National quality registries: how to improve the quality of data?

BACKGROUND: Data of quality registries are increasingly used by healthcare providers, patients, health insurance companies, and governments for monitoring quality of care, hospital benchmarking and outcome research. To provide all stakeholders with reliable information and outcomes, reliable data are of the utmost importance. METHODS: This article describes methods for quality assurance of data-used by the Dutch Institute for Clinical Auditing (DICA)-regarding: the design of a registry, data collection, data analysis, and external data verification. For the Dutch Lung Cancer Audit for Surgery (DLCA-S) results of data analysis and data verification were assessed with descriptive statistics. RESULTS: Of all registered patients in the DLCA-S in 2016 (n=2,391), 98.2% was analysable and completeness of data for calculations of transparent outcomes was 90.7%. Data verification for the year 2014 showed a case ascertainment of 99.4%. Of 15 selected hospitals, 14 were verified. All these hospitals received the conclusion 'sufficient quality' on case ascertainment, mortality (0% under-registration) and complicated course (3.3% wrongly registered complications). One hospital was not able to deliver patients lists, and therefore not verified. CONCLUSIONS: Quality of data can be promoted in many different ways. A completeness indicator and data verification are useful tools to improve data quality. Both methods were used to demonstrate the reliability of registered data in the DLCA-S. Opportunities for further improvement are standardised reporting and adequate data extraction.

Surgery versus conservative management for recurrent and ongoing left-sided diverticulitis (DIRECT trial): an open-label, multicentre, randomised controlled trial.

BACKGROUND: Patients with recurrent or persisting complaints after an episode of left-sided diverticulitis are managed with either conservative measures or elective sigmoidectomy. To date, there are no data from randomised trials. We aimed to establish which treatment leads to a better quality of life for patients with diverticulitis. METHODS: We did an open-label, multicentre, randomised controlled trial (DIRECT trial) in 24 teaching and two academic hospitals in the Netherlands. Patients aged 18-75 years presenting with either recurrent (three or more presentations with clinical signs of acute diverticulitis within 2 years) or persistent abdominal complaints (ongoing lower left abdominal pain or persistent change in bowel habits for ≥3 months) after an episode of left-sided diverticulitis, confirmed by CT, ultrasound, or endoscopy, were included. Patients were excluded if they had previous elective or emergency surgery for acute sigmoid diverticulitis, an absolute operation indication, suspicion of a colorectal malignancy, with a preoperative or postoperative risk greater than III (on the American Society of Anesthesiologists classification), or were unable to complete questionnaire or follow-up. Patients were randomly assigned (3:3) to receive conservative management or elective (laparoscopic) sigmoidectomy using a digital randomisation system, stratified by type of disease and centre, with a block size of six. Patients, physicians, and researchers were not masked to treatment allocation. Our primary endpoint was health-related quality of life, measured by the Gastrointestinal Quality of Life Index (GIQLI) at 6 months after inclusion or surgery, depending on randomisation group. This trial is registered with trialregister.nl, number NTR1478, and is closed for inclusion. FINDINGS: Between July 1, 2010, and April 1, 2014, we randomly assigned 109 patients to receive surgical treatment (resection; n=53) or conservative management (n=56), after which the Data Safety and Monitoring Board prematurely terminated the trial because of increasing difficulties in recruitment. 47 (89%) of 53 patients received surgical treatment and 43 (77%) of 56 patients received conservative management. The GIQLI score at 6 months' follow-up was significantly higher in patients randomly assigned to receive surgical treatment (mean 114·4 [SD 22·3]) than conservative management (100·4 [22·7]; mean difference 14·2, 95% CI 7·2-21·1, p<0·0001). 43 (38%) of 109 patients had a severe adverse event in the first 6 months after treatment (18 [34%] of 53 patients in the surgical treatment group vs 23 [40%] of 57 patients in the conservative treatment group). Seven (15%) patients who received surgical treatment developed anastomotic leakage. Of the 56 patients assigned to be treated conservatively, 13 (23%) ultimately underwent elective resection due to ongoing abdominal complaints, with no anastomotic leakage. We recorded no patient deaths. INTERPRETATION: Elective sigmoidectomy, despite its inherent risk of complications, results in better quality of life than conservative management in patients with recurrent and persisting abdominal complaints after an episode of diverticulitis. FUNDING: Netherlands Organisation for Health Research and Development.

