Alexander C. Poen

Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis.

Extensive population‐based studies are much needed to accurately establish epidemiology and disease course in patients with primary sclerosing cholangitis (PSC). We aimed to obtain population‐based prevalence and incidence figures, insight in disease course with regard to survival, liver transplantation (LT), and occurrence of malignancies, as well as risk factors thereof. Four independent hospital databases were searched in 44 hospitals in a large geographically defined area of the Netherlands, comprising 50% of the population. In addition, all PSC patients in the three Dutch liver transplant centers and all inflammatory bowel disease (IBD) patients in the adherence area of a large district hospital were identified. All medical records were reviewed on‐site, verifying diagnosis. Five hundred and ninety PSC patients were identified, resulting in an incidence of 0.5 and a point prevalence of 6.0 per 100,000. Median follow up was 92 months. Estimated median survival from diagnosis until LT or PSC‐related death in the entire cohort was 21.3 years, as opposed to 13.2 years in the combined transplant centers cohort (n = 422; P < 0.0001). Colorectal carcinoma (CRC) risk was 10‐fold increased, as compared to ulcerative colitis controls, and developed at a much younger age (39 years; range, 26‐64), compared to IBD controls (59 years; range, 34‐73; P = 0.019). Colonoscopic surveillance was associated with significantly better outcome. Conclusion: This study exemplifies that, for relatively rare diseases, it is paramount to collect observational data from large, population‐based cohorts, because incidence and prevalence rates of PSC are markedly lower and survival much longer than previously reported. The selection of a bias‐free, population‐based cohort showed a significantly longer survival, compared to the tertiary referral cohort. CRC can develop at an early age, warranting surveillance from time of PSC diagnosis. (Hepatology 2013; 58:2045–2055)

Hydrogen peroxide-enhanced transanal ultrasound in the assessment of fistula-in-ano

Appropriate classification of the fistulous tracts in patients with fistula-in-ano may be of value for the planning of proper surgery. Conventional transanal ultrasound has limited value in the visualization of fistulous tracts and their internal openings. Hydrogen peroxide can be used as a contrast medium for ultrasound to improve visualization of fistulas. PURPOSE: This prospective study evaluates hydrogen peroxide-enhanced ultrasound in comparison with physical examination, standard ultrasound, and surgery in the assessment of fistula-in-ano. METHODS: Twenty-one consecutive patients (4 women; mean age, 42 years) with fistula-in-ano were evaluated by local physical examination (inspection, probing, and digital examination), conventional ultrasound, and hydrogen peroxide-enhanced ultrasound before surgery. Ultrasound was performed using a B&K Diagnostic Ultrasound System™ with a 7-MHz rotating endoprobe. Hydrogen peroxide (3%) was infusedvia a small catheter into the fistula. The results of physical examination, ultrasound, and hydrogen peroxide-enhanced ultrasound were compared with surgical data as the criterion standard. The additive value of standard ultrasound and hydrogen peroxide-enhanced ultrasound compared with physical examination was also determined. RESULTS: At surgery, 8 intersphincteric and 11 transsphincteric fistulas and 2 sinus tracts (without an internal opening) were found. During physical examination, probing was incomplete in 13 patients, the diagnosis being correct in the other 8 patients (38%) as a low (intersphincteric or transsphincteric) fistula. With conventional ultrasound, the assessment of fistula-in-ano was correct in 13 patients (62%); defects in one or both sphincters could also be found (n=8). With hydrogen peroxide-enhanced ultrasound, the fistulous tract was classified correctly in 20 patients, the overall concordance with surgery being 95%. The internal opening was found at physical examination in 15 patients (71%), with hydrogen peroxide-enhanced ultrasound in 10 patients (48%), and during surgery in 19 patients (90%). Secondary extensions, confirmed during surgery, were found in five cases. In two patients, a secondary extension with hydrogen peroxide-enhanced ultrasound was not confirmed during surgery. Both patients developed a recurrent fistula. CONCLUSION: Hydrogen peroxide-enhanced ultrasound is superior to physical examination and standard ultrasound in delineating the anatomic course of perianal fistulas. It makes accurate preoperative assessment of the fistula possible and may be of value for the surgeon in planning therapeutic strategy.

