J.-F. Bretagne

Long-term Outcome of Perianal Fistulizing Crohn's Disease Treated With Infliximab

BACKGROUND & AIMS Little is known about the long-term efficacy of infliximab for patients with fistulizing perianal Crohns disease. We evaluated outcomes and predictors of outcomes in these patients. METHODS The medical records of 156 patients treated with infliximab for fistulizing perianal Crohns disease at 2 referral centers from 1999 through 2010 were reviewed through September 2011. Cumulative probabilities of fistula closure and recurrence were estimated by using the Kaplan-Meier method. Predictors of outcomes were identified by using a Cox proportional hazards model. RESULTS When infliximab treatment began, only 17.9% of patients had a simple fistula; seton drainage was performed for 97 patients (62%). Concomitant immunosuppressants were given to 90 patients (56%). After a median follow-up period of 250 weeks, 108 patients (69%) had at least 1 fistula closure. Cumulative probabilities of first fistula closure were 40% and 65% at 1 and 5 years, respectively. Factors that predicted fistula closure were ileocolonic disease (hazard ratio [HR] = 1.88), concomitant immunosuppressants (HR = 2.58), duration of seton drainage <34 weeks (HR = 2.31), and long duration of infliximab treatment (HR = 1.76). Of the 108 patients with fistula closure, cumulative probabilities of first fistula recurrence were 16.6% and 40.1% at 1 and 5 years, respectively. Forty-four patients (28.9%) developed an abscess during follow-up. A number of infliximab infusions greater than 19 was associated with less abscess recurrence (HR = 0.33). At the maximal follow-up time, 55% of patients had fistula closure. CONCLUSIONS About two-thirds of patients with fistulizing perianal Crohns disease had fistula closure, and one-third had fistula recurrence after infliximab initiation. Combination therapy, duration of seton drainage less than 34 weeks, and long-term treatment with infliximab were associated with better outcomes.

Dyschezia and rectocele—A marriage of convenience?

Herniation of the anterior rectal wall into the lumen of the vagina (so called rectocele) may be encountered in patients who complain of constipation and emptying difficulties but it is difficult to ascertain whether this anatomic abnormality is an etiologic factor or a consequence of the dyschezia. PURPOSE: The aim of our study was to assess symptomatic, anatomic, and physiologic features encountered in womenwith a clearly defined rectocelein order to determine the predisposing factors, symptoms, functional associations, and effects on quantified rectal emptying. METHODS: Clinical, physiologic (manometry), and anatomic (evacuation proctography) assessments were carried out in 26 consecutive women (mean age, 47.6±12 years) with dyschezia and a large rectocele as evidenced by radiography and compared with a group of 26 consecutive women complaining of dyschezia without a significant rectocele (mean age, 42.6±14 years). Both groups were similar with respect to mean age, parity, laxative abuse, manual anal evacuation, fecal incontinence, urgency, and weekly stool frequency. RESULTS: Patients having a rectocele differed significantly from those without a rectocele in having frequent endovaginal digitation during defecation (7vs.1,P< 0.05), more frequent symptoms of urinary incontinence (14vs.3,P<0.001), and a surgical history of hysterectomy (9vs.2,P< 0.05). The rectocele group differed in having a delayed rectal emptying (55.5±38vs.30.3±23 seconds,P<0.005), a more frequent incomplete rectal emptying (23vs.11,P<0.0005), and was more often associated with a manometric anismus (16vs.6,P<0.01). During the straining effort, there was a correlation between the depth of the rectocele and the duration of rectal emptying (rs=0.3,P<0.05). In the group without manometric anismus, women with a rectocele (n=10) had a more incomplete rectal emptying than those without rectocele (8/10vs.8/19,P=0.05). CONCLUSION: Some of our results indicate that the rectocele itself could be a contributory factor in difficult evacuation. These results also exhibit the importance of other disorders, such as anismus, in the occurrence of dyschezia. Physiologic examination therefore should be made before considering surgical repair in any patient with rectocele and dyschezia.

Transition of patients with inflammatory bowel disease from pediatric to adult care.

AIM This study was designed to ascertain the perception of patients (and their parents) followed-up for inflammatory bowel disease (IBD) concerning the transition from pediatric to adult care. PATIENTS AND METHODS Forty-eight youths with IBD who had transited from pediatric to adult care were surveyed. Their age at transition was 17.9+/-0.9 years. Thirty-four patients (71%) had been referred to a gastroenterologist working in the same hospital and, in 27 cases, after having attended a joint pediatric-adult care visit. RESULTS The response rate was 71%. Twenty-nine patients (85%) and 25 parents (74%) felt they were ready to transit into adult care. Seven patients (22%) and 10 parents (32%) were apprehensive about transition to adult gastroenterology. All patients considered the joint medical visit beneficial in terms of transmitting information from their medical records and 93% considered it beneficial for building confidence in the new gastroenterologist. All parents considered the joint medical visit helpful for building the childrens confidence in their new doctor. At the time of the survey, 29 patients (85%) were continuing to be followed-up by the same gastroenterologist. CONCLUSION Effective planning, including a joint medical visit, enabled successful, well-coordinated transition to adult medical-care follow-up.

