Is the length of postoperative recurrence on the neo ileum terminal ileum predictable in Crohn's disease?

UNLABELLED: Crohn's disease (CD) often has a stricturing phenotype on the terminal ileum requiring surgery due to obstruction. Recurrence is frequent, creating a risk of multiple surgeries. We studied patients with ileal or ileo-colic CD who had undergone at least two surgical bowel resections between 1968 and 2008 for obstructive symptoms. AIMS: The aim of this retrospective study was to determine if the length of the removed diseased bowel varied from one surgical resection to the next. The measurements obtained from radiology (small bowel follow-up), surgery and histology were compared. RESULTS: Twenty four patients were included. Seventeen had 2 resections, 5 patients had 3 resections and two had 4 resections. The resected length of the diseased ileum was significantly shorter for the second intervention than for the first as assessed by radiology (median 16 cm vs 37 cm; p=0.0005), surgery (20 cm vs 40 cm; p=0.005) and histology (15 cm vs 25 cm; p=0.02) while there was no difference between the second and third resections (16 cm, 13 cm, 19.5 cm respectively) for the three types of measurements (p=NS). The surgeon's assessment of the diseased segment was longer than the histologist's (p=0.003). No factor was found to be significantly associated with the length of the diseased bowel on recurrence. CONCLUSION: This study shows that the length of the excised neo-terminal ileum during the first episode of recurrence was shorter than during the first episode of disease and remained stable for the third episode. This is an important prognostic finding that could influence the therapeutic choices for this disease and reduce hesitation to indicate surgery.

A mini geriatric assessment helps treatment decision in elderly patients with digestive cancer. A pilot study.

UNLABELLED: Comprehensive geriatric assessment (CGA) is advocate to improved care of elderly with cancer but is not available in every hospital within a short delay. Therefore, a tool allowing gastroenterologist to detect rapidly specific abnormalities in elderly is needed. PATIENTS AND METHODS: the aim of our pilot study was to evaluate feasibility of a mini geriatric assessment (MGA) to adapt the anticancer treatments. MGA was done by a gastroenterologist and was taken into account during the cancer multidisciplinary team meeting for making decision. Then, CGA was realised and suggested adaptation of care. RESULTS: 21 patients over 75 years treated for different digestive cancers were enrolled. The treatments recommended by the cancer multidisciplinary team meeting after the GMA were: standard treatments in 9 (41%); modified in 10 (47%) and best supportive care in 2 (12%) patients. CGA led to an adaptation of the non-oncological treatment in 15 (72%) and of the social care in 8 (38%) patients, but never modified the oncological strategy. CONCLUSIONS: MGA could help gastroenterologists for adaptation of anticancer treatment. The characteristics of the patients that should subsequently have a geriatric follow-up remain to be defined.

Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease.

BACKGROUND: Ulcerative Colitis (UC) and Crohn's Disease (CD) are two chronic Inflammatory Bowel Diseases (IBD) affecting the intestinal mucosa. Current understanding of IBD pathogenesis points out the interplay of genetic events and environmental cues in the dysregulated immune response. We hypothesized that dysregulated microRNA (miRNA) expression may contribute to IBD pathogenesis. miRNAs are small, non-coding RNAs which prevent protein synthesis through translational suppression or mRNAs degradation, and regulate several physiological processes. METHODOLOGY/FINDINGS: Expression of mature miRNAs was studied by Q-PCR in inactive colonic mucosa of patients with UC (8), CD (8) and expressed relative to that observed in healthy controls (10). Only miRNAs with highly altered expression (>5 or <0.2 -fold relative to control) were considered when Q-PCR data were analyzed. Two subsets of 14 (UC) and 23 (CD) miRNAs with highly altered expression (5.2->100 -fold and 0.05-0.19 -fold for over- and under- expression, respectively; 0.001

Fibrin glue is effective healing perianal fistulas in patients with Crohn's disease.

