Aim The purpose of this trial was to compare the effectiveness of sacral neuromodulation (SNM) with a submucosal injection of collagen (Permacol (R)) in women with faecal incontinence following obstetric anal sphincter injury (OASIS).Method This single-blinded randomized controlled trial at two hospital units in Norway included women with faecal incontinence following OASIS. Eligible women who had had a successful percutaneous nerve evaluation were randomly assigned to SNM or Permacol (R). The primary outcome was the difference in the St Mark's incontinence score between baseline and 6 months. Secondary outcomes were changes in the disease-specific quality of life (FIQL) and urinary incontinence (ICIQ-UI-SF) scores.Results Fifty-eight women were randomly assigned to SNM (n = 30) and Permacol (R) (n = 28). The reduction in the St Mark's score between baseline and 6 months was 11.2 (SD 5.3) in the SNM group vs 2.3 (SD 5.0) in the Permacol (R) group, resulting in a difference of 8.9 (95% CI: 6.1-11.7, P < 0.0001). The differences in the four scales of FIQL (lifestyle, coping, depression, embarrassment) were 0.90 (95% CI: 0.50-1.30, P < 0.001), 1.05 (0.62-1.47, P < 0.001), 0.52 (95% CI: 0.16-0.87, P = 0.005) and 0.95 (95% CI: 0.50-1.40, P < 0.001), respectively, in favour of SNM. The difference in the ICIQ-UI-SF was 5.0 (95% CI: 1.97-8.02, P = 0.002) in favour of SNM. There were nine minor adverse events in the SNM group compared with seven in the Permacol (R) group (P = 0.77).Conclusion SNM was superior to Permacol (R) in terms of reduction of St Mark's score, ICIQ-UI-SF and the change of the FIQL in women with faecal incontinence following OASIS.

Summary Background Patients with primary sclerosing cholangitis ( PSC ) and inflammatory bowel disease ( IBD ) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid ( UDCA ) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long‐term data and larger trials are lacking. Aim To evaluate the effect of high dose (17–23 mg/kg/day) UDCA on colorectal neoplasia in a cohort of patients with PSC and IBD . Methods From our previous 5‐year randomised controlled trial of UDCA vs. placebo in PSC , we performed a follow‐up of 98 patients with concomitant IBD from entry of the trial 1996–1997 until 2009 for development of colorectal cancer or dysplasia. Results The total follow‐up time was 760 person‐years. Dysplasia/cancer‐free survival was compared between placebo‐ ( n = 50) and UDCA ‐treated ( n = 48) patients. There was a similar frequency of dysplasia or cancer after 5 years between patients originally assigned to UDCA or placebo (13% vs. 16%) and no difference in dysplasia/cancer‐free survival ( P = 0.46, log rank test). At the end of 2009 no difference in cancer‐free survival was detected, 30% of the placebo patients compared with 27% of UDCA patients had developed colorectal cancer or dysplasia. Conclusions Long‐term high dose ursodeoxycholic acid does not prevent colorectal cancer or dysplasia in patients with primary sclerosing cholangitis ‐associated inflammatory bowel disease .

Study design, material and methods The study is a part of a cross-sectional, large community-based survey (HUNT 3) conducted in Nord-Trøndelag, Norway. Data were collected through interviews, questionnaires and clinical examinations. In total 40 955 community-dwelling women (aged 30+) were invited to participate. All eligible women attending at the research centre received a questionnaire containing a section about anal incontinence (Q2). They filled in the questionnaire at home and returned it by postal mail. Anal incontinence was defined as involuntary loss of feces or flatus weekly or more. Fecal and flatal incontinence was defined respectively as involuntary loss of feces and flatus weekly or more. Statistical methods included tests of association and logistic regression analysis. Explanatory variables which became significant in age-adjusted bivariate analysis were entered in the multivariate regression model. Data were analysed using SPSS v 17.

