Colonoscopy is the preferred colorectal cancer screening method in a population-based program.

BACKGROUND AND STUDY AIMS: Various screening methods for colorectal cancer (CRC) are promoted by professional societies; however, few data are available about the factors that determine patient participation in screening, which is crucial to the success of population-based programs. This study aimed (i) to identify factors that determine acceptance of screening and preference of screening method, and (ii) to evaluate procedure success, detection of colorectal neoplasia, and patient satisfaction with screening colonoscopy. PATIENTS AND METHODS: Following a public awareness campaign, the population aged 50 - 80 years was offered CRC screening in the form of annual fecal occult blood tests, flexible sigmoidoscopy, a combination of both, or colonoscopy. RESULTS: 2731 asymptomatic persons (12.0 % of the target population) registered with and were eligible to take part in the screening program. Access to information and a positive attitude to screening were major determinants of participation. Colonoscopy was the method preferred by 74.8 % of participants. Advanced colorectal neoplasia was present in 8.5 %; its prevalence was higher in males and increased with age. Significant complications occurred in 0.5 % of those undergoing colonoscopy and were associated with polypectomy or sedation. Most patients were satisfied with colonoscopy and over 90 % would choose it again for CRC screening. CONCLUSIONS: In this population-based study, only a small proportion of the target population underwent CRC screening despite an extensive information campaign. Colonoscopy was the preferred method and was safe. The determinants of participation in screening and preference of screening method, together with the distribution of colorectal neoplasia in different demographic categories, provide a rationale for improving screening procedures.

Correlation between symptoms developed after the oral ingestion of 50 g lactose and results of hydrogen breath testing for lactose intolerance.

BACKGROUND: Lactase deficiency is a common condition responsible for various abdominal symptoms. Lactose hydrogen breath test is currently the gold standard in diagnosing lactose intolerance. AIM: To assess sensitivity and specificity of symptoms developed after oral lactose challenge. METHODS: Intensity of nausea, abdominal pain, borborygmi, bloating and diarrhoea was recorded every 15 min up to 3 h after ingestion of 50 g lactose in patients with positive (i.e. breath H2-concentration > or =20 p.p.m. above baseline) and negative lactose hydrogen breath test. RESULTS: Between July 1999 and December 2005, 1127 patients (72% females) underwent lactose hydrogen breath test. A positive result was found in 376 (33%). Sensitivity of individual symptoms ranged from 39% (diarrhoea) to 70% (bloating) while specificity ranged from 69% (bloating) to 90% (diarrhoea). A positive lactose hydrogen breath test was found in 21% of patients with one symptom, 40% of patients with two symptoms, 44% of patients with three symptoms, 67% of patients with four symptoms and 82% of patients with five symptoms. Symptom intensity was significantly higher for each symptom in the positive group. CONCLUSION: Evaluating symptoms developed after ingestion of 50 g lactose can be used as a simple screening test to select patients who need to be referred for lactose intolerance testing.

Hospital health care resource utilization and costs of colorectal cancer during the first 3-year period following diagnosis in Switzerland.

BACKGROUND: In industrialized countries, colorectal cancer is a leading cause of morbidity and mortality. Decisions on colorectal cancer screening are based on cost-effectiveness analyses that rely on colorectal cancer cost studies. Additionally, the study of the resource utilization pattern may lead to cost-saving strategies in the care of colorectal cancer. AIM: To estimate hospital resource utilization, the use of various therapy modalities and costs of colorectal cancer cases undergoing surgery during the first 3 years following the diagnosis at a Swiss university hospital. METHODS: Consecutive colorectal cancer patients from 1997 to 1998 were identified using the surgery database of the University Hospital of Basel and followed for a period of 3 years. In-hospital resource utilization and costs were retrieved from the computerized administrative records. Treatment outside of the hospital during the study period constituted an exclusion criterion. RESULTS: Eighty-three (94%) of 89 patients undergoing surgery for colorectal cancer were included in the study, 58 with colon cancer and 25 with rectal cancer. The average ages were 70.3 and 63.6 years, respectively. Overall, 59% of the patients were treated with surgery alone, 27% also had chemotherapy and 15% received additional chemoradiotherapy. These percentages and resource utilization varied broadly between the two colorectal cancer groups. On average, patients were admitted to the hospital 2.7 times and the hospital length of stay amounted to 35 days. They were visited by doctors 69 times, and examined with colonoscopy, ultrasonography and computerized tomography 2.7, 3.2 and 2.4 times, respectively. Mean costs incurred for rectal cancer (US dollars 40,230) were about 22% higher than for colon cancer patients (US dollars 33,079). Hospitalization and surgical therapy generated the greatest costs. Expenses were highest for the first year and with more severe disease stages at diagnosis. CONCLUSIONS: Colorectal cancer is an expensive disease. Economic analyses on screening should take into account the large resource utilization and cost variability by performing sensitivity analysis on broad cost ranges. Furthermore, they should consider stage shifting at diagnosis and include stage-specific costs.

