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Contains fulltext : 175643.pdf (publisher's version ) (Closed access), OBJECTIVE: The aim of this study was to investigate the incidence of parastomal hernias (PSHs) after end-colostomy formation using a polypropylene mesh in a randomized controlled trial versus conventional colostomy formation. BACKGROUND: A PSH is the most frequent complication after stoma formation. Symptoms may range from mild abdominal pain to life-threatening obstruction and strangulation. The treatment of a PSH is notoriously difficult and recurrences up to 20% have been reported despite the use of mesh. This has moved surgical focus toward prevention. METHODS: Augmentation of the abdominal wall with a retro-muscular lightweight polypropylene mesh was compared with the traditional formation of a colostomy. In total, 150 patients (1:1 ratio) were included. The incidence of a PSH, morbidity, mortality, quality of life, and cost-effectiveness was measured after 1 year of follow-up. RESULTS: There was no difference between groups regarding demographics and predisposing factors for PSH. Three out of 67 patients (4.5%) in the mesh group and 16 out of 66 patients (24.2%) in the nonmesh group developed a PSH (P = 0.0011). No statistically significant difference was found in infections, concomitant hernias, SF-36 questionnaire, Von Korff pain score, and cost-effectiveness between both study groups. CONCLUSION: Prophylactic augmentation of the abdominal wall with a retromuscular lightweight polypropylene mesh at the ostomy site significantly reduces the incidence of PSH without a significant difference in morbidity, mortality, quality of life, or cost-effectiveness.

Contains fulltext : 174852.pdf (publisher's version ) (Open Access), AIM: To evaluate a step up approach: Taking macrobiopsies and performing excision biopsies in patients with suspected rectal cancer in which biopsies taken though the flexible endoscope showed benign histology. METHODS: Patients with a rectal neoplasm who underwent flexible endoscopy and biopsies were included. In case of benign biopsies rigid rectoscopy and macrobiopsies were employed. If this failed to prove malignancy, transanal endoscopic microsurgery (TEM) was used in a final effort to establish a certain preoperative diagnosis. The preoperative results were compared with the findings after surgical excision and follow up to calculate the reliability of this algorithm. RESULTS: One hundred and thirty-two patients were included. One hundred and ten patients with a carcinoma and 22 with an adenoma. Seventy-five of 110 carcinomas were proven malignant after flexible endoscopy. With the addition of rigid endoscopy and taking of macrobiopsies, this number increased to 89. Performing TEM excision biopsies further enlarged the number of proven malignancies to 100. CONCLUSION: The step-up approach includes taking macrobiopsies through the rigid rectoscope and performing excision biopsies using transanal endoscopic microsurgery in addition to flexible endoscopy. This approach, reduced the number of missed preoperative malignant diagnoses from 32% to 9%.

Contains fulltext : 171283.pdf (publisher's version ) (Closed access), PURPOSE: Parastomal hernia (PSH) is a common complication after colostomy formation. Recent studies indicate that mesh implantation during formation of a colostomy might prevent a PSH. To determine if placement of a retromuscular mesh at the colostomy site is a feasible, safe and effective procedure in preventing a parastomal hernia, we performed a multicentre randomized controlled trial in 11 large teaching hospitals and three university centres in The Netherlands. METHODS: Augmentation of the abdominal wall with a retromuscular light-weight polypropylene mesh (Parietene Light, Covidien) around the trephine was compared with traditional colostomy formation. Patients undergoing elective open formation of a permanent end-colostomy were eligible. 150 patients were randomized between 2010 and 2012. Primary endpoint of the PREVENT trial is the incidence of parastomal hernia. Secondary endpoints are morbidity, pain, quality of life, mortality and cost-effectiveness. This article focussed on the early results of the PREVENT trial and, therefore, operation time, postoperative morbidity, pain, and quality of life were measured. Results : Outcomes represent results after 3 months of follow-up. A total of 150 patients were randomized. Mean operation time of the mesh group (N = 72) was significantly longer than in the control group (N = 78) (182.6 vs. 156.8 min; P = 0.018). Four (2.7 %) peristomal infections occurred of which one (1.4 %) in the mesh group. No infection of the mesh occurred. Most of the other infections were infections of the perineal wound, equally distributed over both groups. No statistical differences were discovered in stoma or mesh-related complications, fistula or stricture formation, pain, or quality of life. CONCLUSIONS: During open and elective formation of an end-colostomy, primary placement of a retromuscular light-weight polypropylene mesh for prevention of a parastomal hernia is a safe and feasible procedure. The PREVENT trial is registered at: ht

