Surgical repair of parastomal bulging: a retrospective register-based study on prospectively collected data.

AIM: The aim of this work was to examine (1) the incidence of primary repair, (2) the incidence of recurrent repair and (3) the types of repair performed in patients with parastomal bulging. METHOD: Prospectively collected data on parastomal bulging from the Danish Stoma Database were linked to surgical data on repair of parastomal bulging from the Danish National Patient Register. Survival statistics provided cumulative incidences and time until primary and recurrent repair. RESULTS: In the study sample of 1016 patients with a permanent stoma and a parastomal bulge, 180 (18%) underwent surgical repair. The cumulative incidence of a primary repair was 9% [95% CI (8%; 11%)] within 1 year and 19% [95% CI (17%; 22%)] within 5 years after the occurrence of a parastomal bulge. We found a similar probability of undergoing primary repair in patients with ileostomy and colostomy. For recurrent repair, the 5-year cumulative incidence was 5% [95% CI (3%; 7%)]. In patients undergoing repair, the probability was 33% [95% CI (21%; 46%)] of having a recurrence requiring repair within 5 years. The main primary repair was open or laparoscopic repair with mesh (43%) followed by stoma revision (39%). Stoma revision and repair with mesh could precede or follow one another as primary and recurrent repair. Stoma reversal was performed in 17% of patients. CONCLUSION: Five years after the occurrence of a parastomal bulge the estimated probability of undergoing a repair was 19%. Having undergone a primary repair, the probability of recurrent repair was high. Stoma reversal was more common than expected.

Pouch failures following ileal pouch-anal anastomosis for ulcerative colitis.

AIM: Ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain the risk factors associated with failure. METHOD: The study included 1991 patients with ulcerative colitis who underwent ileal pouch-anal anastomosis in Denmark in the period 1980-2013. Pouch failure was defined as excision of the pouch or presence of an unreversed stoma within 1 year after its creation. We used Cox proportional hazards regression to explore the association between pouch failure and age, gender, synchronous colectomy, primary faecal diversion, annual hospital volume (very low, 1-5 cases per year; low, 6-10; intermediate 11-20; high > 20), calendar year, laparoscopy and primary sclerosing cholangitis. RESULTS: Over a median 11.4 years, 295 failures occurred, corresponding to 5-, 10- and 20-year cumulative risks of 9.1%, 12.1% and 18.2%, respectively. The risk of failure was higher for women [adjusted hazard ratio (aHR) 1.39, 95% CI 1.10-1.75]. Primary non-diversion (aHR 1.63, 95% CI 1.11-2.41) and a low hospital volume (aHR, very low volume vs high volume 2.30, 95% CI 1.26-4.20) were also associated with a higher risk of failure. The risk of failure was not associated with calendar year, primary sclerosing cholangitis, synchronous colectomy or laparoscopy. CONCLUSION: In a cohort of patients from Denmark (where pouch surgery is centralized) with ulcerative colitis and ileal pouch-anal anastomosis, women had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non-diversion were associated with a higher risk of pouch failure.

Three-year follow-up of implementation of evidence-based transfusion practice in a tertiary hospital.

BACKGROUND AND OBJECTIVES: Traditionally, Denmark has had a high rate of allogeneic red blood cell transfusion caused by a liberal transfusion practice despite the existence of restrictive guidelines. We established a Patient Blood Management programme in a tertiary hospital and report the results of the implementation of evidence-based transfusion practice. MATERIALS AND METHODS: Red blood cell transfusion quality indicators were compared with the evidence-based guideline at hospital and department level. Based on this evaluation, wards were selected for interventions targeting doctors and nurses. The implementation process was monitored by transfusion quality and utilization data over a 3-year period with totally 166 341 admissions in 98 960 mixed, adult medical and surgical patients. RESULTS: At the hospital level, transfusion above the upper guideline limit decreased from 23 to 10% (P < 0·001), and transfusion at or below the restrictive haemoglobin trigger of 7·3 g/dl increased from 7 to 19% (P < 0·001). The percentage of single-unit transfusions increased from 72 to 78% (P < 0·001), and the majority of transfusion rates and volumes decreased significantly. Red cell use decreased with 41% in surgical procedures and 28% in admissions (P < 0·001). CONCLUSION: The intervention was associated with a significant and sustained overall increase in compliance with national guidelines for red blood cell transfusion for non-bleeding patients, and led to significantly fewer patients being exposed to transfusion.