Effect of intravenous infusions of thiamine on the disposition kinetics of thiamine and its pyrophosphate.

BACKGROUND: Thiamine supplementation is necessary in patients with thiamine deficiency syndromes. Experimental evidence suggests that tissue uptake and the elimination of thiamine are dose-dependent. AIM: The aim of the present study was to investigate the effect of different i.v. infusion rates of thiamine on blood concentrations of thiamine and its active metabolite thiamine pyrophosphate (TPP) and on renal excretion of thiamine. METHODS: Twelve healthy subjects received in a two-period block randomized study 150 mg thiamine intravenously over either 1 or 24 h. RESULTS: The maximum blood concentrations (Cmax) of thiamine were significantly higher after the more rapid infusion (RI; 2300 ng/mL) than after the slower infusion (SI; 177 ng/mL). The AUC of thiamine was identical after both infusion protocols. There was a slightly (10%) increased AUC of TPP (P < 0.08) after SI, whereas C(max) values were comparable. Urinary excretion of thiamine was significantly decreased from 83.6% of the applied dose after RI to 57.6% after the SI. CONCLUSIONS: Our data suggest an increased tissue uptake of thiamine when it is given as an SI compared with a RI of the same dose. It is concluded, therefore, that an SI of thiamine may be superior to RI or bolus injections to treat severe deficiency syndromes.

Cost-effectiveness of colonoscopy in screening for colorectal cancer.

BACKGROUND: Fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy are used to screen patients for colorectal cancer. OBJECTIVE: To compare the cost-effectiveness of fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy. DESIGN: The cost-effectiveness of the three screening strategies was compared by using computer models of a Markov process. In the model, a hypothetical population of 100 000 persons 50 years of age undergoes annual fecal occult blood testing, sigmoidoscopy every 5 years, or colonoscopy every 10 years. Positive results on fecal occult blood testing or adenomatous polyps found during sigmoidoscopy are worked up by using colonoscopy. After polypectomy, colonoscopy is repeated every 3 years until no polyps are found. DATA SOURCES: Transition rates were estimated from U.S. vital statistics and cancer statistics and from published data on the sensitivity, specificity, and efficacy of various screening techniques. Costs of screening and cancer care were estimated from Medicare reimbursement data. TARGET POPULATION: Persons 50 years of age in the general population. TIME HORIZON: The study population was followed annually until death. PERSPECTIVE: Third-party payer. OUTCOME MEASURE: Incremental cost-effectiveness ratio. RESULTS OF BASE-CASE ANALYSIS: Compared with colonoscopy, annual screening with fecal occult blood testing costs less but saves fewer life-years. A screening strategy based on flexible sigmoidoscopy every 5 or 10 years is less cost-effective than the other two screening methods. RESULTS OF SENSITIVITY ANALYSIS: Screening with fecal occult blood testing is more sensitive to changes in compliance rates, and it becomes easily dominated by colonoscopy under most conditions assuming less than perfect compliance. Other assumptions about the sensitivity and specificity of fecal occult blood testing, screening frequency, efficacy of colonoscopy in preventing cancer, and polyp incidence have a lesser influence on the differences in cost-effectiveness between colonoscopy and fecal occult blood testing. CONCLUSIONS: Colonoscopy represents a cost-effective means of screening for colorectal cancer because it reduces mortality at relatively low incremental costs. Low compliance rates render colonoscopy every 10 years the most cost-effective primary screening strategy for colorectal cancer.