Contains fulltext : 168316.pdf (publisher's version ) (Closed access), BACKGROUND & AIMS: Although colonic diverticulitis is a common disorder, there is no clear treatment strategy for patients with recurrent episodes of diverticulitis. We investigated whether colonic resection or conservative or medical treatments have the greatest effects on quality-adjusted life-years (QALYs). METHODS: A Markov model simulating patients with 2 episodes of non-surgically treated diverticulitis was used to simulate all relevant outcomes of each treatment strategy. A 1-year cycle length with 10-year follow-up period was used to allow for chance of recurrent diverticulitis. Primary outcome was QALYs gained from each strategy. Factors considered were morbidity, mortality, chance of colostomy formation, risk of recurrence, and persistence of abdominal pain. The probabilities of clinical events were determined by using the best available published data. RESULTS: A strategy in which colonic resection was performed after 2 episodes of diverticulitis was associated with the lowest quality-adjusted survival (a gain of 8.66 QALYs) and highest chance of stoma formation (1.1%) but the lowest chance of a mild (3.5%) or severe (1.1%) recurrence. The strategies of colonic resection or conservative or medical treatment after the third episode of diverticulitis were comparable in terms of quality-adjusted survival, providing 8.78, 8.76, and 8.74 QALYs, respectively. Probabilistic sensitivity analysis did not change these results. Persistent abdominal complaints were lowest in the medical treatment strategy. CONCLUSIONS: Elective surgery after 2 episodes of diverticulitis should be questioned in terms of QALYs. After the third episode of diverticulitis, surgical or conservative or medical treatments provide similar QALYs, but rates of abdominal symptoms are lower with the medical treatment strategy. This Markov decision model has limitations when the individual patient and physician face a complex decision weighing early and long-term risks and benefits of elective sur

Item does not contain fulltext, BACKGROUND: Large ventral hernia repair represents a major reconstructive surgical challenge, especially under contaminated conditions. Synthetic mesh is usually avoided in these circumstances because of fear of mesh infection, although evidence is outdated and does not regard new materials and techniques. The authors evaluated the safety of synthetic mesh in large contaminated ventral hernia repair. METHODS: All large ventral hernias repaired with the components separation technique and polypropylene mesh were included in analysis. Primary outcomes were wound and medical complications, with a focus on surgical-site infection and mesh removal. For risk analysis, patients were stratified by surgical wound class, Ventral Hernia Working Group grade, and modified Ventral Hernia Working Group grade. RESULTS: One hundred thirty-seven patients were included, with a mean age of 58.6 years, mean body mass index of 26.6 cm, and mean defect size of 235.6 cm. Surgical-site infection and total wound complication rates were 16.1 and 48.9 percent, respectively. The surgical wound class distribution of surgical-site infections was as follows: clean, five of 56 (9.1 percent); clean-contaminated, five of 34 (14.7 percent); contaminated, three of 19 (15.8 percent); and dirty/infected, nine of 28 (32.1 percent). Seven meshes (5.1 percent) needed removal, two after clean repairs, three after clean-contaminated repairs, and two after dirty/infected repairs. Surgical wound class (OR, 1.77; 95 percent CI, 1.20 to 2.61) and Ventral Hernia Working Group grade (OR, 2.31; 95 percent CI, 1.24 to 4.28) were predictors of surgical-site infection. CONCLUSION: Rate of surgical-site infection after large contaminated ventral hernia repair with synthetic mesh is considerable but with a low mesh removal rate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Item does not contain fulltext, BACKGROUND: Recurrence rates after component separation technique (CST) are low in the literature but may be underestimated because of inadequate follow-up methods. METHODS: Prospective patient follow-up was performed of consecutive patients who underwent repair of large and complex ventral hernias using CST without mesh utilization. Primary outcome was recurrent hernia determined by clinical examination at least 1 year after surgery in all living patients. Current literature underwent meta-analysis regarding outcomes and mode of follow-up. RESULTS: Seventy-five patients were included with a mean age of 52.2 years and a mean defect size of 214.9 cm(2), respectively. Twenty-nine patients (38.7%) had a recurrent hernia after a mean of 40.9-month follow-up, and this was significantly higher than in the literature (14.0%, P < .01). Sixty-four percent of studies in the literature were unclear about the method of determining recurrent hernia or included telephone follow-up and questionnaires. CONCLUSIONS: CST coincides with a high recurrence rate when clinical follow-up is longer than a year. Reported recurrence rates are probably underestimated because the method and duration of follow-up are inadequate.