Third degree obstetric perineal tears: risk factors and the preventive role of mediolateral episiotomy

Objective To determine risk factors for third degree obstetric perineal tears and to give recommendations for prevention.

Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease

Background: Primary sclerosing cholangitis (PSC) is strongly associated with inflammatory bowel disease (IBD). The aim of this study was to assess the IBD phenotype associated with PSC in a large well‐phenotyped population‐based PSC cohort using endoscopic and histopathologic criteria. Methods: PSC cases were identified and ascertained, fulfilling well‐established criteria, in 39 hospitals in a geographically defined region of The Netherlands. IBD location was recorded according to the Montreal Classification. As this classification does not consider segmental inflammation, backwash ileitis, or rectal sparing, an additional subgroup analysis was performed in 80 cases and 80 age‐ and sex‐matched IBD controls, reviewing all endoscopy and pathology reports filed between 2000 and 2010. Results: In all, 380 (66%) of a total of 579 PSC patients had coexistent IBD, mainly ulcerative colitis (UC) (75%). Overall, 207 (83%) of the PSC‐UC patients had a pancolitis, 32 (13%) a left‐sided colitis, and 9 (4%) a proctitis only. Seventy (95%) PSC‐Crohns disease (CD) patients had an (ileo)colitis and four (5%) ileitis only. In the subgroup analysis 53 (66%) PSC‐UC patients were identified, 24 (30%) PSC‐CD patients, and three (4%) PSC‐IBD‐U patients. Fifty (94%) PSC‐UC patients had a pancolitis, compared with 32 (62%) matched UC patients (P < 0.001). Left‐sided colitis was seen in 16 (31%) UC controls and in one PSC‐UC patient (P < 0.001). Backwash ileitis and rectal sparing were rare findings (<10%) in the cohorts under study. Conclusions: IBD in PSC patients represents a distinct phenotype in that pancolitis is observed in 94% of PSC‐UC and colitis in 96% of PSC‐CD patients. Backwash ileitis and rectal sparing were rare findings in the PSC‐UC patients. (Inflamm Bowel Dis 2012;)

HLA-DRB1*03, BUT NOT THE TNFA-308 PROMOTER GENE POLYMORPHISM, CONFERS PROTECTION AGAINST FISTULISING CROHN'S DISEASE

Abstract Crohn’s disease (CD) appears in forms so diverse that it has been hypothesized CD might be a syndrome, with different pathogenic mechanisms leading to the various clinical phenotypes. This may plausibly explain the conflicting and inconclusive results with regard to HLA associations in unselected groups of patients. The power of these association studies may increase when disease heterogeneity is taken into account. As fistulising CD has been proposed as a separate subgroup of patients with CD, we studied the carrier frequencies (CF) of the DRB1 alleles in 35 unrelated Caucasian Dutch CD patients with proven peri-anal fistulas. A striking decrease in the frequency of the DRB1*03 allele was found in those patients with peri-anal fistulas when compared with a panel of 2400 healthy controls (HC) (3% vs 25%; P = 0.005; Odds Ratio [OR] = 0.09). The DRB1*03 allele is in strong linkage disequilibrium with a polymorphism at position –308 in the promoter region of the gene encoding TNFα (TNFA-308*2). We investigated whether this allele frequency was decreased as well. Surprisingly, the CF of TNFA-308*2 was 29%, not different from the CF of 98 HC (34%; P = 0.7; OR = 0.8). This study is the first showing a significant negative association between DRB1*03 and a particular subgroup of CD patients. Thus, patient selection may largely determine the outcome of genetic association studies in CD, as we previously observed no association with this allele in an unselected population of CD patients. As DRB1*03 frequency, but not the closely linked TNFA-308*2, was decreased, this suggests recombination between the DRB1 and TNFA loci in this group of patients, and may help to define the biological basis of fistula formation.