A decision analysis of surveillance for colorectal cancer in ulcerative colitis.

BACKGROUND: Patients with long standing, extensive ulcerative colitis have an increased risk of developing colorectal cancer. AIMS: To assess the feasibility of surveillance colonoscopy in preventing death from colorectal cancer. PATIENTS: A hypothetical cohort of patients with chronic ulcerative colitis. METHODS: The benefits of life years saved were weighted against the costs of biannual colonoscopy and proctocolectomy, and the terminal care of patients dying from colorectal cancer. Two separate Markov processes were modelled to compare the cost-benefit relation in patients with or without surveillance. The cumulative probability of developing colorectal cancer served as a threshold to determine which of the two management strategies is associated with a larger net benefit. RESULTS: If the cumulative probability of colorectal cancer exceeds a threshold value of 27%, surveillance becomes more beneficial than no surveillance. The threshold is only slightly smaller than the actual cumulative cancer rate of 30%. Variations of the assumptions built into the model can raise the threshold above or lower it far below the actual rate. If several of the assumptions are varied jointly, even small changes can lead to extreme threshold values. CONCLUSIONS: It is not possible to prove that frequent colonoscopies scheduled at regular intervals are an effective means to manage the increased risk of colorectal cancer associated with ulcerative colitis.

At what age should a one-time only colonoscopy for screening of colorectal cancer be performed?

OBJECTIVE: To determine at what age the only screening colonoscopy during lifetime should be performed to achieve the highest yield. METHODS: Medical decision analysis to calculate the loss in life years associated with mortality from colorectal cancer at different ages. RESULTS: The expected loss in life years from colorectal cancer is highest between the ages 70 to 80 years, with a peak occurring at age 75. The length of protection provided by colonoscopy plus polypectomy is estimated to last 5-10 years after the procedure. A screening colonoscopy at age 65 would, thus, protect a subject from age 65 until age 70 or 75 years. Similarly, a screening colonoscopy at age 70 would protect the subject from age 70 until age 75 or 80 years. CONCLUSIONS: The highest yield in life years by preventing death from colorectal cancer is achieved if the only colonoscopy per lifetime is scheduled between the ages of 65 and 70 years.

The unsolved problem of surveillance for colorectal cancer in ulcerative colitis.

The association between long standing extensive ulcerative colitis and the increased risk for developing colorectal cancer suggests that surveillance by frequent and regular colonoscopies may provide a means for reducing cancer-related morbidity and mortality. A crude calculation suggests that such a surveillance program would also be cost effective. None of several clinical trials, however, has been able to provide unequivocal evidence in favour of surveillance. The major reason for this failure relates to the prohibitively large number of patients with ulcerative colitis who need to be followed over a prolonged time period before statistically sound results would be obtained. Because models of decision analyses themselves have to rely on medical evidence, they cannot provide a substitute for deficient clinical data. The issue of surveillance colonoscopy cannot be resolved by the available knowledge or analytical tools. Hopefully, new techniques of surveillance or even a cure for ulcerative colitis will render the question mute of whether or not to screen patients with ulcerative colitis by frequent colonoscopy.

Birth-cohort phenomenon in the time trends of mortality from ulcerative colitis.

It has been suggested that the mortality trends of ulcerative colitis in England and Wales are shaped by an underlying birth-cohort phenomenon. This pattern implies that exposure to an environmental risk factor early in life plays a crucial role in the development of the disease. The authors tested whether the birth-cohort pattern is unique to British mortality statistics or a common feature of ulcerative colitis in western countries by using the vital statistics from England and Wales, Canada, Scotland, Switzerland, The Netherlands, and the United States. Ulcerative colitis death rates from the six countries were plotted against the periods of death or periods of birth. Mortality from ulcerative colitis increased in successive generations born throughout the second half of the 19th century. It peaked in subjects born between 1880 and 1890 and has declined since then. Strikingly similar patterns were found in the six countries and when women and men were analyzed separately. The birth-cohort pattern indicates that development of ulcerative colitis is strongly influenced by one or several environmental risk factors, which act during a short period early in life. In western countries, exposure to this risk has changed in a similar fashion.