Single center cost analysis of single-port and conventional laparoscopic surgical treatment in colorectal malignant diseases.

BACKGROUND AND PURPOSE: Single-port laparoscopy (SPL) is a relatively new technique, used in various procedures. There is limited knowledge about the cost effectiveness and the learning curve of this technique. The primary aim of this study was to compare hospital costs between SPL and conventional laparoscopic resections (CLR) for colorectal cancer; the secondary aim was to identify a learning curve of SPL. METHODS: All elective colorectal cancer SPL and CLR performed in a major teaching hospital between 2011 and 2012 that were registered in the Dutch Surgical Colorectal Audit were included (n = 267). The economic evaluation was conducted from a hospital perspective, and costs were calculated using time-driven activity-based costing methodology up to 90 days after discharge. When looking at SPL only, the introduction year (2011) was compared to the next year (2012). RESULTS: SPL (n = 78) was associated with lower mortality, lower reintervention rates, and more complications as compared to CLR (n = 189); however, none of these differences were statistically significant. A significant shorter operating time was seen in the SPL. Total costs were higher for SPL group as compared to CLR; however, this difference was not statistically significant. For the SPL group, most clinical outcomes improved between 2011 and 2012; moreover, total hospital costs for SPL in 2012 became comparable to CLR. CONCLUSION: No significant differences in financial outcomes between SPL and CLR were identified. After the introduction period, SPL showed similar results as compared to CLR. Conclusions are based on a small single-port group and the conclusions of this manuscript should be an impetus for further research.

Multicenter Stratified Comparison of Hospital Costs Between Laparoscopic and Open Colorectal Cancer Resections: Influence of Tumor Location and Operative Risk.

OBJECTIVE: To compare actual 90-day hospital costs between elective open and laparoscopic colon and rectal cancer resection in a daily practice multicenter setting stratified for operative risk. BACKGROUND: Laparoscopic resection has developed as a commonly accepted surgical procedure for colorectal cancer. There are conflicting data on the influence of laparoscopy on hospital costs, without separate analyses based on operative risk. METHODS: Retrospective analyses using a population-based database (Dutch Surgical Colorectal Audit). All elective resections for a T1-3N0-2M0 stage colorectal cancer were included between 2010 and 2012 in 29 Dutch hospitals. Operative risk was stratified for age (<75 years or ≥75 years) and ASA status (I-II/III-IV). Ninety-day hospital costs were measured uniformly in all hospitals based on time-driven activity-based costing. RESULTS: Total 90-day hospital costs ranged from &OV0556;10474 to &OV0556;20865 in the predefined subgroups. For colon cancer surgery (N = 4202), laparoscopic resection was significant less expensive than open resection in all subgroups, savings because of laparoscopy ranged from &OV0556;409 (<75 years ASA I-II) to &OV0556;1932 (≥75 years ASA I-II). In patients ≥75 years and ASA I-II, laparoscopic resection was associated with 46% less mortality (P = 0.05), 41% less severe complications (P < 0.001), 25% less hospital stay (P = 0.013), and 65% less ICU stay (P < 0.001). For rectal cancer surgery (N=2328), all laparoscopic subgroups had significantly higher total hospital costs, ranging from &OV0556;501 (<75 years ASA I-II) to &OV0556;2515 (≥75 years ASA III-IV). CONCLUSIONS: Laparoscopic resection resulted in the largest cost reduction in patients over 75 years with ASA I-II undergoing colonic resection, and the largest cost increase in patients over 75 years with ASA III-IV undergoing rectal resection as compared with an open approach.