OBJECTIVE:The long-term failure rate of ileal pouch-anal anastomosis (IPAA) is 10-15%. When salvage surgery is unsuccessful, most surgeons prefer pouch excision with conventional ileostomy, thus sacrificing 40-50 cm of ileum. Conversion of a pelvic pouch to a continent ileostomy (CI, Kock pouch) is an alternative that preserves both the ileal surface and pouch properties. The aim of the study was to evaluate clinical outcome after the construction of a CI following a failed IPAA.METHOD:During 1984-2007, 317 patients were operated with IPAA at St Olavs Hospital and evaluated for failure, treatment and outcome. Seven patients with IPAA failure had CI. Four patients with IPAA failure referred from other hospitals underwent conversion to CI and are included in the final analysis.RESULTS:Seven patients had a CI constructed from the transposing pelvic pouch and four had the pelvic pouch removed and a new continent pouch constructed from the distal ileum. Median follow up after conversion to CI was 7 years (0-17 years). Two CI had to be removed due to fistulae. One patient needed a revision of the nipple valve due to pouch loosening. At the end of follow-up, 8 of the 11 patients were fully continent. One patient with Crohn's disease had minor leakage.CONCLUSION:In patients with pelvic pouch failure, the possibility of conversion to CI should be presented to the patient as an alternative to pouch excision and permanent ileostomy. The advantage is the continence and possibly a better body image. Construction of a CI on a new ileal segment may be considered, but the consequences of additional small bowel loss and risk of malnutrition if the Kock pouch fails should be appraised.

AimTo evaluate surgical workload and complications in patients who had undergone restorative proctocolectomy, through long-term follow-up in one single institution.MethodFrom 1984 to 2006, 304 consecutive patients underwent Ileal Pouch-Anal Anastomosis (IPAA). There were 182 stapled and 122 hand-sewn anastomoses. A protective loop ileostomy was established in 256 patients (84%), whereas 48 patients (16%) were without a covering stoma.ResultsTwenty-nine patients (10%) suffered from early anastomotic leakage. A protective stoma did not prevent early anastomotic dehiscence (P = 0.11) or the number of pelvic abscesses (P = 0.09). Early complications required 20 laparotomies with creation of a diverting stoma in nine patients. There were 16 (6%) complications related to closure of the loop ileostomy. Sixty-six patients needed an additional re-operation related to the IPAA procedure. There were 20 removals of pouches and three permanent diverting stomas. The estimated removal rate at 20 years of a functioning pouch was 11% (CI +/- 6). Altogether 100 (33%) patients had one or more surgical procedures, excluding dilations of anastomotic strictures and closing of a loop ileostomy. These 100 patients underwent 187 surgical procedures. The estimated rate of a first re-operation due to complications was 52% (CI +/- 16) in 20 years. Hand-sewn anastomoses had similar complications and failure rates as stapled anastomoses.ConclusionsMore than half of patients operated with restorative proctocolectomy will need surgical intervention within 20 years and the failure rate is more than 10%. The high risk of complications and failure inherent in the procedure should not be ignored.

It is questionable whether a symptomatic condition with few serious medical consequences requires proton pump inhibitor (PPI) treatment. If effective, a less-potent treatment may be preferable.To compare an H2-blocker in an effervescent formulation with a PPI in on-demand treatment of endoscopy-negative gastro-oesophageal reflux disease (GERD).Included were patients with heartburn and/or acid regurgitation for at least 3 months duration, a negative endoscopy and a positive response to 7 days of lansoprazole 60 mg daily. Following pH-metry, the patients were randomized to receive either ranitidine effervescent tablets 75 mg or lansoprazole capsules 15 mg to a maximum of four per day on-demand. The numbers taken were registered monthly for 6 months. If treatment was unsuccessful (lack of efficacy or side effects), patients were registered as failures.One hundred and three patients were included and 63 were considered for statistical analysis; 32 on lansoprazole and 31 on ranitidine. Seventeen (55%) on ranitidine and four (13%) on lansoprazole failed. The average number of tablets per day was 1.2 in the lansoprazole group and 3.1 in the ranitidine group.On-demand treatment in patients with endoscopy-negative GERD gives a high success rate with a fairly low dose of PPI. The H2-blocker had significantly less success; nevertheless, almost half were satisfied with the treatment.