Evaluation of a fast-track programme for patients undergoing liver resection.

BACKGROUND: Recent developments in perioperative pathophysiology and care have documented evidence-based, multimodal rehabilitation (fast-track) to hasten recovery and to decrease morbidity and hospital stay for several major surgical procedures. The aim of this study was to investigate the effect of introducing fast-track principles for perioperative care in unselected patients undergoing open or laparoscopic liver resection. METHODS: This was a prospective study involving the first 100 consecutive patients who followed fast-track principles for liver resection. Catheters and drains were systematically removed early, and patients were mobilized and started eating and drinking from the day of surgery. An opioid-sparing multimodal pain treatment was given for the first week. Discharge criteria were: pain sufficiently controlled by oral analgesics alone, patient comfortable with discharge and no untreated complications. RESULTS: Median length of stay (LOS) for all patients was 5 days, with 2 days after laparoscopic versus 5 days following open resection (P < 0·001). Median LOS after minor open resections (fewer than 3 segments) was 5 days versus 6 days for major resections (3 or more segments) (P < 0·001). Simple right or left hemihepatectomies had a median LOS of 5 days. The readmission rate was 6·0 per cent and 30-day mortality was zero. CONCLUSION: Fast-track principles for perioperative care were introduced successfully and are safe after liver resection. Routine discharge 2 days after laparoscopic resection and 4-5 days after open liver resection may be feasible.

Preoperative high-dose glucocorticoids for early recovery after liver resection: randomized double-blinded trial.

BACKGROUND: Glucocorticoids modulate the surgical stress response. Previous studies showed that high-dose preoperative glucocorticoids reduce levels of postoperative inflammatory markers and specific biomarkers of liver damage compared with placebo, and suggested a reduced complication rate and shorter hospital stay after liver surgery. However, there are no studies with a clinical primary outcome or of early recovery outcomes. The aim of this study was to investigate whether a single high dose of preoperative glucocorticoid reduces complications in the immediate postoperative phase after liver surgery. METHODS: This was a single-centre, double-blinded, parallel-group RCT investigating preoperative methylprednisolone 10 mg/kg (high dose) versus dexamethasone 8 mg (standard-dose postoperative nausea prophylaxis) in patients scheduled for open liver resection. The primary outcome was number of patients with a complication in the postanaesthesia care unit; secondary outcomes included duration of hospital stay, pain and nausea during admission, and 30-day morbidity. RESULTS: A total of 174 patients (88 in high-dose group, 86 in standard-dose group) were randomized and analysed (mean(s.d.) age 65(12) years, 67.2 per cent men); 31.6 per cent had no serious co-morbidities and 25.3 per cent underwent major liver resection. Complications occurred in the postanaesthesia care unit in 51 patients (58 per cent) in the high-dose group and 58 (67 per cent) in the standard-dose group (risk ratio 0.86, 95 per cent c.i. 0.68 to 1.08; P = 0.213). Median duration of hospital stay was 4 days in both groups (P = 0.160). Thirty-day morbidity and mortality rates were similar in the two groups. CONCLUSION: A high dose of preoperative glucocorticoids did not reduce acute postoperative complications after open liver resection compared with a standard dose. Registration number: NCT03403517 (http://www.clinicaltrials.gov); EudraCT 2017-002652-81 (https://eudract.ema.europa.eu/).

Staged or simultaneous resection of synchronous liver metastases from colorectal cancer--a systematic review.