Commonalities in the time trends of Crohn's disease and ulcerative colitis.

OBJECTIVE: The analysis of the time trends of inflammatory bowel disease (IBD) is a powerful research tool to assess the contribution of environmental factors to its etiology and to gain insights about possible causative mechanisms. A previous study revealed a characteristic relationship between the time trends of mortality from Crohn's disease and ulcerative colitis. The present study aimed to test whether the most recent temporal patterns still corroborate the hypothesis of two interacting risk factors in the development of IBD. The time trends of IBD from six countries were checked for common features. METHODS: Mortality data from Australia, Canada, England and Wales, the Netherlands, Sweden, and the United States were analyzed. Age- and sex-specific death rates, as well as total death rates, from Crohn's disease and ulcerative colitis were plotted against the period of death. RESULTS: Mortality from ulcerative colitis decreased continuously during the past 40 years. Mortality from Crohn's disease increased between 1950 and the mid-1970's until reaching a similar level as mortality from ulcerative colitis. Since then the death rates of both diseases have followed a parallel time course. A similar behavior was found, if male and female data were analyzed separately. It could be also discerned in the time trends of each age group. The data from all six countries revealed identical temporal patterns. CONCLUSIONS: The similar time trends of IBD from different countries support the hypothesis that identical causative mechanisms are responsible for the mortality and the occurrence of IBD among populations characterized by different political history and health care systems. The rapidity of the temporal changes implicates environmental agents in the etiology of both diseases. The relationships between the temporal changes of Crohn's disease and ulcerative colitis point at the existence of a shared risk factor responsible for the occurrence of both diseases, and at the existence of at least one additional factor, responsible for the expression of Crohn's disease alone.

Is virtual colonoscopy a cost-effective option to screen for colorectal cancer?

OBJECTIVE: Computed tomography (CT) or magnetic resonance (MR) colonography is a new technique that uses data generated from CT or MR imaging to create two- and three-dimensional scans of the colon. It has been advocated to become the new primary technique of screening for colorectal cancer. The economic feasibility of such recommendation, however, has not yet been evaluated. METHODS: The cost-effectiveness of two screening strategies using CT colonography or conventional colonoscopy was compared by computer models based on a Markov process. We supposed that a hypothetical population of 100,000 subjects aged 50 yr undergoes a screening procedure every 10 yr. Suspicious findings of CT colonography are worked-up by colonoscopy. After polypectomy, colonoscopy is repeated every 3 yr until no adenomatous polyps are found. RESULTS: Under baseline conditions, screening by CT colonography costs $24,586 per life-year saved, compared with $20,930 spent on colonoscopy screening. The incremental cost-effectiveness ratios comparing CT colonography to no screening and colonoscopy to CT colonography were $11,484 and $10,408, respectively. Screening by colonoscopy remains more cost-effective even if the sensitivity and specificity of CT colonography both rise to 100%. For the two screening procedures to become similarly cost-effective, CT colonoscopy needs to be associated with an initial compliance rate 15-20% better or procedural costs 54% less than colonoscopy. CONCLUSIONS: To become cost-effective and be able to compete with colonoscopy in screening for colorectal cancer, CT or MR colonography would need be offered at a very low price or result in compliance rates much better than those associated with colonoscopy.

Limitations of the faecal occult blood test in screening for colorectal cancer.

