Development of pancreatic diseases during long-term follow-up after acute pancreatitis: a post-hoc analysis of a prospective multicenter cohort.

BACKGROUND AND AIM: More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling. METHODS: A long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed. RESULTS: Overall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP. CONCLUSION: Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.

How the concept of biochemical response influenced the management of primary biliary cholangitis over time.

BACKGROUND: Criteria assessing biochemical response to ursodeoxycholic acid (UDCA) are established risk stratification tools in primary biliary cholangitis (PBC). We aimed to evaluate to what extent liver tests influenced patient management during a three decade period, and whether this changed over time. METHODS: 851 Dutch PBC patients diagnosed between 1988 and 2012 were reviewed to assess patient management in relation to liver test results during UDCA treatment. To do so, biochemical response at one year was analysed retrospectively according to Paris-1 criteria. RESULTS: Response was assessable for 687/851 (81%) patients; 157/687 non-responders. During a follow-up of 8.8 years (IQR 4.8-13.9), 141 died and 30 underwent liver transplantation. Transplant-free survival of non-responders (60%) was significantly worse compared with responders (87%) (p < 0.0001). Management was modified in 46/157 (29%) non-responders. The most frequent change observed, noted in 26/46 patients, was an increase in UDCA dosage. Subsequently, 9/26 (35%) non-responders became responders within the next two years. Steroid treatment was started in one patient; 19 patients were referred to a tertiary centre. No trend towards more frequent changes in management over time was observed (p = 0.10). CONCLUSION: Changes in medical management occurred in a minority of non-responders. This can largely be explained by the lack of accepted response criteria and of established second-line treatments for PBC. Nevertheless, the observation that response-guided management did not increase over time suggests that awareness of the concept of biochemical response requires further attention,particularly since new treatment options for PBC will soon become available.

Dutch Chronic Pancreatitis Registry (CARE): design and rationale of a nationwide prospective evaluation and follow-up.

BACKGROUND: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted. METHODS: The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years. RESULTS: A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years. DISCUSSION: The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies.

Nurse endoscopists perform colonoscopies according to the international standard and with high patient satisfaction.

BACKGROUND AND STUDY AIMS: Colonoscopy is increasingly performed by nurse endoscopists. We aimed to assess the endoscopic quality and patient experience of these procedures. PATIENTS AND METHODS: This prospective multicenter study analyzed 100 consecutive colonoscopies each for 10 trained nurse endoscopists with respect to endoscopic quality and patient experience. Colonoscopies were performed under the supervision of a gastroenterologist, using the techniques and protocols of the participating hospitals. Patient experience was assessed using a questionnaire. RESULTS: Most nurse endoscopists were female (90 %; median age 43 [range 35 - 49]). Before the start of the study, they had performed a median of 528 colonoscopies (range 208 - 2103). For the 1000 patients, mean age was 56 ± 15 years; 55 % were women; and 96 % were in class I or II according to the American Society of Anesthesiologists' physical status classification system. Colonoscopies were performed for screening or surveillance in 42 %; for symptomatic indications in 58 % of patients. The unassisted cecal intubation rate was 94 %; the mean withdrawal time was 10 ±â€Š5 minutes. The adenoma detection rate was 26.7 %. In 229 of the colonoscopies (23 %), the nurse endoscopists required assistance from the supervising gastroenterologist. The complication rate was 0.2 %: one perforation and one cardiopulmonary complication. The questionnaire was completed by 734 /1000 patients (73 %) and of these 694 /734 (95 %) were satisfied with the endoscopic procedure. Among the respondents 530 /734 (72 %) had no specific preference for a physician or nurse endoscopist, whereas 113 /734 (15 %) preferred a physician endoscopist, and 91 /734 (12 %) preferred a nurse endoscopist. CONCLUSION: The nurse endoscopists performed colonoscopies according to the internationally recognized quality standards and with high patient satisfaction.