Item does not contain fulltext, OBJECTIVE: To evaluate the safety and long-term durability of 1-stage repair of enteric fistulas in the presence of an abdominal wall defect. BACKGROUND: Patients with enteric fistulas and an abdominal wall defect present an extreme challenge to surgeons and have been associated with significant morbidity and mortality. Durability of repair is unknown as studies fail to report this or use limited follow-up periods. METHODS: Chart review was done of consecutive patients who underwent 1-stage repair. Short-term outcomes included morbidity (wound and medical) and mortality. Long-term durability of repair was determined by prospective outpatient follow-up at least 3 years after surgery. RESULTS: Thirty-nine patients were included with a mean age of 61.2 years, a mean BMI of 24.4 kg/m2, and a mean abdominal wall defect size of 247.9 cm2. Component separation technique was used in 34 (87.2%) and synthetic mesh in 13 (33.3%) patients. There was 1 (2.6%) postoperative death. Twenty-four wound complications developed in 18 (46.2%) patients, including surgical-site infection in 8 (20.5%) patients. Two (5.1%) enteric fistulas recurred and were treated conservatively resulting in closure. Medical complications were seen 36 times in 23 (59%) patients. Twelve of 33 (36.4%) living patients developed a recurrent hernia after a mean follow-up of 62.7 months (range: 36-130). CONCLUSIONS: One-stage abdominal wall reconstruction with enteric fistula takedown is feasible at the cost of considerable morbidity. Our treatment strategy including component separation technique with synthetic mesh on-demand results in a durable repair in 6 to 7 of 10 patients.

Radboud Universiteit Nijmegen, 30 april 2015, Promotores : Goor, H. van, Bleichrodt, R.P., Contains fulltext : 140192.pdf (publisher's version ) (Open Access)

Contains fulltext : 138014.pdf (publisher's version ) (Closed access), AIM: External validation and comparison of the diagnostic accuracy of two predictive tools, the emergency department triad and the clinical scoring tool in diagnosing acute diverticulitis. METHODS: Two derivation datasets were used crosswise for external validation. In addition, both tools were validated in a third independent cohort. Predictive values were reassessed and the Area Under the Curve expressed discriminatory capacity. Performance was compared by calculating positive predictive values of the emergency department triad in the validation cohorts and with a cut-off analysis for the clinical scoring tool at a positive predictive value of 90%. RESULTS: Predictive value of the emergency department triad was comparable to the clinical scoring tool. The positive predictive value of the emergency department triad (97%) decreased in the clinical scoring tool cohort (81%) and was excellent in the independent cohort (100%), identifying 24%, 20% and 14% of the patients. A smaller proportion of patients with diverticulitis could be identified with the clinical scoring tool (6%, 19% and 9%). CONCLUSION: The emergency department triad as well as the clinical scoring tool have significant predictive value in external cohorts of patients suspected of diverticulitis. These tools can be used to select patients in whom additional imaging to diagnose acute diverticulitis may be omitted.

Contains fulltext : 137109.pdf (publisher's version ) (Closed access), Background. The lack of pathognomonic findings and the chance of complicated disease have resulted in the widespread use of additional imaging to diagnose acute colonic diverticulitis (ACD). The added value of additional imaging in the diagnostic workup of patients suspected of ACD is not well defined. Aims. The aim of this study was to systematically review the literature of the accuracy of the clinical evaluation and diagnostic modalities for patients with suspected ACD, to come to an evidence-based approach to diagnose ACD. Methods. A systematic review and meta-analysis of studies that reported diagnostic accuracy of the clinical diagnosis and diagnostic modalities in patients with suspected diverticulitis were performed. Study quality was assessed with the STARD checklist. True-positive, true-negative, false-positive, and false-negative findings were extracted and pooled estimates of sensitivity and specificity per diagnostic test were calculated, if applicable. Results. The overall quality of the studies reporting the diagnostic accuracy of the clinical diagnosis, contrast enema and magnetic resonance imaging (MRI) were moderate to poor and not suitable for meta-analysis. Sensitivity of the clinical diagnosis varied between 64% and 68%. Ultrasound (US) and computed tomography (CT) studies were eligible for meta-analysis. Summary sensitivity estimates for US were 90% (95% CI: 76-98%) versus 95% (95% CI: 91-97%) for CT (p = 0.86). Summary specificity estimates for US were 90% (95% CI: 86-94%) versus 96% (95% CI: 90-100%) for CT (p = 0.04). Sensitivity for MRI was 98% and specificity varied between 70% and 78%. Sensitivity of contrast enema studies varied between 80% and 83%. Conclusion. In two-thirds of the patients, the diagnosis of ACD can be made based on clinical evaluation alone. In one-third of the patients, additional imaging is a necessity to establish the diagnosis. US and CT are comparable in diagnosing diverticulitis and superior to other moda

