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Current guidelines recommend radical resection for stage I rectal cancer. However, since screening programs are being installed, an increasing number of cancers are being detected in early stages. Endoscopic resection is often performed at the time of diagnosis. This systematic review was undertaken to review the evidence on endoscopic approach vs. radical resection for stage I rectal cancer. Recommendations were issued based on the GRADE methodology and risk stratification used in clinical practice. A systematic search (until March 2015) identified 2 meta-analyses and 1 additional randomized trial. For the primary outcomes (overall survival, disease-free survival, local recurrence-free survival and metastasis-free survival) no evidence could be found on the superiority of local or radical resection. Secondary outcomes (blood loss, hospital stay, operative time, number of permanent stomas and perioperative deaths) were in favour of local resection. The authors strongly recommend radical resection for T2 rectal cancer, but consider 'en bloc' local resection sufficient for pT1 sm1 rectal cancers when confirmed pathologically. Discussion by a multidisciplinary team and adequate surveillance remain mandatory., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Adequate estimation of the potential benefits of 'adjuvant' hyperthermia and intraperitoneal chemotherapy (HIPEC) in T4 patients through assessment of the burden of peritoneal carcinomatosis (PC) in T4 tumors and the risk of PC as the only metastatic site., Patients and Methods: Analysis of prospectively collected data on patients who underwent surgery for colon cancer (Jan 2004-Jan 2007)., Results: About 379 patients (M/F = 204/175) were included, with a median age of 71.8 years (range 35.4-95.0): 39 stage I, 126 stage II, 89 stage III, 116 stage IV disease (+9 with unknown stage). The median follow-up was 34.8months [range 0.0-79.4]. The 3- and 5-year overall survival rates (OS) were 68.4% (95% confidence interval (CI) 63.9%-72.4%) and 60.3% (95%CI 55.6%-64.7%). Relapse analysis was restricted to stages II-III T3 (N = 154) and T4 tumors (N = 19) with complete relapse data, of which 13.2% developed PC. PC has a detrimental effect on OS [HR 6.3 (95%CI: 3.1-13.0, P < 0.0001)]. 50% of T4a and 20% of T4b developed PC. The 1- and 3-year PC percentage was significantly lower for T3 (4.5% and 9.3%) than T4 tumors (15.6% and 36.7%) (P = 0.008). PC was the only metastatic site in 3/15 T3 [proportion 0.20, 95%CI (0.043-0.481)] and 5/8 T4 tumors with PC [proportion 0.625, 95%CI (0.245-0.915)] (P = 0.071)., Conclusions: T4a colon tumors have a significantly higher risk of developing PC. Twenty-five percent (5/19) of stages II-III T4 tumors develop PC as the only metastatic site. This could define the possible window of opportunity for adjuvant HIPEC to prevent PC.

Quality of health care is a hot topic, especially with regard to cancer. Although rectal cancer is, in many aspects, a model oncologic entity, there seem to be substantial differences in quality of care between countries, hospitals and physicians. PROCARE, a Belgian multidisciplinary national project to improve outcome in all patients with rectum cancer, identified a set of quality of care indicators covering all aspects of the management of rectal cancer. This set should permit national and international benchmarking, i.e. comparing results from individual hospitals or teams with national and international performances with feedback to participating teams. Such comparison could indicate whether further improvement is possible and/or warranted.

