Michael F. Gerhards

Preoperative biliary drainage for cancer of the head of the pancreas

BACKGROUND The benefits of preoperative biliary drainage, which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head, are unclear. METHODS In this multicenter, randomized trial, we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head. Patients with obstructive jaundice and a bilirubin level of 40 to 250 micromol per liter (2.3 to 14.6 mg per deciliter) were randomly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks, followed by surgery, or surgery alone within 1 week after diagnosis. Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retrograde cholangiopancreatography. The primary outcome was the rate of serious complications within 120 days after randomization. RESULTS We enrolled 202 patients; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage; 6 patients were excluded from the analysis. The rates of serious complications were 39% (37 patients) in the early-surgery group and 74% (75 patients) in the biliary-drainage group (relative risk in the early-surgery group, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). Preoperative biliary drainage was successful in 96 patients (94%) after one or more attempts, with complications in 47 patients (46%). Surgery-related complications occurred in 35 patients (37%) in the early-surgery group and in 48 patients (47%) in the biliary-drainage group (relative risk, 0.79; 95% CI, 0.57 to 1.11; P=0.14). Mortality and the length of hospital stay did not differ significantly between the two groups. CONCLUSIONS Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications. (Current Controlled Trials number, ISRCTN31939699.)

Laparoscopy in combination with fast track multimodal management is the best perioperative strategy in patients undergoing colonic surgery: a randomized clinical trial (LAFA-study).

Objective:To investigate which perioperative treatment, ie, laparoscopic or open surgery combined with fast track (FT) or standard care, is the optimal approach for patients undergoing segmental resection for colon cancer. Summary Background Data:Important developments in elective colorectal surgery are the introduction of laparoscopy and implementation of FT care, both focusing on faster recovery. Methods:In a 9-center trial, patients eligible for segmental colectomy were randomized to laparoscopic or open colectomy, and to FT or standard care, resulting in 4 treatment groups. Primary outcome was total postoperative hospital stay (THS). Secondary outcomes were postoperative hospital stay (PHS), morbidity, reoperation rate, readmission rate, in-hospital mortality, quality of life at 2 and 4 weeks, patient satisfaction and in-hospital costs. Four hundred patients were required to find a minimum difference of 1 day in hospital stay. Results:Median THS in the laparoscopic/FT group was 5 (interquar-tile range: 4–8) days; open/FT 7 (5–11) days; laparoscopic/standard 6 (4.5–9.5) days, and open/standard 7 (6–13) days (P < 0.001). Median PHS in the laparoscopic/FT group was 5 (4–7) days; open/FT 6 (4.5–10) days; laparoscopic/standard 6 (4–8.5) days and open/standard 7 (6–10.5) days (P < 0.001). Secondary outcomes did not differ significantly among the groups. Regression analysis showed that laparoscopy was the only independent predictive factor to reduce hospital stay and morbidity. Conclusions:Optimal perioperative treatment for patients requiring segmental colectomy for colon cancer is laparoscopic resection embedded in a FT program. If open surgery is applied, it is preferentially done in FT care. This study was registered under NTR222 (www.trialregister.nl).

Results of postoperative radiotherapy for resectable hilar cholangiocarcinoma.

The aim of this study was to assess the value of radiotherapy, and especially intraluminal brachytherapy, after resection of hilar cholangiocarcinoma by analyzing long-term complications and survival. Between 1983 and 1998, 112 patients underwent resection of a hilar cholangiocarcinoma. Of the 91 patients who survived the postoperative period, 20 patients had no additional radiotherapy, 30 patients had only external radiotherapy (46 ± 11 Gy), and 41 patients had a combination of external (42 ± 5 Gy) and intraluminal brachytherapy (10 ± 2 Gy). Overall, 88% of the patients had late complications, with a significantly higher rate of complications occurring among patients receiving external beam irradiation and brachytherapy. Second to abdominal pain (56%), cholangitis (49%) was the most frequent complication and occurred significantly more often in patients who had received brachytherapy. Retrograde bile leakage after closure of the temporary jejunostomy was a troublesome complication in 24% of patients treated with brachytherapy. Overall median survival after treatment with adjuvant radiotherapy was longer than after resection without additional radiation (24 months versus 8 months, respectively). There was, however, no significant benefit from the use of intraluminal brachytherapy. In conclusion, additional radiotherapy after resection of hilar cholangiocarcinoma significantly improved survival and is recommended by giving external beam irradiation but not intraluminal brachytherapy.

Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial)

BackgroundRecent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay.The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease.Methods/designThe LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate.Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected.DiscussionThe LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease.

Laparoscopic peritoneal lavage or sigmoidectomy for perforated diverticulitis with purulent peritonitis : a multicentre, parallel-group, randomised, open-label trial

BACKGROUND Case series suggest that laparoscopic peritoneal lavage might be a promising alternative to sigmoidectomy in patients with perforated diverticulitis. We aimed to assess the superiority of laparoscopic lavage compared with sigmoidectomy in patients with purulent perforated diverticulitis, with respect to overall long-term morbidity and mortality. METHODS We did a multicentre, parallel-group, randomised, open-label trial in 34 teaching hospitals and eight academic hospitals in Belgium, Italy, and the Netherlands (the Ladies trial). The Ladies trial is split into two groups: the LOLA group comparing laparoscopic lavage with sigmoidectomy and the DIVA group comparing Hartmanns procedure with sigmoidectomy plus primary anastomosis. The DIVA section of this trial is still underway but here we report the results of the LOLA section. Patients with purulent perforated diverticulitis were enrolled for LOLA, excluding patients with faecal peritonitis, aged older than 85 years, with high-dose steroid use (≥20 mg daily), and haemodynamic instability. Patients were randomly assigned (2:1:1; stratified by age [<60 years vs ≥60 years]) using secure online computer randomisation to laparoscopic lavage, Hartmanns procedure, or primary anastomosis in a parallel design after diagnostic laparoscopy. Patients were analysed according to a modified intention-to-treat principle and were followed up after the index operation at least once in the outpatient setting and after sigmoidoscopy and stoma reversal, according to local protocols. The primary endpoint was a composite endpoint of major morbidity and mortality within 12 months. This trial is registered with ClinicalTrials.gov, number NCT01317485. FINDINGS Between July 1, 2010, and Feb 22, 2013, 90 patients were randomly assigned in the LOLA section of the Ladies trial when the study was terminated by the data and safety monitoring board because of an increased event rate in the lavage group. Two patients were excluded for protocol violations. The primary endpoint occurred in 30 (67%) of 45 patients in the lavage group and 25 (60%) of 42 patients in the sigmoidectomy group (odds ratio 1·28, 95% CI 0·54-3·03, p=0·58). By 12 months, four patients had died after lavage and six patients had died after sigmoidectomy (p=0·43). INTERPRETATION Laparoscopic lavage is not superior to sigmoidectomy for the treatment of purulent perforated diverticulitis. FUNDING Netherlands Organisation for Health Research and Development.

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037)

BackgroundRecently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis).Methods/DesignIn this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmanns procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmanns procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs.DiscussionThe Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis.Trial registrationNederlands Trial Register NTR2037

Therapeutic delay and survival after surgery for cancer of the pancreatic head with or without preoperative biliary drainage.

Objective:To evaluate the relation between delay in surgery because of preoperative biliary drainage (PBD) and survival in patients scheduled for surgery for pancreatic head cancer. Background:Patients with obstructive jaundice due to pancreatic head cancer can undergo PBD. The associated delay of surgery can lead to more advanced cancer stages at surgical exploration, affecting resection rate and survival. Methods:We conducted a multicenter, randomized controlled clinical trial to compare PBD with early surgery (ES) for pancreatic head cancer for complications. We obtained Kaplan-Meier estimates of overall survival for patients with pathology-proven malignancy and compared survival functions of ES and PBD groups using log-rank test statistics. Multivariable Cox regression analyses were performed to evaluate the prognostic role of time to surgery for overall survival. Results:Mean times from randomization to surgery were 1.2 (0.9-1.5) and 5.1 (4.8-5.5) weeks in the ES and PBD groups, respectively (P < 0.001). In the ES group, 60 (67%) of 89 patients underwent resection, versus 53 (58%) of 91 patients in the PBD group (P = 0.20). Median survival after randomization was 12.2 (9.1-15.4) months in the ES group versus 12.7 (8.9-16.6) months in the PBD group (P = 0.91). A longer time to surgery was significantly associated with slightly lower mortality rate after surgery (hazard ratio = 0.90, 95% CI, 0.83-0.97), when taking into account resection, bilirubin, complications, pancreatic adenocarcinoma, tumor-positive lymph nodes, and microscopically residual disease. Conclusions:In patients with pancreatic head cancer, the delay in surgery associated with PBD does not impair or benefit survival rate.