Age at diagnosis of inflammatory bowel disease influences early development of colorectal cancer in inflammatory bowel disease patients: a nationwide, long-term survey.

BACKGROUND: Data on clinical characteristics of patients with inflammatory bowel disease (IBD)-related colorectal cancer (CRC) are scarce and mainly originate from tertiary referral centres. We studied patient and disease characteristics of IBD-related CRC in a nationwide IBD cohort in general hospitals. Main outcome parameters were time to develop CRC, and factors associated with early CRC development. METHODS: All IBD patients diagnosed with CRC between 1 January 1990 and 1 July 2006 were identified using a nationwide automated pathology database (PALGA). Patient charts were assessed to confirm diagnosis and collect clinical data. Early CRC was defined as CRC diagnosed less than 8 years after IBD diagnosis. Statistical analysis was performed using descriptive statistics, independent t tests, binary logistic regression and Cox-regression analysis. RESULTS: Diagnosis of IBD-related CRC was confirmed in 251 patients (171 ulcerative colitis, 77 Crohn's disease, 3 unclassified colitis), 161 males (64 %). Median time from IBD diagnosis to CRC diagnosis was 12 years (IQR 4-20); 89 patients (35 %) developed early CRC. Type of IBD, gender, concomitant PSC, pseudopolyps, extent of inflammation, and medication use were not related to early CRC (p > 0.05). IBD diagnosis at older age (HR for 10 years older age 2.25; 95 % CI 1.92-2.63) was related to early CRC. Twenty-three patients (12 %) had been included in a surveillance programme prior to CRC diagnosis. Patients in the surveillance group had a significantly better tumor stage (p = 0.004). CONCLUSIONS: We emphasize the problem of a high proportion of IBD-associated CRCs developing before the recommended start of surveillance. Therefore, we suggest that older age at IBD onset could be an additional factor to start surveillance in IBD patients.

[As-needed treatment with gastric acid inhibitors in gastroesophageal reflux disease]. / 'Zo nodig'-gebruik van zuurremmende middelen bij refluxziekte.

Although proton pump inhibitors and H2-receptor antagonists are usually prescribed for continuous use by patients with gastro-oesophageal reflux disease, at least 50% of such patients do not take their medication daily and some take it only sporadically. On-demand treatment with proton pump inhibitors or H2-receptor antagonists is safe and cost-effective. Indications are: (a) incidental reflux episodes of short duration, (b) periodic reflux lasting several weeks or months, (c) chronic reflux not requiring continuous treatment. On-demand treatment is unsuitable for patients with reflux disease who either require daily medication or in whom the maximal dosage is insufficient. There are three types of on-demand treatment. Type 1: use of medication only in case of incidental symptoms. Type 2: continuous medication for 2-4 weeks when symptoms appear. Type 3: continuous use because of chronic symptoms, but the interval between doses is determined by the patient on the basis of his symptoms. All antacids can in principle be used for on-demand treatment; for type 3 treatment, antacids with a rapid onset of action are preferred. A favourable response to the two weeks of initial therapy is a good predictor for successful on-demand treatment.

Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipation.

BACKGROUND: There is a need for better tolerated drugs to normalize bowel function in chronic constipation. Prucalopride is a highly selective, specific, serotonin4 receptor agonist with enterokinetic properties. AIM: To evaluate the effects of prucalopride on bowel function, colonic transit and anorectal function in patients with chronic constipation. METHODS: Twenty-eight patients were enrolled in this double-blind, placebo-controlled, crossover study (prucalopride: 1 mg, n=12; 2 mg, n=16). Patients kept a bowel function diary. Colonic transit times and anorectal function (anal manometry, rectal sensitivity and rectal compliance) were assessed. RESULTS: Prucalopride (1 mg) compared to placebo significantly increased the mean number of spontaneous complete, spontaneous and all bowel movements per week. Prucalopride (1 mg) significantly decreased the percentage of bowel movements with hard/lumpy stools and straining and increased the urge to defecate. Prucalopride (1 and 2 mg) decreased the mean total colonic transit time by 12.0 h (prucalopride 42.8 h vs. placebo 54.8 h; P=0.074). No statistically significant effects were found in any of the anorectal function parameters. Prucalopride was well tolerated. There were no clinically relevant changes in standard safety parameters. CONCLUSIONS: Prucalopride significantly improves stool frequency and consistency, and the urge to defecate, and may decrease colonic transit times in patients with chronic constipation.