BACKGROUND & AIMS: Fibrin glue is a therapeutic for fistulas that activates thrombin to form a fibrin clot, which mechanically seals the fistula tract. We assessed the efficacy and safety of a heterologous fibrin glue that was injected into the fistula tracts of patients with Crohn's disease (ClinicalTrials.gov No. NCT00723047). METHODS: This multicenter, open-label, randomized controlled trial included patients with a Crohn's disease activity index < or =250 and fistulas between the anus (or low rectum) and perineum, vulva, or vagina, that drained for more than 2 months. Magnetic resonance imaging or endosonography was performed to assess fistula tracts and the absence of abscesses. Patients were stratified into groups with simple or complex fistulas and randomly assigned to receive fibrin glue injections (n = 36) or only observation (n = 41) after removal of setons. The primary end point was clinical remission at week 8, defined as the absence of draining, perianal pain, or abscesses. At week 8, a fibrin glue injection was offered to patients who were not in remission. RESULTS: Clinical remission was observed in 13 of the 34 patients (38%) of the fibrin glue group compared with 6 of the 37 (16%) in the observation group; these findings demonstrate the benefit of fibrin glue (odds ratio, 3.2; 95% confidence interval: 1.1-9.8; P = .04). The benefit seemed to be greater in patients with simple fistulas. Four patients in the fibrin glue group and 6 in the observation group had adverse events. CONCLUSIONS: Fibrin glue injection is a simple, effective, and well-tolerated therapeutic option for patients with Crohn's disease and perianal fistula tracts.

Half of elderly patients routinely treated for colorectal cancer receive a sub-standard treatment.

BACKGROUND: Several database studies report a lack of care in elderly patients with colorectal cancer. PURPOSE: To describe the management of elderly patients admitted for colorectal cancer; to identify factors associated with standard management according to recommendations and to study factors influencing the survival. PATIENTS AND METHODS: All consecutive patients over 75 years managed for a colorectal adenocarcinoma in our hospital from 1995 to 2000 and followed until 2006 were retrospectively included. The appropriateness of the management of their disease according to the recommendations available at that time was assessed. Several risk factors in receiving the standard cancer treatment were tested using univariate and then multivariate logistic regression. Risk factors of survival were studied using univariate and then multivariate survival analysis. RESULTS: One hundred and ten patients were included. Median age was 82 years (range: 75-96). A surgical treatment was performed in 96 patients. The median overall survival was 32 (1-108) months. A standard cancer treatment according to recommendations was performed in 53 (48%) patients: adjuvant chemotherapy in 6/23 patients with stage III tumour, palliative chemotherapy in 3/18 patients with stage IV tumour and adjuvant radiotherapy in 4/14 patients who had a rectal tumour resection. Multivariate analysis retains tumour stage I or II (OR=7.6, 95% C.I.=[2.9-19.9], p<0.0001) as the only factor associated with standard treatment and presence of metastasis (HR=3.9, 95% C.I. [1.4-10.8], p=0.005), and Charlson's score >3 (HR=28.9, 95% C.I. [2.5-335.6], p=0.001) as independent risk factors of poor survival. CONCLUSIONS: Fifty two percent of elderly patients have had a sub-standard cancer treatment. The majority had a surgical treatment, but only a few received chemotherapy or radiotherapy. Metastasis, older age and Charlson's comorbidity score are the main prognosis factors of poor survival.

Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse.