Use of a multi-instrument access device in abdominoperineal resections.

BACKGROUND: Laparoscopic colorectal surgery results in less post-operative pain, faster recovery, shorter length of stay and reduced morbidity compared with open procedures. Less or minimally invasive techniques have been developed to further minimise surgical trauma and to decrease the size and number of incisions. This study describes the safety and feasibility of using an umbilical multi-instrument access (MIA) port (Olympus TriPort+) device with the placement of just one 12-mm suprapubic trocar in laparoscopic (double-port) abdominoperineal resections (APRs) in rectal cancer patients. PATIENTS AND METHODS: The study included 20 patients undergoing double-port APRs for rectal cancer between June 2011 and August 2013. Preoperative data were gathered in a prospective database, and post-operative data were collected retrospectively. RESULTS: The 20 patients (30% female) had a median age of 67 years (range 46-80 years), and their median body mass index (BMI) was 26 kg/m2 (range 20-31 kg/m2). An additional third trocar was placed in 2 patients. No laparoscopic procedures were converted to an open procedure. Median operating time was 195 min (range 115-306 min). A radical resection (R0 resection) was achieved in all patients, with a median of 14 lymph nodes harvested. Median length of stay was 8 days (range 5-43 days). CONCLUSION: Laparoscopic APR using a MIA trocar is a feasible and safe procedure. A MIA port might be of benefit as an extra option in the toolbox of the laparoscopic surgeon to further minimise surgical trauma.

Single-port laparoscopic cholecystectomy vs standard laparoscopic cholecystectomy: A non-randomized, age-matched single center trial.

AIM: To compare the safety of single-port laparoscopic cholecystectomies with standard four-port cholecystectomies. METHODS: Between January 2011 and December 2012 datas were gathered from 100 consecutive patients who received a single-port cholecystectomy. Patient baseline characteristics of all 100 single-port cholecystectomies were collected (body mass index, age, etc.) in a database. This group was compared with 100 age-matched patients who underwent a conventional laparoscopic cholecystectomy in the same period. Retrospectively, per- and postoperative data were added. The two groups were compared to each other using independent t-tests and χ(2)-tests, P values below 0.05 were considered significantly different. RESULTS: No differences were found between both groups regarding baseline characteristics. Operating time was significantly shorter in the total single-port group (42 min vs 62 min, P < 0.05); in procedures performed by surgeons the same trend was seen (45 min vs 59 min, P < 0.05). Peroperative complications between both groups were equal (3 in the single-port group vs 5 in the multiport group; P = 0.42). Although not significant less postoperative complications were seen in the single-port group compared with the multiport group (3 vs 9; P = 0.07). No statistically significant differences were found between both groups with regard to length of hospital stay, readmissions and mortality. CONCLUSION: Single-port laparoscopic cholecystectomy has the potential to be a safe technique with a low complication rate, short in-hospital stay and comparable operating time. Single-port cholecystectomy provides the patient an almost non-visible scar while preserving optimal quality of surgery. Further prospective studies are needed to prove the safety of the single-port technique.

Re-interventions following laparoscopic surgery for colorectal cancer: data from 818 individuals from the Dutch surgical colorectal audit.