Background: Laparoscopic segmental bowel resection and reanastomosis for endometriosis with colorectal wall invasion can be associated with high complication rates. This study was performed to test the hypothesis that this high complication rate can be prevented and combined with a good clinical outcome, following a multidisciplinary surgical approach., Methods: A retrospective cohort study of all patients with deep endometriosis and colorectal invasion treated by CO₂ laser laparoscopic radical excision between September 2004 and September 2006 (n = 45) to document the clinical outcome: complications, recurrence and fertility (life table analysis), pain, quality of life (QOL) and sexual function., Results: No immediate major post-operative complications requiring surgical reintervention were recorded. Gynaecological pain (P < 0.0001), sexual function (P < 0.03) and QOL (P< 0.0001), improved significantly after a median follow-up period of 27 (range: 16-40) months. Although five patients (11%) had a surgical reintervention, histologically proven recurrent endometriosis was observed in only two (4%), with a cumulative endometriosis recurrence rate of 2.2 and 4.4% after 1 and 3 years, respectively. Thirteen of 28 patients who wanted to become pregnant conceived after surgery. One patient delivered twice. These 14 pregnancies were achieved spontaneously (n = 9) or after IVF (n = 5). The cumulative pregnancy rate was 47% after 3 years., Conclusion: Pain, sexual function and QOL improved significantly and were associated with a good fertility rate and a low complication and recurrence rate after a CO₂ laser laparoscopic radical excision of endometriosis with colorectal wall invasion combined with laparoscopic segmental bowel resection and reanastomosis.

Background: Multidisciplinary laparoscopic treatment is the standard of care for radical treatment of deep infiltrating pelvic endometriosis. If bowel resection is necessary, a muscle-split or Pfannenstiel incision is also required. The avoidance of any laparotomy could decrease surgical stress response, give a faster return to normal bowel function, decrease post-operative pain and reduce wound complications and incisional hernias. We assessed post-operative outcome after a full laparoscopic sigmoid resection for bowel endometriosis., Patients and Methods: Twenty-one patients who underwent elective full laparoscopic sigmoid resection for bowel endometriosis from September 2009 to September 2010 were matched for age, American Society of Anesthesiologists class and BMI to 21 patients who underwent a conventional laparoscopic sigmoid resection. Groups were compared for peri-operative factors, complications, length of hospital stay, post-operative pain (Visual Analog Scale: VAS), analgesics consumption and inflammatory response (plasma C-reactive protein: CRP)., Results: Median operating time was 15 min shorter with transrectal specimen extraction (P = 0.003). VAS-scores and use of analgesics were higher in the conventional laparoscopic group (P = 0.0005). Mean CRP-level tended to be higher in the transrectal specimen extraction group (38%, P = 0.054) but there was no difference in increase in CRP level between groups (P = 0.15). There were no anastomotic leaks or reinterventions in either group, and the median hospital stay was similar. At follow-up, no wound infections or incisional hernias were observed and no patients reported anal dysfunction., Conclusion: Full laparoscopic sigmoid resection reduced operating times and decreased post-operative VAS-scores and analgesic requirements compared with the conventional laparoscopic sigmoid resection for bowel endometriosis.

Background: Treatment of colorectal endometriosis is difficult and challenging. We reviewed the clinical outcome of surgical treatment of deeply infiltrating endometriosis (DIE) with colorectal involvement., Methods: Review was based upon a literature search using following search terms: (1) 'surgery' and 'colorectal endometriosis', (2) 'bowel' and 'endometriosis' and 'surgery'., Inclusion Criteria: clear explanation of surgical technique and follow-up data on at least one of the following items: complications, pain, quality of life (QOL), fertility and recurrence., Results: Most of the 49 studies included complications (94%) and pain (67%); few studies reported recurrence (41%), fertility (37%) and QOL (10%); only 29% reported (loss of) follow-up. Out of 3894 patients, 71% received bowel resection anastomosis, 10% received full-thickness disc excision and 17% were treated with superficial surgery. Comparison of clinical outcome between different surgical techniques was not possible. Post-operative complications were present in 0-3% of the patients. Although pain improvement was reported in most studies, pain evaluation was patient-based in <50% (Visual Analogue Scale in only 18%). While QOL was improved in most studies, prospective data were only available for 149 patients. Pregnancy rates were 23-57% with a cumulative pregnancy rate of 58-70% within 4 years. The overall endometriosis recurrence rate in studies (>2 years follow-up) was 5-25% with most of the studies reporting 10%. Owing to highly variable study design and data collection, a CONSORT-inspired checklist was developed for future studies., Conclusions: Prospective studies reporting standardized and well-defined clinical outcome after surgical treatment of DIE with colorectal involvement with long-term follow-up are needed.