Value of Early Blood Th-1 Cytokine Determination in Predicting Severity of Acute Pancreatitis

BACKGROUND Early evaluation of the severity of acute pancreatitis (AP) requires measurement of many variables within 48 h after admission. Septic complications (SC) are frequent, and preliminary studies have highlighted the value of prophylactic antibiotherapy; however, single and reliable predictive markers of sepsis are not yet available. The aim of this study was to assess the value of determining early blood Th-1 cytokines and their natural antagonists (interleukin-6 (IL-6), IL-1, IL-1ra, and the soluble form of tumor necrosis factor (sTNF) receptors RI and RII) to predict the severity and SC during AP. METHODS Thirty-seven patients with AP were prospectively included; 25 of them had severe AP, including 8 with SC. Serum cytokines were measured 48 h and 72 h after the onset of AP with an enzyme-linked immunosorbent assay. The optimal severity or SC diagnostic thresholds was determined using receiver operative curves. RESULTS Severe AP in accordance with the Atlanta criteria were better predicted by C-reactive protein and IL-6 serum determination, albeit these levels could not predict absolutely the death of two patients. In severe AP cases (n = 25) the IL-1 to IL-1-ra ratio was lower in cases further complicated by sepsis ((6+/-4) 10(-3) versus (34+/-13) 10(-3), P < 0.05); moreover, sTNF RI (2497+/-270 pg/ml versus 2133+/-611 pg/ml, P < 0.05) and RII (3751+/-400 pg/ml versus 3045+/-509 pg/ml, P < 0.05) were higher in AP characterized by further SC. The IL-1 to IL-1-ra ratio and IL-1 concentration were dramatically decreased within the first 48 h ((0.4+/-0.4) 10(-3) versus (30+/-11) 10(-3), P < 0.05, and 0.3+/-0.3 versus 15+/-3 ng/l, P < 0.05) in patients with further infection of the pancreatic necrosis (n = 3). The SC diagnosis was better anticipated by an IL-1 to IL-1-ra ratio lower than 5 x 10(-3) or by an sTNF RI higher than 1750 pg/ml and sTNF RII higher than 2750 pg/ml, and the infection of the pancreatic necrosis by an IL-1 concentration <2 ng/l or an IL-1 to IL-1-ra ratio <2 x 10(-3). CONCLUSION Besides severity markers, IL-1, IL-1-ra, and sTNF RI and RII should be considered in base-line AP assays and, if confirmed by larger studies, could help to screen patients at risk for SC and candidates for prophylactic antibiotherapy with a good negative predictive value.

Comparative study of characteristics and disease management between subjects with frequent and occasional gastro‐oesophageal reflux symptoms

Background  Little is known about the distinctive characteristics of subjects with frequent (at least weekly) and occasional gastro‐oesophageal reflux symptoms.

Leiden factor V mutation in four patients with small bowel infarctions

The Leiden factor V mutation is observed in 20% of unexplained lower limb venous thromboses and involves substitution of the arginine residue at position 506 by glutamine (R506Q). It is known to decrease the anticoagulant activity of activated protein C. This case report describes 4 cases of small bowel infarction (SBI) associated with the presence of this mutation. Two cases of arterial and 2 cases of venous SBI were observed. Extensive assessment excluded the usual causes of SBI and plasma hypercoagulation syndrome (antithrombin III, protein C, and protein S deficiency and myeloproliferative syndrome). An abnormal resistance to activated protein C was observed. Molecular analysis consisting of polymerase chain reaction amplification and digestion with MnlI showed that 2 patients were heterozygous and 2 were homozygous for the R506Q mutation. Despite familial history of thrombosis in only 1 patient, first- and second-degree relatives of 2 patients also had the presence of the mutation. Examination for the presence of abnormal resistance to activated protein C should be part of the etiological assessment of SBI. Its presence may warrant consideration of long-term anticoagulant therapy, especially for patients with shortened small bowel who are treated by home parenteral nutrition with deep venous access.

Long-term outcome of non-fistulizing (ulcers, stricture) perianal Crohn's disease in patients treated with infliximab

Background  In Crohn’s disease, anal ulcers and stricture can be disabling.

Measurement of adenoma detection and discrimination during colonoscopy in routine practice: an exploratory study.

