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Summary Background Lymphoproliferative disorders in patients with liver cirrhosis, although uncommon, have been reported in at least 49 cases. Some authors have suggested that the association between chronic liver disease and lymphoma is not coincidental, that immune mechanisms may be pathogenetically involved. Patients and methods In the present study we calculated the incidence rate of lymphoproliferative disorders in 334 liver cirrhosis patients (201 males, mean age 59 ± 12; 133 females, mean age 61 ± 11) treated at the Gastroenterology Department of the Mauriziano Hospital in Turin from January 1987 to September 1990. Results We diagnosed 12 lymphoproliferative disorders, corresponding to an incidence of 9.56/1,000 person-years, a figure much higher than expected on the basis of the incidence rate registered in the Turin general population. Six of the 12 lymphoproliferative disorders were non-Hodgkin's lymphomas of the stomach, a proportion by far exceeding expectation. Conclusions Our data support the hypothesis that the association between chronic liver disease and lymphoproliferative disorders is not just coincidental, and suggest that liver cirrhosis might be considered an immunological disturbance which entails an increased risk of developing lymphoproliferative disorders. Mechanisms causing lymphoproliferative disorders to develop in the course of chronic liver disease have been hypothesized.

We evaluated the circadian pattern of gastric acidity by prolonged intraluminal pHmetry in 15 "responder" and 10 "nonresponder" duodenal ulcer patients after nocturnal administration of placebo, ranitidine, and famotidine. Acidity was measured during predefined periods under the different drug regimens in the two groups of subjects, and a comparison was performed both within and between groups. With placebo, significantly lower median 24-h pH values were detected in patients with resistant ulcer than in responders (1.13 versus 1.63). On the contrary, no statistical difference was detected between the two groups during any time of day after administration of either ranitidine or famotidine. Within each group, no significant difference was noted between the two different H2-blockers. Thus, our data suggest that patients with resistant duodenal ulcer display an increased gastric acidity in control conditions but a "normal" response to administration of antisecretory drugs.

Therapy with oral 5-aminosalicylic acid for inflammatory bowel disease has been reported as effective and safe. We report two cases of biochemically proven mild acute pancreatitis occurring 2 and 14 days, respectively, after oral 5-aminosalicylic acid therapy was instituted for inflammatory bowel disease. A hypersensitivity mechanism might be involved, owing to possible erratic systemic absorption of the drug. We suggest clinical and biochemical monitoring for patients undergoing oral 5-aminosalicylic acid therapy in order to confirm its possible association with acute pancreatitis and to assess the actual incidence of such an adverse reaction.

The prevalence of the small intestine bacterial overgrowth syndrome has been assessed in 109 in-patients affected by various gastrointestinal disorders using the 1 g [14C]-xylose breath test; 18 healthy subjects acted as a control group: none of them showed abnormal results (100% specificity). None of 14 patients with colonic disease had abnormal results, whereas in 44 patients with ileal diseases the test was positive in 12% to 39% of the cases. Abnormal results were found in 46% of patients who underwent partial gastric resection greater than 20 years before, 29% of patients with irritable bowel syndrome without diarrhoea (faecal wet weight less than or equal to 600 g/72 h), 56% of those with diarrhoea of obscure origin, and 25% of celiac patients. Eight out of 8 patients with altered results showed normalization of the test after antibiotic therapy. Despite its high diagnostic value in the setting of clinical research, the 1 g [14C]-xylose breath test cannot as yet be proposed as a routine investigation.

The development of lymphoproliferative disorders in association with a chronic liver disease, although uncommon has been documented in several reports and a review of the available literature yielded a total of 34 cases. It has been suggested that this association is probably not a fortuitous coincidence and several mechanisms explaining the development of lymphoproliferative diseases in the course of liver disease have been offered. We have evaluated the annual cumulative incidence of such an association in the specific population of patients with liver cirrhosis (N.:344) admitted to our Department of Gastroenterology, Mauriziano Hospital, in Turin, within 3.5 years, from January 1987 to June 1990: it resulted to be 9.56/1,000 subjects per year. This figure is much higher than the annual incidence registered in Turin within the years 1985-87 for the same lymphoproliferative disease, 39.6/100,000 inhabitants. Our data add value to the hypothesis that this association is not incidental and suggest that chronic liver disease should be added to the list of the pathological conditions with immunological disturbances associated with lymphoproliferative disorders.

