Mechanical and oral antibiotic bowel preparation versus no bowel preparation in right and left colectomy: subgroup analysis of MOBILE trial.

BACKGROUND: In retrospective series, mechanical and oral antibiotic bowel preparation (MOABP) has been reported to reduce surgical-site infections (SSIs) after colectomy compared with no bowel preparation (NBP). METHOD: This was a subgroup analysis of a multicentre randomized trial that included patients scheduled for elective colectomy. The MOABP group underwent mechanical bowel preparation, and took 2 g neomycin and 2 g metronidazole orally during the day before surgery. The NBP group did not undergo bowel preparation. Patients were categorized according to the side of resection (right versus left colectomy), and these subgroups compared for postoperative outcomes. RESULTS: Among 217 patients undergoing right colectomy (106 in MOABP and 111 in NBP group), SSI was detected in seven (7 per cent) and 10 (9 per cent) patients (odds ratio (OR) 0.71, 95 per cent c.i. 0.26 to 1.95; P = 0.510), anastomotic dehiscence in two (2 per cent) and two (2 per cent) patients (OR 1.05, 0.15 to 7.58; P = 1.000), and the mean(s.d.) Comprehensive Complication Index (CCI) score was 9.4(12.9) and 10.5(18.0) (mean difference -1.09; 95 per cent c.i. -5.29 to 3.11; P = 0.608) in the MOABP and NBP groups respectively. Among 164 patients undergoing left colectomy (84 in MOABP and 80 in NBP group), SSI was detected in five (6 per cent) and eight (10 per cent) patients (OR 0.57, 0.18 to 1.82; P = 0.338), anastomotic dehiscence in four (5 per cent) and five (6 per cent) patients (OR 0.75, 0.19 to 2.90; P = 0.742), and the CCI score was 10.2(13.1) and 6.5(11.0) (mean difference 3.68, -0.06 to 7.42; P = 0.053) in the MOABP and NBP groups respectively. CONCLUSIONS: MOABP did not decrease the rate of SSI or complications in patients undergoing either right or left colectomy compared with NBP.

Virtual reality simulator training of laparoscopic cholecystectomies - a systematic review.

BACKGROUND AND AIMS: Simulators are widely used in occupations where practice in authentic environments would involve high human or economic risks. Surgical procedures can be simulated by increasingly complex and expensive techniques. This review gives an update on computer-based virtual reality (VR) simulators in training for laparoscopic cholecystectomies. MATERIALS AND METHODS: From leading databases (Medline, Cochrane, Embase), randomised or controlled trials and the latest systematic reviews were systematically searched and reviewed. Twelve randomised trials involving simulators were identified and analysed, as well as four controlled studies. Furthermore, seven studies comparing black boxes and simulators were included. RESULTS: The results indicated any kind of simulator training (black box, VR) to be beneficial at novice level. After VR training, novice surgeons seemed to be able to perform their first live cholecystectomies with fewer errors, and in one trial the positive effect remained during the first ten cholecystectomies. No clinical follow-up data were found. Optimal learning requires skills training to be conducted as part of a systematic training program. No data on the cost-benefit of simulators were found, the price of a VR simulator begins at EUR 60 000. CONCLUSIONS: Theoretical background to learning and limited research data support the use of simulators in the early phases of surgical training. The cost of buying and using simulators is justified if the risk of injuries and complications to patients can be reduced. Developing surgical skills requires repeated training. In order to achieve optimal learning a validated training program is needed.

Randomized comparison of self-fixating and sutured mesh in open inguinal hernia repair.

BACKGROUND: Chronic groin pain after mesh repair of inguinal hernia has been attributed to the presence of sutures. METHODS: This randomized clinical trial compared inguinal hernia repair using a self-fixating composite mesh or a sutured lightweight mesh, with pain at 1 year as primary outcome. Patients completed a self-evaluation questionnaire at 2 weeks and were examined after 1 year. RESULTS: Some 198 patients received self-fixating mesh and 196 sutured mesh. There were no differences between the groups in mean pain scores measured on a visual analogue scale during 2 weeks of immediate convalescence or at 1 year. Chronic pain and discomfort was experienced by 36.3 per cent of patients in the self-fixating and 34.1 per cent in the sutured mesh group (P = 0.658), affecting the everyday life of 1.1 and 2.8 per cent respectively (P = 0.448). CONCLUSION: Open inguinal hernia repair with a composite self-fixating mesh resulted in similar pain in the early postoperative convalescence period and at 1 year as repair with a sutured lightweight mesh.

