Development and psychometric evaluation of a dutch questionnaire for the assessment of anorectal and lower urinary tract symptoms.

BACKGROUND AND STUDY AIMS: Epidemiological studies have shown a frequent coexistence of symptoms and diseases affecting the anorectum and lower urinary tract. To further investigate combined symptoms and pathology of both pelvic viscera we developed a self-reported questionnaire, in Dutch, which extensively evaluates habits, complaints and symptoms of both viscera. We describe the construction and the psychometric properties of this questionnaire. PATIENTS AND METHODS: This prospective study was conducted in 56 patients with anorectal symptoms, 41 patients with lower urinary tract symptoms and in a control group of 91 people. The following psychometric properties of the questionnaire were evaluated: content validity, construct validity, criterion validity, test-retest reliability and internal consistency. RESULTS: The questionnaire covered all important domains, was well interpreted and showed good acceptability (content validity). The questionnaire clearly differentiated the patient populations (construct validity). The criterion validity of the questionnaire was excellent. The test-retest reliability of the questionnaire was acceptable in all three the study populations (overall median kappa: 0.64; Inter Quartile Range: 0.56-0.75; mean agreement: 88%). The internal consistency of both anorectal and lower urinary tract symptom questions was high (Crohnbach's alpha of 0.78 and 0.80 respectively). CONCLUSIONS: This questionnaire is a valid and reliable instrument for the assessment of anorectal and lower urinary tract symptoms. It can provide further insights into the epidemiology of concomitant bowel and bladder disorders and, accordingly, can contribute to a more efficient diagnostic and therapeutic approach in patients with such disorders.

Limitations of extensive TPMT genotyping in the management of azathioprine-induced myelosuppression in IBD patients.

BACKGROUND AND AIMS: TPMT deficiency is associated with azathioprine (AZA)-induced myelosuppression (MS). However, in one previous study, only about » of MS episodes in Crohn's Disease patients under AZA can be attributed to TPMT deficiency. Recently, new TPMT mutations have been described and our aim is to investigate their clinical relevance before and after a first MS episode on thiopurine therapy. METHODS: Clinical data from 61 IBD patients having developed MS during AZA therapy were collected. Sequencing analysis was carried out on TPMT cDNA for the presence of all currently known mutations. RESULTS: Only TPMT *2, *3A and *3C mutations were found in this cohort. TPMT mutations were observed in 15 out of 61 patients (25%). Four out of 15 were homozygous for a TPMT mutation (low methylator, LM genotype) and 11 were heterozygous (intermediate methylator, IM genotype). Median delays of MS onset were 2, 2.75 and 6months in the LM, IM and HM (high methylator, wild type TPMT) groups, respectively. After the first MS episode, 36 patients resumed thiopurine treatment of which 13 experienced a second MS episode. This second episode was also rarely associated with TPMT mutations. CONCLUSIONS: One quarter of MS episodes during AZA were associated with TPMT deficient genotype. After a first leucopenia episode, thiopurine therapy may be resumed in a majority of patients independently of their TPMT genotype.

Clinical trial: the efficacy of open-label prucalopride treatment in patients with chronic constipation - follow-up of patients from the pivotal studies.

BACKGROUND: Prucalopride is approved in Europe for symptomatic treatment of chronic constipation in women with inadequate relief from laxatives. AIM: To evaluate efficacy of prucalopride during long-term treatment of patients with chronic constipation. METHODS: Patients from three pivotal double-blind, placebo-controlled, 12-week studies with prucalopride could continue treatment in open-label studies up to 24 months. Efficacy was evaluated every 3 months using the Patient Assessment of Constipation-Quality of Life (PAC-QOL) satisfaction scale. Laxative use and reasons for study discontinuation were recorded. RESULTS: Eighty-six percent of patients who completed the pivotal studies continued prucalopride treatment in the open-label studies (n = 1455, 90% female). Improvement in average PAC-QOL satisfaction score observed after 12-week, double-blind prucalopride was maintained during open-label treatment for up to 18 months; in each 3 month period, 40-50% of patients did not use any laxatives. Most frequent adverse events (AEs) resulting in discontinuation were gastrointestinal events (3.3%) and headache (1.0%). Only 10% of patients who had normalized bowel function on prucalopride at the end of pivotal trials discontinued due to insufficient response during open-label treatment. CONCLUSION: Satisfaction with bowel function is maintained for up to 18 months of treatment with prucalopride. Gastrointestinal events and headache cause discontinuation of prucalopride treatment in ∼5% of patients (ClinicalTrials.gov identifiers: NCT01070615 and NCT00987844).

Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives.

OBJECTIVE: To determine the efficacy, impact on quality of life (QOL) and safety of prucalopride, a selective, high-affinity 5-HT(4) receptor agonist, in patients with chronic constipation. METHODS: In this multicentre, randomised, placebo controlled, parallel-group, phase III study, patients with chronic constipation (two or fewer spontaneous complete bowel movements (SCBM)/week) received 2 mg or 4 mg prucalopride or placebo, once daily, for 12 weeks. The primary efficacy endpoint was the proportion of patients reaching three or more SCBM/week. The key secondary efficacy endpoint was the proportion of patients having an increase of one or more SCBM/week. The primary QOL endpoint was the patient assessment of constipation QOL satisfaction subscale score. Safety parameters included adverse events, laboratory values and cardiovascular events. RESULTS: Efficacy was evaluated over 713 patients. Averaged over 12 weeks, higher proportions of patients on prucalopride 2 mg (19.5%; p<0.01), 4 mg (23.6%; p<0.001) had three or more SCBM/week (or normalisation of bowel function) compared with placebo (9.6%). Similar results were seen in the subgroup (83%) of patients dissatisfied with previous laxative treatment. Both doses of prucalopride also significantly improved secondary efficacy and QOL endpoints, including the proportion of patients with an increase of one or more SCBM/week, evacuation completeness, perceived disease severity and treatment effectiveness and QOL. Prucalopride 4 mg significantly reduced the need for straining versus placebo (p<0.05). The most frequent treatment-related adverse events were headache and diarrhoea. Both doses of prucalopride were safe and well tolerated. CONCLUSION: Prucalopride significantly and consistently improved bowel function, associated symptoms and satisfaction in chronically constipated patients.

Physiopathology of the anal fissure.

The physiopathology of anal fissures is still not completely elucidated. Most probably, chronic anal fissures are ischaemic ulcers, continuously enhanced by sphincter hypertonia. The dorsal location of most fissures is attributed to the scarcity of arteriolar anastomoses dorsally. The healing process is obstructed by fibrosis, provoked by repeated mechanical injuries and chronic inflammation.

GLEM/LOK report on proctology practice in Belgium. Results, comments and recommendations.

The article summarizes the response of eighty-eight Belgian gastroenterologists to a questionnaire on proctology practice, established by the common evaluation groups (GLEM/LOK) of medical practice. The results of the inquiry concerning haemorrhoids, anal fissure, abscess and fistula, and faecal incontinence are discussed separately. Each chapter is completed by specific therapeutic and/or diagnostic recommendations. These are based on the official statements of the American Gastroenterological Association and on our own clinical practice. There are still no official guidelines on proctology in Belgium and neighbouring countries. The diagnostic and therapeutic quality of the approach of our proctologic patients should improve by appropriate proctologic education and training in selected centres.

Renal impairment in patients with inflammatory bowel disease: association with aminosalicylate therapy?