OBJECTIVE: A systematic review of the literature was undertaken to estimate the differences in length of hospital stay, morbidity, mortality and long-term survival between staged and simultaneous resection of synchronous liver metastases from colorectal cancer to determine the level of evidence for recommendations of a treatment strategy. METHOD: A Pub-med search was undertaken for studies comparing patients with synchronous liver metastases, who either had a combined or staged resection of metastases. Twenty-six were considered and 16 were included based on Newcastle Ottawa Quality Assessment Scale. All studies were retrospective and had a general bias, because the staged procedure was significantly more often undertaken in patients with left-sided primary tumours and larger, more numerous and bi-lobar metastases. Analyses of primary outcomes were performed using the random effects model. RESULTS: For the reason of the heterogeneity of the observational studies, no odds ratios were calculated. In 11 studies, there was a tendency towards a shorter hospital stay in the synchronous resection group. Fourteen studies compared total perioperative morbidity and lower morbidity was observed in favour of a combined resection. Fifteen studies compared perioperative mortality, which seemed to be lower with the staged approach. Eleven studies compared 5-year survival, which seemed to be similar in the two groups. CONCLUSION: No randomized controlled trials were identified, and hence a meta-analysis was not performed. The evidence level is II to III with grade C recommendations. Synchronous resections can be undertaken in selected patients, provided that surgeons specialized in colorectal and hepatobiliary surgery are available.

Hyaluronic Acid Is a Biomarker for Allograft Dysfunction and Predicts 1-Year Graft Loss After Liver Transplantation.

BACKGROUND: Allograft dysfunction after liver transplantation has a profound impact on the risks of death and retransplantation within the first year. We tested whether elevated hyaluronic acid (HA; a glycosaminoglycan cleared by hepatic sinusoidal endothelium) levels may predict excess risk of graft loss. METHODS: This was a retrospective single-center prognostic cohort study. Patients with either a plasma sample before transplantation, an early post-transplantation sample nearest day 30 (range 10-89 d, 80% within days 15-60), or both were included. Plasma HA was measured with the use of enzyme-linked immunosorbent assays. The primary end point was 1-year graft loss (all-cause mortality and retransplantation). A secondary end point was biliary stricture. RESULTS: In this study, 169 of 196 patients who received a liver transplant in the study period were included. Pre-transplantation HA (n = 152) did not predict graft loss. Post-transplantation HA (n = 124) was higher among patients with graft loss (median, 177 µg/L [interquartile range (IQR), 89-465] vs 54 µg/L [IQR 37-93]) and was a strong predictor of this outcome (hazard ratio per 50 µg/L, 1.24 [95% confidence interval [CI], 1.14-1.34]). The discriminatory ability of HA was high (area under the receiver operating characteristic curve, 0.86 [95% CI, 0.77-0.94]) and noninferior to other liver function tests. When adjusted for known risk factors of graft loss, HA remained an independent predictor of graft loss. CONCLUSIONS: High post-transplantation plasma HA level was a strong predictor of 1-year all-cause mortality and retransplantation, whereas pre-transplantation levels were not, despite variety in the time span of blood sampling. Prospective studies are warranted to assess the utility of HA in liver transplantation.

Post-endoscopic retrograde cholangiopancreaticography complications in liver transplanted patients, a single-center experience.