Protein-losing enteropathy (PLE) is a rare but severe complication of Crohn's disease (CD) and hypoalbuminemia can be one of the presenting symptoms of this illness. The diagnosis of PLE can only be made after exclusion of malnutrition and liver or kidney failure. Significant intestinal leakage can be caused by mucosal injury, increased lymphatic pressure or dilated lymphatics and has been reported in a large number of diseases. The protein-losing can be diagnosed by assessing the excretion of different radiolabeled macromolecules in the faeces or by the clearance of alpha-1-antitrypsine in stools. The primary approach should be the optimization of the nutritional status. Medical treatment of the underlying disease is primordial. In other cases surgical resection of the most affected areas is inevitable. We report a case of a 21-year-old male with a 4 year history of CD, who developed significant hypoproteinemia with pitting oedema, initially in the absence of any other sign of severe disease activity. A "Cr-chloride albumin excretion confirmed our hypothesis of protein-losing enteropathy. Because of sub-obstruction signs some months later, a laparotomy was performed which revealed a severely affected loop with dilatation of the proximal jejunum. Interestingly, multiple large lymph nodes and dilated lymphatics were seen. A partial jejunal resection was performed for stricturing Crohn's disease. Histology showed severe mesenteric granulomatosis, dilated lymph vessels and granulomatous vasculitis. After the resection our patient improved without further albumin infusions and the oedema resolved.

Background & Aims: Early ileocolonoscopy allows detection of recurrence after surgically induced remission of Crohn's disease (CD). Unequivocal histologic markers predicting recurrence have not been identified. We assessed the predictive value of neural lesions for early endoscopic CD recurrence and long-term reintervention risk., Methods: Ileocolonic resection specimens from 59 patients with CD and 21 control patients were histologically scored for typical inflammatory bowel disease lesions, neural hypertrophy, and presence and severity of inflamed ganglia and nerve bundles. Endoscopic recurrence was determined at 3 months in all patients and at 1 year in 32 patients as part of 2 prospective clinical trials., Results: Myenteric plexitis of the proximal resection margin was present in 32 patients with CD (54%) in absence of surrounding inflammation. Patients with this feature had a higher endoscopic recurrence (Rutgeerts score >/=2) at 3 months (75% vs 41%; odds ratio, 4.36; 95% confidence interval, 1.44-13.23; P = .008) and at 1 year (93% vs 59%; odds ratio, 9.80; 95% confidence interval, 1.04-92.70; P = .041) and had a trend toward an earlier reintervention (mean, 7.00 vs 5.30 years; P = .174). The severity of myenteric plexitis in the proximal resection margin correlated with the severity of endoscopic recurrence at 3 months (r = 0.334, P = .010) and 1 year (r = 0.560, P = .001). Myenteric plexitis was the only consistent predictor of endoscopic recurrence., Conclusions: The presence of myenteric plexitis in proximal margins of ileocolonic resection specimens is predictive of early endoscopic CD recurrence.

We present a case of miliary tuberculosis diagnosed 15 months after infliximab treatment despite negative screening for previous exposure to Mycobacteria on skin PPD and chest X-ray. This case shows that--although screening for TB with a skin PPD and a chest X-ray should be performed in all patients--this is not 100% effective and may be a problem in patients on concomitant immunosuppression. The clinical course of this patient further shows that in a patient treated with anti-TNF antibodies who's condition does not improve one should always be aware of the possibility of a tuberculosis infection. Even though tuberculosis is usually not rapidly fatal, the disease may show a fulminant course in immunocompromised patients.