BACKGROUND: In recent years, several case reports have been published suggesting an association between the use of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) and the development of chronic tubulo-interstitial nephritis. Apart from lesions associated to 5-ASA treatment, however, it is clear that IBD itself may also induce renal impairment, albeit the frequency is unknown. METHODS: During 1 year, all IBD patients seen at the outpatient clinic of 27 European centres of gastro-enterology were registered and screened for renal impairment controlling for a possible association with 5-ASA therapy. Patients were questioned about their medical and drug history and their IBD disease activity. Renal screening (calculated creatinine clearance) was performed at baseline, after 6 and 12 months. RESULTS: Included patients (n = 1,529) had a mean age of 39 (range 14-98), 56% had Crohn's disease, 42% ulcerative colitis and 2% indeterminate colitis. Half of the patients used 5-ASA during the study period. Decreased creatinine clearance was observed in 34 patients, among them 13 with chronic renal impairment. Comparing patients with and without renal impairment, no difference could be observed in 5-ASA consumption. In contrast, patients with renal impairment were significantly older, had a lower body mass index and showed a higher frequency of male sex, bowel resection and stoma. CONCLUSION: Although the association between 5-ASA therapy and chronic tubulo-interstitial nephritis is clearly described in several case reports, this prospective study came to the reassuring conclusion that renal impairment in IBD patients is not frequently observed and is rarely associated with 5-ASA therapy.

Asymptomatic aneurysm of the hepatic artery. Management options.

Hepatic aneurysms are rare. The majority of patients present acutely with aneurysm rupture, with an attended high mortality. Diagnosis is difficult and often delayed, owing to the non-specific symptoms and lack of clinical findings. We present three cases of hepatic artery aneurysm diagnosed in a pauci- or asymptomatic stage, illustrating the different therapeutic options described when these aneurysms are diagnosed in this stage: expectant management, embolization, or surgery.

Is anorectal endosonography valuable in dyschesia?

AIMS: Dyschesia can be provoked by inappropriate defecation movements. The aim of this prospective study was to demonstrate dysfunction of the anal sphincter and/or the musculus (m.) puborectalis in patients with dyschesia using anorectal endosonography. METHODS: Twenty consecutive patients with a medical history of dyschesia and a control group of 20 healthy subjects underwent linear anorectal endosonography (Toshiba models IUV 5060 and PVL-625 RT). In both groups, the dimensions of the anal sphincter and the m. puborectalis were measured at rest, and during voluntary squeezing and straining. Statistical analysis was performed within and between the two groups. RESULTS: The anal sphincter became paradoxically shorter and/or thicker during straining (versus the resting state) in 85% of patients but in only 35% of control subjects. Changes in sphincter length were statistically significantly different (p<0.01, chi(2) test) in patients compared with control subjects. The m. puborectalis became paradoxically shorter and/or thicker during straining in 80% of patients but in only 30% of controls. Both the changes in length and thickness of the m. puborectalis were significantly different (p<0.01, chi(2) test) in patients versus control subjects. CONCLUSIONS: Linear anorectal endosonography demonstrated incomplete or even absent relaxation of the anal sphincter and the m. puborectalis during a defecation movement in the majority of our patients with dyschesia. This study highlights the value of this elegant ultrasonographic technique in the diagnosis of "pelvic floor dyssynergia" or "anismus".

Acute lower gastrointestinal bleeding in Crohn's disease: characteristics of a unique series of 34 patients. Belgian IBD Research Group.

OBJECTIVE: Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease, which represents a diagnostic and therapeutic challenge. The aim of this study was to define epidemiological characteristics and therapeutic options of hemorrhagic forms of Crohn's disease. METHODS: Thirty-four cases of hemorrhagic forms of Crohn's disease were studied retrospectively. Acute lower gastrointestinal hemorrhage was defined as acute rectal bleeding originating in diseased bowel and requiring a transfusion of at least 2 units of red blood cells within 24 h. Upper gastrointestinal tract hemorrhage or anal lesions and postoperative bleeding were excluded. RESULTS: Mean age at time of hemorrhage was 34.2 +/- 14 yr. Mean duration of disease before the hemorrhage was 5.6 +/- 6 yr. The hemorrhage occurred during a flare up of the disease in 35% of cases. The hemorrhage revealed Crohn's disease in 23.5% of cases. The hemorrhage was more frequent in colonic disease (85%) than in isolated small bowel disease (15%) (p < 0.0001). The origin of bleeding was identified in 65% of cases, by colonoscopy (60%), by angiography (3 patients), or at surgery (1 patient). The bleeding lesion was an ulcer in 95% of cases, most often in the left colon. The treatment was surgical in 20.5% (colectomy in 36%), endoscopical (7 patients, including 5 successes), or medical. Hemorrhage recurred in 12 patients (35%) within a mean time of 3 yr (4 days-8 yr), requiring surgery in 3 cases. No death was observed. CONCLUSIONS: This study performed in a series characterized by a nonsurgical recruitment, the largest to date, shows that hemorrhagic forms of Crohn's disease may reveal disease in 23.5%, occurs in quiescent Crohn's disease in two-thirds of cases. Given the potential efficacy of endoscopical or medical treatment, as well as the absence of mortality, a conservative approach may be suggested as first-line therapy in the majority of patients.

Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease with special attention for IgA-class antibodies.

Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) of the IgG class have been reported in inflammatory bowel disease, mainly in ulcerative colitis. Since this disease affects the gastrointestinal tract, we determined whether IgA class ANCA were present in inflammatory bowel disease. We used an indirect immunofluorescence assay for IgG and IgA ANCA testing. Sera from 34 patients with Crohn's disease and 29 patients with ulcerative colitis were collected together with clinical and laboratory data. We found IgA class ANCA of a perinuclear type in 52% of patients with ulcerative colitis and in 9% of Crohn's disease patients. There was a significant association between the presence of IgA ANCA and the occurrence of blood in the feces in the ulcerative colitis group (P = 0.03). IgG ANCA was found in 56% of patients with ulcerative colitis and in 7% of patients with Crohn's disease. Because of partial overlap between IgG and IgA ANCA positivity, the sensitivity of ANCA testing in ulcerative colitis increased from 56% up to 78% by combining IgG and IgA assays. In conclusion, IgA ANCA occurs with a high prevalence in ulcerative colitis. Moreover there is a possible relationship between IgA ANCA and disease activity in ulcerative colitis.

Short- and long-term efficacy of cyclosporin administration in patients with acute severe ulcerative colitis. Belgian IBD Group.

Cyclosporin (CsA) has been proposed in the management of patients with acute ulcerative colitis (UC) in whom standard therapy failed and who were candidates for colectomy. Seven academic hospitals contributed to this retrospective study that included 29 patients (median age: 33 y. (15-74 y.); 12 females and 17 males). The median duration of the disease was 4 y. (0.3 to 33 y.). Before initiating CsA, patients were unresponsive to treatment including i.v. corticosteroids (n = 29), 5-ASA or salazopyrine (n = 19), azathioprine (n = 3), antibiotics (n = 14). The i.v. mean dose was 4 mg/kg/day and was adapted to blood level. Concomitant treatment included corticosteroids (n = 27). The median duration of i.v. CsA administration was 10 days (4 to 41 days). At the end of CsA administration, a global improvement was described in 20 patients while a surgery had to be performed immediately in 8 patients because of exacerbation of symptoms (n = 7) or perforation (n = 1). One other patient (74 y.) died because of Pneumocystis carinii infection. For the responders, maintenance therapy included: tapering dose of steroids (n = 12), azathioprine (n = 12), 5-ASA or salazopyrine (n = 10), methotrexate (n = 1) or oral CsA (n = II). The median duration of follow-up was 12 months (4 to 48 months). Among the 20 responders, 7 were subsequently referred for colectomy either electively (n = 3) or because of recurrence of the disease (n = 4). Among the 12 patients treated by azathioprine as a maintenance therapy, only 3 had to be referred for surgery (25%). Among the 8 patients who did not receive azathioprine, 4 were subsequently referred for a colectomy (50%) (NS). In patients with acute refractory UC who received CsA, the short-term efficacy (avoidance of immediate colectomy) was obtained in 20 out of 29 patients (69%). However, after a median follow-up of 12 months, only 13 patients were colectomy free (45%).