BACKGROUND: Complications in the biliary tract occur in 5%-30% after liver transplantation and the main part of the complications is successfully managed with endoscopic retrograde cholangiopancreaticography (ERCP). The incidence and risk factors for post-ERCP complications in liver transplantation patients are not well described. Our objective was to define the frequency of post-ERCP complications in liver transplantation patients at the Abdominal Center, Rigshospitalet, the only Liver Transplantation Center in Denmark. METHODS: Retrospective study of all ERCPs performed in liver transplantation patients during a 9-year period. RESULTS: A total of 292 ERCPs were included. Overall post-ERCP complications occurred in 24 procedures (8.2%): pancreatitis in 8 (2.7%), bleeding in 5 (1.7%), and cholangitis in 13 (4.5%) procedures. Simultaneous pancreatitis and cholangitis, and simultaneous bleeding and cholangitis occurred after two procedures, respectively. Multivariate analysis concerning overall complications identified biliary sphincterotomy (p = 0.006) and time since liver transplantation within 90 days postoperatively (p = 0.044) as risk factors for post-ERCP complications. Specifically concerning post-ERCP pancreatitis (PEP), it was found that pre-ERCP cholangitis was another independent risk factor for PEP (p = 0.026). Stent in the biliary tract prior to ERCP seemed to be protective (p = 0.041). CONCLUSIONS: Complications were of surprisingly mild degree. The rates of post-ERCP complications in our study were in line with previous studies with liver transplantation patients. Cholangitis prior to ERCP may be another risk factor for post-ERCP pancreatitis.

The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33.

Cholecystokinin (CCK) occurs in multiple molecular forms; the major ones are CCK-58, -33, -22, and -8. Their relative abundance in human plasma and intestine, however, is debated. To settle the issue, extracts of intestinal biopsies and plasma from 10 human subjects have been examined by chromatography, enzyme cleavages, and measurements using a library of sequence-specific RIAs. Plasma samples were drawn in the fasting state and at intervals after a meal. The abundance of the larger forms varied with the 8 C-terminal assays in the library, as 2 assays overestimated and 3 underestimated the amounts present. One assay, however, measured carboxyamidated and O:-sulfated CCKs with equimolar potency before and after tryptic cleavage. This assay showed that the predominant plasma form is CCK-33, both in the fasting state ( approximately 51%) and postprandially ( approximately 57%), whereas CCK-22 is the second most abundant ( approximately 34% and 30%, respectively). In contrast, CCK-58 is less abundant in human intestines ( approximately 18%) and plasma ( approximately 11%). Its predominance in feline intestines, however, was confirmed. Hence, the results show a significant species variation and emphasize the necessity of highly specific and well characterized assays in molecular studies of CCK.

Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis.

BACKGROUND: 5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response in a number of human inflammatory diseases, such as ulcerative colitis. MK-0591 (3-(1((4-chlorophenyl)methyl)-3((1,1-dimethyl-ethyl)thio)-5(quinolin+ ++-2ylmethyl-oxy)-1H-indol-2yl)-2,2-dimethyl-propanoate) exerts its effect by binding to the 5-lipoxygenase activating protein, thereby inhibiting the translocation and activation of 5-lipoxygenase. METHODS: Concentrations of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) in rectal dialysis fluid, ex vivo biosynthesis of LTB4 in whole blood, and urinary excretion of leukotriene E4 (LTE4) from 16 patients with mild to moderately active distally located ulcerative colitis were measured by use of radioimmunoassays in a double-blind, placebo-controlled parallel-design study before and after oral administration of a 250 mg dose of MK-0591 or placebo. RESULTS: The mean LTB4 concentration in rectal dialysis fluid was lowered after MK-0591 by > 90% (p < 0.05) from 4 to 8 hours, with a maximum inhibition of 97.5% +/- 3.4% (mean +/- SD) at 20 to 24 hours after dosing, whereas PGE2 was unchanged. In whole blood, MK-0591 decreased ex vivo biosynthesis of LTB4 (p < 0.01), with a maximum inhibition of 96.4% +/- 2.1% at 4 hours after dosing. Urinary excretion of LTE4 was reduced by more than 85% (p < 0.001) from 4 to 48 hours. No adverse events were observed. CONCLUSION: These findings show that a single oral 250 mg dose of MK-0591 results in nearly complete blockade of systemic leukotriene production and LTB4 formation in the target tissue of inflammation (the rectum). Controlled multiple-dose trials to assess the clinical efficacy of this novel 5-lipoxygenase-activating protein inhibitor seem to be worthwhile.

[Abscess in the right flank--a late complication of laparoscopic cholecystectomy]. / Absces i højre flanke--senkomplikation til laparoskopisk kolecystektomi.