Objective: To evaluate the expression of carbonic anhydrase IX (CA IX) and vascular-endothelial growth factor (VEGF) in esophageal and gastric adenocarcinomas and in turn with the histologic subtype., Summary Background Data: Tumor hypoxia is an important factor in therapy resistance. A low oxygen concentration in tumors stimulates a.o. the expression of CA IX, a marker of hypoxia, and VEGF, a pro-angiogenic factor., Methods: We evaluated the immunohistochemical expression of CA IX and VEGF on paraffin-embedded material of 154 resection specimens: 39 esophageal, 73 cardiac, and 42 distal gastric adenocarcinomas (UICC classification). The adenocarcinomas were subtyped according to the Lauren classification (intestinal- and diffuse-type)., Statistical Analysis: chi test, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards model., Results: CA IX and VEGF expression were independent of the localization of the tumor. However, intestinal-type adenocarcinomas showed a significantly higher expression of CA IX as well as VEGF than diffuse-type tumors. VEGF expression was associated with a high microvessel density. Although survival analysis showed that CA IX expression (P = 0.008) as well as the coexpression of CA IX and VEGF (P = 0.008) correlate with a poor outcome, only CA IX expression is an independent prognostic factor for overall survival and metastasis-free survival., Conclusion: The difference in expression of CA IX and VEGF between intestinal- and diffuse-type adenocarcinomas may possibly explain the different clinical behavior of these tumors. CA IX expression, rather than VEGF positivity in tumors, enables the identification of a subpopulation, characterized by a more aggressive behavior and a poorer prognosis.

Background & Aims: Crohn's disease almost inevitably recurs after ileocolonic resection, and effective prophylactic therapy has not been identified. We investigated the efficacy and safety of ornidazole, a nitroimidazole antibiotic, for the prevention of clinical recurrence of Crohn's disease after curative ileocolonic resection in a placebo-controlled double-blind clinical trial., Methods: Eighty patients were randomized to ornidazole 1 g/day or placebo started within 1 week of resection and continued for 1 year. The primary end point was the proportion of patients with clinical recurrence at 1 year. Secondary end points were endoscopic recurrence at 3 months and 12 months after resection., Results: Two patients in the ornidazole group withdrew consent and were not dosed. Ornidazole significantly reduced the clinical recurrence rate at 1 year from 15 of 40 (37.5%) patients in the placebo group to 3 of 38 (7.9%) patients in the ornidazole group (Fisher exact test, 8.03; P = .0046; odds ratio, 0.14; 95% confidence interval, 0.037-0.546). Ornidazole reduced endoscopic recurrence at 12 months from 26 of 33 (79%) in the placebo group to 15 of 28 (53.6%) in the ornidazole group (chi2 , 4.37; P = .037; odds ratio, 0.31; 95% confidence interval, 0.10-0.94). Endoscopic recurrence at 3 and 12 months predicted clinical recurrence. Significantly more patients in the ornidazole group dropped out from the study because of side effects (P = .041)., Conclusions: Ornidazole 1 g/day is effective for the prevention of recurrence of Crohn's disease after ileocolonic resection.

Background: By temporarily suppressing the immune response, the anti-tumour necrosis factor agent, infliximab, may increase the risk of peri-operative complications., Aim: To test this hypothesis for intestinal resection in a cohort of 313 Crohn's disease patients treated with infliximab. Forty received one or more infusions prior to intestinal resection (31/40 within 12 weeks)., Methods: The post-operative events of these patients were compared with those of a control group (infliximab naive) of 39 patients adjusted for age, gender and surgical procedure. Early (10 days) and late (3 months) major or minor complications were identified., Results: The incidence of early minor (15.0% vs. 12.8%) and major (12.5% vs. 7.7%) and late minor (2.5% vs. 5.1%) and major (17.5% vs. 12.8%) complications and the mean hospital stay after surgery (10.3 +/- 4.0 days vs. 9.9 +/- 5.5 days) were similar in both groups. A trend towards an increased early infection rate was found in infliximab pre-treated patients (6 vs. 1; P = 0.10), but more patients in this group received corticosteroids and/or immunosuppressives (29 vs. 16 patients; P < 0.05)., Conclusion: The use of infliximab before intestinal resection does not prolong the hospital stay and does not increase the rate of post-operative complications.

