlying trials a pragmatic RCT is recommended to prove the findings of this systematic review.

[Clinical trials beyond the German Drug Law. Clinical trials in surgery]. / Klinische Studien ausserhalb des Arzneimittelgesetzes. Klinische Studien in der Chirurgie.

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.

Randomized clinical trial of a modified Seldinger technique for open central venous cannulation for implantable access devices.

INTRODUCTION: Totally implantable access ports (TIAPs) are often used for patients who need permanent venous access. The primary success rate using direct open insertion is about 80 per cent, so rescue strategies are needed. This study compared the primary success rates of standard open insertion and a modified Seldinger technique. METHODS: This randomized trial recruited 164 patients scheduled for primary implantation of a TIAP and compared two interventions. The primary endpoint was the success rate of the implantation technique. RESULTS: The primary success rates were similar: 66 (80 per cent) of 82 patients who had standard open insertion versus 69 (84 per cent) of 82 patients undergoing the modified Seldinger method (P = 0.686). A logistic mixed regression analysis including treatment group, age, Karnofsky index, body mass index and surgeon's experience showed no advantage for the Seldinger method: odds ratio 1.30 (95 per cent confidence interval 0.62 to 2.70). TIAPs were eventually implanted successfully in 163 (99.4 per cent) of 164 patients. In 11 patients randomized to standard surgery, the Seldinger method was a successful rescue strategy. CONCLUSION: The primary success rate was similar for both open insertion methods. The modified Seldinger method is useful if standard open insertion fails. REGISTRATION NUMBER: ISRCTN 52368201 (http://www.controlled-trials.com).

Clinical trial: alvimopan for the management of post-operative ileus after abdominal surgery: results of an international randomized, double-blind, multicentre, placebo-controlled clinical study.

BACKGROUND: Post-operative ileus (POI) affects most patients undergoing abdominal surgery. AIM: To evaluate the effect of alvimopan, a peripherally acting mu-opioid receptor antagonist, on POI by negating the impact of opioids on gastrointestinal (GI) motility without affecting analgesia in patients outside North America. METHODS: Adult subjects undergoing open abdominal surgery (n = 911) randomly received oral alvimopan 6 or 12 mg, or placebo, 2 h before, and twice daily following surgery. Opioids were administered as intravenous patient-controlled analgesia (PCA) or bolus injection. Time to recovery of GI function was assessed principally using composite endpoints in subjects undergoing bowel resection (n = 738). RESULTS: A nonsignificant reduction in mean time to tolerate solid food and either first flatus or bowel movement (primary endpoint) was observed for both alvimopan 6 and 12 mg; 8.5 h (95% CI: 0.9, 16.0) and 4.8 h (95% CI: -3.2, 12.8), respectively. However, an exploratory post hoc analysis showed that alvimopan was more effective in the PCA (n = 317) group than in the non-PCA (n = 318) group. Alvimopan was well tolerated and did not reverse analgesia. CONCLUSION: Although the significant clinical effect of alvimopan on reducing POI observed in previous trials was not reproduced, this trial suggests potential benefit in bowel resection patients who received PCA.

DISPACT trial: a randomized controlled trial to compare two different surgical techniques of DIStal PAnCreaTectomy - study rationale and design.