BACKGROUND: The surgical procedure of choice for the resection of colorectal cancer has shifted in favor of laparoscopic surgery. Although increasing data prove advantages of elective laparoscopic surgery, less is known about the results in acute indications such as surgical re-interventions following colorectal resections. This study aims to assess the clinical benefits in recovery following laparoscopic re-interventions compared with open re-interventions following laparoscopic colorectal cancer surgery. SUBJECTS AND METHODS: We performed an analysis of data from the Dutch Surgical Colorectal Audit from January 2010 to December 2012. All patients requiring surgical re-intervention after initial laparoscopic colorectal surgery were analyzed. RESULTS: Out of 27,448 patients, 11,856 underwent laparoscopic surgery. Following laparoscopic surgery, 159 patients (1.3%) had a laparoscopic re-intervention, and 659 patients (5.6%) had an open re-intervention. In a multivariable analysis adjusting for patients' demographics and risk factors, the length of hospital stay was 17 days (interquartile range, 11-16 days) for the laparoscopic group and 23 days (interquartile range, 14-37 days) for the open group (odds ratio [OR]=0.74; 95% confidence interval [CI], 0.65-0.84). In the laparoscopic group the intensive care unit admission rate was 39% compared with 66% in the open group. The 30-day mortality rate was 7 (4%) in the laparoscopic group compared with 89 (14%) in the open group (OR=0.31; 95% CI, 0.13-0.73). CONCLUSIONS: Laparoscopic re-intervention following laparoscopic surgery for colorectal cancer is feasible in selected patients. Because of the unknown extent of selection bias, prospective studies are needed to define the exact position and benefits of laparoscopic re-interventions.

Surgical re-interventions following colorectal surgery: open versus laparoscopic management of anastomotic leakage.

BACKGROUND: Increasing numbers of colorectal resections are performed laparoscopically each year. In 2010, 42% of all colorectal procedures in The Netherlands were performed laparoscopically. Although the anastomotic leakage rate is 3%-19% of all patients, little is known about laparoscopic options for re-intervention. Our study aims to evaluate the safety and feasibility of laparoscopic re-intervention compared with open surgery following colorectal surgery. PATIENTS AND METHODS: All patients who required a surgical re-intervention for an anastomotic leak, bowel perforation, or abscess after laparoscopic colorectal surgery between January 2008 and June 2012 were analyzed retrospectively. Demographic data, operative management, morbidity, hospital stay, and mortality were collected and analyzed for each patient. RESULTS: Fifty-six patients were included. Eighteen patients had a laparotomy following laparoscopy, and 38 patients had a laparoscopic re-intervention following laparoscopy. The median age was 65 years, with a median body mass index of 26 kg/m(2). Four patients had a previous laparotomy, and 73% had surgery for malignant colorectal disease. The length of hospital stay was 20 days in the laparoscopic group versus 31 days in the open group (P=.044). Six out of 38 versus 7 out of 18 patients required an additional re-intervention (P=.056). Fewer patients developed fascial dehiscence in the laparoscopic group (P=.033). In-hospital mortality was 4 out of 18 in the open group compared with 2 out of 38 in the laparoscopic group (P=.077). CONCLUSIONS: Laparoscopic re-intervention could be a safe and feasible treatment for anastomotic leakage after laparoscopic colorectal surgery. These promising results need to be further investigated in a prospective study to reduce uncertainty in the patient's condition and perioperative findings.

Nature and timing of incidents intercepted by the SURPASS checklist in surgical patients.

INTRODUCTION: More than half of in-hospital adverse events can be attributed to a surgical discipline. Checklists can effectively decrease errors and adverse events. However, the mechanisms by which checklists lead to increased safety are unclear. This study aimed to assess the number, nature and timing of incidents intercepted by use of the Surgical Patient Safety System (SURPASS) checklist, a patient-specific multidisciplinary checklist that covers the entire surgical patient pathway. METHODS: The checklist was implemented in two academic hospitals and four teaching hospitals in the Netherlands. Users of the checklist had three options for each item that was checked: 'not applicable', 'yes' and 'intercepted by checklist'. In each hospital, the first 1000 completed checklists were entered into an online central database. RESULTS: In six participating hospitals, 6313 checklists were collected. One or more incidents were intercepted in 2562 checklists (40.6%). In total, 6312 incidents were intercepted. After correction for the number of items and the extent of adherence in each part of the checklist, the number of intercepted incidents was highest in the preoperative and postoperative stages. CONCLUSIONS: The checklist intercepts many potentially harmful incidents across all stages of the surgical patient pathway. The majority of incidents were intercepted in the preoperative and postoperative stages of the pathway. The degree to which these incidents would have been intercepted by a single checklist in the operating room only, compared with a checklist for the entire surgical pathway, remains a subject for future study.