An imbalance of immunoregulatory factors and/or cells contributes to uncontrolled mucosal T cell activation and inflammation in Crohn's disease (CD). Bioactive interleukin (IL)-18 has been shown to be produced by macrophages in CD lesions. We report here that T cells freshly isolated from inflamed tissue of CD patients (and not T cells from control intestinal tissue) were responsive to IL-18. In the presence of IL-18, these T cells produced more interferon (IFN)-gamma and less IL-10. To analyse further the role of IL-18 in this disease, an acute and a chronic model of murine colitis were used. IL-18 mRNA was significantly enhanced in trinitrobenzene sulphonic acid (TNBS) induced colitis, and treatment with IL-18 binding protein (IL-18BPa), which neutralizes IL-18 bioactivity, significantly reduced the severity of colitis. However, IL-18BPa did not affect the course of chronic colitis in CD45RBhighCD4+ T cell reconstituted SCID mice. Production of IFN-gamma in lamina propria mononuclear cell cultures from IL-18BPa-treated SCID mice was decreased, but at the same time fewer lamina propria CD4+ T cells harvested from IL-18BPa-treated mice compared to non-treated mice were in apoptosis. We conclude that IL-18 clearly has a modulatory role in the inflammatory cascade of CD and experimental colitis by affecting IFN-gamma and IL-10 production, and apoptosis. In view of the divergent effects of IL-18 neutralization in the two different murine colitis models, it is unlikely that IL-18 is at the top of this cascade.

Surgical treatment and prognosis is different in esophageal, cardiac and distal gastric adenocarcinomas. Determination of the origin, in particular of adenocarcinomas situated at the gastroesophageal junction, may be difficult. It has been suggested that esophageal adenocarcinomas are characterized by a specific cytokeratin pattern, namely the CK7+/CK20- pattern. According to the same authors, this cytokeratin pattern is absent in gastric adenocarcinomas. The aim of our study is to evaluate if this cytokeratin pattern CK7+/CK20- is absent in cardiac and distal gastric adenocarcinomas. Therefore, we evaluated the combined immunohistochemical expression of CK7 and CK20 on paraffin-embedded material of 214 resection specimens for adenocarcinoma, comprising 66 esophageal, 73 cardiac and 75 distal gastric adenocarcinomas (UICC-classification). The adenocarcinomas were subtyped into intestinal- and diffuse-type according to the Lauren classification. The immunohistochemical staining was considered as positive if 50% or more of the tumor cells were stained. Statistical analysis has been performed applying the chi2-test. The tumors situated at the gastroesophageal junction, esophageal as well as cardiac adenocarcinomas, showed predominantly a CK7+/CK20- expression pattern (67 vs 68%), whereas this cytokeratin pattern is rather uncommon in distal gastric adenocarcinomas (31%, P<4 x 10(-5)). Independent of their localization, intestinal- as well as diffuse-type adenocarcinomas have a similar cytokeratin pattern. Our data show that the combined expression of CK7 and CK20 is different for the adenocarcinomas situated on both sides of the gastroesophageal junction compared to the distal gastric adenocarcinomas. However, in contrast to data in the literature, the combined expression of CK7 and CK20 has a low specificity in the distinction between esophageal and cardiac adenocarcinomas. This may suggest a similar origin (cell lineage) and thus may have an impact on therapeutic strategies.