We studied antipyrine clearance (APC1) in 19 healthy controls, 10 cirrhotic patients, 20 patients undergoing partial hepatectomy for liver tumors (14 with cirrhosis and 6 without cirrhosis). The aim of the study was to evaluate if the test represents a measure of the residual hepatic function and a useful index of surgical risk in cirrhotic patients following partial hepatectomy. The APC1 was significantly reduced in cirrhotic patients ws healthy controls. It is reduced following partial hepatectomy in cirrhotic patients (p less than 0.001) and in non cirrhotic patients (n.s.). The APC1 was found to be related with the plasma level of albumin and pseudocholinesterase; it also was related with the Pugh's score for hepatic function. The APC1 is a satisfactory index of residual hepatic function. On the other hand it does not provide more useful information than the Pugh's score for surgical risk in liver resection.

A physiologic and metabolic assessment was carried out on eight patients six months after total proctocolectomy with ileal reservoir for ulcerative colitis and familial adenomatosis coli. All patients were continent and able to defecate spontaneously, stool frequency ranging from two to five per 24 hours. Anal sphincter resting pressures (35 +/- 14 mmHg) and squeeze pressures (88 +/- 24.2 mmHg) were similar to those of a healthy population, with the exception of one patient's complaint of nocturnal mucous leakage per anus. Biopsies of the ileal mucosa of the reservoirs showed a mild inflammation in seven patients; in one a subtotal villous atrophy (plus glandular pattern) was found. Anthropometric measurements, lymphocyte counts, hemoglobin, albumin, transferrin, iron, B12, and folate were normal in all. In the majority of patients there was no evidence of bacterial overgrowth. Vitamin B12 absorption was reduced slightly in only one patient. Lipid absorption (as judged by the 14C-Triolein breath test) was abnormal in three patients. Fecal clearance of alpha 1 antitrypsin as protein losses index was abnormal in three patients. Bile acid malabsorption was the most important ileal dysfunction observed in the patients.

A computer-assisted technique for prolonged gastric pH monitoring has been developed using a personal computer. Segments of signal from several studies performed in controls and on patients with duodenal ulcers were chosen for comparison between manual and digital pH readings; no significant difference was detected. In clinical practice this system might provide an additional tool in the diagnostic and therapeutic treatment of peptic ulcer disease.

Although the association between acute pancreatitis and pleuropulmonary damage is well documented, so far no information on lung function in patients with chronic pancreatitis is available. In this study functional, radiological, and clinical investigations have been carried out in 42 patients affected by chronic calcific pancreatitis (CCP) and in 50 controls in a case-control study. An impairment of pulmonary diffusing capacity has been detected in CCP patients, while all the parameters of ventilatory function were not different from controls. This finding suggests the presence of early lung parenchymal damage in chronic pancreatitis secondary to either emphysema or pulmonary fibrosis.

Sixteen gastrectomized patients underwent surgical treatment for alkaline reflux gastritis by means of a Roux-en-Y loop duodenal diversion. Long-term evaluation of results was performed 5-9 years later. Ten patients (62.5%) showed good results, with absence of digestive symptoms and with an increase in body weight. Two patients (12.5%) had moderate results, with presence of sporadic and mild epigastric pain. Four patients (25%) had unsatisfactory results, with persistence of epigastric pain and absence of body weight increase. No patient had recurrent biliary vomiting or endoscopic evidence of endogastric biliary reflux. Among the six patients with moderate and unsatisfactory results, two had a significant alcoholic intake, two showed a high degree of anxiety on psychological assessment, and two had both factors. Alcoholism and psychological disturbances should be considered exclusion criteria when evaluating a gastrectomized patient for surgical cure of alkaline reflux gastritis.

The purpose of the present trial was to verify the efficacy and safety of long-term ranitidine treatment (150 mg at bedtime for 1 year) for the maintenance of duodenal ulcer healing in 22 patients following a successful short-term course of therapy with ranitidine at the full dose of 300 mg per day. Of the 16 patients who completed the trial - there were 6 drop-outs - 4 suffered relapses during the year of treatment (25% cumulative recurrence rate), while remission persisted in the remaining 12 patients (75%). Biochemical tests revealed no statistically significant differences in mean fasting serum pepsinogen and trypsinogen as compared to mean basal values. Mean fasting serum gastrin showed a statistically significant rise from 156 +/- 27 S.D. to 258 +/- 110 S.D. pg/ml (p less than 0.01) only at the 12th month of therapy and rapidly returned to normal (162 +/- 34 S.D.) as soon as therapy was discontinued. No side-effects of any consequence were observed.