BACKGROUND: A screening test should be acceptable, safe, simple, accurate, reliable, effective, and inexpensive. Screening for colorectal cancer with the faecal occult blood test is done to reduce the incidence and mortality from colorectal cancer. How does this test measure up to these requirements? METHODS: The characteristics of faecal occult blood test are described by means of clinical epidemiology, analysing its compliance, sensitivity, specificity, positive predictive value, and its test performance in Bernoulli trials. A decision tree and a Markov model are used to compare the cost-effectiveness of screening strategies involving faecal occult blood test and colonoscopy. RESULTS: After 5-10 years, patient compliance in a faecal occult blood test screening programme falls below 50%. Over 80% of the patients are likely to leave the programme before its completion. Although the test itself may seem safe and simple, the high rate of false-positive outcomes exposes many subjects to the potential complications of colonoscopy. The high rate of false-negative tests gives patients with colorectal cancer a false sense of security and delays their proper diagnostic work-up. In populations with low prevalence rates of colorectal cancer, faecal occult blood test becomes very inaccurate in diagnosing colorectal cancer, as its positive predictive value falls below 5%. Its long-term test performance is unreliable in that it comes to depend on the frequency, with which the test is repeated. Any negative or positive test result can be achieved by varying the frequency of test repetition. Screening by colonoscopy every five or ten years is more cost-effective than screening by annual faecal occult blood test in preventing the occurrence of colorectal cancer and its associated mortality. CONCLUSIONS: Screening strategies for colorectal cancer involving faecal occult blood test should be abandoned.

Celiac sprue among US military veterans: associated disorders and clinical manifestations.

The present study aimed to describe the clinical manifestations of celiac sprue related to malnutrition and to analyze the associations between celiac sprue and other diagnoses. A case-control study compared the occurrence of comorbid diagnoses in case and control subjects with and without celiac sprue, respectively. All patients with a primary or secondary diagnosis of celiac sprue (ICD-579.0) who were discharged from hospitals of the Department of Veterans Affairs between 1986 and 1995 were selected as case subjects. In a multivariate logistic regression analysis, the occurrence of celiac disease served as outcome variable, while age, gender, ethnicity, and the comorbid occurrences of other diagnoses served as predictor variables. A total of 458 individual patients with celiac sprue were identified. The data confirmed the known associations of celiac sprue with dermatitis herpetiformis, lactase deficiency, enlargement of lymph nodes, and lymphoma. Celiac sprue was also found to be statistically significantly associated with pancreatic insufficiency, Crohn's disease, functional bowel symptoms, chronic nonalcoholic hepatitis, and pulmonary eosinophilia. The nutritional manifestations associated with celiac disease included nutritional marasmus, cachexia, weight loss, hypocalcemia, osteoporosis, vitamin B-complex deficiency, and various types of iron- and vitamin-deficiency anemias. The large variety of complex associations clearly indicates that celiac sprue is a systemic disease that involves multiple organs and exceeds an isolated nutritional intolerance to gluten.

Exposure to risk factors for ulcerative colitis occurs during an early period of life.

OBJECTIVE: It has been speculated that environmental factors play a role in the etiology of ulcerative colitis. A previous analysis revealed that the time trends of ulcerative colitis in England were shaped by an underlying birth-cohort pattern. We undertook this study to test whether the birth-cohort pattern was a unique feature of the English vital statistics or whether a similar phenomenon could also be ascertained in the mortality statistics from a different country, such as Switzerland. Besides comparing the data of ulcerative colitis from Switzerland and England, the trends of ulcerative colitis were compared with those of gastric and duodenal ulcer. METHODS: Death rates from ulcerative colitis, gastric ulcer, and duodenal ulcer were plotted against the period of death and period of birth. An age-standardized cohort mortality ratio was calculated as a summary statistic of the overall mortality associated with each consecutive birth-cohort. RESULTS: Mortality from ulcerative colitis increased among successive generations born throughout the 19th century. It peaked in individuals born around 1890 and has declined since then. Strikingly similar patterns were found in Switzerland and England. The birth-cohort pattern underlying the time trends of ulcerative colitis applied equally to the data for women and men. In comparison with peptic ulcer, the birth-cohort pattern of ulcerative colitis was almost identical to that of duodenal ulcer. It peaked in both countries 10-20 yr later than gastric ulcer. CONCLUSIONS: The birth-cohort pattern indicates that acquisition of ulcerative colitis is strongly influenced by environmental risk factors and that the exposure to these factors occurs during an early period of life. The similarity in the birth-cohort patterns of duodenal ulcer and ulcerative colitis could hint at a childhood infection or a related mode of transmission in both diseases.