OBJECTIVE:The aim of the study was to evaluate the results of Kock continent ileostomy (CI) during the same period when ileal pouch-anal anastomosis was the preferred operation for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP).METHOD:During the period 1983-2002, 50 patients underwent CI. The surgical technique was unchanged during the period. Follow-up included all patients. Forty-eight patients had UC, two of these had the diagnosis later changed to Crohn's disease and two had FAP.RESULTS:Twenty-two patients had 38 reoperations, four (8%) of whom had the pouch removed. The main causes for reoperation included leakage and difficulty in intubation due to sliding of the nipple valve (42%), fistula formation (29%) and stenosis (21%). Seventeen (45%) underwent a revision of the nipple valve and the pouch and nine (24%) a local procedure. The reoperation rate was higher among patients having a conventional ileostomy converted to CI than among those having CI. As a primary procedure (P = 0.016). The risk of a second reoperation was higher for those reoperated within the first year after having a CI, than for those reoperated later (P = 0.007).CONCLUSIONS:The reoperation rate of patients with CI is high but the removal rate of the pouch is low and is not associated with a high rate of revision. CI is a good alternative to conventional ileostomy in patients not suitable for restorative proctocolectomy or where this procedure has failed.

BACKGROUND & AIMS There is no medical treatment of proven benefit for primary sclerosing cholangitis. This study aimed at studying the effect of a higher dose of ursodeoxycholic acid than previously used on survival, symptoms, biochemistry, and quality of life in this disease. METHODS A randomized placebo-controlled study was performed in tertiary and secondary gastroenterology units. A total of 219 patients were randomized to 17 to 23 mg/kg body weight per day of ursodeoxycholic acid (n = 110) or placebo (n = 109) for 5 years. Follow-up data are available from 97 patients randomized to ursodeoxycholic acid and for 101 randomized to placebo. Quality of life was assessed by using the Medical Outcomes Study 36-item Short-Form Health Survey. RESULTS The combined end point "death or liver transplantation" occurred in 7 of 97 (7.2%) patients in the ursodeoxycholic acid group vs 11 of 101 (10.9%) patients in the placebo group (P = .368; 95% confidence interval, -12.2% to 4.7%). The occurrence of liver transplantation as a single end point showed a similar positive trend for ursodeoxycholic acid treatment (5/97 [5.2%] vs 8/101 [7.9%]; 95% confidence interval, -10.4% to 4.6%). Three ursodeoxycholic acid and 4 placebo patients died from cholangiocarcinoma, and 1 placebo patient died from liver failure. Alkaline phosphatase and alanine aminotransferase tended to decrease during the first 6 months. There were no differences between the 2 groups in symptoms or quality of life. Analyses of serum ursodeoxycholic acid concentration gave no evidence that noncompliance may have influenced the results. CONCLUSIONS This study found no statistically significant beneficial effect of a higher dose of ursodeoxycholic acid than previously used on survival or prevention of cholangiocarcinoma in primary sclerosing cholangitis.