Sequential measurement of postprandial serum levels of bile acids was carried out in ten healthy controls and in four patients with different impairment of bile acids enterohepatic circulation. An enzymathic fluormetric method was used for SBA analysis. The peak of increase above fasting baseline in normal subjects was 11.8 +/- 1.2 microM/1 (mean +/- SD). In a cholecystectomized subject no SBA peak was observed. Two patients with mild and severe liver impairment (i.e. alcoholic steatosis and Summerskill-Walshe disease during an acute attack of jaundice) had postprandial SBA increase of 20 microM/1 and 70 microM/1 respectively. In a patient affected by Crohn's disease, with proved bile acids malabsorption, a negligible postprandial SBA increase was noted (6.65 microM/1). It is concluded that meal stimulated response of SBA levels might be useful index of altered hepatobiliary and intestinal function.

Total serum bile acids measured by enzymatic fluorometry and routine liver function tests were determined in a large population including 97 healthy subjects, 138 patients free of hepatobiliary diseases but affected by other diseases, and 344 patients with mild or severe hepatobiliary diseases. In order to define the diagnostic value and some operational characteristics of serum bile acids, sensitivity, specificity, and several predictive value tables for increasing cutoff levels of serum bile acids were calculated by means of a computer program. Serum bile acids and aspartate aminotransferase were found to be similar in sensitivity, specificity, and predictive value. Serum aspartate aminotransferase was found to be more suitable than serum bile acids in detecting mild hepatobiliary diseases, whereas serum bile acids were more sensitive than routine liver tests in the evaluation of severe hepatobiliary diseases. In view of its ability to detect severe hepatobiliary diseases, serum bile acids test may play a decisive role in clinical practice (eg, decision to perform a liver biopsy).

A 60-yr old Italian woman presented with repeated gastrointestinal hemorrhages due to ruptured esophageal varices. No evidence of liver disease could be demonstrated by laboratory tests or by multiple liver biopsies. Angiography revealed a patent portal trunk and the presence of esophageal varices. A side-to-side portacaval shunt was performed, which caused the disappearance of the esophageal varices. There was no recurrent digestive hemorrhage during a 24-month follow-up. A mild deterioration of liver function was demonstrated by laboratory data 16 months after surgical operation and some mild episodes of hepatic encephalopathy occurred. This case can be considered an example of idiopathic portal hypertension, a rare pathological condition with a higher prevalence in certain geographical areas. Its etiology is not known. One important aspect of this entity is its potential to evaluate the effects of surgical portacaval shunt procedure in the absence of liver damage.

Serum immunoreactive cationic trypsinogen (ICT) response to bolus injection of secretin (1 Clinical Units/kg of body weight) has been evaluated in 123 normal controls and related to sex, age, smoking habit, and alcohol and coffee consumption. A 100% increase of serum immunoreactive cationic trypsinogen levels after secretin has been considered as a positive response (R+). When the population was considered as a whole, 55% of subjects proved to be R+ and the remaining were R-. In the R+ group the serum immunoreactive cationic trypsinogen response was appreciated as early as 5 min after secretin and even after 2 min in the few cases in which it was evaluated. It is suggested that this direct leakage of the proenzyme from the pancreas may be due to an increased sensitivity of the pancreas to secretin. Coffee consumption and age of subjects did not affect the test. Male sex, smoking habit, and alcohol intake were associated with a significantly higher percentage of R+. Therefore, we suggest that alcohol and smoking might result in the development of biochemical abnormalities in pancreatic function before the appearance of clinical evidence of pancreatic disease.

Serum immunoreactive trypsinogen (IT) levels were measured in 479 normal controls and in 604 patients (510 with nonpancreatic diseases and 94 with pancreatic diseases) in order to evaluate the distribution of IT values in the control population and the accuracy of the assay in the diagnosis of pancreatic diseases. IT concentrations were normally distributed in the healthy population; children showed mean IT values significantly lower than adults. The sensitivity, specificity, and predictive value of a positive and negative result in diagnosing acute or chronic pancreatitis were evaluated vs normals and vs normals plus all patients. With an IT value higher than 80 ng/ml, the likelihood that a patient is not affected by acute pancreatitis is less than 5%. An IT value lower than 9 ng/ml detected 44% of chronic pancreatitis and was related to a 52% probability of such a condition. The 48% false positive results also include patients with pancreatic tumor (31% of cases), so that the chance of finding reduced IT levels in subjects without pancreatic damage drops to 17%. In view of the low prevalence of pancreatic diseases, IT assay should not be taken into consideration as a diagnostic screening test in the general population and its use should be limited to a hospitalized population.