Radboud Universiteit Nijmegen, 4 december 2014, Promotores : Bleichrodt, R.P., Goor, H. van, Contains fulltext : 132073.pdf (publisher's version ) (Open Access), Incisional hernia is by far the most common complication after laparotomies, occurring in 10 – 20%. Its occurrence is secondary to insufficient healing of the postoperative scar, resulting in wound dehiscence and protrusion of abdominal contents through an opening in the musculo-fascial layer of the abdominal wall. The mainstay of treatment for small and simple incisional hernias is the placement non-absorbable synthetic mesh to bridge the defect, the focus of most literature. The current thesis focusses on the more complex cases of incisional hernia. These include parastomal hernias, very large and contaminated hernias. The modes of treatment are more elaborate and patient-tailored, as synthetic bridging usually does not suffice. An autologous method of abdominal wall repair, ‘Component Separation Technique’, was investigated. Large contaminated midline abdominal wall defects can be repaired with this method, but this coincides with a high recurrence rate when synthetic mesh is not additionally used. In contrast with the paradigm that synthetic mesh is contraindicated in contaminated wound environment, it seems that in selected cases this is a safe and durable option for reconstruction, provided modern mesh materials and surgical technique and adequate perioperative measures are taken. The use of more expensive biologic mesh does not result in superior results compared to synthetic mesh, although they may be salvaged more often when infection occurs. For parastomal hernia repair, the Sugarbaker underlay technique is superior to the keyhole technique regarding recurrence rate and also results in low infection rate.

Item does not contain fulltext, INTRODUCTION Adhesion formation is the most common complication following peritoneal surgery and the leading cause of small bowel obstruction, acquired infertility and inadvertent organ injury at reoperation. Using a 'good surgical technique' is advocated as a first step in preventing adhesions. However, the evidence for different surgical techniques to reduce adhesion formation needs confirmation. METHODS Pubmed, Embase and CENTRAL were searched to identify randomized controlled trials that investigated the effect of various aspects of surgical technique on adhesion-related outcomes. Clinical outcomes and incidence of adhesions were the primary endpoints. Identification of papers and data extraction were performed by two independent researchers. RESULTS There were 28 papers with 27 studies included for a systematic review. Of these, 17 studies were eligible for meta-analysis and 11 for qualitative assessment only. None of the techniques that were compared significantly reduced the incidence of adhesive small bowel obstruction. In a small low-quality trial, the pregnancy rate increased after subserous fixation of suture knots. However, the incidence of adhesions was lower after laparoscopic compared with open surgery [relative risk (RR) 0.14; 95% confidence interval (CI): 0.03-0.61] and when the peritoneum was not closed (RR 0.36; 95% CI: 0.21-0.63). CONCLUSIONS None of the specific techniques that were compared reduced the two main adhesion-related clinical outcomes, small bowel obstruction and infertility. The meta-analysis provides little evidence for the surgical principle that using less invasive techniques, introducing less foreign bodies or causing less ischaemia reduces the extent and severity of adhesions.

Item does not contain fulltext, BACKGROUND: Biologic grafts hold promise of a durable repair for ventral hernias with the potential for fewer complications than synthetic mesh. This systematic review was performed to evaluate the effectiveness and safety of biologic grafts for ventral hernia repair. METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for studies on biologic grafts for the repair of ventral hernias. Outcomes are presented as weighted pooled proportions. RESULTS: Twenty-five retrospective studies were included. Recurrence depended on wound class, with an overall rate of 13.8% (95% confidence interval [CI], 7.6-21.3). The recurrence rate in contaminated/dirty repairs was 23.1% (95% CI, 11.3-37.6). Abdominal wall laxity occurred in 10.5% (95% CI, 3.7-20.3) of patients. The surgical morbidity rate was 46.3% (95% CI, 33.3-59.6). Infection occurred in 15.9% (95% CI, 9.8-23.2) of patients but only led to graft removal in 4.9% of cases. CONCLUSIONS: No randomized trials are available to properly evaluate biologic grafts for ventral hernia repair. The current evidence suggests that biologic grafts perform similarly to other surgical options. Biologic grafts are associated with a high salvage rate when faced with infection.

