Search

Purpose Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer. Methods Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Results The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3‑year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3‑year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3‑year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3‑year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067). Conclusion Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.

History and findings A now 54-year-old woman was 32 years ago found to have immune thrombocytopenia and 3 years ago ANA-positive and HBsAg-negative hepatitis with cirrhotic metaplasia. Numerous small asymptomatic carcinoids with marked hypergastrinaemia (1626 ng/l) were also first found 3 years ago. No gastrinoma could be found. Severe arthralgia was the main symptom on admission. Investigations Gastroscopy revealed a polypoid carcinoid, 1 cm in diameter. There was total achlorhydria. No pernicious anaemia or carcinoid syndrome was found. Treatment and course Total gastrectomy with construction of a jejunal substitute stomach was performed. Histology showed typical chronic-atrophic gastritis type A, all stages of an argyrophilic endocrine cell hyperplasia, as well as microcarcinoidosis and multicentric carcinoid, in part with submucosal infiltration and lymph node metastases. Immunohistology revealed immune reaction for the global endocrine marker. No specific hormones were demonstrable in the carcinoid cells. The postoperative course was without complications. Serum gastrin levels have since been normal. Conclusions The case confirms the possibility of an achlorhydria-hypergastrinaemia-carcinoid sequence. Now new stage-related therapeutic guidelines for this disease are needed.

Eleven patients (8 male, 3 female, age 21-53 years) with dyspeptic symptoms and no gastrointestinal organic diseases were studied for their gallbladder contractile function. A comparative sonographic study of gallbladder contraction was performed after exogenous and endogenous stimulation. On day 1, ceruletide was infused at a dose of 2.5 ng/kg/min about 10 minutes. On day 2, a semi-liquid test meal of 1450 kJ (44 kJ% carbohydrates, 24 kJ% protein, 32 kJ% fat) was administered. Gallbladder volume was determined for 30 minutes before and 5, 10, 20, 30, 40, 60, 80, 100 and 120 minutes after both stimulations by means of realtime ultrasonography. Three diameters in two plains were measured for calculation of gallbladder volume. Following ceruletide, peak gallbladder contraction (range 7-48% of initial volume) was observed within 10 (n = 5) or 20 (n = 6) minutes. Following the test meal, peak gallbladder contraction ranged from 27-80% and was observed within 30 to 100 minutes. Variations in time and amount of peak gallbladder contraction does hardly allow to establish normal values. No significant correlation was found between both types of stimulation concerning peak gallbladder contraction or time to peak contraction. We conclude that for the assessment of gallbladder contractility, ceruletide infusion and determination of gallbladder volume after 20 minutes (upper range 48% of initial volume) is the most valuable procedure. Impaired gallbladder contractility can be diagnosed with certainty only after exogenous stimulation.

A double-blind, randomized, placebo-controlled crossover study was performed to assess the influence of one week of selective M1-muscarinic receptor blockade on pancreatic exocrine secretion in man. Ten healthy subjects received telenzepine (3 mg p.o.) and placebo each for 8 days, with a 6-day drug-free washout interval between treatment sequences. On Day 8 of each sequence, pancreatic secretion was stimulated for 2 h by infusion of submaximal secretin (0.2 U.kg/h) followed by maximal stimulation with secretin (1.0 U.kg/h) and ceruletide (120 ng.kg/h). Telenzepine had no significant effect on secretory parameters during submaximal stimulation with secretin. During maximal stimulation, total protein, secretory volume, and output of amylase, trypsin and bicarbonate were unexpectedly increased by telenzepine. These findings might be partially explained by removal of the inhibitory influence of pancreatic polypeptide, which was depressed by telenzepine. Acute studies have shown that M1-receptor antagonists inhibit exocrine secretion. Our results suggest that adaptation of physiological mechanisms governing the exocrine pancreas may occur after one week of receptor blockade by a therapeutic dosage of telenzepine, to the extent that M1-blockade no longer inhibits secretion.

