Christoph M. Seiler

Protection From Colorectal Cancer After Colonoscopy: A Population-Based, Case–Control Study

BACKGROUND Colonoscopy with detection and removal of adenomas is considered a powerful tool to reduce colorectal cancer (CRC) incidence. However, the degree of protection achievable in a population setting with high-quality colonoscopy resources remains to be quantified. OBJECTIVE To assess the association between previous colonoscopy and risk for CRC. DESIGN Population-based case-control study. SETTING Rhine-Neckar region of Germany. PATIENTS A total of 1688 case patients with colorectal cancer and 1932 control participants aged 50 years or older. MEASUREMENTS A detailed lifetime history of CRC risk factors and preventive factors, including history and results of previous colonoscopies, and of medical data obtained by self-reports and medical records. Odds ratios of CRC associated with colonoscopy in the preceding 10 years were estimated, after adjustment for sex, age, education level, participation in a general health screening examination, family history of CRC, smoking status, body mass index, and use of nonsteroidal anti-inflammatory drugs or hormone replacement therapy. RESULTS Overall, colonoscopy in the preceding 10 years was associated with 77% lower risk for CRC. Adjusted odds ratios for any CRC, right-sided CRC, and left-sided CRC were 0.23 (95% CI, 0.19 to 0.27), 0.44 (CI, 0.35 to 0.55), and 0.16 (CI, 0.12 to 0.20), respectively. Strong risk reduction was observed for all cancer stages and all ages, except for right-sided cancer in persons aged 50 to 59 years. Risk reduction increased over the years in both the right and the left colon. LIMITATION The study was observational, with potential for residual confounding and selection bias. CONCLUSION Colonoscopy with polypectomy can be associated with strongly reduced risk for CRC in the population setting. Aside from strong risk reduction with respect to left-sided CRC, risk reduction of more than 50% was also seen for right-sided colon cancer. PRIMARY FUNDING SOURCE German Research Council and German Federal Ministry of Education and Research.

Challenges in evaluating surgical innovation

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures-for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.

Evaluation and stages of surgical innovations

Surgical innovation is an important part of surgical practice. Its assessment is complex because of idiosyncrasies related to surgical practice, but necessary so that introduction and adoption of surgical innovations can derive from evidence-based principles rather than trial and error. A regulatory framework is also desirable to protect patients against the potential harms of any novel procedure. In this first of three Series papers on surgical innovation and evaluation, we propose a five-stage paradigm to describe the development of innovative surgical procedures.

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.

Systematic review and meta-analysis of technique for closure of the pancreatic remnant after distal pancreatectomy

Appropriate closure of the pancreatic remnant after distal pancreatectomy is still debated. A variety of procedures have been recommended to reduce the frequency of pancreatic fistula. This review quantitatively compares the available techniques.

A systematic review and meta-analysis of pylorus-preserving versus classical pancreaticoduodenectomy for surgical treatment of periampullary and pancreatic carcinoma.

Objective:Comparison of effectiveness between the pylorus-preserving pancreaticoduodenectomy (“pylorus-preserving Whipple” [PPW]) and the classic Whipple (CW) procedure. Methods:A systematic literature search (Medline, Embase, Cochrane Library, Biosis, Science Citation Index, Ovid Journals) was performed to identify all eligible articles. Randomized controlled trials (RCTs) comparing PPW versus CW for periampullary and pancreatic carcinoma were eligible for inclusion. The methodologic quality of included studies was evaluated independently by 2 authors. Quantitative data on perioperative parameters (blood loss, transfusion, operation time, and length of hospital stay), mortality, morbidity, and survival were extracted from included studies for meta-analysis. Pooled estimates of overall treatment effect were calculated using a random effects model. Results:In total, 1235 abstracts were retrieved and checked for eligibility and 6 RCTs finally included. The critical appraisal revealed vast heterogeneity with respect to methodologic 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), morbidity (odds ratio 0.89; 95% CI, 0.48 to 1.62; P = 0.69), and survival (hazard ratio, 0.74; 95% CI, 0.52 to 1.07; P = 0.11) showed no significant difference. However, operating time (weighted mean difference, −68.26 minutes; 95% CI, −105.70 to −30.83; P = 0.0004), and intraoperative blood loss (weighted mean difference, −766 mL; 95% CI, −965.26 to −566.74; P = 0.00001) were significantly reduced in the PPW group. Conclusion:Hence, in the absence of relevant differences in mortality, morbidity, and survival, the PPW seems to be as effective as the CW. Given obvious clinical and methodological interstudy heterogeneity, efforts should be intensified in the future to perform high quality RCTs of complex surgical interventions on the basis of well defined outcome parameters.

Interrupted or continuous slowly absorbable sutures for closure of primary elective midline abdominal incisions: a multicenter randomized trial (INSECT: ISRCTN24023541).