Associations between hemorrhoids and other diagnoses.

PURPOSE: The risk factors and mechanisms that contribute to the occurrence of hemorrhoids are not well understood. The study of the comorbid occurrences of hemorrhoids with other diagnoses in identical patients may point to a common underlying pathophysiology. The present study was undertaken to determine which diagnoses are associated with the occurrence of hemorrhoids. METHODS: A case-control study compared the occurrence of comorbid diseases in case subjects with hemorrhoids with that of control subjects without hemorrhoids. The case population comprised all patients with hemorrhoids (International Classification of Diseases codes 455.0-455.9), who were discharged from hospitals of the U.S. Department of Veterans Affairs between 1986 and 1996. In a multiple logistic regression analysis, the occurrence of hemorrhoids served as outcome variable, and age, gender, ethnicity, and the comorbid occurrence of other diagnoses served as predictor variables. RESULTS: A total of 96,314 individual patients with hemorrhoids and the same number of control subjects were identified. In a chart review of a random sample of 100 cases, the diagnosis of hemorrhoids could be confirmed in 97 percent of all instances checked. The variety of diagnoses associated with hemorrhoids could be broken down into five large categories: 1) diseases associated with diarrhea (odds ratio, 1.30; 95 percent confidence interval, 1.27-1.33); 2) spinal cord injuries (odds ratio, 1.17; 95 percent confidence interval, 1.09-1.26); 3) constipation and related diseases (odds ratio, 1.48; 95 percent confidence interval, 1.43-1.54); 4) various types of anorectal diseases (odds ratio, 4.71; 95 percent confidence interval, 4.44-5.0); and 5) conditions that could be considered manifestations or sequelae of the hemorrhoidal disease itself (odds ratio, 3.41; 95 percent confidence interval, 3.30-3.51). CONCLUSIONS: The types and spectrum of comorbid diagnoses associated with hemorrhoids suggest that an increased tone of the anal sphincter constitutes a common pathophysiologic mechanism for the development of hemorrhoids.

Military history of patients with inflammatory bowel disease: an epidemiological study among U.S. veterans.

OBJECTIVES: The military history of patients with inflammatory bowel disease (IBD) contains types of exposure that are not available through other sources and may provide clues about the as-yet unknown etiology of IBD. We therefore sought to describe the epidemiology of IBD among veterans, with particular emphasis on their military history. METHODS: A case-control study compared 10,544 IBD patients and 42,026 controls with respect to age, gender, ethnicity, time period of military service, military duty in Vietnam, status as prisoner of war, and exposure to Agent Orange. RESULTS: Subjects with Crohn's disease were younger than those with ulcerative colitis or without IBD (odds ratio: 0.85; 95% confidence interval [CI]: 0.83-0.87). Both types of IBD affected female veterans significantly more often than male veterans, the relative female predominance being more pronounced in Crohn's disease than ulcerative colitis (0.70; 0.61-0.81 vs 0.83; 0.71-0.96). Whites were more prone to develop both types of IBD than nonwhites (2.46; 2.27-2.68 vs 2.11; 1.95-2.27). Military duty in Vietnam and a status as prisoner of war both exerted a protective influence against Crohn's disease (0.84; 0.75-0.96 and 0.60; 0.41-0.87, respectively), but not ulcerative colitis. CONCLUSIONS: The results are consistent with the hypothesis that exposure to poor sanitation decreases the future risk of developing Crohn's disease.

Empirical therapy versus diagnostic tests in gastroesophageal reflux disease: a medical decision analysis.