BACKGROUND & AIMS: Azathioprine (AZA) withdrawal in Crohn's disease after long-term remission under treatment is controversial. In a Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif randomized, double-blind, placebo-controlled trial, the hypothesis that AZA withdrawal was not inferior to AZA continuation in patients in prolonged clinical remission could not be shown. METHODS: A cohort of 66 patients in prolonged remission while being treated with AZA who stopped AZA, during or at the end of the randomized controlled trial, underwent long-term follow-up evaluation. The primary end point was clinical relapse. Prognostic factors of relapse were looked for through a proportional hazards model. RESULTS: Median durations of AZA therapy and of clinical remission were 68.4 months (interquartile range, 52.8-85.2 mo) and 63.6 months (interquartile range, 48.0-55.7 mo), respectively. The median follow-up time after AZA interruption was 54.5 months; 32 of 66 patients had a relapse. The cumulative probabilities +/- SE of relapse at 1, 3, and 5 years were 14.0% +/- 4.3%, 52.8% +/- 7.1%, and 62.7% +/- 7.2%, respectively. C-reactive protein concentration of 20 mg/L or greater (risk, 58.6; 95% confidence interval, 7.5-457; P = .002), hemoglobin level less than 12 g/dL (risk, 4.8; 95% confidence interval, 1.7-13.7; P = .04), and neutrophil count 4 x 10(9)/L or greater (risk, 3.2; 95% confidence interval, 1.6-6.3; P = .003) were associated independently with an increased risk of relapse. Among the 32 relapsing patients, 23 were retreated by AZA alone, all but 1 up to successful remission. CONCLUSIONS: Our results confirm that AZA withdrawal is associated with a high risk of relapse, whatever the duration of remission under this treatment. These data suggest that if AZA is well tolerated, it should not be interrupted.

The V249I polymorphism of the CX3CR1 gene is associated with fibrostenotic disease behavior in patients with Crohn's disease.

OBJECTIVES: CX3CR1, the receptor of CX3CL1/fractalkine, is involved in regulation of inflammatory response and the CX3CR1-I249-M280 naturally occurring mutants are associated with altered binding to the ligand. Our aim was to evaluate the frequency of CX3CR1 V249I and T280M polymorphisms and NOD2/CARD15 mutations in Crohn's disease patients and to search for a relationship with phenotype. METHODS: Clinical data were retrospectively collected. V249I and T280M polymorphisms of CX3CR1 gene and NOD2/CARD15 mutations (R702W, G908R, 3020InsC) were identified. RESULTS: Two hundred and thirty-nine patients (140 females, 39.7+/-14.1 years) were included. About 37.4% were heterozygous and 8.8% were homozygous for the V249I CX3CR1 polymorphism, 18.1% were heterozygous and 1.3% homozygous for the T280M CX3CR1 polymorphism and 35.9% had at least one of the three mutations of NOD2/CARD15. The T280M CX3CR1 polymorphism was not associated with any phenotype. In univariate analysis, stenosis was significantly associated with both V249I CX3CR1 polymorphism and 3020InsC NOD2/CARD15 mutations. In smoker patients carrying the CX3CR1 allele I249, there was a significant increase in the frequency of fibrostenosing disease [P=0.005, odds ratio (OR): 3.25] whereas this relationship disappeared in the group of nonsmokers (P=0.72). In multivariate analysis, 3020InsC NOD2/CARD15 mutations and the V249I CX3CR1 polymorphism were independent risk factors for intestinal stenosis (P=0.046, OR: 1.8 and P=0.044, OR: 2.4, respectively). CONCLUSION: In Crohn's disease, V249I CX3CR1 polymorphism is associated with intestinal strictures, particularly in smokers. This association is independent of CARD15 mutations.

Anal squamous intraepithelial lesions and condyloma in HIV-infected heterosexual men, homosexual men and women: prevalence and associated factors.