Late mesh migration through the stomach wall after laparoscopic refundoplication using a dual-sided PTFE/ePTFE mesh.

We report a rare complication after laparoscopic fundoplication using a dual-sided PTFE/ePTFE (Bard® Crurasoft™) mesh fixation. A 53-year-old man was re-operated for a recurrent hiatal hernia. The hiatal hernia was reinforced using a mesh. Two years later, the patient presented with serious dysphagia and weight loss. An endoscopy revealed a migrated mesh in the stomach. The mesh was excreted within the stool without notice. The PTFE/ePTFE mesh, which is designed for treating hiatal defects, is considered to have superior tissue incorporation, together with less adhesion formation and fistulation. As mesh migration into the upper gastrointestinal tract is possible, it should be used with great care in the peri-oesophageal region.

Smoking increases the incidence of complicated diverticular disease of the sigmoid colon.

BACKGROUND AND AIMS: The aim of this study was to establish whether smoking is associated with complicated diverticular disease and adverse outcomes of operative treatment of diverticular disease. Smoking has been associated with increased rate of perforations in acute appendicitis as well as failure of colonic anastomosis in patients resected for colonic tumours. It has also been suggested that smoking is a risk factor for complicated diverticular disease of the colon. MATERIAL AND METHODS: Retrospective investigation of records of 261 patients electively operated for diverticular disease in Helsinki University Central Hospital during a period of five years. RESULTS: The smokers underwent sigmoidectomy at a younger age than the non-smokers (p = 0.001) and they had an increased rate of perforations (p = 0.040) and postoperative recurrent diverticulitis episodes (p = 0.019). CONCLUSIONS: We conclude that smoking increases the likelihood of complications in diverticulosis coli. The development of complicated disease also seems to proceed more rapidly in smokers.Key words: Sigmoid resection; laparoscopy; laparoscopic sigmoidectomy; smoking and diverticular disease; complicated diverticular disease; diverticulitis.

Laparoscopic cholecystectomy with carbon dioxide pneumoperitoneum is safe even for high-risk patients.

BACKGROUND: Because of absorbed carbon dioxide (CO(2)) and elevated intraabdominal pressure (IAP), CO(2) pneumoperitoneum (CO(2)PP) has potentially harmful intraoperative circulatory and ventilatory effects. Although not clinically significant for healthy patients, these effects are assumed to be deleterious for patients with a high risk for anesthesia (American Society of Anesthesiology [ASA] 3 and 4) and significant cardiopulmonary, renal, or hepatic diseases. The authors assessed CO(2)PP-related adverse effects by comparing ASA 3 and 4 patients who underwent laparoscopic cholecystectomy (LC) with or without CO(2)PP. METHODS: A total of 20 successive ASA 3 and 4 patients who underwent LC were randomized into CO(2)PP (n = 10) and abdominal wall elevator (Laparolift) (n = 10) groups. The parameters for perioperative hemodynamics, ventilation, perfusion of intraabdominal organs, and blood chemistry were recorded periodically from before the induction of the anesthesia until postoperative day 2 and compared between the groups. RESULTS: Mean age, height, weight, the proportional number of ASA 3 vs ASA 4 patients, the volume of perioperative fluid loading, and the dose of analgesics did not differ significantly between the groups. The length of the operation was 49.9 +/- 10.6 min for the CO(2)PP group and 50.6 +/- 17.2 min for Laparolift group (nonsignificant difference). The mean central venous pressure (CVP) 30 min after insufflation was higher (12.3 +/- 4.8 vs 7.9 +/- 3.7 mmHg) and the (Gastric Mucosal pH) pHi at the end of the operation was lower (7.29 +/- 0.07 vs 7.35 +/- 0.04) in the CO(2)PP group than in the Laparolift group (p < 0.05). Later, CVP and pHi did not differ significantly. Other parameters of hemodynamics including oxygenation, perfusion, and blood chemistry did not differ significantly. CONCLUSIONS: For LC for patients with an ASA 3 and 4 risk for anesthesia, no significant adverse effects could be attributed to CO(2 )pneumoperitoneum. For high-risk patients, preoperative preparation and active perioperative monitoring are essential for safe anesthesia for LC with or without CO(2)PP.

Laparoscopic rectal prolapse surgery combined with short hospital stay is safe in elderly and debilitated patients.