Laparoscopic cholecystectomy (LC) is the treatment of choice in cases of symptomatic gallstones. A 74-year-old female presented with a spontaneously perforated abscess in her right flank and passage through it of gallstones. Four years previously during LC the gallbladder perforated and 10-15 stones were lost intraperitoneally. In case of perforation of the gallbladder during LC it is essential to reduce loss of and remove all gallstones. In case of abdominal symptoms postoperatively, an intra-abdominal abscess must be suspected.

[Eleven years in a specialist practice dealing with reporting of occupational diseases can be rewarding]. / Elleve år i speciallaegepraksis med anmeldelse af arbejdsbetingede lidelser--det kan nytte.

During a period of 11 years in specialist practice, the authors notified 309 cases of occupationally-conditioned disease and occupational accidents. The majority of diseases were in the locomotor system. The authors reviewed the sex and age distributions and the distribution of the conditions involved. Their share of notifications from specialist practice during the period 1983-1986 was also reviewed together with the relevant specialties and the action taken by the Workers Supervision Authorities. The authors found their share in the notifications was relatively excessive but that it was declining because a great number of specialists have begun to notify conditions in the locomotor system. In addition, the authors have observed a considerable reduction in the rime taken to analyse cases by the Workers Supervision Authorities and an increase in the number of factory visits. The number of factory visits on account of the authors' notifications constituted 11% which shows that notification of occupationally-conditioned diseases is worth while.

[Changed working plans can improve medical training]. / En aendret arbejdstilrettelaeggelse kan medføre en forbedret laegeuddannelse.

INTRODUCTION: The quality of clinical medical training in Denmark has been closely debated and criticised in recent years. Reorganisation of the daily working plans is one of the recommendations for improvement. METHOD: In the Department of Gastrointestinal Surgery, we made changes in the daily working plans in order to improve supervision and training. These changes included firmer attachment of the young residents to specialised medical teams in the department and the creation of more supervised working situations. The morning rounds were done by all the senior and junior doctors in the team together, which meant that the rounds could be completed in half-an-hour and consequently more senior doctors were available for supervision during the rest of the day. This was adopted by the outpatient clinic, the endoscopy unit, and the operating rooms, where activities did not start until after the rounds. RESULTS: The changes led to a considerable increase in the number of working situations with supervision. Assessment by a questionnaire showed that residents also found significant improvements in supervision during all clinical activities. Overall satisfaction with the department and working conditions increased. CONCLUSION: Many different aspects must be considered if clinical medical training is to improve. One key factor is a thorough revision of the daily working plans, so as to establish as many supervised teaching situations as possible.

[Parvovirus B19 as a cause of acute liver symptoms in adults]. / Parvovirus B19 som årsag til akut leverpåvirkning hos voksne.

Parvovirus B19 (B19), also known as "erythema infectiosum", is a disease that occurs in smaller outbreaks during late winter and early summer; and in Denmark an epidemic occurs every three years. The symptoms vary from fever, fatigue and the characteristic maculopapoulous erythema to asymptomatic cases in 50% of the infected patients. Two-thirds of the Danish population have been infected. The virus has a broad spectrum of clinical manifestations ranging from erythema nodosum in children, arthralgia/arthritis (especially in adults), aplastic crisis in patients with haemolytic anaemia, chronic anaemia in immunocompromised patients, to hydrops foetalis following acute infection during pregnancy. In two adult females aged 41 and 35 years with persisting fatigue, malaise, transitory swelling and arthralgia we found elevated ALT and alkaline phosphatase (pt. 1), despite no serological evidence of hepatitis, cytomegalovirus (CMV), or Epstein-Barrvirus and no story of alcohol consumption or recent travelling outside Denmark. Ongoing B19 infection was diagnosed by ELISA and confirmed by B19 DNA PCR in case 2 and IgG avidity and epitope-type specificity in case 1, who was B19 DNA negative in three different samples. The concentrations of alkaline phosphatase and ALT returned to normal as the antibody response shifted from acute B19 infection to IgG positivity. In conclusion we suggest that a serological test and/or B19 DNA for B19 infection is a relevant test to undertake when screening patients for viral hepatitis especially during B19 epidemics and in exposed individuals.