Assessment and classification of fistula-in-ano in patients with Crohn's disease by hydrogen peroxide enhanced transanal ultrasound.

Crohn's disease is well known for its perianal complications, among which fistulas-in-ano are the most common abnormalities. Fistulas-in-ano in Crohn's disease tend to be complex and have a high recurrence rate. Therefore the role of surgery is generally more conservative. Hydrogen peroxide enhanced transanal ultrasound has proven superior to physical examination, fistulography, computed tomography, and conventional ultrasound in demonstrating the fistula tract. This study examined the fistula tracks in patients with Crohn's disease. Forty-one patients with Crohn's disease and fistula-in-ano were investigated using physical examination, sondage of the fistula, proctoscopy and transanal ultrasound. Hydrogen peroxide was infused via a small catheter into the fistula. The main track and the ramification of the fistula were classified according to the anatomical Parks' classification. Only 9 (22%) patients had a single inter- or transsphincteric fistula. In 5 (12%) patients a single supra- or extrasphincteric fistula (high fistula) was found, in 14 (34%) more than one fistula track (ramified), and in 13 (32%) an anovaginal fistula. Thus 78% of patients had a surgically difficult to treat fistula. In the ramified fistula the main track follows the Parks' classification, but ramifications can have a bizarre pattern which is not in agreement with this classification. Optimal documentation by means of hydrogen peroxide enhanced transanal ultrasound is therefore mandatory before surgery or before other therapies such as anti-tumor necrosis factor treatment.

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

OBJECTIVE: 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. PATIENTS AND METHODS: Eighty-one patients with never operated (48) or recurrent (33) cryptoglandular fistulas-in-ano were assessed by clinical examination and HPUS. RESULTS: Never operated fistulas were single track, trans- or inter-sphincteric fistulas in 80%. In 15%, the tracks were sinus with no connection to the pectinate line. Two patients (5%) had a transsphincteric fistula with a ramification. No supra- or extra-sphincteric fistulas were found in the never operated fistula group. In the recurrent fistula patients, 57% had a single trans or intersphincteric track, 15% of the patients had a single track supra or extrasphincteric fistula and 27% had a ramified fistula. CONCLUSIONS: All never operated cryptoglandulair fistulas-in-ano were inter- or trans-sphincteric. An extra track was found in 5%. Recurrent fistulas-in-ano were supra or extrasphincteric in 15% and ramified in 27%. Therefore, never operated fistula-in-ano does not require any special investigation before surgical treatment. However, before treating recurrent fistulas, visualization by HPUS is recommended to detect supra or extrasphincteric fistulas or ramification.

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.

Rectal compliance as a routine measurement: extreme volumes have direct clinical impact and normal volumes exclude rectum as a problem.

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 and P < 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.

Effect of prucalopride, a new enterokinetic agent, on gastrointestinal transit and anorectal function in healthy volunteers.