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Radboud Universiteit Nijmegen, 26 april 2012, Promotor : Bleichrodt, R.P. Co-promotores : Goor, H. van, Wilder-Smith, O.H.G., Contains fulltext : 110390.pdf (publisher's version ) (Open Access)

Radboud Universiteit Nijmegen, 13 december 2012, Promotor : Bleichrodt, R.P. Co-promotor : Bremers, A.J.A., Contains fulltext : 100900.pdf (publisher's version ) (Open Access)

Radboud Universiteit Nijmegen, 13 december 2012, Promotor : Bleichrodt, R.P. Co-promotor : Hingh, I.H.J.T. de, Contains fulltext : 100901.pdf (publisher's version ) (Open Access)

1 augustus 2012, Item does not contain fulltext, OBJECTIVES: To establish the incidence and predictive factors of enterotomy made during adhesiolysis in abdominal wall repair and to assess the impact of enterotomies and long-lasting adhesiolysis on postoperative morbidity such as sepsis, wound infection, abdominal complications and pneumonia, and socioeconomic costs. BACKGROUND: Adhesions frequently complicate surgical repair of abdominal wall hernia. Enterotomies made during adhesiolysis specifically have a large impact on morbidity of patients, especially surgical site infections. Little is known on the incidence and burden of enterotomies and long-lasting adhesiolysis in abdominal wall repair. METHODS: Between June 2008 and June 2010 demographics, disease characteristics and perioperative data of all patients undergoing elective abdominal wall repair were included in a prospective cohort study that was focused on adhesiolysis-related problems. A trained researcher observed all surgeries and collected data on adhesion location, tenacity, adhesiolysis time, and inadvertent organ damage such as enterotomies. Primary outcome was the incidence of enterotomy, and predictive factors for enterotomy were assessed through univariate and multivariate analyses. In addition, we evaluated the impact of adhesiolysis and enterotomy on morbidity. RESULTS: A cohort of 133 abdominal wall repairs was analyzed. Adhesiolysis was required in 124 (93.2%), with a mean adhesiolysis time of 35.7 +/- 29.8 minutes. Thirty-three enterotomies were made in 17 patients (12.8%). Two patients had a delayed diagnosed bowel perforation. Adhesiolysis time, hernia size greater than 10 cm, and fistula were significant predictive factors in univariate analysis. In multivariate analysis, only adhesiolysis time was a significant and independent predictive factor for enterotomy (P = 0.004). Trends toward an increased risk were seen for patients with mesh in situ and hernia size greater than 10 cm. Patients with enterotomy had significantly more urgent re

Item does not contain fulltext, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a known method to diagnose inflammatory processes and thus may be a promising imaging technique to detect anastomotic bowel leak. The aim of this study was to assess postoperative FDG uptake in colorectal anastomosis in patients without suspicion of active infection or anastomotic leakage. Patients, methods: Design of a prospective observational pilot study in order to assess normal FDG uptake in the patient anastomosis after colorectal surgery. Patients that underwent colorectal surgery with primary anastomosis received FDG-PET of the abdomen, 2-6 days postoperatively. Results: 35 patients met the inclusion criteria. Three patients were not scanned for various reasons. Of the remaining 32 patients, one demonstrated an increased uptake of FDG at the site of the anastomosis. In the other 31 patients FDG uptake was negligible (n = 17) or scored as physiological (n = 14). None of the scanned patients developed a clinical relevant anastomotic leakage within the first 30 days after surgery. Conclusion: The present study shows that FDG uptake in colorectal anastomosis remains low within the first six days after surgery in patients without anastomotic leakage. Therefore, FDG-PET might be useful to investigate further as a tool to detect anastomotic leakage in an the early postoperative phase.

Radboud Universiteit Nijmegen, 13 april 2012, Promotor : Bleichrodt, R.P. Co-promotores : Hendriks, T., Hingh, I.H.J.T. de, Lemmens, V.E., Contains fulltext : 93554.pdf (publisher's version ) (Open Access)