OBJECTIVE: To assess the prevalence of and factors associated with squamous intraepithelial lesions and condyloma [human papillomavirus (HPV)-related lesions) in HIV-infected patients. DESIGN: A cross-sectional study in a tertiary-care university hospital conducted in 516 consecutive outpatients. INTERVENTION: A systematic examination for macroscopic HPV-related lesions through anoscopy with histological confirmation, evaluation of dysplasia and HPV typing. Sexual behaviours were assessed using a semi-directive questionnaire. RESULTS: Of 473 patients examined, (200 homosexual men, 123 heterosexual men, 150 women), 108 (23%) had histologically confirmed anal HPV-related lesions (36, 15 and 11% of the respective populations), including 51 (47%) with only endoanal localization. Among these 108 patients, histological dysplasia of grades I or II and grade III were noted in 59 and two patients, respectively, invasive endoanal cancer in one; three patients also had high-risk oncogenicity HPV without dysplasia. Independent identified associated factors of HPV-related condyloma were the number of incidents of sexual intercourse per month [odds ratio (OR) 1.04; 95% confidence interval (CI) 1.01-1.06], CD4 cell count below 200 x 10 cells/l (OR 3.22; 95% CI 1.37-7.60), history of anal HPV lesion (OR 4.57; 95% CI 2.13-9.81), and receptive anal intercourse (OR 2.30; 95% CI 1.11-4.77). The two latter factors remained associated with histological dysplasia (OR 2.82; 95% CI 1.38-5.76 for history of anal condyloma, and OR 4.29; 95% CI 2.18-8.44 for receptive anal intercourse). CONCLUSION: The high rate of condyloma and histological dysplasia seen argues for a systematic screening for these lesions in HIV-infected individuals.

Applicability and efficacy of qualifying criteria for an appropriate use of diagnostic upper gastrointestinal endoscopy.

UNLABELLED: Appropriate indication for upper gastrointestinal endoscopy (UGE) may be facilitated by referring to qualifying criteria such as those devised by the European Panel (EPAGE) and French Experts (ANAES). This prospective study evaluates the applicability and efficacy of these criteria in clinical practice. PATIENTS AND METHODS: A total of 522 patients was included (55% inpatients, 57% male, mean age 55 years). Appropriateness of referral was evaluated using EPAGE and ANAES criteria sets by a single independent expert. RESULTS: EPAGE criteria were applicable in 71% of cases. Indications for UGE were appropriate, inappropriate and uncertain in 62%, 27% and 11% respectively; 74%, 16% and 10% of clinically significant lesions detected by UGE were disclosed in patients having appropriate, inappropriate and uncertain indications respectively. ANAES criteria were applicable in 81% of cases. Indications for UGE were appropriate in 74%, inappropriate in 26%; 76% and 24% of clinically significant lesions detected by UGE were disclosed in patients having appropriate and inappropriate indications respectively. Whatever the criteria set used, all cancers and most of the severe lesions were observed in patients with appropriate indications: those patients were more often in-patients and were significantly older than patients belonging to the inappropriate group. CONCLUSION: Reference to EPAGE and ANAES qualifying criteria facilitates patient selection for UGE. Final decision must however rely upon practitioner advice. ANAES criteria are significantly more often applicable than EPAGE ones. However EPAGE referential when applicable is more predictive of the UGE findings.

[The gastric antrum: a rare primitive location of a gastrinoma within a type I multiple endocrine neoplasia]. / L'antre gastrique, localisation primitive exceptionnelle d'un gastrinome dans le cadre d'une néoplasie endocrine multiple de type I.

We report the case of an 18-year-old man, with no previous medical history, presenting with recurrent hemorrhagic duodenal ulcers revealing a Zollinger-Ellison syndrome. The initial diagnosis of sporadic gastrinoma of the antrum associated with satellite lymph nodes led to surgical treatment. The evolution of clinical and secretory tests associated with the outbreak of a primary hyperparathyroïdism demonstrated that the patient had a type I multiple endocrine neoplasia. To our knowledge, this is the first described case of primitive gastrinoma of the antrum occurring in a type I multiple endocrine neoplasia.

Efficacy of infliximab in Crohn's disease. Results of a retrospective multicenter study with a 15-month follow-up.