BACKGROUND: Surgery is of increasing importance in the treatment and outcome of diseases of the pancreas worldwide. The incidence of pancreatic cancer (7-11/ 100,000 per year) has risen over the last years and surgical resection remains the only option for definite cure. Twenty-five percent of all resections are left of the superior mesenteric vein (distal pancreatectomy) and the appropriate closure technique for the pancreatic remnant remains unclear. Pancreatic fistulas are the most common (0-40%) and relevant postoperative complication. The optimal surgical strategy for pancreatic resection needs to be identified from the large number of surgical procedures available today. PURPOSE: To evaluate the effectiveness of the two most common surgical techniques for distal pancreatectomy: stapler versus hand-sewn closure of the pancreatic remnant. METHODS: In order to account for the uncertainty and clinical heterogeneity in the management of the pancreatic remnant following distal pancreatectomy, a study protocol is developed on the basis of a retrospective survey of patients in a center of excellence for pancreatic surgery and a systematic review with meta-analysis. RESULTS: The DISPACT trial is a multicentered, randomized, controlled and patient-and observer-blinded trial using a two-group parallel group-sequential superiority design to compare the two techniques mentioned above. It will include approximately 336 randomized patients at up to 20 centers of excellence in pancreatic surgery, who are undergoing elective distal pancreatectomy for resectable benign, malign, and neuroendocrine tumors, chronic pancreatitis and pseudocysts of the pancreatic body and tail. The combination of the rate of postoperative pancreatic fistula and mortality will be evaluated as the primary endpoint. In addition, a set of general and surgical parameters will be analyzed. Pre-specified treatment manuals and continuous intra-operative (photo-documentation of surgical procedures and blinded evaluation thereafter) and on-site monitoring will assure that the treatment of the study patients conforms to protocol and will minimize clinical heterogeneity. Due to uncertainties about the effect sizes of the primary endpoint, an a priori planned interim analysis of the primary endpoint will be conducted after 224 evaluable patients are selected in order to reassess the initially planned sample size. LIMITATIONS: Since pre-existing evidence was limited our initial sample size calculation is based on uncertain assumptions and may need to be modified in a planned interim analysis. Moreover, since surgical experience remains a potential confounder in surgical trials, learning curve bias has to be taken into account when analyzing the results. Given the participating trial sites, standardization of peri-and postoperative treatment represents a major issue of trial conduct. CONCLUSIONS: A group-sequential study design accounts for the uncertainty of pre-existing evidence. Also, standardization of surgical and postoperative care and blinded outcome assessment as well as adjustment for varying surgical expertise will contribute to a high validity and generalizability of the results.

Early results from a randomized clinical trial of colon J pouch versus transverse coloplasty pouch after low anterior resection for rectal cancer.

BACKGROUND: Patients with primary rectal cancer undergoing low anterior resection are often reconstructed using a pouch procedure. The aim of this trial was to compare colon J pouch (CJP) with transverse coloplasty pouch (TCP) reconstruction with regard to functional results, perioperative mortality and morbidity. As there is considerable uncertainty over the true anastomotic leak rate in patients with a TCP, the study analysed short-term outcome data. METHODS: Elective patients suitable for either procedure after sphincter-saving low anterior resection were eligible. Randomization took place during surgery. The primary endpoint was the rate of late evacuation problems after 2 years; secondary endpoints were anastomotic leak rate, perioperative morbidity and mortality. RESULTS: Between 21 October 2002 and 5 December 2005, 149 patients were randomized. All 76 patients randomized to TCP had the procedure compared with 68 of the 73 patients (93 percent) randomized to CJP. Both groups were comparable with regard to demographic and clinical characteristics. Surgical complications (CJP: 19 percent; TCP: 18 percent) and the overall anastomotic leak rate (8 percent) were equally distributed in both groups. CONCLUSION: This trial demonstrated a comparable early outcome for TCP and CJP. This contradicts previous reports suggesting a higher leak rate after TCP. REGISTRATION NUMBER: ISRCTN78983587 (http://www.controlled-trials.com).