Comparison of short-term surgical outcomes after single-incision laparoscopic versus multiport laparoscopic right colectomy: a two-center, prospective case-controlled study of 100 patients.

BACKGROUND: Recent case studies have demonstrated the feasibility of single-incision laparoscopic colectomy (SILC). Few comparative studies for SILC and multiport laparoscopic colectomy (MLC) have been conducted. The aim of this case-controlled study was to compare the short-term surgical outcomes between SILC and MLC for right-sided colectomies. METHODS: Between January 2010 and February 2012, data from the first 50 consecutive patients that underwent right SILS at one of the two institutions were compared with a group of 50 consecutive patients that underwent right MLC in the same period. RESULTS: Median operative time was significantly shorter in SILC (97 vs. 112 min; p < 0.001). Between both groups, no statistically significant differences were found regarding number and nature of short-term complications, number of reoperations [4 (8%) vs. 6 (12%)], and mortality rate [1 (2%) vs. 2 (4%)]. Median postoperative hospital stay was 6 days for both groups. CONCLUSION: SILC is a safe and feasible procedure when performed by experienced laparoscopic surgeons. Length of hospital stay and overall complication rates are comparable with MLC. Until today, no clear advantages of SILC over MLC have been demonstrated. However, due to its smaller incisional trauma, SILC could be a major step in improving cosmetic outcomes.

Effect of a comprehensive surgical safety system on patient outcomes.

BACKGROUND: Adverse events in patients who have undergone surgery constitute a large proportion of iatrogenic illnesses. Most surgical safety interventions have focused on the operating room. Since more than half of all surgical errors occur outside the operating room, it is likely that a more substantial improvement in outcomes can be achieved by targeting the entire surgical pathway. METHODS: We examined the effects on patient outcomes of a comprehensive, multidisciplinary surgical safety checklist, including items such as medication, marking of the operative side, and use of postoperative instructions. The checklist was implemented in six hospitals with high standards of care. All complications occurring during admission were documented prospectively. We compared the rate of complications during a baseline period of 3 months with the rate during a 3-month period after implementation of the checklist, while accounting for potential confounders. Similar data were collected from a control group of five hospitals. RESULTS: In a comparison of 3760 patients observed before implementation of the checklist with 3820 patients observed after implementation, the total number of complications per 100 patients decreased from 27.3 (95% confidence interval [CI], 25.9 to 28.7) to 16.7 (95% CI, 15.6 to 17.9), for an absolute risk reduction of 10.6 (95% CI, 8.7 to 12.4). The proportion of patients with one or more complications decreased from 15.4% to 10.6% (P<0.001). In-hospital mortality decreased from 1.5% (95% CI, 1.2 to 2.0) to 0.8% (95% CI, 0.6 to 1.1), for an absolute risk reduction of 0.7 percentage points (95% CI, 0.2 to 1.2). Outcomes did not change in the control hospitals. CONCLUSIONS: Implementation of this comprehensive checklist was associated with a reduction in surgical complications and mortality in hospitals with a high standard of care. (Netherlands Trial Register number, NTR1943.).

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

BACKGROUND: Recently, 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/DESIGN: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's 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 Hartmann's 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. DISCUSSION: The 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 REGISTRATION: Nederlands Trial Register NTR2037.

DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative treatment. A multicenter randomised clinical trial.

BACKGROUND: Persisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses.Both conservative and operative management of patients with persisting abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management.We, therefore, constructed a randomised clinical trial comparing these two treatment strategies. METHODS/DESIGN: The DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years) presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management). Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used.The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, Short-Form 36, EQ-5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and total costs. The total follow-up will be three years. DISCUSSION: Considering the high incidence and the multicenter design of this study, it may be assumed that the number of patients needed for this study (n = 214), may be gathered within one and a half year.Depending on the expertise and available equipment, we prefer to perform a laparoscopic resection on patients randomised for elective surgery. Should this be impossible, an open technique may be used as this also reflects the current situation. TRIAL REGISTRATION: (Trial register number: NTR1478).