BACKGROUND: Prucalopride (PR) is a novel 5-HT4 agonist enterokinetic compound. AIM: To evaluate its effect on bowel function, gut transit and anorectal function in healthy volunteers using a double-blind, placebo-controlled crossover study. METHODS: Twenty-four healthy volunteers (12 men, 12 women, mean age 25 years, range 20-53 years) were randomly assigned to 1 mg/placebo or 2 mg/placebo (PL). The trial consisted of five consecutive 1 week periods: no drug treatment, PR treatment or PL, washout, PL or PR, no treatment. Subjects maintained a diary of bowel function during the entire study period. Total intestinal transit time (TITT), mean colonic transit time (MCTT) and anorectal function (anal manometry, rectal sensitivity and rectal compliance) were assessed at the end of both treatment periods. Electrocardiography and blood sampling were performed for safety analysis; blood sampling was also used to check compliance. RESULTS: No subjects withdrew from the study. Treatment with PR 2 mg showed a statistically significant increase in mean number of weekly stools (11.5 vs. 7.1 compared to PL, P = 0.04) and in the percentage of loose/watery stools (48 vs. 12% compared to PL, P = 0.005). Within 1 week, stool frequency and consistency returned to baseline values when treatment was stopped. MCTT was shortened significantly with both doses, i.e. from 35 h on PL to 25 h on PR 1 mg (P = 0.01) and from 43 h on PL to 22 h on PR 2 mg (P = 0.02). Anorectal function was unaffected by PR. Transient and moderate headache occurred in nine subjects during PR treatment and in six subjects during PL treatment. CONCLUSION: Prucalopride is well tolerated by healthy subjects and has a marked and consistent effect on stool frequency and consistency, and on colonic transit. In the present study prucalopride did not affect visceral sensitivity or sphincter function. It holds promise for patients with slow transit constipation.

Endosonography in benign anorectal disease: an overview.

BACKGROUND: Endosonography may be used for diagnosing various anorectal disorders. This review addresses its technique and clinical use in benign anorectal disease. METHODS: The English literature available on anal endosonography was reviewed. The different modalities, the endosonography technique itself and its value in benign anorectal disease were described. RESULTS: Anal endosonography is easy to perform, has a short learning curve and causes less discomfort than routine digital examination. Anal sphincters can be clearly visualized and distinction is possible between the internal (hypoechoic) and external (hyperechoic) anal sphincters. Other pelvic floor structures, like the puborectalis muscle, can also be visualized. Endosonography is mostly used in the assessment of faecal incontinence; it has brought new insight into the pathophysiological mechanisms of this disorder and can select patients with traumatic incontinence for sphincter repair. It has replaced electromyographical sphincter mapping, which is a painful and time-consuming procedure. In perianal sepsis, endosonography assists in defining fistula tract anatomy. The use of contrast agents has significantly increased the accuracy of endosonography in the assessment of perianal fistulae. In addition, endosonography is an excellent alternative to expensive MRI. Besides its use in incontinence and perianal sepsis, with anal endosonography surgical possibilities can be evaluated in individual patients, for example, to decide whether a sphincter repair or a lateral sphincterectomy is preferable. Finally, endosonography may occasionally identify internal sphincter myopathy in patients with intractable constipation or proctalgia. CONCLUSION: Anal endosonography images the internal and external sphincters with high accuracy. It is easy to perform and is especially valuable in the diagnosis of anal incontinence and perianal sepsis.

Referral for anorectal function evaluation: therapeutic implications and reassurance.

AIM: To determine the impact of anorectal function evaluation (AFE) on patients and referring specialists. PATIENTS AND METHODS: In one year, 135 patients were referred for AFE, which consisted of proctoscopy, anal manometry, rectal compliance, anal sensitivity measurement and anal endosonography. Questionnaires were sent to the patients and referring specialists. RESULTS: In 70% of the 135 patients there was total agreement about the referring and final diagnosis. The response rate of the patients was 78% (n = 100) and that of the specialists was 91% (n = 117). The experience with regard to pain and embarrassment during AFE was good. Of the women, 13% preferred a female investigator. Fifty-nine patients answered that they had received one or more treatments after referral: surgery (n = 32), medication (n = 16), diet (n = 5), physiotherapy (n = 1) or a combination of the above (n = 5). Of the 41 patients who did not receive another treatment, 29 were reassured and 12 did not experience any benefit from the visit, thus bringing the total benefit of the referral to 88%. The anorectal complaints before AFE and at follow-up improved significantly in the treated group (P < 0.0001). The advice given was followed by the referring specialist in 98 cases (84%). The quality of the advice given was considered good in 98 (84%). The opportunity of referral for AFE was considered useful in 108 cases (93%). In 71 patients, information from both the specialist and the patient was obtained. Three patients had therapies that were not advised and 19 patients did not follow the advice (mainly dietary). In the 135 patients, AFE changed the management in 34 patients (25%). In the other 101 patients, endosonography was of value in determining the size of sphincter defects or the fistula tracks. CONCLUSION: AFE was well tolerated and changed the management in 25% of patients. Additional advice and reassurance were given in many patients; only 12% of patients claimed to have no benefit from the referral. Anal endosonography seems the most valuable test.