Objective:In patients undergoing midline incisions, the abdominal fascia can be closed with a continuous or interrupted suture using various materials. The aim of this study is to compare: (1) interrupted technique with rapidly absorbable sutures and (2) continuous techniques with different slowly absorbable sutures, focusing on the incidence of incisional hernias within 1 year. Summary of Background Data:A meta-analysis suggested that the incidence of incisional hernias can be more effectively reduced with slowly absorbable continuous sutures. Methods:Multicenter randomized surgical trial with 3 parallel groups. Patients were scheduled for primary elective midline incisions. All surgeons were trained (4:1 suture wound length in continuous groups) and monitored. Primary end point, measured within 1 year after surgery, was the frequency of incisional hernias diagnosed by clinical examination and confirmed by ultrasound. Complications and safety were used as secondary end points. This study has been registered with the ISRCTN Register (INSECT: ISRCTN24023541). Results:Conducted on 625 randomized patients (210 interrupted Vicryl, 205 continuous polydioxanone suture (PDS), 210 continuous Monoplus), the primary analysis showed an incidence of 28 incisional hernias (15.9%) versus 15 (8.4%) versus 22 (12.5%) for the 3 closure techniques, respectively (P = 0.09). No significant difference was observed between the 3 groups with regard to burst abdomen (4 [2.0%] vs. 6 [3.0%] vs. 8 [4.0%], P = 0.46), wound infection (26 [12.7%] vs. 39 [19.4%] vs. 33 [16.3%], P = 0.19), pulmonary infections (9 [4.4%] vs. 5 [2.5%] vs. 5 [2.5%], P = 0.46), serious adverse events (63 [30.0%] vs. 57 [27.8%] vs. 61 [29.1%], P = 0.89), and 1-year mortality (16 [7.9%] vs. 11 [5.5%] vs. 16 [7.9%], P = 0.54). Conclusions:The incidence of incisional hernias and the frequency of wound infection was higher than expected in all groups. New concepts need to be developed and studied to substantially reduce the frequency of incisional hernias.

Elective midline laparotomy closure: the INLINE systematic review and meta-analysis.

Objective:To evaluate the optimal technique and material for abdominal fascia closure after midline laparotomy, first by means of a precisely defined study population and follow-up period and second by the surgically driven aspects. Methods:Overview of existing systematic reviews and meta-analysis of randomized controlled trials. A systematic literature search (Medline, Embase, and The Cochrane Central Register of Controlled Trials) was performed to identify randomized controlled trials in elective and emergency populations comparing suture techniques (continuous vs. interrupted) and materials (rapidly vs. slowly vs. nonabsorbable). Random effects conventional and cumulative meta-analyses were calculated and presented as odds ratios and the corresponding 95% confidence intervals. Results:Five systematic reviews and 14 trials including 7711 patients (6752 midline incisions) were analyzed. None of the systematic reviews differentiated elective versus emergency laparotomy. The analysis of available primary studies revealed significant lower hernia rates using a continuous (vs. interrupted) technique (OR: 0.59; P = 0.001) with slowly absorbable (vs. rapid-absorbable) suture material (OR: 0.65; P = 0.009) in the elective setting, which was in contrast to the conflicting results of existing systematic reviews. No statistical heterogeneity was detected in the elective setting (I2 = 0%). Seven studies incorporating elective and emergency procedures revealed inconclusive and heterogeneous results (I2 = 45%–85%). No studies have evaluated closure methods solely in the emergency setting so far. Conclusion:No further trials should be conducted for evaluation of technique and available materials for elective midline abdominal fascial closure, according to the results of our cumulative meta-analysis. Future trials will have to define the optimal closure strategy in the emergency setting and relevance of new suture materials and other strategies such as the use of prophylactic mesh in targeted subpopulations.

Does a negative screening colonoscopy ever need to be repeated

Background and aims: Screening colonoscopy is thought to be a powerful and cost-effective tool to reduce colorectal cancer incidence and mortality. Whether and when colonoscopy with negative findings has to be repeated is not well defined. The aim of this study was to assess the long term risk of clinically manifest colorectal cancer among subjects with negative findings at colonoscopy. Patients: 380 cases and 485 controls participating in a population based case-control study in Germany. Methods: Detailed history and results of previous colonoscopies were obtained by interview and from medical records. Adjusted relative risks of colorectal cancer among subjects with a previous negative colonoscopy compared with those without previous colonoscopy were estimated according to time since colonoscopy. Results: Subjects with previous negative colonoscopy had a 74% lower risk of colorectal cancer than those without previous colonoscopy (adjusted odds ratio (aOR) = 0.26 (95% confidence interval, 0.16 to 0.40)). This low risk was seen even if the colonoscopy had been done up to 20 or more years previously. Particularly low risks were seen for sigma cancer (aOR = 0.13 (0.04 to 0.43)) and for rectal cancer (aOR = 0.19 (0.09 to 0.39)), and after a negative screening colonoscopy at ages 55 to 64 (aOR = 0.17 (0.08 to 0.39)) and older (aOR = 0.21 (0.10 to 0.41)). Conclusions: Subjects with negative findings at colonoscopy are at very low risk of colorectal cancer and might not need to undergo repeat colonoscopy for 20 years or more, if at all. The possibility of extending screening intervals to 20 years or more might reduce complications and increase the feasibility and cost-effectiveness of colonoscopy based screening programmes.

Perspectives of Evidence-Based Surgery

The assessment of the optimal treatment option based on best current knowledge is called evidence-based medicine (EBM). Considering the cost explosion in public health systems, EBM should also incorporate proper utilization of the restricted economical resources and should enforce quality assurance in medicine. It is imperative that surgeons realize that randomized controlled trials are applicable to the operative specialties in a large scale, and are necessary to provide evidence-based surgery. So far, only 3.4% of all publications in the leading surgical journals are randomized controlled trials. Furthermore, only 44.1% of the published surgical randomized controlled studies compared different surgical procedures, whereas 55.9% of the articles compared medical therapies in surgical patients. Evidence-based surgical therapy is essential for further development of a high- quality surgical standard, which will also provide quality assurance in future surgical care. This article presents the definition of EBM and discusses specific problems involved in the introduction of its principles into the surgical discipline.