Our objective was to describe the conditions that determine the costs of empirical therapy in gastroesophageal reflux disease (GERD). Our design was a threshold analysis using a decision tree. The costs of medications were estimated from the average wholesale prices. The costs of diagnostic procedures were expressed as the sum of physician and facility costs. A decision tree was modeled to calculate the threshold probability of GERD, for which empirical therapy became the preferred management strategy. Bayes' formula was used to transform the sensitivity and specificity of various symptoms and the joint occurrence of multiple symptoms into disease probabilities. The decision in favor of empirical therapy is influenced by four factors: the probability of GERD, the duration or costs of GERD therapy, the costs of erroneous empirical therapy in patients with diagnosis other than GERD, and the costs of diagnostic procedures. In general, the expected benefit of saving the costs of a diagnostic procedure outweighs the costs of occasional erroneous empirical therapy. However, if surgical therapy is considered or antisecretory therapy is administered for a time period of 10 or more years, diagnostic confirmation of GERD should be sought. In the long run, the failure to differentiate between peptic ulcer and GERD results in the highest cost associated with erroneous empirical therapy. In patients with multiple characteristic symptoms of GERD, the diagnosis can be ascertained with sufficient confidence to warrant empirical therapy.

Spontaneous biliothorax (thoracobilia) following cholecystopleural fistula presenting as an acute respiratory insufficiency. Successful removal of gallstones from the pleural space.

A patient presented to the emergency department with tachypnea, fever, a right pleural effusion, and lung consolidation. The computed tomographic guided thoracentesis yielded a greenish fluid with bilirubin. The ultrasound examination demonstrated a distended gallbladder with stones, positioned on the ventral face of the liver and a free communication between the fundus and the pleural cavity. The cholecystopleural fistula was confirmed at operation.

Cholecystokinin is a physiological regulator of gastric acid secretion in man.

CCK8 is a poor stimulant of gastric acid secretion in vivo, but is equipotent to gastrin-17 (G17) in in vitro systems. To further evaluate the role of cholecystokinin (CCK) in regulating acid output in humans, dose-response curves were constructed to CCK8 or G17 (6.4-800 pmol kg-1 per h) with and without a specific CCK-A receptor antagonist (loxiglumide). During loxiglumide infusion, G17-stimulated acid output was unchanged, whereas CCK8-stimulated secretion increased significantly. Gastric somatostatin-14 release increased fivefold with CCK8 alone, but was blocked with loxiglumide administration. These data suggest that CCK8 directly stimulates acid secretion by binding to a CCK-B/gastrin receptor on parietal cells, but at the same time inhibits acid responses by stimulating gastric somatostatin release to a CCK-A receptor-mediated pathway. To test which action of CCK is relevant under physiological circumstances, the effect of loxiglumide on fasting and post-prandial acidity was measured through continuous pH-metry. After eating, gastrin levels increased fourfold compared to controls with concomitant increases in acid secretion. These results suggest that post cibum, CCK is an inhibitor of acid secretion by regulating gastrin through local somatostatin; they support the hypothesis that CCK acts as an enterogastrone.

Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man.

To explore the interactions between cholecystokinin (CCK) and the cholinergic system, we compared the effect of cholinergic or peptidergic CCK blockade on gallbladder contraction and pancreatic enzyme secretion using atropine and loxiglumide (a specific CCK antagonist) as pharmacological tools. Gallbladder contraction was measured by sonography and pancreatic secretion by a marker perfusion and aspiration technique. Graded doses of exogenous CCK8 induced dose-dependent contractions of the gallbladder and increasing enzyme outputs. Loxiglumide (10 mg kg-1 h-1) abolished the gallbladder response and prevented an increase in pancreatic enzyme secretion to CCK8. Atropine (5 micrograms kg-1 h-1), however, only reduced gallbladder contraction and enzyme output to CCK8. Gallbladder volumes decreased maximally to 12 +/- 4% after oral food, whereas enzyme output and plasma CCK levels increased 6- to 8-fold. Loxiglumide completely abolished gallbladder contraction and inhibited enzyme secretion by 30%. Atropine caused a small reduction in gallbladder volumes, but essentially blocked postprandial enzyme secretion. The results indicate that CCK is the major regulator of gallbladder contraction with the cholinergic system modulating the response, while the exocrine pancreas is crucially dependent on a cholinergic background with CCK modulating the secretory response.