BACKGROUND: We report the results of patients treated from January 2000 to June 2004 for full-thickness rectal prolapse with trans-abdominal surgery in Helsinki. METHODS: Sixty-five of 75 patients were treated laparoscopically, with a 6% conversion rate. Ten patients were operated on openly. Half of the patients were scored as American Society for Anesthesiologists III or IV. RESULTS: The operation time was similar in the laparoscopic and the open rectopexy procedures (p = 0.15), whereas laparoscopic resection rectopexy was more time-consuming compared to the open procedure (p = 0.007). Intraoperative bleeding during laparoscopic surgery was minimal in comparison to open surgery (p = 0.006). Patients treated laparoscopically had a shorter median hospital stay than those treated with an open procedure (rectopexy, 3 and 7 days, respectively; resection rectopexy, 4 and 7.5 days, respectively) (p < 0.00001). There was no mortality and minor morbidity. During follow-up, there were two prolapse recurrences. All surgical techniques improved fecal continence considerably. Eighty-four percent of rectopexy patients and 92% of resection rectopexy patients considered the surgical outcome to be excellent or good. CONCLUSIONS: Both rectopexy and resection rectopexy cure prolapse with good results and can be performed safely in older and debilitated patients. The laparoscopic approach enables a shortened hospital stay and is well tolerated in elderly patients.

Validation of the interleukin-10 knockout mouse model of colitis: antitumour necrosis factor-antibodies suppress the progression of colitis.

Advances in understanding pathogenesis and developing new therapies are hastened by the use of effective animal models of disease. In inflammatory bowel disease, such as Crohn's disease, a variety of models have been used, including the IL-10 knockout mouse. However, in order to be truly valuable, the models need to respond to existing therapy in a way which resembles the human disease. In the light of recent developments, in which refractory Crohn's disease responds well to anti-TNF antibody therapy, we set out to validate the IL-10 knockout model of Crohn's disease by examining its response to anti-TNF therapy. We developed a new scoring system for IL-10 knockout mice, similar to the Crohn's Disease Activity Index in humans, analysed stool samples for cytokines and compared the findings with histology. We found that anti-TNF antibody therapy starting at 4 weeks markedly ameliorated the disease, as judged by the clinical score or by histological analysis of the gut. Furthermore, analysis of stool samples for cytokines revealed a marked diminution of inflammatory cytokines, adding a further accurate measure of the improvement. This model may thus be useful for evaluating other therapeutic modalities of relevance to Crohn's disease.

Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis.

INTRODUCTION: Interleukin 10 knockout (IL-10-/-) mice spontaneously develop a Th1 T cell mediated colitis with many similarities to Crohn's disease. Daily injections of IL-10 are unable to induce remission in mice with established disease. In contrast, we have shown previously that intravenous administration of adenoviral vectors encoding IL-10 (AdvmuIL-10) induces hepatic IL-10 release and leads to long term disease suppression with profound systemic immunoregulatory changes. AIMS: To determine whether rectal delivery of AdvmuIL-10 induces localised colonic IL-10 expression without systemic immune suppression, and assess its therapeutic efficacy in IL-10-/- mice with established colitis. RESULTS: A single rectal infusion of 5 x 10(8) PFU AdvmuIL-10 to 10 week IL- 10-/- mice resulted in a median level of 27.3 pg/mg IL-10 in colonic homogenates harvested one week later. IL-10-/- mice with established colitis treated with an enema of 5 x 10(8) PFU AdvmuIL-10 entered clinical and histological remission whereas empty cassette adenovirus (Adv0) or phosphate buffered saline (PBS) treated mice developed progressive disease. After four weeks, the histological score of AdvmuIL-10 treated mice (4.4 (1.5)) was significantly lower than that of Adv0 (11.1 (1.1); p<0.001) and PBS (10.9 (1.0); p<0.01) treated controls. In addition, the stool concentration of IL-1beta over the four week experiment was significantly higher in mice treated with saline or Adv0 than in those treated with AdvmuIL-10 (p<0.01). CONCLUSION: Local AdvmuIL-10 therapy reverses colitis in IL-10-/- mice without the systemic effects seen after intravenous administration. Gene therapy strategies using adenoviral vectors encoding immunoregulatory cytokines may prove to be a potent approach to the treatment of chronic inflammatory diseases such as Crohn's disease.

Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis.