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

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer death for men and the fifth for women. The standard treatment for resectable tumours is either a classic Whipple operation or a pylorus-preserving pancreaticoduodenectomy but it is still unclear which of the two procedures is more favourable in terms of survival, mortality, complications, perioperative factors and quality of life. OBJECTIVES: Several publications pointed out both advantages and disadvantages of both techniques and the current basis of evidence remains unclear. The objective of this systematic review is to compare the effectiveness of each technique. SEARCH STRATEGY: A search was conducted to identify all published and unpublished randomised controlled trials. Trials were identified by searching the following electronic databases - The Cochrane Library, MEDLINE, EMBASE and Current Contents. Reference lists from trials selected by electronic searching were hand-searched to identify further relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the classical Whipple (CW) with the pylorus-preserving pancreaticoduodenectomy (PPW) were considered eligible if patients with periampullary or pancreatic carcinoma were included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data for included studies. A random-effects model was used for pooling data from the different trials. Binary outcomes were compared using odds ratios, continuous outcomes were pooled using weighted mean differences and hazard ratios were used to for the meta-analysis of survival data. The methodological quality of included studies was evaluated independently by two authors according to quality standards and by using a questionnaire that covers different aspects of quality. MAIN RESULTS: 1235 abstracts were retrieved and checked for eligibility and seven RCTs were finally included. The critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. The comparison of overall in-hospital mortality (odds ratio 0.49; 95% CI 0.17 to 1.40; P=0.18), overall survival (hazard ratio 0.84; 95% CI 0.61 to 1.16; P=0.29) and morbidity showed no significant difference. However, operating time (weighted mean difference -68.26 min; 95% CI -105.70 to -30.83; P=0.0004) and intra-operative blood loss (weighted mean difference -0.76 ml; 95% CI -0.96 to -0.56; P<0.00001) were significantly reduced in the PPW group. AUTHORS' CONCLUSIONS: There is no evidence of relevant differences in mortality, morbidity and survival between the PPW and the CW. Given obvious clinical and methodological inter-study heterogeneity, future efforts have to be undertaken to perform high quality RCTs of complex surgical interventions on the basis of well defined outcome parameters.

[Multicentric randomised controlled trials in Germany: overview and interim analysis 1 year after inclusion of in the rubric "Clinical Trials"]. / Rekrutierende multizentrische chirurgische Studien in Deutschland : Zwischenbilanz ein Jahr nach Einführung der Rubrik.

BACKGROUND: For 1 year now, German surgical multicentric randomised controlled trials (MRCT) in Germany may be included under the heading "Clinical Trials" in our monthly updated trial list. MATERIAL AND METHODS: Quantitative and qualitative analysis of MRCT presented in the trial list was performed to give an overview and interim statement 1 year after implementation of the journal heading "Clinical Trials". RESULTS: In 1 year, the study list increased from four to eleven MRCT and the numbers of randomized patients from 396 to 1511. The MRCT show distinct differences regarding funding sources and reimbursement for participating centres per patient included. The study protocols of four of 11 MRCT were published in scientific journals. CONCLUSION: The new regular heading gives important details about ongoing surgical trials in Germany. The steady growth of trials and recruited patients demonstrates the practicability of randomized controlled trials in surgery.

Influence of two different resection techniques (conventional liver resection versus anterior approach) of liver metastases from colorectal cancer on hematogenous tumor cell dissemination - prospective randomized multicenter trial.

BACKGROUND: Surgical hepatic resection remains the treatment of choice for patients with liver metastases from colorectal cancer despite the use of alternative therapeutic strategies. Although this procedure provides long-term survival in a significant number of patients, 50-75% of the patients develop intra- and/or extrahepatic recurrence. One possible reason for tumor recurrence may be intraoperative hematogenous tumor cell dissemination due to mechanical manipulation of the tumor during hepatic resection. Surgical technique may have an influence on hematogenous tumor cell spread. We hypothesize that hematogenous tumor cell dissemination may be reduced by using the anterior approach technique compared to conventional liver resection. METHODS/DESIGN: This is a multi-centre prospective randomized controlled, superiority trial to compare two liver resection techniques of liver metastases from colorectal cancer. 150 patients will be included and randomized intraoperatively after surgical exploration just prior to resection. The primary objective is to compare the anterior approach with the conventional liver resection technique with regard to intraoperative haematogenous tumor cell dissemination. As secondary objectives we examine five year survival rates (OS and DFS), blood loss, duration of operation, requirement of blood transfusions, morbidity rate, prognostic relevance of tumor cell detection in blood and bone marrow and the comparison of tumor cell detection by different detection methods. CONCLUSION: This trial will answer the question whether there is an advantage for the anterior approach technique compared to the conventional resection group with regard to tumor cell dissemination. It will also add further information about prognostic differences, safety, advantages and disadvantages of each technique. TRIAL REGISTRATION: Current controlled trials - ISRCTN45066244.