GOALS:To evaluate the need for on-demand treatment with proton pump inhibitor in patients with endoscopy-negative GERD.BACKGROUND:Studies indicate that on-demand therapy is suitable for patients without mucosal disease, but the need for PPI in a monotherapy situation is not known.STUDY:Forty-one patients with heartburn and/or acid reflux of more than 3 months duration participated in the study. All were endoscopy-negative and had responded positive to a test with lansoprazole 60 mg x 1 for 7 days. Twenty-four hour pH monitoring was attempted in all, but failed in 4. Twenty-eight had pH <4 more than 4% of the time, 9 had less. During a 3-month period, the patients were allowed to take 1 capsule 30 mg lansoprazole on-demand, maximum 2 capsules a day. The remaining capsules were counted monthly.RESULTS:In the 3-month period, the median mean daily consumption was 1.06 capsule (95% CI: 0072-1.09). No significant difference was found between those with normal or abnormal 24-hour pH-metry. Sixty-three percent used 6 or more capsules a week.CONCLUSION:Patients with longstanding negative-endoscopy reflux disease, whether abnormal or normal 24-hour pH-metry, have symptoms that demand effective therapy. Using PPI on-demand as monotherapy, most patients will need 1 capsule per day.

Background: Our aim in this study was to evaluate a simple test with proton-pump inhibitor (PPI) for use in everyday clinical practice in diagnosing endoscopy-negative reflux disease. Methods: 68 patients with heartburn and/or acid regurgitation as their main complaint, symptoms of at least 3 months' duration prior to inclusion, all with a negative gastroscopy were included. The patients were given 60 mg of lansoprazole before breakfast for 7 days. After the test week, patients had to answer one single question on a formula. `Did you essentially, without any doubt, have less heartburn and/or acid regurgitation during the treatment?' The only alternative answers were 'Yes' or 'No'. Patients in doubt were told to answer 'No'. 24-h pH monitoring was performed at the earliest 14 days after the test. Results: 65 completed the PPI test and 52 fulfilled the pH monitoring. Defined by < 4% time oesophageal pH < 4, 34 (65%) had pathological reflux. The PPI test was positive in all patients with pathological reflux but also in 17 of 18 with normal pH-metry, giving the test a sensitivity of 97% and specificity of 6%. Conclusion: Application of a diagnostic PPI test in clinical practice gave a high sensitivity and unusually low specificity compared to placebo-controlled studies, indicating that a test of this nature should be used with caution in everyday practice. Most patients with endoscopy-negative GORD will be diagnosed clinically. A positive test with PPI strengthens the diagnosis but has insufficient specificity to be an objective criterion alone. pH-metry should be unnecessary for the diagnosis of ENGORD in patients with typical reflux symptoms.

Protective vasodilation during acid back diffusion into the rat gastric mucosa depends on activation of sensory neurons and mast cell degranulation with histamine release. We hypothesized that these two mediator systems interact and that histamine partly exerts its effect via sensory nerves. Gastric blood flow (GBF) and luminal histamine were measured in chambered stomachs, and mast cell numbers were assessed by morphometry. Ablation of sensory neurons and depletion of mast cells were produced by pretreatment with capsaicin or dexamethasone, respectively. Mucosal exposure to 1.5 M NaCl and then to pH 1.0 saline in ablated and control rats caused increased luminal histamine and reduced numbers of mast cells. Enterochromaffin-like cell marker pancreastatin remained unchanged. Only control rats responded with an increase in GBF. Capsaicin stimulation (640 microM) of the undamaged mucosa induced identical increase in GBF and unchanged mast cell mass in normal and dexamethasone-treated rats. Increase in GBF after topical exposure to histamine (30 mM) in rats pretreated with capsaicin or a calcitonin gene-related peptide (CGRP)(1) antagonist human CGRP(8-37) or exposed to the calcium pore blocker ruthenium red was less than one-half of that in control rats. These data suggest that mast cell-derived histamine is involved in gastric vasodilatation during acid back diffusion partly via sensory neurons.