[Surgical treatment of stomach cancer at a university hospital. A retrospective survey of the period 1990-1995]. / Kirurgisk behandling af cancer ventriculi på et universitetshospital. En retrospektiv opgørelse for perioden 1990-1995.

AIM: A retrospective study of 69 cases of gastric cancer seen during the period from 1/1-1990 to 31/12-1994 treated in a University Hospital. The aim of the study was to describe morbidity, mortality and identify independent prognostic variables for mortality. METHOD: Patient data were recovered from the hospital's central database. Mortality was chosen as end-parameter. Univariate log-rank-test identified statistically significant variables which were then analysed by Cox backward stepwise regressional analysis. MATERIAL: Sixty-nine patients were available for analysis, median age 73 years. Fifty-one patients underwent operation. Eighteen patients did not have a surgical procedure due to disseminated disease. The overall postoperative morbidity was 25% and postoperative mortality 10%. The overall five-year survival rate was 8%, 12% for operated patients, 35% after radical and 0% after non-radical or omitted surgery. Age, radicality of operation, type of operation, Borrmann's tumour classification, and degree of depth of local infiltration were identified as significant factors for survival. Cox's analysis identified type of operation (p = 0.0002) and Borrmann's tumour classification (p = 0.001) as independent variables. DISCUSSION: The overall five-year survival is low and has not changed over two decades in Denmark, whereas mortality and morbidity rates have improved. It should be recommended that: The treatment of gastric cancer must be centralised in order to develop preoperative examinations, operative technique and the necessary routine for the surgeons. All gastric ulcers must be considered malignant and biopsies taken accordingly.

Focused Assessment with Sonography for Trauma in patients with confirmed liver lesions.

BACKGROUND AND AIMS: The objective was to determine the sensitivity and specificity of Focused Assessment with Sonography for Trauma (FAST) in patients with confirmed liver lesions and also to compare results from surgeons trained in FAST with results from radiologists trained in general abdominal ultrasound as part of the specialist training. Explorative laparotomy or CT served as gold standard. MATERIALS AND METHODS: This retrospective study included all patients admitted to our institution from 2003 to 2010 registered with the diagnosis "Injury of the liver or gallbladder". Of 405 patients, 135 patients were eligible for analysis. Seventy-two patients were examined by radiologists and 63 by surgeons. RESULTS: We found FAST to have a sensitivity, specificity, PPV, and NPV of 79.6%, 100%, 100%, and 68.9%. There was no statistically significant difference between FAST performed by radiologists and surgeons trained in FAST. CONCLUSION: FAST remains an important screening tool in abdominal trauma including liver lesions, and can be performed at a satisfactory level by surgeons trained in the FAST procedure only.

Arterial hypoxaemia in cirrhosis: fact or fiction?

BACKGROUND: Although low arterial oxygen tension (Po2) has been claimed to occur in one to two thirds of patients with cirrhosis, hypoxaemia appears to be rare in clinical practice. AIMS: To assess the frequency of arterial hypoxaemia in cirrhosis in relation to clinical and haemodynamic characteristics. PATIENTS: One hundred and forty two patients with cirrhosis without significant hepatic encephalopathy (grades 0-I) (41 patients in Child class A, 57 in class B, and 44 in class C) and 21 patients with hepatic encephalopathy. RESULTS: Mean Po2 in kPa was 11.3 in Child class A, 10.8 in class B, 10.6 in class C, and 10.6 in patients with encephalopathy (p < 0.05). The fraction of patients with Po2 below the lower normal limit of 9.6 kPa was 10%, 28%, 25%, and 43%, respectively in class A, B, C, and in patients with encephalopathy (p < 0.05). Oxygen saturation (So2) in these groups was respectively: 96%, 96%, 96%, and 93% (NS). So2 was below the lower limit of 92% in 0%, 9%, 7%, and 24% (p < 0.05). In patients without hepatic encephalopathy, a multivariate regression analysis revealed that independent determinants of a low Po2 were a high arterial carbon dioxide tension, a low systemic vascular resistance, and a low indocyanine green clearance (p < 0.0001). CONCLUSION: The prevalence of arterial hypoxaemia in cirrhosis is about 22% in patients without encephalopathy, but it varies from 10-40% depending on the degree of hepatic dysfunction. Arterial hypoxaemia in patients with cirrhosis of differing severity seems lower than previously reported, and patients with severe arterial hypoxaemia are rare.