Gastrointestinale Stromatumoren (GIST) sind seltene Ursachen fur Blutungen aus dem Gastrointestinaltrakt. GIST sind am haufigsten in Magen und Dunndarm, seltener in Kolon oder Osophagus lokalisiert. Ursprungszellen der GIST sind wahrscheinlich pluripotente mesenchymale Zellen. Entscheidend fur die Pathogenese dieser Tumoren sind offensichtlich Genmutationen, die zu einer kontinuierlichen Aktivierung der Tyrosinkinase fuhren. Folgen dieser Aktivierung sind unkontrollierte Proliferation und Schutz vor Apoptose. Der immunhistochemische Nachweis des Proteins CD 117 (c-kit) hat erhebliche differentialdiagnostische Bedeutung. Aktivierende c-kit-Mutationen sind in den meisten GIST nachweisbar. Das Grading der Tumoren erweist sich oft als schwierig. Wichtige prognostische Faktoren sind die Mitoserate und die Tumorgrose. Die haufigsten Symptome der GIST sind Schmerzen und gastrointestinale Blutung. Hinweise auf das Vorliegen eines GIST ergeben sich endoskopisch, sonographisch, szintigraphisch oder durch radiologische—Computertomographie (CT), Magnetresonanztomographie (MRT) oder Enteroklysma—Bildgebung. Die Therapie der GIST besteht in der chirurgischen Resektion. Im Fall von fortgeschrittenen oder metastasierenden GIST wurden nach systemischer Therapie mit Imatinib, einem Tyrosinkinaseinhibitor, zahlreiche partielle Remissionen mit klinischer Besserung bei akzeptabler Vertraglichkeit beobachtet. Berichtet wird uber funf Patienten mit GIST, die sich als gastrointestinale Blutung manifestierten. Alle Tumoren wurden reseziert und blieben in der Nachsorge bisher (19–51 Monate postoperativ) ohne Rezidiv oder Metastasen.

Background: Gastric regional CO2 accumulation indicates gastric mucosal hypoperfusion in critically ill patients. CO2 is also a reaction product of urea degradation, and we therefore tested the hypothesis if regional pCO2 is influenced by Helicobacter pylori infection. Material: Seven H. pylori-positive and 7 H. pylori-negative volunteers (age range 21–30 years) were investigated. During a 6- to 7-hour observation period, we obtained every 30 min arterial blood gases, gastric juice pH from a glass pH electrode and regional pCO2 from a gastric tonometer. The study protocol included subsequent periods of baseline measurements, pentagastrin stimulation (0.6 µg/kg/h/i.v.) and application of omeprazole (40 mg i.v.). Results: Gastric regional pCO2 was increased in H. pylori-positive versus H. pylori-negative subjects before (64.4 ± 3.1 vs. 50.0 ± 2.9 mm Hg, p < 0.005) but not after application of omeprazole. The effect of omeprazole on gastric juice pH was increased in H. pylori-positive subjects (mean pH during 4 h 6.1 ± 0.3 in H. pylori-positive vs. 2.5 ± 0.2 in H. pylori-negative subjects; p < 0.0001). There was a difference in arterial pCO2 between H. pylori-positive and H. pylori- negative subjects (43.1 ± 0.3 versus 38.9 ± 0.3 mm Hg; p < 0.0001). Conclusion:H. pylori infection has a significant effect on gastric regional CO2 that is suppressed by application of a proton pump inhibitor.

Background/Aim: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity (VH) is a key factor in the pathophysiology of IBS. The role of Helicobacter pylori infection in the induction of VH in the upper gastrointestinal tract is controversially discussed. The aim of this study is to evaluate the value of rectal barostat in eliciting abdominal symptoms in patients with IBS in relation to H. pylori infection. Patients and Methods: 31 patients (19 female, 12 male, mean age 45.6 ± 10 years) with normal colonoscopy and clinical signs of IBS were examined by rectal barostat (pressure-controlled balloon distension in the rectum). Induction of typical abdominal discomfort (far from the balloon) defined the examination positive. Level of nonpainful perception (L1), feeling of defecation (L2), and pain or stool urgency (L3) were registered in comparison with a healthy control group (CG; n = 15, 9 female, 6 male). The H. pylori status was defined by 13C-urea breath test (n = 46). Results: Typical abdominal discomfort was induced in 9 patients (pain group, PG) by pressure-controlled rectal distension (H. pylori status: 8 positive, 1 negative). Patients not presenting with abdominal pain to rectal distension (nonpain group, NPG) were all H. pylori negative (p < 0.001). L3 as an indicator of VH was reached at a lower pressure threshold in PG than in NPG or CG (p < 0.05). The perception was not different between NPG and CG (p > 0.05). Conclusions: The induction of typical abdominal discomfort in patients with IBS by the use of rectal barostat occurred predominantly in H. pylori infected patients and suggests that H. pylori infection may be involved in triggering VH in patients with IBS. Further studies in larger patient groups and after H. pylori eradication therapy are needed to confirm and extend this observation.

