Sacral neuromodulation compared with injection of bulking agents for faecal incontinence following obstetric anal sphincter injury - a randomized controlled trial.

AIM: The purpose of this trial was to compare the effectiveness of sacral neuromodulation (SNM) with a submucosal injection of collagen (Permacol®) 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®. 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® (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® 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® group (P = 0.77). CONCLUSION: SNM was superior to Permacol® 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.

High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia.

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.

Failed pelvic pouch substituted by continent ileostomy.

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.

Long-term surgical load in patients with ileal pouch-anal anastomosis.

AIM: To evaluate surgical workload and complications in patients who had undergone restorative proctocolectomy, through long-term follow-up in one single institution. METHOD: From 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. RESULTS: Twenty-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. CONCLUSIONS: More 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.

On-demand requirements of patients with endoscopy-negative gastro-oesophageal reflux disease: H2-blocker vs. proton pump inhibitor.

BACKGROUND: 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. AIM: To compare an H2-blocker in an effervescent formulation with a PPI in on-demand treatment of endoscopy-negative gastro-oesophageal reflux disease (GERD). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Surgical load and long-term outcome for patients with Kock continent ileostomy.

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.

Endoscopy-negative reflux disease: what is the value of a proton-pump inhibitor test in everyday clinical practice?

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.

Reference intervals for procalcitonin and C-reactive protein after major abdominal surgery.

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.

Does short-term treatment with proton pump inhibitors cause rebound aggravation of symptoms?

BACKGROUND: Rebound acid hypersecretion might occur after treatment with proton pump inhibitors. This study looks for a rebound aggravation of symptoms after short-term treatment with lansoprazole. STUDY: Sixty-two patients (19 men and 43 women; mean age, 54 years; range, 32-77 years) with heartburn and regurgitation and normal upper endoscopy findings were studied in a randomized, double-blind, placebo-controlled trial with a crossover design. There were two 5-day treatment periods with lansoprazole 60 mg once daily or placebo in random order, separated by a 9-day washout period. Reflux, total, and antacid scores were calculated for each of the treatment periods. Higher scores during the placebo period in the group given lansoprazole first than in the group given placebo first indicated a rebound aggravation of symptoms. RESULTS: The mean symptom scores during the placebo period in the groups given lansoprazole first and placebo first were as follows: reflux score, 21.5 and 17.6, respectively (not significant); total score, 11.2 and 10.3, respectively (not significant); and antacid score, 8.2 and 7.2, respectively (not significant). CONCLUSIONS: There is no indication of a rebound aggravation of symptoms 12 to 14 days after a 5-day treatment with lansoprazole 60 mg once daily in patients with reflux symptoms.

High-dose proton-pump inhibitors as a diagnostic test of gastro-oesophageal reflux disease in endoscopic-negative patients.

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.

Mast cells are involved in the gastric hyperemic response to acid back diffusion via release of histamine.

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.

[Gastrointestinal endoscopy in children]. / Gastrointestinale endoskopier av barn.

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.

Substance P may attenuate gastric hyperemia by a mast cell-dependent mechanism in the damaged gastric mucosa.

Calcitonin gene-related peptide (CGRP) released from sensory neurons, which are closely apposed to mast cells and blood vessels, mediates gastric hyperemia in response to acid challenge of the damaged mucosa. Substance P (SP) is coreleased with CGRP from sensory neurons, but the role of this peptide in gastric blood flow regulation is largely unknown. Chambered rat stomachs were exposed to 1.5 M NaCl and acidic saline after treatment with SP, aprotinin (serine protease inhibitor), and the mast cell stabilizers ketotifen and sodium cromoglycate (SCG). Gastric hyperemia (measured with a laser Doppler flow velocimeter) after hypertonic injury and acid challenge was nearly abolished by SP. Aprotinin infused together with SP and pretreatment with ketotifen and SCG before SP restored the gastric hyperemia. Ketotifen and SCG inhibited mast cell degranulation in SP-treated rats. Preservation of gastric hyperemia was correlated with improved mucosal repair. These data suggest that impaired hyperemia by SP during acid challenge of the gastric mucosa may be mediated by a mast cell-dependent mechanism involving the release of proteases from mast cells.

[Invagination in children]. / Invaginasion hos barn.