01 april 2012, Contains fulltext : 109648.pdf (publisher's version ) (Closed access), BACKGROUND: Parastomal hernias are a frequent complication of enterostomies that require surgical treatment in approximately half of patients. This systematic review aimed to evaluate and compare the safety and effectiveness of the surgical techniques available for parastomal hernia repair. METHODS: Systematic review was performed in accordance with PRISMA. Assessment of methodological quality and selection of studies of parastomal hernia repair was done with a modified MINORS. Subgroups were formed for each surgical technique. Primary outcome was recurrence after at least 1-year follow-up. Secondary outcomes were mortality and postoperative morbidity. Outcomes were analyzed using weighted pooled proportions and logistic regression. RESULTS: Thirty studies were included with the majority retrospective. Suture repair resulted in a significantly increased recurrence rate when compared with mesh repair (odds ratio [OR] 8.9, 95% confidence interval [CI] 5.2-15.1; P < 0.0001). Recurrence rates for mesh repair ranged from 6.9% to 17% and did not differ significantly. In the laparoscopic repair group, the Sugarbaker technique had less recurrences than the keyhole technique (OR 2.3, 95% CI 1.2-4.6; P = 0.016). Morbidity did not differ between techniques. The overall rate of mesh infections was low (3%, 95% CI 2) and comparable for each type of mesh repair. CONCLUSIONS: Suture repair of parastomal hernia should be abandoned because of increased recurrence rates. The use of mesh in parastomal hernia repair significantly reduces recurrence rates and is safe with a low overall rate of mesh infection. In laparoscopic repair, the Sugarbaker technique is superior over the keyhole technique showing fewer recurrences.

Item does not contain fulltext, During the treatment of colorectal liver metastases, evaluation of treatment efficacy is of the utmost importance for decision making. The aim of the present study was to explore the ability of preclinical imaging modalities to detect experimental liver metastases. Nine male Wag/Rij rats underwent a laparotomy with intraportal injection of CC531 tumor cells. On days 7, 10, and 14 after tumor induction, sequential positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI) scans were acquired of each rat. At each time point, three rats were euthanized and the metastases in the liver were documented histologically. Topographically, the liver was divided into eight segments and the image findings were compared on a segment-by-segment basis with the histopathologic findings. Sixty-four liver segments were analyzed, 20 of which contained tumor deposits. The overall sensitivity of PET, CT, and MRI was 30%, 25%, and 20%, respectively. For the detection of tumors with a histologic diameter exceeding 1 mm (n = 8), the sensitivity of PET, CT, and MRI was 63%, 38%, and 38%, respectively. The overall specificity of PET, CT, and MRI was 98%, 100%, and 93%, respectively. This study showed encouraging detectability and sensitivity for preclinical imaging of small liver tumors and provides valuable information on the imaging techniques for designing future protocols.

Contains fulltext : 96614.pdf (publisher's version ) (Closed access), OBJECTIVE: The aim of this study was to test the hypothesis that adjuvant radioimmunotherapy (RIT) prevents recurrent liver metastases and/or results in improved survival after tumorectomy in an experimental model. BACKGROUND: Although partial hepatectomy can improve 5-year survival of patients with colorectal liver metastases up to 58%, recurrent tumor growth in the liver occurs frequently. Radioimmunotherapy using radiolabeled monoclonal antibodies directed against tumor-associated antigens is considered most suited for treating minimal residual disease and could therefore serve as an adjuvant after surgery. METHODS: Liver metastases were induced in male Wag/Rij rats by a mini-laparotomy with intrahepatic injection of 0.3 x 106 CC531 tumor cells. The biodistribution of the radiolabeled monoclonal antibody MG1, directed against a 80-kDa cell surface antigen on CC531 tumors, in this model was determined at 1, 3, and 7 days after intravenous administration. The therapeutic efficacy of 177Lu-MG1 was compared with that of a sham antibody (UPC10), labeled with the same activity dose of Lu-177, and saline only. Radioimmunotherapy was administered either at the day of the tumorectomy (day 14 after tumor cell inoculation) or 7 days later. Primary endpoint was survival. RESULTS: Radiolabeled MG1 preferentially accumulated in tumor lesions in the liver reaching a maximum 3 days postinjection (8.7 +/- 0.6% injected dose per gram). Both the administration of 177Lu-MG1 and 177Lu-UPC10 resulted in a transient decrease in body weight. No other signs of clinical discomfort were registered. The survival curves of the group that received 177Lu-UPC10 and the group that received saline only did not differ (P=0.886). Administration of RIT immediately after surgery improved survival compared to administration of the control antibody (hazard ratio [HR], 1.54; P = 0.051), which was even more pronounced when survival was adjusted for the weight of the resected tumor (HR, 1.71; P = 0.027).