Indomethacin decreases gastroduodenal mucosal bicarbonate secretion in humans.

BACKGROUND: Cyclooxygenase inhibitors reduce mucosal bicarbonate secretion in the duodenum, but the evidence for their effect on bicarbonate secretion in the stomach remains controversial. We have, therefore, studied how indomethacin influences gastroduodenal bicarbonate secretion and luminal release of prostaglandin (PG) E2 by means of a method that enables simultaneous measurements in the stomach and the duodenum. METHODS: Gastric and duodenal perfusions were performed twice in random order during control conditions or after pretreatment with indomethacin (100 mg intravenously) in eight healthy volunteers. Bicarbonate and PGE2 were measured in the gastroduodenal effluents by back-titration and radioimmunoassay, respectively. RESULTS: Vagal stimulation and duodenal luminal acidification (0.1 M HCl; 20 ml; 5 min) increased gastroduodenal bicarbonate secretion (p < 0.05). Indomethacin markedly inhibited both basal and stimulated gastric and duodenal mucosal bicarbonate secretion, and this reduction was similar to the degree of cyclooxygenase inhibition estimated by the luminal release of PGE2 (p < 0.05). CONCLUSION: These results unequivocally demonstrate that endogenous PG modulates basal and stimulated bicarbonate secretion, both in the stomach and in the duodenum.

Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative.

Gastric bicarbonate secretion and release of prostaglandin E2 are increased in duodenal ulcer patients but not in Helicobacter pylori-positive healthy subjects.

BACKGROUND: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E2 than healthy subjects. Our purpose was to determine whether this abnormality was present also in the stomach of DU patients. METHODS: Simultaneous determinations of gastric and duodenal bicarbonate secretion and luminal release of PGE2 were performed in 16 healthy volunteers (5 Helicobacter pylori-positive) and 8 inactive DU patients (all H. pylori-positive). RESULTS: In healthy volunteers the rates of gastroduodenal bicarbonate secretion and the release of PGE2 were not influenced by H. pylori status. In inactive DU patients the rates of basal (704 +/- 84 versus 356 +/- 40 mumol/h; mean +/- SEM) and vagally stimulated (modified sham feeding) (1724 +/- 376 versus 592 +/- 52 mumol/h) gastric bicarbonate secretion were higher (p < 0.05) than in the health, whereas the corresponding rates (339 +/- 42 versus 591 +/- 51 mumol/h and 543 +/- 99 versus 778 +/- 69 mumol/h) in duodenal bicarbonate secretion were lower (p < 0.05). In addition, inactive DU patients had higher basal (148 +/- 32 versus 53 +/- 5 ng/h) and stimulated (291 +/- 84 versus 131 +/- 25 ng/h) gastric release of PGE2, but only the basal release of PGE2 into the duodenum was significantly increased (20 +/- 3 versus 5 +/- 1 ng/h; p < 0.05). CONCLUSION: Increased mucosal production of PGE2 may be responsible for the abnormally high gastric secretion of bicarbonate in inactive DU patients. The defective duodenal secretion of bicarbonate observed in these patients may be a consequence of previous ulceration rather than the mere presence of H. pylori infection.