Low arginine/asymmetric dimethylarginine ratio deteriorates systemic hemodynamics and organ blood flow in a rat model.

OBJECTIVE: Both arginine and asymmetric dimethylarginine (ADMA) play a crucial role in the arginine-nitric oxide pathway. Low arginine and high ADMA levels can be found in critically ill patients after major surgery. The aim of this study was to evaluate the effects of low arginine plasma concentrations in combination with high ADMA plasma concentrations on hemodynamics and organ blood flow. DESIGN: Randomized, placebo-controlled animal laboratory investigation. SUBJECTS: Male Wistar rats (n = 21), anesthetized. INTERVENTIONS: Rats were randomly assigned to three groups: a control group, an ADMA group, or an arginase (ASE)/ADMA group. In the control group, rats received (at t = 0) an intravenous (IV) infusion of 1.5 mL 0.9% NaCl during a 20-minute period. After 60 minutes (t = 60), rats received an IV bolus of 1.0 mL 0.9% NaCl. In the ADMA group, rats received an IV infusion of 1.5 mL 0.9% NaCl during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). In the ASE/ADMA group, rats received an IV infusion of 1.5 mL ASE (3200 IU) solution during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). MEASUREMENTS AND MAIN RESULTS: Infusion of ADMA (20 mg/kg) and ASE (3200 IU) resulted in increased plasma ADMA levels and decreased arginine levels. During the whole experiment, systemic hemodynamics (heart rate, mean arterial pressure [MAP], and cardiac output) were measured. In addition, organ blood flow was measured at t = 90 and t = 180 minutes, using fluorescent microspheres. Compared with the control group, MAP and systemic vascular resistance were increased after infusion of ADMA. Infusion of ASE in combination with ADMA significantly deteriorated systemic hemodynamics (MAP, cardiac output, stroke volume, and systemic vascular resistance) and organ blood flow through the kidney and spleen. In addition, an initial decrease in arterial flow, followed by a later major increase, and panlobular apoptosis and necrosis of the liver was observed. CONCLUSIONS: The current study shows that low arginine plasma levels in combination with high ADMA plasma levels deteriorates systemic hemodynamics and reduces blood flow through the kidney and spleen and liver. These data suggest that a diminished nitric oxide production may be involved in the onset of organ failure.

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).

BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction. The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150.

The long-term results of a randomized clinical trial of laparoscopy-assisted versus open surgery for colon cancer.

OBJECTIVE: The aim of this study was to compare the long-term outcome of laparoscopy-assisted colectomy (LAC) and open colectomy (OC) for nonmetastatic colon cancer. METHODS: From November 1993 to July 1998 all patients with adenocarcinoma of the colon were assessed for entry in this single center, clinically randomized trial. Adjuvant therapy and postoperative follow-up were similar in both groups. The primary endpoint was cancer-related survival and secondary endpoints were probability of overall survival and probability of being free of recurrence. Data were analyzed according the intention-to-treat principle. RESULTS: Two hundred and nineteen patients entered the study (111 LAC group and 108 OC group). The median follow-up was 95 months (range, 77-133). There was a tendency of higher cancer-related survival (P = 0.07, NS) and overall survival (P = 0.06, NS) for the LAC group. Probability of cancer-related survival was higher in the LAC group (P = 0.02) when compared with OC. The regression analysis showed that LAC was independently associated with a reduced risk of tumor relapse (hazard ratio 0.47, 95% CI 0.23-0.94), death from a cancer-related cause (0.44, 0.21-0.92) and death from any cause (0.59, 0.35-0.98). CONCLUSIONS: LAC is more effective than OC in the treatment of colon cancer.

The clinical significance of asymmetric dimethylarginine.