Background Faecal elastase 1 (FE1) and the pancreolauryl test (PLT) are widely used for the non-invasive diagnosis of exocrine pancreatic insufficiency (EPI). Whether one of these two tests is superior for the detection of mild-to-moderate EPI is the subject of controversy. The aim of this study was to compare the diagnostic performance of the PLT and FE1 for the detection of EPI in patients with chronic pancreatitis. Methods Forty consecutive patients (27 males, 13 females, 23-72 years) with chronic pancreatitis based on imaging procedures (computed tomography, endoscopic retrograde pancreatography and endoscopic ultrasound) were admitted to the study. A secretin-caerulein test (SCT) was performed after an overnight fast by giving secretin (1 U/kg/h) and caerulein (100 ng/kg/h) intravenously over 90 min. Duodenal contents were aspirated at 15 min intervals and analysed for pH, bicarbonate, amylase, lipase and elastase. EPI was graded on the basis of the results of the SCT as absent, mild, moderate or severe. A serum PLT was performed in accordance with a modified protocol previously described. A commercial ELISA was used for determination of FE1. The cut-off values were ≥ 4.5 mg/I for PLT and ≥ 200 μg/g for FE1. Results Thirty-three patients had EPI (20 mild/moderate and 13 severe) on the basis of the results of the SCT. The sensitivity of the PLT for diagnosing EPI of all degrees of severity was 82% (27/33), compared with 50% for FE1 (16/ 33). In patients with severe EPI, the PLT was abnormal in 100% (13/13) and FE1 was abnormal in 85% (11/13) of the cases. The sensitivity decreases for both tests in the group of mild/moderate EPI (PLT 70% (14/20), FE1 35% (7/20)). In all seven patients with normal exocrine pancreatic function, both PLT and FE1 were also normal. Conclusions The PLT is more sensitive than FE1 for the diagnosis of mild-to-moderate EPI, and is therefore more appropriate for completing the staging of chronic pancreatitis.

The aim of this study was to determine the value and limitations of 18F-fluorodeoxyglucose (FDG)-position-emission tomography (PET) for differentiating benign and malignant pancreatic disease and for staging malignant disease. One hundred fifty-nine patients with 89 malignant and 70 benign pancreatic lesions all received PET, computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) before pancreatic surgery. The original reports were compared for all patients (group I; N = 159), for a subgroup that neither had fasting plasma glucose levelsor =130 mg/dL or known elevated levels of C-reactive protein ([CRP], group II; n = 123), and for the remaining patients (group III; n = 36). For group I, accuracy values (areas under receiver operating characteristic [ROC] curves) for differentiation of benign/malignant masses were 0.86 (PET), 0.93 (ERCP), 0.82 (CT), and 0.95 for ERCP + PET (N = 159). For group II, ROC areas increased to 0.92 (PET), 0.94 (p0.05; n = 123) (ERCP), 0.82 (CT), 0.97 (p0.05; n = 123) (ERCP + PET). The results for group III were 0.71 (PET), 0.81 (CT), and 0.93 (ERCP); (n = 36). With 54 patients of group II that either had contradictory or indeterminate/technically unsuccessful CT/ERCP, PET was correct in 43 patients (84%). Sensitivity/specificity for lymph node staging was 49%/63%, respectively. For patients with hepatic metastasis, PET was 70% sensitive and 95% specific, missing some metastasis that were1 cm. PET detected peritoneal metastasis in 25% of patients, missing poorly localized microscopic spread. For selected patients who have indeterminate pancreatic masses but no hyperglycemia or serologic evidence of active inflammation, FDG-PET is an independent functional assay that significantly adds to the diagnostic accuracy of ERCP and CT in the differentiation of benign and malignant pancreatic disease. PET can reliably detect hepatic, peritoneal, and other distant metastases that areor =1 cm.