Third-degree obstetric perineal tear: long-term clinical and functional results after primary repair.

BACKGROUND: This study was designed to investigate the long-term clinical and anorectal functional results after primary repair of a third-degree obstetrical perineal rupture. METHODS: One hundred and fifty-six consecutive women who had a primary repair of a third-degree perineal rupture were sent a questionnaire and asked to undergo anorectal function testing (anal manometry, anorectal sensitivity, anal endosonography and pudendal nerve terminal motor latency (PNTML)) RESULTS: Some 117 women (75 per cent) responded. Anal incontinence was present in 47 women (40 per cent); however, in most cases only mild symptoms were present. In 40 women additional anorectal function tests were performed and compared with findings in normal controls. Mean(s.d.) maximum squeeze pressure (31(15) versus 63(17) mmHg, P< 0.001) was decreased and first sensation to filling of the rectum (88(47) versus 66(33) ml, P=0.03) and anal mucosal electrosensitivity (4.7(1.7) versus 2.5(0.8) mA, P=0.003) were increased compared with values in normal controls. In 35 women (88 per cent) a sphincter defect was found with anal endosonography. Factors related to anal incontinence were the presence of a combined anal sphincter defect (relative risk (RR) 1.7 (95 per cent confidence interval (c.i.) 1.1-2.8)) or subsequent vaginal delivery (RR 1.6 (95 per cent c.i. 1.1-2.5)). CONCLUSION: Anal incontinence prevails in 40 per cent of women 5 years after primary repair of a third-degree perineal rupture. The presence of a combined sphincter defect or subsequent vaginal delivery increase the risk of anal incontinence.

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

UNLABELLED: 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 infused via 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.

HLA-DRB1*03, but not the TNFA -308 promoter gene polymorphism, confers protection against fistulising Crohn's disease.

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 TNFalpha (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.

Vaginal endosonography of the anal sphincter complex is important in the assessment of faecal incontinence and perianal sepsis.

BACKGROUND: Anal endosonography is an established technique in the evaluation of anorectal disease. However, it is sometimes difficult to visualize the anterior part of the sphincter complex and anal endosonography may be impossible when anal pain or stenosis is present. The aim of this study was to evaluate vaginal endosonography in the diagnosis of faecal incontinence and perianal sepsis. METHODS: Anal and vaginal endosonography were performed in 56 women with faecal incontinence (n = 36) or perianal sepsis (n = 20). The technique and pelvic floor anatomy were described, anal sphincter measurements with anal and vaginal endosonography were compared, and the additive value of vaginal over anal endosonography in the diagnosis of faecal incontinence and perianal sepsis was assessed. RESULTS: The pelvic floor was clearly imaged with vaginal endosonography. However, after a relatively short learning curve it was still not possible to image the anal sphincters in three of 28 patients. Except for external anal sphincter thickness, which was significantly lower, all anal canal structure measurements were greater with vaginal than with anal endosonography. Concerning the diagnosis of either faecal incontinence or perianal sepsis, vaginal endosonography added important information in comparison with anal endosonography in 14 (25 per cent) of 56 patients. CONCLUSION: Vaginal endosonography provides reliable images of the anal sphincters in an undistorted fashion, thereby increasing the diagnostic yield of faecal incontinence and perianal sepsis in 25 per cent of patients. Therefore, endosonographists should become acquainted with this technique.