A randomized controlled trial of rubber band ligation versus infra-red coagulation in the treatment of internal haemorrhoids

Objective Despite the presence of numerous non‐surgical therapies for the treatment of haemorrhoids, none of these therapies has clearly been proven to be superior. The effectiveness and patient tolerance of rubber band ligation (RBL) and infra‐red coagulation (IRC) in the treatment of haemorrhoids was assessed. Design Prospective randomized trial. Setting Academic hospital (tertiary care). Participants A total of 133 consecutive patients (73 males, 60 females, mean age 48 years (range 19‐82)) with internal haemorrhoids, and without concomitant anorectal disease, were randomized to rubber band ligation (RBL, n = 65) or infra‐red coagulation (IRC, n = 68). Interventions Rubber band ligation or infra‐red coagulation was performed in one or more sessions with four‐week intervals until symptoms had resolved. Treatment outcome and side‐effects were assessed after each treatment session and one month after the last treatment by proctological examination and a questionnaire, including a pain score (visual analogue scale from 0 to 10). Recurrence of complaints was assessed by telephone questionnaire [mean follow‐up of 19.2 months (SD 7.8)]. Results Treatment outcome was assessed in 124 patients (60 RBL, 64 IRC). The mean number of treatment sessions was 1.6 (SD 0.9) for both therapies. For RBL, 58 patients (97%), and for IRC, 59 patients (92%) were symptom‐free or had satisfactorily improved. Only third‐degree haemorrhoids seemed to respond better to RBL (five of five patients symptom‐free) than to IRC (two of four patients symptom‐free). Pain following treatment was more common and more severe after RBL (VAS 5.5 ± 3.7) than after IRC (VAS 3.3 ± 3.3, P = 0.018). The telephone questionnaire was answered by 105 patients. Nine of 50 patients (18%) treated with RBL and 11 of 55 patients (20%, P = 0.81) treated with IRC had experienced symptomatic relapse to pre‐treatment levels. Conclusions Infra‐red coagulation and rubber band ligation are equally effective in the treatment of haemorrhoids. The rate and severity of pain is higher after rubber band ligation. Infra‐red coagulation should be the first‐line treatment for haemorrhoids. Eur J Gastroenterol Hepatol 12:535‐539

Rising incidence and prevalence of primary biliary cirrhosis: a large population-based study.

Large population‐based studies are much needed to accurately establish the epidemiology of primary biliary cirrhosis (PBC). We aimed to collect all PBC patients in a geographically defined area to evaluate the epidemiology of PBC and examine the possible association of PBC with smoking, age at menarche, age at first pregnancy and number of pregnancies.