Although rare, childhood intussusception is one of the most common causes of small bowel obstruction in infancy. In these very young patients it can sometimes be difficult to interpret the clinical signs and symptoms correctly. This retrospective study comprises 79 children (median age 7.5 months; 24% girls and 76% boys) who experienced 83 episodes of intussusception. At admission the diagnosis made by the referring physicians could be confirmed in only about one-third of the cases. A barium enema was part of the inhospital diagnostic process. Non-operative treatment was attempted in 70 patients (89%), and barium enema reduction was successful in 64%. Laparotomy was required in 33 (42%) of the patients. No mortality, bowel perforation, or any other major complications were encountered. The diagnosis of childhood intussusception seems difficult to achieve in many cases, and the interpretation of, at times vague clinical signs and symptoms remains a challenge for all clinicians who are involved in the care of these very young patients.

[Incidence and prevalence of autoimmune liver diseases]. / Insidens og prevalens av autoimmune leverlidelser.

We studied prevalence and incidence of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis in a Norwegian population. A search in patient databases was performed and medical records from the period 1985-94 were reviewed. Commonly accepted diagnostic criteria were used for inclusion. All three diseases were found to be rare, with a marked female preponderance in primary biliary cirrhosis (female 21/male 0) and to a lesser extent in autoimmune hepatitis (female 20/male 9). The age distribution shows that autoimmune hepatitis and primary sclerosing cholangitis are diagnosed in patients who are on an average 12 years younger than patients with primary biliary cirrhosis. The mean annual incidence was 1.6/100,000 for autoimmune hepatitis, 1.2/100,000 for primary biliary cirrhosis and 0.7/100,000 for primary sclerosing cholangitis. The end of study point prevalence was 14/100,000, 12/100,000 and 5.6/100,000, respectively.

[Autoimmune hepatitis--a rare cause of elevated transaminases]. / Autoimmun hepatitt--en sjelden årsak til forhøyede transaminaser.

Autoimmune hepatitis is a rare chronic hepatitis of unknown etiology. Immunological changes are conspicuous, with tissue antibodies found in a high proportion of patients. There is a female preponderance of 2-3:1 and the disease often affects young people. The presenting symptoms are vague, fatigue being the most important general symptom. The diagnosis is often made at a late stage of the disease when symptoms of liver decompensation and cirrhosis are obvious. We present two cases of AIH in young women diagnosed at a late stage with advanced cirrhosis, for whom symptoms of liver disease had been intermittently present for 12 and 9 months, but wrongly attributed to presumed acute viral hepatitis acquired on holiday in the Mediterranean. In order not to miss the diagnosis, it is important to confirm suspected viral hepatitis serologically, to look for liver disease stigmata in patients with abnormal liver enzymes, and to be especially aware of the possibility of AIH in young women with concommittant or family history of other autoimmune diseases.

Effect of wheat fibre supplements on duodenal ulcer recurrence.

In the present study the prophylactic effect of concentrated wheat fibre on duodenal ulcer recurrence was evaluated. Eleven grams of fibre (Fiberform) or placebo was added to an ordinary Norwegian diet for 1 year after endoscopic healing of duodenal ulcer. The ulcer recurrence rates were 84% (31 of 37 patients) in the fibre-supplemented group and 85% (30 of 36 patients) in the placebo group (NS). The effect on ulcer symptoms was similar in both groups. Side effects were infrequently seen. A concentrated wheat fibre supplement seems to have no preventive effect when given to duodenal ulcer patients living on a traditional Norwegian diet.

Factors of prognostic importance in primary biliary cirrhosis.

To determine survival and the risk factors of death in primary biliary cirrhosis, data from 52 symptomatic and 13 asymptomatic patients were analyzed. The mean follow-up time was 6.3 years (range, 0.4-23 years). The average length of survival was 18 years for the symptomatic and 8.4 years for the asymptomatic patients. By a univariate analysis, ascites, presence of esophageal varices, gastrointestinal bleeding, jaundice, hepatomegaly and the logarithms of albumin and bilirubin were all associated with a poor prognosis. A multivariate analysis of the clinical features showed that the presence of bleeding from esophageal varices and the logarithm of bilirubin were the only predictors for poor prognosis. The survival of the symptomatic patients is longer than reported previously, while the life expectancy for the asymptomatic patients seems no better than for the symptomatic group.