Background. Due to its unique pharmacokinetic properties, azithromycin may be an attractive combination partner for H. pylori eradication regimens. However, up to 15% of clinical isolates are primarily resistant to azithromycin as well as to other macrolide antibiotics. Combination therapy with lansoprazole, a proton pump inhibitor known to have intrinsic antibacterial activity against H. pylori, may be useful to counteract such resistance. We therefore evaluated the combined effects of azithromycin and lansoprazole in vitro. Materials and Methods. Minimal inhibitory concentrations (MICs) of azithromycin and lansoprazole alone and in combination were determined for 106 clinical H. pylori isolates by means of an agar dilution technique. Killing kinetics of seven isolates were also studied in fluid medium. Results. MIC values for 50 and 90% of the isolates (MIC50, MIC90) were 0.19 and 0.5 mg/l for azithromycin, and 44.5 and 104 mg/l for lansoprazole. Nine strains (8.5%) had an MIC of azithromycin ≥ 16 mg/l and were regarded as resistant. An additive interaction between the two drugs was found in 72 (68%), and indifferent effects in 24 strains (23%). Three of 9 azithromycin-resistant strains regained sensitivity in the presence of lansoprazole. In fluid culture, synergism between the two drugs occurred in 6 out of 7 strains tested. Conclusion. In the majority of strains, lansoprazole and azithromycin interacted in an additive or synergistic manner depending on the test method employed. Addition of lansoprazole restored in vitro sensitivity to azithromycin in 3 out of 9 azithromycin-resistant strains. Such effects may enhance the elimination of H. pylori during clinical eradication therapy.

We report on a 58-year-old Caucasian woman who went to a general practitioner about recurrent abdominal pain, night sweats and weight loss of a few weeks' duration. Once gynaecological disease had been ruled out, the patient was admitted to hospital with severe abdominal pain and intestinal obstruction and a right-sided hemicolectomy was performed. Following the investigation of osteolytic lumbar vertebrae, 18 months after visiting the general practitioner the patient was finally found to be suffering from generalized AA-amyloidosis secondary to gastrointestinal tuberculosis. This had been misinterpreted as Crohn's disease. Re-examination of the specimens from the right-sided hemicolectomy demonstrated that scanty deposits of AA-amyloid were present 9 months after the first presentation. AA-amyloid can thus be present in serious inflammatory disease even during the first 9 months after the initial clinical presentation.

Background: Intraduodenal proteases exert a negative feedback on pancreatic secretion. Aim: To investigate the effect of two pancreatic enzyme preparations (enteric-coated tablets, and capsules with enteric-coated microtablets) on postprandial pancreatic and bile acid secretion, gastroduodenal motility and release of gastrin and pancreatic polypeptide in healthy humans. Methods: Twenty healthy males were studied on two different days one week apart. After an overnight fast a nine-lumen motility tube was positioned with the distal tip at the Treitz angle. On each study day, 30 min after an interdigestive migrating motor complex-phase III, a semi-liquid test meal was given either alone (n=20) or with enzymes (3 tablets (n=10) or 2 capsules with microtablets (n=10); 40000 U lipase and 2000 proteases) in a randomized order, and the study continued over 2 h. Motility was continuously recorded with four ports in the antrum and three in the duodenum, using a low-compliance pneumohydraulic perfusion system. Secretion of human-specific pancreatic elastase and bile acids was measured by a standard duodenal intubation perfusion technique. Plasma concentrations of gastrin and pancreatic polypeptide were measured by specific radioimmunoassays. Results: Postprandial pancreatic secretion was significantly reduced by administration of microtablets (median 82 mg/2 h vs. 70 mg/2 h, P

Visceral hypersensitivity is claimed to beinvolved in the pathogenesis of nonulcer dyspepsia(NUD). We evaluated whether gastric hypersensitivity isa consistent finding in an unselected group of NUDpatients. In 11 patients and 20 healthy controls, astandardized gastric distension was performed using agastric barostat. Perception was scored by aquestionnaire and compared between the two groups. Therewas a linear pressure/volume relationship duringgastric distension in both groups. The pain threshold inNUD patients was significantly lower compared tocontrols [5.5 ± 4.0 mm Hg above minimaldistending pressure (mdp) and 10.2 ± 2.2 mm Hg above mdp,respectively, P < 0.004], irrespective of the H.pylori status. However, more than 50% of the NUDperception scores were in the control range at mostdistension levels. Gastric hypersensitivity could be confirmed inNUD patients as a group. However, there is aconsiderable overlap concerning perception in responseto distension between unselected NUD patients andcontrols.