9 september 2011, Promotor : Bleichrodt, R.P. Co-promotores : Goor, H. van, Reijnen, M.M.P.J., Contains fulltext : 90827.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, OBJECTIVE: The aim of this study was to assess and compare the diagnostic value of elements of the disease history, physical examination, and routine laboratory tests in patients with suspected acute left-sided colonic diverticulitis (ALCD). BACKGROUND: Misdiagnosis rates for diverticulitis vary in literature between 34% and 68% which needs improvement. Because of the frequent misdiagnosis, liberal use of imaging has been recommended. Before making a plea for routine imaging, the diagnostic accuracy of different variables of disease history, physical examination, and routine laboratory tests needs to be specified. METHODS: All patients seen on the emergency department because of acute abdominal pain suspected of ALCD in whom an abdominal computed tomography was performed, between January 2002 and March 2006, were studied. Univariate logistic regression was used to study differences in patients' characteristics and symptoms, findings at physical examination and routine laboratory tests between patients with and without ALCD. Independent predictors to the risk of ALCD were identified using multivariate logistic regression and used to create a clinical scoring system. RESULTS: Of 1290 patients with acute abdominal pain, 287 patients were eligible for analysis. Acute left-sided colonic diverticulitis was the final diagnosis in 124 patients (43%). Age, 1 or more previous episodes, localization of symptoms in the lower left abdomen, aggravation of pain on movement, the absence of vomiting, localization of abdominal tenderness in the lower left abdomen, and C-reactive protein 50 or more were found to be independent predictors of ALCD. A nomogram was constructed based on these independent predictors with a diagnostic accuracy of 86%. CONCLUSIONS: This study showed that the clinical diagnosis of diverticulitis is difficult to make but can be improved using a clinical scoring system. In case of a high chance of ALCD based on the nomogram, additional imaging may not be needed.

Contains fulltext : 96613.pdf (publisher's version ) (Closed access), PURPOSE: Radiofrequency ablation (RFA) has shown to improve survival in patients not eligible for surgical resection of colorectal liver metastases. However, recurrences after RFA are a major problem. Adjuvant radioimmunotherapy (RIT) after surgical resection of liver metastases has shown to improve survival. The aim of the present study was to test the hypothesis that adjuvant RIT might be an effective way to prevent recurrent liver metastases after RFA in an experimental model. METHODS: Tumours in the liver were induced by intrahepatic injection of 300,000 CC531 cells in male Wag/Rij rats (n = 60). Ten days later, the intrahepatic tumours were treated with RFA. Adjuvant RIT ((177)Lu-labelled monoclonal antibody MG1 at 300 MBq/kg) was administered intravenously either at the day of RFA (day 10) or 7 days later. Control rats received no treatment. Primary endpoint was survival. RESULTS: Administration of (177)Lu-MG1 resulted in a transient decrease in body weight, compared to no adjuvant treatment. However, no other signs of clinical discomfort were registered. Log rank test showed that the survival curves of the groups treated with RIT, either at day 10 or day 17, did not differ significantly from the survival curve of the rats that did not receive adjuvant treatment (P = 0.902). CONCLUSION: This study shows that adjuvant RIT does not increase survival after RFA of colorectal liver metastases in rats.

Contains fulltext : 95886.pdf (publisher's version ) (Closed access), BACKGROUND: Radioimmunotherapy (RIT) has been shown to reduce the incidence of local recurrence of colorectal cancer in an experimental model. The aim of the present study was to investigate the survival benefit of RIT compared with chemotherapy. METHODS: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of CC531 tumour cells. The therapeutic efficacy of (177) Lu-labelled MG1 (single intravenous dose of 300 MBq/kg, n = 20) was compared with that of 5-fluorouracil-based chemotherapy (6 weekly cycles administered intraperitoneally, n = 20) and no treatment (n = 20). The primary endpoint was survival. Toxicity was monitored by bodyweight measurement. RESULTS: Both chemotherapy and RIT affected bodyweight, but the weight of animals in the RIT group remained significantly higher than in the chemotherapy group (median slope of bodyweight plot 0.48 versus 0.30 g/day; P < 0.001). Kaplan-Meier analysis showed that overall survival in the RIT and chemotherapy groups was significantly better than that in the control group (50 and 46 per cent versus 25 per cent respectively after 170 days; P = 0.024 and P = 0.029). Survival after treatment with RIT did not differ from that after chemotherapy (P = 0.911). CONCLUSION: RIT is as effective as chemotherapy in experimental colorectal cancer.