INTRODUCTION: Interleukin 10 knockout (IL-10-/-) mice spontaneously develop a Th1 T cell mediated colitis with many similarities to Crohn's disease. Daily injections of IL-10 are unable to induce remission in mice with established disease. In contrast, we have shown previously that intravenous administration of adenoviral vectors encoding IL-10 (AdvmuIL-10) induces hepatic IL-10 release and leads to long term disease suppression with profound systemic immunoregulatory changes. AIMS: To determine whether rectal delivery of AdvmuIL-10 induces localised colonic IL-10 expression without systemic immune suppression, and assess its therapeutic efficacy in IL-10-/- mice with established colitis. RESULTS: A single rectal infusion of 5 x 10(8) PFU AdvmuIL-10 to 10 week IL-10-/- mice resulted in a median level of 27.3 pg/mg IL-10 in colonic homogenates harvested one week later. IL-10-/- mice with established colitis treated with an enema of 5 x 10(8) PFU AdvmuIL-10 entered clinical and histological remission whereas empty cassette adenovirus (Adv0) or phosphate buffered saline (PBS) treated mice developed progressive disease. After four weeks, the histological score of AdvmuIL-10 treated mice (4.4 (1.5)) was significantly lower than that of Adv0 (11.1 (1.1); p<0.001) and PBS (10.9 (1.0); p<0.01) treated controls. In addition, the stool concentration of IL-1 beta over the four week experiment was significantly higher in mice treated with saline or Adv0 than in those treated with AdvmuIL-10 (p<0.01). CONCLUSION: Local AdvmuIL-10 therapy reverses colitis in IL-10-/- mice without the systemic effects seen after intravenous administration. Gene therapy strategies using adenoviral vectors encoding immunoregulatory cytokines may prove to be a potent approach to the treatment of chronic inflammatory diseases such as Crohn's disease.

The prevention and treatment of murine colitis using gene therapy with adenoviral vectors encoding IL-10.

IL-10-deficient (IL-10(-/-)) mice develop colitis with many similarities to Crohn's disease. Daily IL-10 injections have a short systemic half-life and are unable to induce complete remission in IL-10(-/-) mice with established disease. In this paper, we investigate the duration, potency, and immunogenicity of gene therapy using an adenoviral vector encoding murine IL-10 (AdvmuIL-10). A single systemic injection of AdvmuIL-10 was sufficient not only to prevent the onset of colitis for at least 10 wk but also to induce clinical and histological remission in mice with established disease. In addition, AdvmuIL-10 diminished the systemic manifestations of disease, including elevated acute-phase proteins, as well as the local consequences of inflammation such as raised stool IL-1beta concentrations. Both IL-10 protein and the effects of secreted IL-10 were detectable for 10 wk after AdvmuIL-10 injection. Furthermore, the immunoregulatory effect of a single AdvmuIL-10 injection was manifest both by a reduction in TNF-alpha, IFN-gamma, and RANTES release from stimulated splenocyte cultures, and also by a change in the proportion of CD45RB(high/low) lymphocytes in the spleen compared with control mice. The delivery of AdvmuIL-10 resulted in a significantly diminished host antiadenoviral response compared with control adenoviral vectors. Thus, gene therapy strategies using adenoviral vectors encoding immunoregulatory and antiinflammatory cytokines may prove to be a potent approach for the treatment of chronic inflammatory disease. Antiinflammatory cytokine expression protects against immune responses directed at gene vectors.

Laparoscopic repair of rectal prolapse: a prospective study evaluating surgical outcome and changes in symptoms and bowel function.

BACKGROUND: There have been few large series that have focused on the feasibility of the laparoscopic approach for rectal prolapse. This single-institution study prospectively examines the surgical outcome and changes in symptoms and bowel function following the laparoscopic repair of rectal prolapse. METHODS: In a selected group of 34 patients (total prolapse, 28; intussusception, six), 17 patients underwent laparoscopic-assisted resection rectopexy and 17 patients received a laparoscopic sutured rectopexy. Preoperative and postoperative evaluation at 3, 6, and 12 months included assessment of the severity of anal incontinence, constipation, changes in constipation-related symptoms, and colonic transit time. RESULTS: Median operation time was 255 min (range, 180-360) in the resection rectopexy group and 150 min (range, 90-295) in the rectopexy alone group. Median postoperative hospital stay was 5 days (range, 3-15) and median time off work was 14 days (range, 12-21) in both groups. There were no deaths. Postoperative morbidity was 24%. Incontinence improved significantly regardless of which method was used. The main determinant of constipation was excessive straining at defecation. Constipation was cured in 70% of the patients in the rectopexy group and 64% in the resection rectopexy group. Symptoms of difficult evacuation improved, but the changes were significant only after resection rectopexy. Two patients (7%) developed recurrent total prolapse during a median follow-up of 2 years (range 12-60 months). CONCLUSIONS: Laparoscopic-sutured rectopexy and laparoscopic-assisted resection rectopexy are feasible and carry an acceptable morbidity rate. They eliminate prolapse and cure incontinence in the great majority of patients. Constipation and symptoms of difficult evacuation are alleviated.