The role of altered gastric motor functions for the development of obesity is still unclear. In this study, we investigated whether severe obesity is related to gastric dysfunctions or to abnormal perception in response to distension. 31 obese patients and 20 healthy volunteers were studied using an electronic barostat. Basal gastric tone, gastric accommodation, and perception in response to distension were not altered in obese patients. The median minimal distending pressure, reflecting the intra-abdominal pressure, was significantly elevated in obese patients, being 12 versus 7 mm Hg, respectively (p < 0.0001). We conclude that the proximal gastric motility, including perception and accommodation in response to intragastric distension, is not impaired in severe obesity. Whether disturbances of gastric reflex relaxation in response to a meal are involved in the pathogenesis of obesity remains to be established.

To test the diagnostic accuracy of faecal elastase (FE), a new test of exocrine pancreatic function, in a large prospective population of patients with abdominal complaints.Between January 1994 and December 1995, 131 patients (age range 17-82 years) were submitted for exocrine pancreatic function testing. Sixty-three patients had a firm diagnosis of chronic pancreatitis (CP) at stage I-III according to endoscopic retrograde cholangiopancreatography (ERCP). Twenty patients suffered from other pancreatic diseases (PD), and 48 patients had various other gastrointestinal diseases (GD). Fifty-seven healthy controls (HC) were also investigated. Stool specimens were analysed for FE by enzyme-linked immunosorbent assay (ELISA) and for faecal chymotrypsin (FC). The pancreolauryl serum test (PLT) was also performed in 97 patients and 23 healthy controls.FE was 200; 45-500 micrograms/g (median; range) in CP-I (n = 19), 94; 0-400 micrograms/g in CP-II (n = 14) and 38; 0-135 micrograms/g in CP-III patients (n = 30). With a cutoff of 200 micrograms/g, abnormal test results were found in 47% of CP-I, 79% of CP-II and 100% of CP-III patients; in 30% of PD patients, in 38% of GD patients and in 7% of HC. Sensitivity of abnormal FE in diagnosing CP was 79% (FC: 48%; PLT: 71%). The specificity of only 62% (FC: 73%; PLT: 67%) in the GD group increased to 78% (FC: 81%; PLT: 77%) when patients with small bowel diseases and diarrhoea (n = 22) were excluded.Faecal elastase is more sensitive than chymotrypsin and comparable to the pancreolauryl test in the diagnosis of chronic pancreatitis. Indirect exocrine pancreatic function tests are not helpful to differentiate between pancreatic and small bowel diseases in a prospective population of patients with abdominal complaints.

Using a group-specific PCR assay, we investigated the presence of enterohepatic Helicobacter species in gut specimens from patients with inflammatory bowel disease. Enterohepatic Helicobacter species were detected in 12% (3 of 25) of the patients with Crohn's disease, in 17% (3 of 18) of the ulcerative colitis samples, and in 4% (1 of 23) of the controls.

We investigated pancreatic polypeptide (PP) release by chew and spit sham feeding as a test of autonomic function in 33 patients with diabetes mellitus (DM) and 24 age-matched healthy controls. Plasma samples were taken at nine 5-min time intervals, and PP plasma levels were determined by radioimmunoassay. Autonomic neuropathy (AN) was diagnosed and staged according to four standardized tests of cardiovascular autonomic function. The integrated PP response during sham feeding was decreased in DM patients (1067 + or - 397 vs. 2670 + or - 394 pg/ml/30 min; P0.05). The maximum increase of PP plasma levels was significantly different between the DM subgroups with AN (36 + or - 19 pg/ml; n = 13) and without AN (132 + or - 36 pg/ml; n = 20) but varied widely in healthy controls (219 + or - 29 pg/ml; range 20-460 pg/ml). A cutoff of maximum PP increase20 pg/ml (specificity 100%) resulted in only 46% sensitivity, while a cutoff160 pg/ml (sensitivity 100%) yielded 38% specificity for diagnosis of AN. The diagnostic value of the PP test for identifying individual patients against the variable reference range is therefore limited. Maximum PP increase20 pg/ml indicates AN, while maximum PP increase160 pg/ml excludes AN in diabetic patients.