In 1992, asymmetrical dimethylarginine (ADMA) was first described as an endogenous inhibitor of the arginine-nitric oxide (NO) pathway. From then, its role in regulating NO production has attracted increasing attention. Nowadays, ADMA is regarded as a novel cardiovascular risk factor. The role of the kidney and the liver in the metabolism of ADMA has been extensively studied and both organs have proven to play a key role in the elimination of ADMA. Although the liver removes ADMA exclusively via degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), the kidney uses both metabolic degradation via DDAH and urinary excretion to eliminate ADMA. Modulating activity and/or expression of DDAH is still under research and may be a potential therapeutic approach to influence ADMA plasma levels. Interestingly, next to its association with cardiovascular disease, ADMA also seems to play a role in other clinical conditions, such as critical illness, hepatic failure, and preeclampsia. To elucidate the clinical significance of ADMA in these conditions, the field of research must be enlarged.

The role of Kupffer cells after major liver surgery.

BACKGROUND: Kupffer cells (KCs) are the resident macrophages of the liver. KCs have an enormous endotoxin eliminating capacity. Endotoxins play an important role in the development of systemic complications after partial hepatectomy by activating KCs. The role of KCs and endotoxins after partial hepatectomy is investigated. METHODS: Wistar rats (n = 16, 250-275 g) were randomly assigned to have 1 mL dichloromethylene-diphosphonate (CL2MDP) or 1 mL NaCl 0.9% i.v. Forty-eight hours later, all rats received a two-thirds liver resection. Twenty-four hours later, rats received at random 50 microg/kg endotoxin (LPS) in 1 mL or 1 mL of NaCl 0.9% IV. The rats were killed 4 hours after LPS or SAL infusion. RESULTS: CL2MDP infusion resulted in a complete KC elimination. KC-depleted rats had the lowest mean arterial pressure, the highest heart and ventilatory rate after endotoxemia. All rats were able to maintain pH in normal ranges. The KC-depleted rats after partial hepatectomy had the lowest CO2 levels and the highest levels of lactate during endotoxemia. Oxygen levels were similar in all groups. Hepatic, pulmonary, and renal mRNA expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta were decreased in KC-depleted rats. Plasma levels of TNF-alpha were significantly decreased in KC-depleted rats. Furthermore, the highest influx of macrophages and polymorphonuclear cells in the lung and kidney were measured in KC-depleted rats during endotoxemia. CONCLUSIONS: Partial hepatectomy in KC-depleted rats result in a more pronounced endotoxin-mediated systemic inflammation and decreased synthesis of cytokines.

Elevation of asymmetric dimethylarginine (ADMA) in patients developing hepatic failure after major hepatectomy.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the arginine-nitric oxide pathway. It is conceivable that its concentration is tightly regulated by urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver. In rats, we showed a high net hepatic uptake of ADMA. Therefore, we aimed to confirm the role of the liver in humans and hypothesized elevated ADMA levels after major liver resection by a reduction of functional liver mass and injury to the remnant liver. METHODS: Patients undergoing a major hepatic resection (HEP, n = 17) or major abdominal surgery (MAS, n = 12) were included and followed in time. In addition, ADMA levels were measured in 4 patients having severe hepatic failure after a liver resection. Plasma ADMA concentration was measured by high-performance liquid chromatography. RESULTS: Preoperatively and on days 1, 3, and 5, plasma levels of ADMA were higher in HEP patients when compared with MAS patients. In HEP patients with prolonged (>7 days) hepatic injury, ADMA levels were especially elevated. On the first postoperative day, ADMA significantly correlated to bilirubin concentration (r = .528, p < .05) as a marker of postoperative hepatic function. Besides, in patients with severe hepatic failure, ADMA levels were highly elevated. CONCLUSIONS: In the present study, evidence was found for the role of the liver in the elimination of ADMA in humans. Increased levels of ADMA occur in the postoperative course after a major hepatic resection, especially when liver function is severely impaired. Further studies need to assess the role of ADMA in the development of complications after liver surgery.