Background and Aims: Cyclosporine A is highly effective in severe attacks of ulcerative colitis (UC) but is associated with important adverse effects that are mainly dose dependent. Our single center, randomized, double-blind, controlled trial aimed to evaluate the additional clinical benefit of 4 mg/kg over 2 mg/kg IV cyclosporine in the acute treatment of severe UC., Methods: Primary end point was the proportion of patients with a clinical response. Secondary end points included time to response, colectomy rate, and adverse effects., Results: Seventy-three patients were included. Day-8 response rates were 84.2% (32 of 38, 4 mg/kg) and 85.7% (32 of 35, 2 mg/kg) after a median of 4 days in both groups. Short-term colectomy rates were 13.1% (4 mg/kg) and 8.6% (2 mg/kg). Mean cyclosporine blood levels were 237 +/- 33 in the 2-mg/kg group and 332 +/- 43 ng/mL in the 4-mg/kg group. Active smoking was inversely correlated with clinical response (odds ratio, 0.06), but concomitant azathioprine or steroids were not predictive. A trend toward a higher incidence of hypertension was observed in the 4-mg/kg group (23.7% vs. 8.6%, 2 mg/kg, P < 0.08)., Conclusions: High-dose IV cyclosporine has no additional clinical benefit over low dose in the treatment of severe UC. Although we did not observe differences in adverse effects on the short term, the use of 2 mg/kg IV cyclosporine should provide an improved toxicity profile for medical treatment of severe UC.

Aim: To summarise the magnitude and mechanisms of surgeon-related variability in the outcome after radical resection for rectal cancer and to present a solution and targets., Methods: A review of the literature, consultation of the "Guidelines for the management of colorectal cancer" published by the Association of Coloproctology of Great-Britain and Ireland, and analysis of data from the database of the Belgian Ministry of Health, RIZIV-INAMI, on radical resection for rectal cancer in Belgium during the years 1995-1997., Results: The proportion of abdominoperineal excision of the rectum (APER) varies between 23-58% in specialised centres and 43-57% general practice. In Belgium the APER rate for rectal cancer located between 4 and 16 cm above the anal verge is 50% with an overall in-hospital mortality of 3.5%; both APER rate and postoperative mortality are lower in university than in community hospitals. Most studies observe an effect of specialisation, reducing mortality with a factor of 2.5-3. The magnitude of surgeon-related variability in the oncological outcome has been well documented indicating that the impact of the surgeon-factor is considerably larger than that of adjuvant therapy. When comparing subspecialised with general surgeons, relative risk factors of 0.3-0.8 are reported for local recurrence rate, and 0.7-0.8 for disease free survival., Conclusion: Inter-surgeon variability is to be related with surgical skill and adequate implementation of recent diagnostic and therapeutic methods. Guidelines and centralisation are appropriate concepts, but do not guarantee improved quality of care. The targets are an APER rate of < 40% with an operative risk of < 2%, a local recurrence rate of < 10% and a disease free survival of > 70%. External audit is essential, but subspecialty training is a prerequisite and the surgeon is not the only factor to be audited.

Background & Aims: Cyclosporine has been effective in patients with steroid-refractory attacks of ulcerative colitis (UC). We investigated the effects of intravenous (IV) cyclosporine as single IV therapy (without glucocorticosteroids) for severe UC and compared these with the response to glucocorticosteroids., Methods: Patients with a severe attack of UC were randomized to treatment with IV cyclosporine, 4 mg x kg(-1) x day(-1), or with methylprednisolone, 40 mg/day, in a randomized, double-blind, controlled trial. After 8 days, patients who had a response received the same medication orally in combination with azathioprine. Patients were followed up clinically, endoscopically, and by scintigraphy. Renal function was assessed using urinary inulin clearances. Endpoints were clinical improvement, discharge from the hospital, and remission up to 12 months after intravenous therapy., Results: Thirty patients were included. After 8 days, 8 of 15 patients (53%) who received methylprednisolone had a response to therapy vs. 9 of 14 (64%) receiving cyclosporine. In nonresponders, 3 of 7 methylprednisolone patients and 1 of 3 cyclosporine patients improved when both treatments were combined. No serious drug-related toxicity was observed with either treatment. At 12 months, 7 of 9 patients (78%) initially controlled with cyclosporine maintained their remission vs. 3 of 8 (37%) initially treated with methylprednisolone. No clinically significant decrease of renal function was observed., Conclusions: Cyclosporine monotherapy is an effective and safe alternative to glucocorticosteroids in patients with severe attacks of UC.