To determine the influence of changes in gastric juice pH due to intravenous administration of pentagastrin and omeprazole on intramucosal regional PCO2 (Pr(CO2)), we investigated 17 healthy human volunteers. Gastric juice pH was obtained from a glass pH electrode for continuous gastric juice pH measurement and Pr(CO2))was measured by using automated air tonometry. After baseline (8:00 A.M.-9:00 A.M.) the subjects received 0.6 microg/kg/h pentagastrin intravenously for 1 h (9:00 A.M.-10:00 A.M., after stimulation 10:00 A.M.-11:00 A.M.) and 40 mg omeprazole intravenously (after omeprazole 11:00 A.M.-3:00 P.M.). Following pentagastrin administration gastric juice pH significantly decreased from 1.2 +/- 0.4 to 0.6 +/- 0.4 (mean +/- SD, p0.007, versus baseline), whereas omeprazole transiently increased luminal pH up to 4.4 +/- 1.7 (p0.007 versus baseline). These subsequent changes in gastric juice pH were accompanied by a significant increase in Pr(CO2) from 48 +/- 12 to 61 +/- 17 mm Hg (p0.007 versus baseline) and a decrease to 44 +/- 5 mm Hg (p0.002 versus pentagastrin), respectively. A gastric juice pH4 considerably reduces mean gastric Pr(CO2) and interindividual variability. Thus omeprazole may improve the validity of gastric tonometry data.

Billroth II subtotal gastrectomy (B II) in rats results in pancreatic hyperplasia and hypertrophy, and affects pancreatic enzyme composition. A postulated mechanism for this effect is an increased postprandial release of endogenous CCK. In the present study, the influence of chronic administration of the CCK receptor antagonist CR 1409 was tested in B II and control rats. Forty male Wistar rats underwent B II subtotal gastrectomy and were divided into three groups. Group A: 20 rats with a standard diet; group B: 10 rats with low dose CR 1409 (0.3 mg/kg bw/d) in the diet; group C: 10 rats with high dose CR 1409 (3.0 mg/kg bw/d). Each rat of groups B and C was pair-fed with one animal of group A. Further, 40 control rats with no operation served as controls, and were, similarly to the B II rats, divided into three groups. After 28 d, the animals were sacrificed; wet wt, DNA-, protein-, amylase-, trypsin, and lipase content and concentration of the pancreas were determined. Basal CCK plasma levels were measured at the day of pancreatic explantation. Low dose CR 1409 induced an increase of pancreatic wet wt by 28%, and of DNA content by 26% in B II rats. High dose CR 1409 had no effect. Both doses of CR 1409 had similar effects on pancreatic enzyme concentrations (U/mg DNA); amylase increased by 50% in group B, and by 86% in group C, trypsin by 35% in group B, and by 41 % in group C; lipase was unchanged. In control rats, low dose CR 1409 induced pancreatic growth (wet wt + 27%; DNA content +24%) and enzyme adaptation (amylase +96%, trypsin +54%). High dose CR 1409 had no effect. Basal CCK plasma levels after an overnight fast were unaltered in all groups. In summary, low dose CR 1409 promotes pancreatic growth and affects enzyme composition in control rats. In B II rats, the trophic pancreatic response is further increased by low dose CR 1409. High dose CR 1409 had no effect in both experimental groups.

Gastrointestinal stromal tumors (GIST) are rare causes of gastrointestinal bleeding. In most cases these tumors are localized in the stomach and small intestine, more rarely in the esophagus and colon.Pluripotent mesenchymal cells are the suspected origin of GIST. The pathogenesis is obviously initiated by gene mutations, leading to an overexpression and activation of tyrosine kinase proteins. This activation is followed by uncontrolled proliferation and loss of apoptosis. The immunohistochemical detection of the protein CD 117 (c-kit) is an important diagnostic tool. Activating c-kit mutations are observed in most cases of GIST. Grading of GIST remains a problem. Size and mitotic rate are the most powerful predictive factors associated with malignant behavior. The most common symptoms of GIST are pain and gastrointestinal bleeding. Endoscopy, sonography, scintigraphy or radiology -- enteroclysma, computed tomography (CT) and magnetic resonance imaging (MRI) -- are possible methods to detect a GIST. Surgical resection is the standard therapy of GIST. In cases of metastatic GIST, systemic therapy with imatinib, a tyrosine kinase inhibitor, frequently leads to partial remission and clinical improvement. Only few side effects are described. Five patients with GIST are reported. In all cases gastrointestinal bleeding was the main symptom. All tumors were surgically resected, and no signs of recurrence or metastasis have been observed in any of the patients so far (19-51 months postoperatively).