The anal fistula plug treatment compared with the mucosal advancement flap for cryptoglandular high transsphincteric perianal fistula: a double-blinded multicenter randomized trial.

BACKGROUND: The anal fistula plug was developed as an alternative treatment for perianal fistulas. OBJECTIVE: This study aimed to compare the anal fistula plug with the mucosal advancement flap for the treatment of high transsphincteric fistulas. DESIGN: This study was a double-blinded, multicenter, randomized trial. PATIENTS: Sixty patients with perianal fistulas were randomly assigned to receive an anal fistula plug or a mucosal advancement flap and were blinded for the type of treatment. MAIN OUTCOME MEASURES: The outcome measures comprised the closure rate, postoperative pain, continence (colorectal functional outcome, Vaizey, and Wexner scores), and quality of life. Closure was determined by clinical examination by a surgeon blinded for the intervention. RESULTS: At a follow-up of 11 months the recurrence rates were 71% (n = 22) in the anal fistula plug group and 52% (n = 15) in the mucosal advancement flap group, which was not significantly different. There were no significant differences in postoperative pain, in pre- and postoperative incontinence scores, soiling, and quality of life. CONCLUSIONS: The results of the anal fistula plug and advancement flap procedures are disappointing in the multicenter setting. There were no significant differences in recurrence, functional outcome, and quality of life between the plug and the advancement flap. Because the plug is simple to apply and minimally invasive, it can be considered as an initial treatment option for high transsphincteric fistulas.

Anal inspection and digital rectal examination compared to anorectal physiology tests and endoanal ultrasonography in evaluating fecal incontinence

BackgroundAnal inspection and digital rectal examination are routinely performed in fecal incontinent patients but it is not clear to what extent they contribute to the diagnostic work-up. We examined if and how findings of anal inspection and rectal examination are associated with anorectal function tests and endoanal ultrasonography.MethodsA cohort of fecal incontinent patients (n=312, 90% females; mean age 59) prospectively underwent anal inspection and rectal examination. Findings were compared with results of anorectal function tests and endoanal ultrasonography.ResultsAbsent, decreased and normal resting and squeeze pressures at rectal examination correlated to some extent with mean (±SD) manometric findings: mean resting pressure 41.3 (±20), 43.8 (±20) and 61.6 (±23) Hg (p<0.001); incremental squeeze pressure 20.6 (±20), 38.4 (±31) and 62.4 (±34) Hg (p<0.001). External anal sphincter defects at rectal examination were confirmed with endoanal ultrasonography for defects <90 degrees in 36% (37/103); for defects between 90-150 degrees in 61% (20/33); for defects between 150-270 degrees in 100% (6/6). Patients with anal scar tissue at anal inspection had lower incremental squeeze pressures (p=0.04); patients with a gaping anus had lower resting pressures (p=0.013) at anorectal manometry. All other findings were not related to any anorectal function test or endoanal ultrasonography.ConclusionsAnal inspection and digital rectal examination can give accurate information about internal and external anal sphincter function but are inaccurate for determining external anal sphincter defects <90 degrees. Therefore, a sufficient diagnostic work-up should comprise at least rectal examination, anal inspection and endoanal ultrasonography.

Treatment of Fistulas in ano with Fibrin Glue

Background: Recent publications show promising results using fibrin glue in the treatment of anal fistulas. The technique is simple, repeatable, with minor surgical trauma so that sphincter function is preserved and further treatment options are not compromised. The aim of this pilot study was to analyse if we could reproduce the results reported in the literature, using this simple technique. Methods: Patients with a primary or recurrent anal fistula were included in this trial. Patients with a complex fistula were excluded. Under general or spinal anaesthesia, the fistulas were curetted and injected with fibrin glue. Follow-up visits were scheduled for 1 week, 6 weeks and 6 months. Results: Twenty-seven patients were included. The overall success rate was 33% after a mean follow-up of 27 weeks. Patients with a recurrent fistula had a poorer outcome (success rate 14%). None of the patients suffered from postoperative continence problems, and no other complications were recorded. Conclusion: This study confirms the safety of fibrin glue in the treatment of anal fistulas. However, a high success rate could not be reproduced.