A simple method for total faecal bile acid (FBA) determination was carried out. This test involves a 72 hour stool collection, homogenization and FBA determination by means of an enzymatic-fluorimetric method (3 -Hydroxysteroid-dehydrogenase). The reliability of this test was discussed. FBA levels were tested in twelve healthy volunteers. In addition, two patients with bile acid malabsorption syndrome due to terminal ileitis and one patient with cholegenic diarrhoea caused by biliocolonic fistula were examined. The mean +/- SD of FBA values in healthy subjects was 0.49 +/- 0.3 g/72 hours. However, all patients tested show a marked increase of FBA levels. In conclusion the present method for bile acid determination in the faeces seems to be a useful tool in the diagnosis of bile acid malabsorption syndrome and in cholegenic diarrhoea.

Total serum bile acids (SBA) have been evaluated in 28 healthy subjects by an enzymatic-fluorimetric method using the enzyme 3 alpha-hydroxysteroid dehydrogenase. The healthy subjects showed a value of 2.78 +/- 1.84 microM/1 (mean +/- SD), ranging 0.5 to 4.7 microM/1. In addition, two hours postprandial evaluation of SBA was carried out in five of the above subjects. The mean value of SBA before and after the meal was 2.58 +/- 1.4 and 8.73 +/- 1.7 microM/1 respectively and the postprandial increase was found statistically significant (P less than 0.001). The present method for quantitative determination of SBA seems to be sensitive, reliable and useful as a routine clinical aid.

A case of alpha-chain disease is presented. Diagnosis was clinched by the discovery of typical heavy alpha-chains on analysis of serum proteins. The clinical picture included non-gluten-dependent semi-coeliac malabsorption, Hippocratic fingers, flattened villi, plasma cell infiltration of the jejunal mucosa, alpha- and beta-globulin dysprotidaemia, and abdominal masses; these signs are indicative of, but not conclusive evidence of alpha-chain disease. The presence of Coccidioides organules in the mucosa and glandular tuberculosis rises aetiopathogenetic questions that suggest that due attention be given to microbiological examination. Rapid progression to neoplasia following immunodepressive management underscores the risks associated with the administration of immunodepressors in patients with immunitary deficiencies. It is still not clear whether alpha-chain disease should be regarded as a self-perpetuating immunoproliferative disease, or as a form neoplasia ab initio, with a protracted, though of inevitably fatal, course.

A personal series of 28 cases of malabsorption with villopathy (22 Gee, 1 Whipple, 1 alpha-chain, 1 hypogammaglobulinaemia, 3 not yet diagnosed) is presented. The response to a gluten-free diet is the essential clue to diagnosis. Where sensitivity is not found, diagnosis becomes difficult and requires careful immunological, histopathological and parasitological investigation, which is not always conclusive. The main features of the series are indicated, along with the criteria employed in the diagnosis of some unusual forms.

Gastric pH was monitored, by means of a computerized system, in healthy controls (C) and in patients with active duodenal ulcer (ADU) and inactive duodenal ulcer (IDU). The test was performed before treatment and during administration of a single dose of ranitidine 150 mg, cimetidine 400 mg, and pirenzepine 50 mg, in random sequence at 12-h intervals, (10 am, 10 pm). Under basal conditions, progressively lower median pH values were detected in ADU and IDU patients, compared with controls. A significant difference was found between C and ADU during daytime (1.38 vs. 0.85), nighttime (1.29 vs. 0.81), and 24 h (1.35 vs. 0.81) and between C and IDU during 24 h (1.35 vs. 1.11). However, no statistical difference was observed between patients with active and inactive ulcer disease. Administration of ranitidine and cimetidine significantly increased gastric pH during nighttime but not during daytime. Ranitidine, at the doses studied, proved to be more potent than cimetidine in suppressing gastric acidity. Gastric pH was unaffected by pirenzepine in most cases.