Since its introduction in the 1980s endoscopic ultrasound (EUS) has added significantly to the diagnosis of gastrointestinal diseases.1 One key function has become the staging of esophageal and gastric tumors.2–7 In pancreatic diseases EUS offers much better access than transabdominal ultrasound for visualization of the whole pancreas and its surroundings, and pancreatic ductal and parenchymal changes may be detected with high resolution. In experienced hands EUS has the highest detection rate of pancreatic neuroendocrine tumors compared to computed tomography (CT), angiography and somatostatin receptor scintigraphy. In particular insulinomas, which are usually small lesions, are detected with high accuracy by EUS.8–10 In comparison with endoscopic retrograde cholangiopancreatography (ERCP), the technique of EUS is less invasive and carries no risk of pancreatitis or infection. In recent years EUS has progressed from a purely imaging modality to one that can provide tissue diagnosis by EUS-guided fine needle aspiration (FNA). EUS has also evolved into a treatment modality, for example drainage of pancreatic pseudocysts.11–17

The aims of this study were to investigate the value of interventional endoscopy in patients with strictures of the common bile duct (CBD) caused by chronic pancreatitis (CP), and to define the subset of patients who may be at risk for failure of endoscopic intervention, in a prospective follow-up study.A total of 61 patients with symptomatic CBD strictures caused by alcoholic CP were treated by endoscopic stent insertion for 1 yr with scheduled stent changes every 3 months. After the treatment period, all patients entered a follow-up program.Initial endoscopic drainage was successful in all cases, with complete resolution of obstructive jaundice. After 1 yr from the initial stent insertion, in 19 patients (31.1%) the obstruction was resolved, and stents were removed without any need of additional procedures. During a median follow-up of 40 months (range 18-66 months), 16 patients had no recurrence of symptomatic CBD stricture (long term success rate 26.2%). Of 45 patients who needed definitive therapy, 12 patients (19.7%) were treated with repeated plastic stent insertion and three (4.9%) with insertion of a metal stent, and 30 patients (49.2%) underwent surgery. Among the variables tested, calcification of the pancreatic head was the only factor that was found to be of prognostic value. Of 39 patients with calcification of the pancreatic head, only three (7.7%) were successfully treated by a 1-yr period of plastic stent therapy, whereas in 13 of 22 patients (59.1%) without calcification, this treatment was successful (p0.001).Endoscopic drainage of biliary obstruction provides excellent short term but only moderate long term results. Patients without calcifications of the pancreatic head benefit from biliary stenting. Patients with calcifications were identified to have a 17-fold (95% CI=4-74) increased risk of failure of a 12 month course of endoscopic stenting.

This study was done to evaluate if the accuracy of FDG-PET concerning the differentiation of benign and malignant pancreatic masses differs for patients with and without elevated C-Reactive Protein (CRP). Three hundred-four patients (165 neoplasms, 98 chronic pancreatitis, and 41 benign lesions) received FDG-PET of the abdomen prior to planned resective surgery. CRP was unknown, normal, and elevated with 211, 71, and 22 patients, respectively. For differentiation of benign and malignant lesions, specificity was 87% for patients with unknown or normal CRP, and it was 40% for patients with elevated CRP (P < 0.01). Thirty-five percent of those patients with both a positive PET and elevated CRP were false positive. On the contrary, sensitivity was slightly higher in the group with elevated CRP (92% vs. 80%, NS). FDG-PET is a sensitive and specific test for patients with normal CRP, however, FDG-PET may be false positive if CRP is elevated. Proper patient selection is therefore important. CRP or other parameters indicative of active inflammation appear useful adjuncts for the interpretation of increased FDG-accumulation.

Aim: To determine the efficacy the value of self-expandable metal stents in patients with benign biliary strictures caused by chronic pancreatitis. Method: 61 patients with symptomatic common bile duct strictures caused by alcoholic chronic pancreatitis were treated by interventional endoscopy. Results: Initial endoscopic drainage was successful in all cases, with complete resolution of obstructive jaundice. Of 45 patients who needed definitive therapy after a 12-months interval of interventional endoscopy, 12 patients were treated with repeated plastic stent insertion (19.7%) or by surgery (n = 30; 49.2%). In 3 patients a self-expandable metal stent was inserted into the common bile duct (4.9%). In patients treated with metal stents, no symptoms of biliary obstruction occurred during a mean follow-up period of 37 (range 18–53) months. The long-term success rate of treatment with metal stents was 100%. Conclusions: Endoscopic drainage of biliary obstruction by self-expandable metal stents provides excellent long-term results. To identify patients who benefit most from self-expandable metal stent insertion, further, prospective randomized studies are necessary.