Endoscopic ultrasonography in inflammatory bowel disease, paracolorectal inflammatory pathology, and extramural abnormalities.

Endoscopic ultrasound (EUS) is easy to perform, noninvasive, and well tolerated in individuals with inflammatory bowel disease. In the anorectal region, the examination takes minimal preparation and has become a routine procedure in the diagnosis and therapeutic follow-up of malignant and nonmalignant disorders. Topics discussed in this article include techniques, abscesses, and fistulas.

A double-blind crossover comparison study of the safety and efficacy of mebeverine with mebeverine sustained release in the treatment of irritable bowel syndrome.

The safety and efficacy of the sustained release (SR) mebeverine capsule was compared to the standard plain mebeverine capsule in the treatment of 60 patients suffering from irritable bowel syndrome. Patients, with a score of at least 44 on the Kruis scale, were randomized into a two-period crossover trial. Each treatment period lasted for 6 weeks during which the patients took mebeverine plain 135 mg, two capsules t.i.d., or mebeverine sustained release 200 mg (SR), two capsules b.i.d. After 6 weeks of each treatment, both treatments were regarded 'effective' or 'very effective' by the patient as well as the investigator in more than 80% of the cases. After 3 weeks of the first treatment, the disease score was rated light in 73% of the patients with both medications. After 6 weeks, nine patients (33%) were symptom-free with mebeverine plain, and five (18%) with mebeverine SR. During the second treatment period the number of symptom-free cases reached about 40% with both formulations. Considering the clinical general improvement, more than 70% of all patients had improved after 3 weeks of the first treatment. An additional improvement was reported in 13 patients with mebeverine plain and in 10 patients with mebeverine SR after the next 3 weeks. Abdominal pain was still present in more than 50% of patients but with lower intensity compared with baseline values. Mean scores of efficacy were very similar for both treatments after 3 and 6 weeks (2.0 for mebeverine plain vs. 1.9 for mebeverine SR). The statistical comparison of all scores between the two formulations did not show a significant difference at any time. Very few adverse events were noted and a causal relationship with the study medications was judged as improbable or definitely unrelated. Compliance was close to 100% for most of the patients. The results of the present study indicate that the mebeverine SR capsule provides equivalent efficacy and tolerance to mebeverine plain in the treatment of irritable bowel syndrome (IBS), while reducing the number of daily doses from three to two.

Loperamide oxide for the treatment of chronic diarrhoea in Crohn's disease.

Loperamide oxide was compared with placebo for the treatment of chronic diarrhoea in patients with Crohn's disease. After initially receiving 2 mg loperamide oxide or placebo, hospital out-patients with Crohn's disease were instructed to take one tablet of loperamide oxide (1 mg) or placebo after passage of each unformed stool in a 1-week double-blind investigation. Patients who responded to this treatment by passing less than three unformed stools per 24 h continued to receive the drug, twice daily, for a further week. At the end of the initial 1-week treatment phase both the investigator's and the patients' global evaluations of efficacy were significantly in favour of the active treatment (P = 0.025 and P = 0.020, respectively). The investigator's assessment of the change in abdominal pain was significant for loperamide oxide (P = 0.020) but not for placebo. Improvements in patient-rated severity of diarrhoea were significantly greater for loperamide oxide than for placebo (P = 0.046). The mean daily dose of loperamide oxide was 2.7 mg. During the second week, both the investigator's and the patients' assessments of global efficacy and symptom improvement continued to favour loperamide oxide though the differences were not significant. Adverse events were rare. The results suggest that loperamide oxide (3 mg/per day) provides a safe and effective treatment for the chronic diarrhoea associated with Crohn's disease.

Meckle's diverticulum in association with Crohn's disease.

Although it is not uncommon to encounter a Mecklel's diverticulum in a patient with Crohn's disease, the involvement of this diverticulum by Crohn's disease is less common. A well performed radiological small intestinal study strongly suggests the diagnosis, which is definite after histologic examination of the reported.