OBJECTIVES: To evaluate prescription practices and response to infliximab treatment for Crohn's disease (CD). PATIENTS AND METHODS: The files of CD patients treated with at least one infusion of infliximab treated in gastroenterology units belonging to university teaching hospitals of the Parisian hospitals group (Assistance Publique-Hôpitaux de Paris (AP-HP) during the year 2000 were analyzed retrospectively. RESULTS: One hundred and thirty-seven patients (36.0 +/- 12.7 years, 92 females) from 12 centers were studied. Indication for treatment was fistulae or perianal disease in 39% of patients, active Crohn's disease in 45% and mixed conditions in 16%. Mean follow-up was 15.2 +/- 7.2 months. The overall response rate was 85%. No predictive factor of sustained remission could be identified. The mean time to relapse was to 3.9 +/- 3.1 months. Thirty-eight patients were on maintenance therapy at the end of the follow up; 37% exhibiting progressive lost of response to treatment. Immunosuppressive therapy was added to infliximab in 78% of cases but response to infliximab was not modified by addition of immunosuppressive drugs. Adverse events, most frequently minor, were noted in 23% of the patients. CONCLUSION: This retrospective study confirms the efficacy and safety of infliximab in CD.

A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine.

BACKGROUND & AIMS: An open study reported that patients with Crohn's disease in remission who have taken azathioprine for longer than 3.5 years are at low risk of relapse when azathioprine is discontinued. To confirm this observation, we performed a multicenter, double-blind, noninferiority withdrawal study. METHODS: Patients who were in clinical remission on azathioprine for > or = 42 months were randomized to continue azathioprine or to receive an equivalent placebo for 18 months. The primary end point was clinical relapse at 18 months. RESULTS: Forty patients were randomly assigned to receive azathioprine and 43 to receive placebo. Characteristics of patients at entry were similar in the 2 study groups. At 18 months, 3 patients had a relapse in the azathioprine group, and 9 had a relapse in the placebo group. Kaplan-Meier estimates of the relapse rate at 18 months were 8% +/- 4% and 21% +/- 6%, respectively. The hypothesis that placebo was inferior to azathioprine was not rejected (P = .195). Among the baseline variables, C-reactive protein level > 20 mg/L, time without steroids < 50 months, and hemoglobin level < 12 g/dL were found to be predictive of relapse in the multivariate analysis. CONCLUSIONS: This study shows that azathioprine withdrawal is not equivalent to continued therapy with azathioprine for maintenance of remission in patients with Crohn's disease who have been in remission on azathioprine for > or = 3.5 years. Thus, azathioprine maintenance therapy should be continued beyond 3.5 years.

Anal carcinoma: incidence and effect of cumulative infections.

INTRODUCTION: Human papilloma virus (HPV) causes anal condyloma that is a risk factor for anal carcinoma. The incidence and mechanism of invasive anal carcinoma in patients with anal condyloma are prospectively determined. PATIENTS AND METHODS: From 1993 to 2002, 228 consecutive patients (164 HIV positive) with anal canal condylomas were included in the study, after curing of their lesions. They were asked to attend follow-up visits at 3- or 6-month intervals. We checked for anal co-infection with syphilis, gonococci, viruses (Epstein-Barr virus, cytomegalovirus, herpes simplex, HPV types), and quantified Langerhans' cells (LC) in anal mucosa at baseline and during follow up. We cured and analysed relapsed condylomas during follow up (3-112 months; median 26). Serum HIV loads and CD4 T-lymphocyte counts were determined at each visit and the densities of LC in consecutive specimens from patients with cancers were compared with that for a matched control group (n = 23). RESULTS: Analysis of 199 patients showed high-grade dysplasia (HGD) in 13.6% of patients, more in HIV-positive (16%) than in HIV-negative (6%) patients at baseline. During follow up, 3.5% (7/199; six HIV positive) patients developed invasive carcinoma after 13-108 months and 112 (56%) patients relapsed condylomas. HIV and anal co-infection were identified as independent risk factors (P < 0.01) for HGD and cancer: odd ratio (95% confidence interval) of 9.4 (2.4-37.4) and 3.67 (0.95-14.2), respectively. LC densities in anal mucosa were lower in patients with invasive carcinoma than in controls. CONCLUSION: The risk of invasive carcinoma in HPV-infected patients is increased by HIV and anal co-infection. Decreases in LC numbers in anal mucosa may favour this outcome.