Rectal compliance as a routine measurement

PURPOSE: The clinical impact of rectal compliance and sensitivity measurement is not clear. The aim of this study was to measure the rectal compliance in different patient groups compared with controls and to establish the clinical effect of rectal compliance. METHODS: Anorectal function tests were performed in 974 consecutive patients (284 men). Normal values were obtained from 24 controls. Rectal compliance measurement was performed by filling a latex rectal balloon with water at a rate of 60 ml per minute. Volume and intraballoon pressure were measured. Volume and pressure at three sensitivity thresholds were recorded for analysis: first sensation, urge, and maximal toleration. At maximal toleration, the rectal compliance (volume/pressure) was calculated. Proctoscopy, anal manometry, anal mucosal sensitivity, and anal endosonography were also performed as part of our anorectal function tests. RESULTS: No effect of age or gender was observed in either controls or patients. Patients with fecal incontinence had a higher volume at first sensation and a higher pressure at maximal toleration (P=0.03), the presence of a sphincter defect or low or normal anal pressures made no difference. Patients with constipation had a larger volume at first sensation and urge (P<0.0001 andP<0.01). Patients with a rectocele had a larger volume at first sensation (P=0.004). Patients with rectal prolapse did not differ from controls; after rectopexy, rectal compliance decreased (P<0.0003). Patients with inflammatory bowel disease had a lower rectal compliance, most pronounced in active proctitis (P=0.003). Patients with ileoanal pouches also had a lower compliance (P<0.0001). In the 17 patients where a maximal toleration volume<60 ml was found, 11 had complaints of fecal incontinence, and 6 had a stoma. In 31 patients a maximal toleration volume between 60 and 100 ml was found; 12 patients had complaints of fecal incontinence, and 6 had a stoma. Proctitis or pouchitis was the main cause for a small compliance. All 29 patients who had a maximal toleration volume>500 ml had complaints of constipation. No correlation between rectal and anal mucosal sensitivity was found. CONCLUSION: Rectal compliance measurement with a latex balloon is easily feasible. In this series of 974 patients, some patient groups showed an abnormal rectal visceral sensitivity and compliance, but there was an overlap with controls. Rectal compliance measurement gave a good clinical impression about the contribution of the rectum to the anorectal problem. Patients with proctitis and pouchitis had the smallest rectal compliance. A maximal toleration volume<60 ml always led to fecal incontinence, and stomas should be considered for such patients. A maximal toleration volume>500 ml was only seen in constipated patients, and therapy should be given to prevent further damage to the pelvic floor. Values close to or within the normal range rule out the rectum as an important factor in the anorectal problem of the patient.

Assessment and classification of never operated and recurrent cryptoglandular fistulas-in-ano using hydrogen peroxide enhanced transanal ultrasound

Classification and visualization of fistula‐in ano is used to determine surgical treatment according to the type of fistula, predict the recurrence rate and incontinence risk and compare the results of treatment published in literature. Hydrogen peroxide enhanced transanal ultrasound (HPUS) with the peroxide introduced through the external opening of the fistula gives a clear and accurate visualization of the track in relation to the sphincters. The aim of this study was to review never operated and recurrent cryptoglandular fistulas‐in‐ano visualized with the aid of HPUS in order to establish the anatomical differences.

Normal values and reproducibility of anal endosonographic measurements

Abstract Objective : Endosonographic measurements of anal canal structures are used in the description of various anorectal disorders. This study was designed to determine normal values and reproducibility of anal endosonographic measurements. Methods : Anal endosonography was performed in 40 healthy individuals (18 females, 22 males, mean age 45 (range 25–75) years). The mean internal anal sphincter thickness (IST), external anal sphincter thickness (EST), submucosal thickness (SMT) and puborectal muscle thickness (PRT) were assessed and tested for association with physiologic parameters (age, sex and parity). Furthermore, intra- and inter-observer variability were assessed for anal canal measurements and for detected sphincter defects in 19 patients with anorectal disease (ten females, nine males, mean age 53 (range 24–75) years). Results: In healthy individuals mean IST was significantly lower in males (1.3±0.4 vs. 1.8±0.8 mm, p =0.007), while mean EST was significantly lower in females (6.9±1.1 vs. 8.3±1.3 mm, p =0.001). No significant gender differences were found in mean PRT (8.2±1.9 mm) and mean SMT (2.3±0.5 mm). IST ( r =0.41, p =0.008) and SMT ( r =0.33, p =0.04) increased with age. Parity was not associated with any of the measured structures. Although at least 95% of all repeated measurements was within the limits of agreement, most reliability coefficients were relatively low. (respectively for intra- and inter-observer variability: IST r i =0.60/0.64, EST r i =0.70/0.84, SMT r i =0.65/0.62, PRT r i =0.83/0.71). Kappa values for the reproducibility of sphincter defects varied from moderate (interobserver κ =0.48; intraobserver κ =0.60) for internal sphincter defects to good or very good ( κ =0.79; κ =0.89) for external sphincter defects. Conclusion : We determined normal values of anal canal structure measurements. EST and IST are associated with gender and IST and SMT with age. The reproducibility of anal canal measurements is relatively poor, but not investigator dependent. The reproducibility of sphincter defects is good, external sphincter defects being reproduced better than internal sphincter defects.