Transrectal ultrasonographic examination of the anal sphincter.

Transrectal Ultrasonography (TRU) provides an excellent imaging of the rectal wall, the perirectal structures (1) and especially of the anal sphincter (2,3). We used a rigid endorectal probe with a linear and a radial ultrasonic window, and with a frequency of 5 MHz (model IUV 5060; Toshiba, Japan). The linear scanning provided a better imaging of the anal sphincter and was preferred to the radial scanning, especially when measuring the sphincter dimensions.

Transrectal ultrasound study of the pathogenesis of solitary rectal ulcer syndrome.

Transrectal ultrasonography is of clinical value in anorectal carcinoma and in inflammatory diseases of the anorectum. In this study a rigid linear endorectal probe was used to examine 15 patients with endoscopically and biopsy proved diagnosis of solitary rectal ulcer syndrome. In 13 of the 15 patients the rectal wall was thicker (mean (SEM) 5.7 (0.4) mm; normal values: 2.8 (0.1) mm) near the rectal ulcer. In all these cases the muscularis propria layer exceeded the maximum normal diameter of 2 mm. In nine of the 15 patients the normal rectal wall echo-structure, with five distinct layers, was disturbed and there was fading of the borders between the mucosa and the muscularis propria. Poor relaxation of the puborectalis muscle during straining was seen on ultrasound in 11 patients, as was intussusception of the rectal wall. The obvious enlargement of the muscularis propria points to a chronic mechanical load on the rectal wall. The ulcerative lesions are formed in this area of overloaded rectal wall. The direct visualisation of the puborectalis muscle during dynamic transrectal ultrasonography indicates that the fact that it does not relax is an important element in the pathogenesis of solitary rectal ulcer syndrome.

Efficacy of cisapride in functional dyspepsia resistant to domperidone or metoclopramide: a double-blind, placebo-controlled study.

A double-blind, placebo-controlled trial was performed to determine the therapeutic efficacy of cisapride in patients with refractory functional dyspepsia. A total of 147 patients with functional dyspepsia characterized by prominent epigastric pain or discomfort were randomized to 2 weeks' treatment with metoclopramide or domperidone (both 30 mg/day); of these, 53 patients unresponsive to dopamine antagonist treatment were randomized to cisapride 30 mg/day or placebo for an additional 2 weeks. Metoclopramide and domperidone produced comparable alleviation of epigastric symptoms; global efficacy was good or excellent in 62% and 57% of patients, respectively. In refractory patients, cisapride tended to display greater efficacy than placebo against epigastric pain, particularly at night. Global assessments of efficacy significantly favored cisapride over placebo, with good or excellent ratings in 65% and 32% of patients, respectively. Cisapride was well tolerated. Thus, cisapride appears to be an effective agent in functional dyspepsia unresponsive to other gastrokinetic agents.

Value of transrectal ultrasonography in Crohn's disease.

Anorectal lesions are common and can develop silently in patients with Crohn's disease. Transrectal ultrasound examinations were performed to study 40 healthy individuals and 40 patients with Crohn's disease. A rigid linear endorectal probe was used to examine the rectal wall, the perirectal tissues, and the anal sphincter. In healthy individuals, the rectal wall showed five layers with a total diameter of maximum 4 mm. The anal sphincter was clearly visualized as an echo-poor and sharply delineated structure. No pathological lesions were detected perirectally. In Crohn's disease, an enlargement of the rectal wall was seen in 16 patients and heterogeneity of the anal sphincter in 19 patients. This technique detected lesions missed with the routine proctological examinations: four pararectal abscesses, two pararectal fistulas, two para-anal abscesses, and one para-anal fistula. In all examined subjects, the anal sphincter increased in breadth during squeezing and in length during straining. It is concluded that transrectal ultrasonography sharply delineates the rectal wall and the anal sphincter at rest and under dynamic conditions and detects unknown abscesses and fistulas in the pararectal and para-anal tissues in patients with Crohn's disease.