The management of anal fistulas in patients with IBD continues to be extremely challenging and, indeed, somewhat frustrating. Despite a global closure rate of about 75%, all patients should be informed about the risk of infection, early failure, eventual temporary disfunctioning stoma and the possibility of late recurrence (about 15%). Closure of a RVF in Crohn's disease should not be considered an easy undertaking, especially in patients with several Crohn localisations. The technique can be adapted to the local situation. Construction of a temporary stoma is not mandatory. However, stoma construction seems to be beneficial when extensive perianal or recto-vaginal dissection including eventual tissue interposition is required. Advancement flaps are an attractive surgical alternative for the management of all anal transsphincteric fistulas, also in Crohn's disease, because sphincter architecture and function are well preserved. Improved medical treatment and the changed approach from conservative to reparative surgery may well have resulted in a decreased need or at least in a delay of the need for a proctectomy. Although the surgical principles of advancement flap techniques are sound, these techniques have not been used for many decades. Skills needed, problematic approach, suboptimal quality of local tissues have contributed to its selective use and to the absence of prospective randomised studies.

Background & Aims: Postoperative recurrence of Crohn's disease may be triggered by agents in the fecal stream. The aim of this study was to examine intestinal mucosal inflammation induced by contact with intestinal fluids in surgically excluded ileum., Methods: The effects of infusion of intestinal luminal contents into excluded ileum in 3 patients with Crohn's disease who had undergone a curative ileocolonic resection with ileocolonic anastomosis and temporary protective proximal loop ileostomy were studied by histopathology and electron microscopy., Results: Contact with intestinal fluids for 8 days induced focal infiltration of mononuclear cells, eosinophils, and polymorphonuclear cells in the lamina propria, small vessels, and epithelium in the excluded neoterminal ileum that was previously normal. Epithelial HLA-DR expression increased, and mononuclear cells expressed the KP-1 antigen associated with activation. Marked up-regulation of RFD-7, RFD-9, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 1 was observed after infusion, reflecting epithelioid transformation and transendothelial lymphocyte recruitment. At the ultrastructural level, dilatation of the endoplasmic reticulum and Golgi apparatus occurred in epithelial cells, where also basally located transport vesicles were identified., Conclusions: Intestinal contents trigger postoperative recurrence of Crohn's disease in the terminal ileum proximal to the ileocolonic anastomosis in the first days after surgery.

Background & Aims: Standard corticosteroid therapy for Crohn's ileitis induces symptom relief without improvement of endoscopically visible lesions. In this study, the effect of azathioprine therapy on the inflammatory lesions in the neoterminal ileum of patients with severe postoperative Crohn's recurrence was examined., Methods: Macroscopic ileal lesions were studied endoscopically or radiologically after at least 6 months of azathioprine therapy after complete weaning of corticosteroids. All patients who underwent an ileocecal resection for Crohn's disease at our institution between January 1989 and December 1993 and who subsequently developed severe recurrent ileitis treated with azathioprine were included., Results: Of the 19 patients treated with azathioprine for recurrent ileitis, 15 could be reevaluated by endoscopy or radiological examination. The therapy resulted in induction and maintenance of clinical remission in all 15 patients, at least 6 months after complete weaning of the corticosteroids. Complete macroscopic healing of the neoterminal ileum was observed in 6 of 15 patients, near-complete healing with only superficial erosions remaining in 5 of 15 patients, partial healing in 3 of 15 patients, and unchanged inflammatory lesions in 1 patient., Conclusions: It is concluded that azathioprine leads to mucosal healing in severe recurrent Crohn's ileitis and may be the treatment of choice in this indication.