Item does not contain fulltext, OBJECTIVE: Hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C can improve survival if used as an adjunct to cytoreductive surgery (CS) for treatment of peritoneal carcinomatosis (PC). It remains unclear if both hyperthermia and chemotherapy are essential for the reported survival benefit. METHODS: Eighty WAG/Rij rats were inoculated intraperitoneally with the rat colon carcinoma cell line CC-531. Animals were randomly assigned to 1 of the 4 treatment groups (n = 20): CS only, CS followed by HIPEC (mitomycin 35 mg/m(2) at 41 degrees C), CS followed by intraperitoneal mitomycin perfusion at 37 degrees C, CS followed by intraperitoneal saline perfusion at 41 degrees C. Survival was the primary outcome with a maximum follow up of 126 days. RESULTS: Median survival was 62 days in rats treated with CS only and 57 days in rats treated with CS followed by hyperthermic saline perfusion. Rats receiving HIPEC had a median survival of 121 days (P = 0.022 when compared with CS only). In the group treated with chemotherapy at 37 degrees C, 13 of 20 animals were still alive at the end of the experiment so median survival was not reached. (CS vs. IPEC: P = 0.002, hazard ratio 0.36, 95% CI 0.19-0.69) Rats treated with hyperthermic saline perfusion did not have an increased survival as compared with CS only. CONCLUSIONS: The effectiveness of intraoperative intraperitoneal perfusion after CS is highly dependent on the presence of chemotherapeutic agents in the perfusate but not on hyperthermia. The need to include hyperthermia in the adjuvant intraoperative treatment after CS for PC should be further investigated.

Item does not contain fulltext, BACKGROUND: Enhanced recovery after surgery programs have been developed to improve recovery, shorten hospital stays, and reduce morbidity. OBJECTIVE: The aim of the current study was to examine the effects of the enhanced recovery program on the outcome of rectal surgery. DESIGN: A cohort of patients who underwent open rectal surgery after an enhanced recovery program was compared with a historic case-matched control group receiving conventional perioperative care. Patients were matched for type of surgery, disease, comorbidity, and demographic characteristics. Data regarding fast-track targets, length of hospital stay, mortality, complications, relaparotomies, and readmissions were collected. RESULTS: Forty-one patients in the enhanced recovery group were compared with 82 case-matched patients receiving conventional care. The length of hospital stay (median: 8 days vs 12 days, P < .005) was reduced in the enhanced recovery after surgery group. There were no significant differences in epidural use, mortality, morbidity, and readmission rates between groups. LIMITATIONS: This study performed an intention-to-treat analysis for the multimodal enhanced recovery program in rectal surgery. Specific elements of the program were not analyzed separately. The study used nonrandomly assigned historic controls for comparison. CONCLUSION: Enhanced recovery after surgery programs help to reduce the length of hospital stay after rectal surgery.

Contains fulltext : 97239.pdf (publisher's version ) (Open Access), BACKGROUND: Preoperative risk prediction to assess mortality and morbidity may be helpful to surgical decision making. The aim of this study was to compare mortality and morbidity of colorectal resections performed in a tertiary referral center with mortality and morbidity as predicted with physiological and operative score for enumeration of mortality and morbidity (POSSUM), Portsmouth POSSUM (P-POSSUM), and colorectal POSSUM (CR-POSSUM). The second aim of this study was to analyze the accuracy of different POSSUM scores in surgery performed for malignancy, inflammatory bowel diseases, and diverticulitis. POSSUM scoring was also evaluated in colorectal resection in acute vs. elective setting. In procedures performed for malignancy, the Association of Coloproctology of Great Britain and Ireland (ACPGBI) score was assessed in the same way for comparison. METHODS: POSSUM, P-POSSUM, and CR-POSSUM predictor equations for mortality were applied in a retrospective case-control study to 734 patients who had undergone colorectal resection. The total group was assessed first. Second, the predictive value of outcome after surgery was assessed for malignancy (n = 386), inflammatory bowel diseases (n = 113), diverticulitis (n = 91), and other indications, e.g., trauma, endometriosis, volvulus, or ischemia (n = 144). Third, all subgroups were assessed in relation to the setting in which surgery was performed: acute or elective. In patients with malignancy, the ACPGBI score was calculated as well. In all groups, receiver operating characteristic (ROC) curves were constructed. RESULTS: POSSUM, P-POSSUM, and CR-POSSUM have a significant predictive value for outcome after colorectal surgery. Within the total population as well as in all four subgroups, there is no difference in the area under the curve between the POSSUM, P-POSSUM, and CR-POSSUM scores. In the subgroup analysis, smallest areas under the ROC curve are seen in operations performed for malignancy, which is significantl