Effect of anal epidermoid cancer-related viruses on the dendritic (Langerhans') cells of the human anal mucosa.

PURPOSE: The incidence of anal cancer is high in patients with anal condyloma. HIV increases this risk. We analyzed anal mucosa from normal individuals and individuals with condyloma. EXPERIMENTAL DESIGN: Normal anal mucosa from 155 consecutively recruited patients (102 HIV-positive and 53 HIV-negative) with anal condyloma was compared with that obtained from 30 HIV-negative patients after hemorrhoid surgery (controls). Langerhans' cells (LCs), T lymphocytes, and viruses [EBV, cytomegalovirus, herpes simplex virus 1, and human papillomavirus (HPV) types] in anal mucosa and HIV load and CD4 T-lymphocyte counts in the serum were characterized. RESULTS: None of the control individuals had anal squamous intraepithelial lesion or HPV versus 19 HIV-positive and 4 HIV-negative patients with anal condyloma (P = 0.07). The number of LCs/mm in anal tissue was significantly higher in HIV-negative patients with condylomata (median, 30; range, 2-130) than in HIV-positive patients (median, 15; range, 0-100) or in controls (median, 17; range, 4-35). In HIV-negative individuals, the occurrence of condylomata was linked with a higher number of LCs. Significant differences were observed between HIV-positive and HIV-negative patients with anal condylomata:number of LCs/mm anal tissue, oncogenic HPV (26% versus 8%), other current infections (35.6% versus 5%), being male (93% versus 74%). Multivariate regression analysis found HIV as the only risk factor for a decrease in the number of LCs (odds ratio, 6; 95% confidence interval, 2.28-16.1; P < 0.001) and the serum HIV load (odds ratio, 4.9; 95% confidence interval, 1.1-21.4 log/ml; P < 0.03) but not the serum CD4 T-lymphocyte rate as a predictive risk factor for having <17 LCs/mm tissue. CONCLUSION: HPV increases the number of LCs in anal mucosa in HIV-negative individuals. HIV alters anal dendritic cells, likely leading to an increase in anal cancer risk.

[Anal canal squamous-cell carcinomas in HIV positive patients: clinical features, treatments and prognosis]. / Caractéristiques cliniques, thérapeutiques et pronostiques des carcinomes épidermoïdes du canal anal chez les malades VIH positifs.

UNLABELLED: The prevalence of squamous-cell carcinoma of the anus seems to be increasing in HIV positive patients. Clinical features and prognosis in this population have not been well evaluated. AIMS: To assess the prognosis of anal squamous-cell carcinoma in HIV positive patients as well as clinical features and treatment procedures. METHODS: A series of 20 HIV positive patients presenting with invasive anal squamous-cell carcinoma was retrospectively analyzed. Data have been compared to those obtained from 24 randomly selected HIV negative patients who were followed during the same periods in the same centers for anal carcinoma with similar histopathological features. RESULTS: The follow-up ranged from 10 to 172 months. No difference was observed between the two groups concerning the clinical features leading to anal cancer diagnosis, although HIV positive patients were younger. Anal cancer was more frequently associated with lymph node metastasis in HIV positive (60%) than in HIV negative (17%) patients, although its size was similar in both groups. Radiotherapy was similarly performed in both groups, while chemotherapy was administered less frequently in HIV positive than in HIV negative patients (54% vs 25%). Immediate side effects and mortality at 1 year follow-up were similar in both groups, whereas the objective initial response to therapy (50% versus 88%), the remission rate with anal conservation at 1 year follow-up (45% versus 88%), and the mortality at 3 years were better in HIV negative patients. CONCLUSION: The prognosis of anal squamous-cell carcinoma is poor in HIV positive patients. This correlates with a more advanced tumor stage and an alteration of systemic immunity status at the time of diagnosis and less response rate to treatment. Detection of precancerous lesions and treatment procedures should be evaluated in HIV infected patients.