BACKGROUND Measuring neoplasia yield is a priority in the quality improvement process for colonoscopy. However, neither the most appropriate quality indicator nor the standard threshold has been established. OBJECTIVE To determine the most appropriate quality indicators to assess the yield of routine colonoscopy. DESIGN Retrospective. SETTING Population-based colorectal cancer screening program in 3 French administrative areas. SUBJECTS One hundred gastroenterologists and their average-risk asymptomatic patients aged 50 to 74 years undergoing colonoscopy for positive guaiac-based fecal occult blood test results. MAIN OUTCOME MEASUREMENTS Comparison of several indicators, mainly the adenoma detection rate (ADR) and polyp detection rate (PDR), the mean number of adenomas per colonoscopy (MNA) and mean number of polyps (MNP) and the proportion of adenomas among polyps (PAP). RESULTS Correlations were good between the ADR and PDR (Pearson coefficient r = 0.88 [95% CI, 0.78-0.94]) and between MNA and MNP (r = 0.89 [95% CI, 0.79-0.94]) (P < .0001 for both). Gastroenterologists were classified as higher or lower detectors in comparison with the lower limit of the 95% confidence interval of the median value for each indicator. The MNP (MNA) provided better discrimination than the PDR (ADR). Concordance between classifications of gastroenterologists according to their MNA and MNP was excellent (κ = 0.89). PAP varied dramatically from 38% to 95% between gastroenterologists and was very poorly correlated with the ADR (r = -0.27 [95% CI, -0.54 to 0.07; P = .11]) and the MNA (r = 0.03 [95% CI, -0.29 to 0.36; P = .88]). LIMITATIONS Some factors influencing the neoplasia yield were not taken into account. CONCLUSIONS The MNP could replace the ADR for the assessment of adenoma detection in routine practice. A separate indicator, PAP, would be necessary to assess adenoma discrimination ability.

Anticipation in Crohn's disease may be influenced by gender and ethnicity of the transmitting parent

Objective:We sought to examine whether anticipation (an earlier age of onset in succeeding generations) is observed in Crohns disease (CD) patients within the New York metropolitan area, and whether there are differences in the degree of anticipation with respect to gender and ethnicity of the affected parent.Methods:Sixty-one parent-child pairs both affected by CD were identified; about half of the pairs were of Ashkenazi Jewish descent. An additional 17 pairs of second-degree relatives with CD were also identified. The intergenerational difference in age at diagnosis (AAD) was used to perform regression analysis and the degree of anticipation among subsets of patients separated on the basis of gender and ethnicity of the transmitting parent was determined.Results:The AAD was consistently (90% of the time) lower in the younger member of the 61 parent-child pairs (35.3 ± 1.6 yr vs 20.8 ± 1.1 yr, p= 0.0001). Furthermore, the degree of anticipation was significantly greater for father-child pairs (20.6 ± 3.2 yr) than for mother-child pairs (11.7 ± 2.1 yr). However, when the patient population where the parent had an AAD of < 28 was analyzed separately, there was a lack of clear-cut evidence of anticipation in the population as a whole. Only when the population was subdivided by ethnicity was there convincing evidence of anticipation in the Jewish population.Conclusions:Ascertainment bias may be responsible for the apparent anticipation observed in the CD population as a whole or in the nonJewish CD subgroup. However, the Jewish CD population displays strong evidence of anticipation even after correction for ascertainment bias.

TAP gene transporter polymorphism in inflammatory bowel diseases

BACKGROUND Many studies suggest the implication of genetic factors in inflammatory bowel diseases. Despite some associations with HLA genes, the lack of definite data may be due to ethnic variations, clinical heterogeneity, or the involvement of additional susceptibility genes beside or within the major histocompatibility complex (MHC), such as TAP genes. The aim of this study was to analyze in patients with ulcerative colitis (UC) or Crohns disease (CD) the polymorphism of TAP genes that encode the proteins necessary for the transfer of antigenic peptides through the endoplasmic reticulum membrane. METHODS One hundred and one UC and 148 CD patients were compared with 173 unrelated healthy controls. Dimorphisms within the TAP1 and TAP2 alleles were analyzed by sequence-specific oligonucleotide typing. RESULTS No difference was found between patient groups and controls. However, when CD patients were classified on the basis of their responsiveness to steroid therapy, a significant decrease of TAP2 AA (*0101/*0101) genotype was found in CD patients who did not respond to steroid therapy (22.9% versus 43.7% in steroid responder group; Pc < 0.05; odds ratio = 2.6; 95% confidence limits (CL) = 1.2-5.9). These data appear independent of the distribution of HLA DRB1*01 or DRB1*03 alleles despite a significant linkage disequilibrium between these alleles and TAP2A. CONCLUSIONS This result suggests, despite the absence of arguments favoring a genetic susceptibility to CD, that the TAP2 gene or other genes located on chromosome 6 may be involved in the genetic heterogeneity of CD.