Decreased expression of protectin (CD59) in gut epithelium in ulcerative colitis and Crohn's disease.

Without adequate protection, the cells of the human body would be susceptible to destruction by the complement system. The main defense against complement lysis is a molecule called protectin (CD59) that is widely distributed in human tissues. Because the complement system has been suggested to be involved in the pathogenesis of inflammatory bowel diseases, we examined the expression of protectin in the colonic epithelium of patients with ulcerative colitis or Crohn's disease and controls. Colorectal specimens from 6 patients with ulcerative colitis, 8 patients with Crohn's disease, and 4 controls were obtained from surgical resections. Frozen sections of the specimens were immunostained for protectin using the Bric 229 monoclonal antibody. The expression of protectin was found to be decreased in the epithelium of patients with ulcerative colitis. In patients with Crohn's disease, the epithelial expression of protectin was decreased in diseased areas of gut while the expression did not significantly differ from that in controls in macroscopically normal areas. There was no difference in the expression of protectin on vascular endothelium, mononuclear cells, or smooth muscle. The reduction in epithelial expression of protectin in patients with ulcerative colitis or Crohn's disease may render epithelial cells vulnerable to complement lysis and lead to the destruction of gut epithelium as seen typically in these diseases.

Effect of temperature of insufflated CO2 during and after prolonged laparoscopic surgery.

BACKGROUND: Pneumoperitoneum with room temperature carbon dioxide (CO2) has been shown to decrease core temperature and urine output. METHODS: The effect of 37 degrees C (warm) and room temperature (cool) CO2 pneumoperitoneum on core temperature, urine output, and central hemodynamics was compared in 26 randomized patients undergoing prolonged laparoscopic surgery (>90 min). RESULTS: The core temperature (p < 0.05) and cardiac index (p < 0.05) were significantly higher after warm than after cool pneumoperitoneum. Urine output was significantly higher during warm (2.3 +/- 1.6 ml/kg/h) than during cool (0.9 +/- 0.7 ml/kg/h) insufflation (p < 0. 05). Two of 13 patients with warm and 11 of 13 patients with cool pneumoperitoneum needed mannitol to maintain adequate diuresis (p < 0.05). CONCLUSIONS: Warm insufflation probably causes a local vasodilation in the kidneys and may be beneficial to patients with borderline renal function.

Number of activated T-helper cells and NK cells in peripheral blood is decreased in severe Crohn's disease.

Monoclonal antibodies and flow cytometry were used to analyse the proportions of T-cell subsets and NK cells in blood of patients (n = 45) with Crohn's disease. In patients with severe activity disease decreased numbers of activated (CD25+CD4+) T-helper cells and NK (CD16+CD56+) cells were found, while in patients with low activity disease the numbers of activated T-helper cells were increased and the numbers of NK cells were similar to those in normal controls. Thus, 8% of T cells were CD25+CD4+ and 16% of mononuclear cells were CD16+CD56+ in patients with severe disease. In patients with quiescent disease, 11% of T cells were CD25+CD4+ and 26% of mononuclear cells were CD16+CD56+. The results suggest that disease activity may be reflected in the proportions of blood circulating mononuclear cells, perhaps because of accumulation of CD25+CD4+ T-helper cells and NK cells in the affected tissue during exacerbation of the disease.

Islet cell and glutamic acid decarboxylase antibodies and heat-shock protein 65 responses in children with newly diagnosed insulin-dependent diabetes mellitus.

Islet cell antibodies (ICA) were detected in 66% and glutamic acid decarboxylase (GAD) antibodies in 64% of children (n = 47) with newly diagnosed insulin-dependent diabetes mellitus (IDDM). Fifteen percent of the patients had neither GAD nor ICA antibodies. Responses to mycobacterial heat-shock protein 65 (Hsp65) were detected in all patients. There was a significant correlation between anti-GAD antibodies and proliferation of peripheral blood mononuclear cells to Hsp65, and between ICA and antibodies to Hsp65.