Procalcitonin (PCT), a new marker proposed as a diagnostic tool for bacterial infections, triggers a systemic-inflammatory reaction in the body (sepsis, septic shock) and has potential use in a wide range of patient settings. To interpret the results from PCT measurements, we depend on reference intervals established from relevant populations. PCT and C-reactive protein (CRP) concentrations were analysed in 47 patients with a normal postoperative course after major abdominal surgery. The mean concentration of PCT declines from the first day and reaches half its initial values on the second day after the operation, whereas the mean concentration of CRP increases in the first 48 h and reaches half its maximum value on the fifth day after the operation. We present a continuous reference interval for plasma PCT and CRP concentrations in the first week following major abdominal surgery. For PCT we also present a graphic display of expected mean and expected upper reference limits predicted from the value measured on the first postoperative day.

Acid back diffusion into the rat stomach mucosa leads to gastric vasodilation. We hypothesized that histamine, if released from the rat mucosa under such conditions, is mast cell derived and involved in the vasodilator response. Gastric blood flow (GBF) and luminal histamine were measured in an ex vivo chamber. Venous histamine was measured from totally isolated stomachs. Mucosal mast cells (MMC), submucosal connective tissue mast cells (CTMC), and chromogranin A-immunoreactive cells (CgA IR) were assessed morphometrically. After mucosal exposure to 1.5 M NaCl, the mucosa was subjected to saline at pH 5.5 (control) or pH 1.0 (H(+) back diffusion) for 60 min. H(+) back diffusion evoked a marked gastric hyperemia, increase of luminal and venous histamine, and decreased numbers of MMC and CTMC. CgA IR cells were not influenced. Depletion of mast cells with dexamethasone abolished (and stabilization of mast cells with ketotifen attenuated) both hyperemia and histamine release in response to H(+) back diffusion. GBF responses to H(+) back diffusion were attenuated by H(1) and abolished by H(3) but not H(2) receptor blockers. Our data conform to the idea that mast cells are involved in the gastric hyperemic response to acid back diffusion via release of histamine.

BACKGROUND:To evaluate a high dose of a proton-pump inhibitor as a diagnostic test in endoscopy-negative patients presenting with symptoms indicating gastro-oesophageal reflux disease.METHODS:64 patients were studied in a prospective, randomized, double-blind study, using a cross-over design. After a run-in period with the diary registration of basic GORD symptoms and recording of the consumption of antacid tablets, the patients were given either 60 mg of lansoprazole once daily or placebo in randomized order. Symptoms were recorded, as well as antacid tablets taken in order to relieve pain. GORD was determined by 24-h oesophageal pH monitoring. The test was considered positive when consumption of antacid tablets was reduced > or = 75% compared to pretreatment.RESULTS:In the GORD group, 29 (85%) tested positive during active treatment compared to 3 (9%) when on placebo. Corresponding figures for the non-GORD patients were 50% and 27%, giving a test sensitivity and specificity of 85% and 73%, respectively. During active treatment, VAS scores for acid regurgitation, heartburn and over all were significantly lowered in GORD patients, compared to heartburn only in the non-GORD group.CONCLUSIONS:60 mg lansoprazole once daily for 5 days is an easy to use method for diagnosing GORD in endoscopy-negative patients. Using 24-h oesophageal pH monitoring as the reference method, the sensitivity was relatively high, while the specificity was lower. Further studies are needed to determine how a PPI could be used as a diagnostic test in GORD.

BACKGROUND:Abdominal pain and other gastrointestinal symptoms in children may be, but are not always due to disease. Endoscopy in general anaesthesia may be necessary in children with long-term symptoms from the gastrointestinal tract.MATERIAL AND METHODS:We present a retrospective study of all children under the age of 15 who underwent endoscopy at the Central Hospital in Akershus (SIA) in the period 1993-98. 254 gastro-, 123 colono- and 43 sigmoideoscopies were performed. A conclusive diagnosis was made following endoscopy. There were few complications to the endoscopies.RESULTS AND INTERPRETATION:Our results indicate a higher incidence of inflammatory bowel disease than in similar studies, but with the same relative rates. Celiac disease occurs at a rate similar to the Swedish epidemic in the 1980s.