The complications during and following endoscopic excision of deep endometriosis were analysed. The data of 225 excisions performed in 212 women had been collected prospectively into a database immediately following surgery and during the follow-up visit. The data confirmed the association of severe pelvic pain and deep endometriosis, severe pelvic being the only indication for surgery in 67, 78 and 76% of women with type I (n = 99), type II (n = 55) and type III (n = 71) lesions respectively. They confirmed that type II and type III were the largest lesions and that they were found predominantly in revised American Fertility Society (AFS) class II. The duration of surgery decreased with expertise (P < 0.01), but increased when deeper or larger lesions were excised (P < 0.0001) and when cystic ovarian endometriosis was also present (P < 0.001). Excision was clinically judged to be complete in 94, 96 and 85% of women with type I, II or III lesions respectively. In order to achieve this, part of the bowel wall had to be resected in 6.3% and part of the posterior vaginal fornix in 13.6% of cases. This risk was associated mainly in type II or III lesions and with larger lesions (P = 0.001). This was not considered as a complication, since all lesions could be repaired endoscopically and since follow-up was uneventful. Complications were one ureter lesion and seven late bowel perforations with periotonitis. Our data did not permit the evaluation as to whether medical pretreatment could improve completeness of surgery or decrease the risk. They revealed, however, that in six of seven women with type III lesions--in whom excision was judged to be complete--no pretreatment had been given and that luteinizing hormone releasing hormone (LHRH) agonist treatment decreased the volume of type II lesions (P = 0.04). In conclusion, complete endoscopic excision could be performed in over 90% of women with deep endometriosis, but required bowel surgery in over 6% of cases. Ureter lesions were rare, but postoperative bowel perforations with periotonitis occurred in 2-3% of cases. Medical pretreatment is advocated since LHRH agonist treatment was shown to shrink the deep endometriotic lesion.

Background/aims: New lesions recur within weeks to months after ileal resection and ileocolonic anastomosis for Crohn's ileitis. A double-blind controlled trial was performed using metronidazole to prevent recurrence after ileal resection., Methods: Sixty patients who underwent curative ileal resection and primary anastomosis were included within 1 week after surgery. Thirty patients received metronidazole (20 mg/kg body wt) daily for 3 months, and 30 patients received placebo. Treatment was then discontinued. Nine patients dropped out during treatment, 7 in the metronidazole group and 2 in the placebo arm., Results: At 12 weeks, 21 of 28 patients (75%) in the placebo group had recurrent lesions in the neoterminal ileum as compared with 12 of 23 patients (52%) in the metronidazole group (P = 0.09). The incidence of severe endoscopic recurrence was significantly reduced by metronidazole (3 of 23; 13%) as compared with placebo (12 of 28; 43%; P = 0.02). Patients in the metronidazole arm had more frequent side effects. Metronidazole therapy statistically reduced the clinical recurrence rates at 1 year (4% vs. 25%). Reductions at 2 years (26% vs. 43%) and 3 years (30% vs. 50%) were not significant., Conclusions: Metronidazole therapy for 3 months decreases the severity of early recurrence of Crohn's disease in the neoterminal ileum after resection and seems to delay symptomatic recurrence.

Widespread alterations of the gut autonomic nervous system have been described in Crohn's disease. Immunohistochemistry shows that these alterations are associated with the expression of major histocompatibility (MHC) class II antigens (HLA-DR) on enteroglial cells in the ganglia of the submucous and myenteric plexuses and on the enteroglial sheaths of the nerve extensions. Neuronal cell bodies and extensions do not express MHC class II antigens. The class II expression is associated with the presence of UCHL1-positive T lymphocytes. MHC class II expression can also be found on endothelial cells and vascular smooth muscle cells but not on smooth muscle cells of the muscularis mucosae or propria. The intensity of MHC class II expression on the glial cells of the enteric nervous plexus and on endothelial cells correlates well with the intensity of class II expression on epithelial cells.

Twelve selected patients undergoing cholecystectomy were operated in a prospective randomised study by laparoscopy (CO2 laser) or by classic surgery. Our preliminary results suggest that laparoscopic cholecystectomy is of clinical benefit as compared to classic cholecystectomy since it reduces the surgical trauma, limiting weight loss and shortening the hospital stay.