Gastric regional CO(2) accumulation indicates gastric mucosal hypoperfusion in critically ill patients. CO(2) is also a reaction product of urea degradation, and we therefore tested the hypothesis if regional pCO(2) is influenced by Helicobacter pylori infection.Seven H. pylori-positive and 7 H. pylori-negative volunteers (age range 21-30 years) were investigated. During a 6- to 7-hour observation period, we obtained every 30 min arterial blood gases, gastric juice pH from a glass pH electrode and regional pCO2 from a gastric tonometer. The study protocol included subsequent periods of baseline measurements, pentagastrin stimulation (0.6 microg/kg/h/i.v.) and application of omeprazole (40 mg i.v.).Gastric regional pCO(2) was increased in H. pylori-positive versus H. pylori-negative subjects before (64.4 +/- 3.1 vs. 50.0 +/- 2.9 mm Hg, p0.005) but not after application of omeprazole. The effect of omeprazole on gastric juice pH was increased in H. pylori-positive subjects (mean pH during 4 h 6.1 +/- 0.3 in H. pylori-positive vs. 2.5 +/- 0.2 in H. pylori-negative subjects; p0.0001). There was a difference in arterial pCO(2) between H. pylori-positive and H. pylori- negative subjects (43.1 +/- 0.3 versus 38.9 +/- 0.3 mm Hg; p0.0001).H. pylori infection has a significant effect on gastric regional CO(2) that is suppressed by application of a proton pump inhibitor.

Chronic pancreatitis is a well-defined disease on histopathological grounds, but for clinical purposes diagnosis is generally not based on histological specimens. Imaging procedures, non-invasive or with different degrees of invasiveness, and pancreatic function tests are therefore the diagnostic mainstay in patients with suggestive clinical history. The correct diagnosis of chronic pancreatitis is easy in late stages but difficult in an early stage of the disease. A particular challenge is the differentiation between acute or recurrent acute and early chronic pancreatitis. Earlier classifications (Cambridge and Marseille) did not consider the complex interrelationship between (especially alcoholic) acute and chronic pancreatitis. A possible solution is to separate the entities into probable and definite alcoholic chronic pancreatitis, with the assignment into the latter category achieved by follow-up investigations. Up to now the best diagnostic accuracy at an early stage is achieved by the detection of abnormalities of the ductal system in endoscopic retrograde pancreatography or by assessing exocrine function with the secretin-ceruletide test. The endoscopic ultrasound may substitute the endoscopic retrograde pancreatography as superior imaging modality that detects both parenchymal and ductal changes of chronic pancreatitis at an early stage. Magnetic resonance pancreatography is a further promising diagnostic tool without the risk of pancreatitis after endoscopic retrograde pancreatography, but imaging of the side branches, which is crucial for detection of early chronic pancreatitis, is not yet sufficient. Faecal elastase is a progress in non-invasive testing of exocrine pancreatic function, but its value for the diagnosis of chronic pancreatitis under conditions of clinical practice is limited. Several (13)C breath tests have been developed, but their availability and their diagnostic accuracy in chronic pancreatitis is still limited. Light to moderate exocrine pancreatic insufficiency is not detectable with adequate accuracy by tubeless function tests. A specific serum marker of pancreatic fibrosis which would reliably indicate the presence of chronic pancreatitis or its progression to is not available.

The aim of this prospective, follow-up study was to investigate the value of EUS in the diagnosis of alcohol-induced chronic pancreatitis.One hundred thirty patients with known (n = 51) or clinically suspected (n = 79) chronic pancreatitis were included. Patients with a history of chronic use of alcohol and recurrent abdominal pain underwent endoscopic retrograde pancreatography and EUS. The 38 patients with normal endoscopic retrograde pancreatography but signs of chronic pancreatitis on EUS were included in a follow-up program.All patients with chronic pancreatitis confirmed by retrograde pancreatography (n = 92; 70.8%) had ductal or parenchymal changes detectable with EUS. Among 38 patients (29.2%) with normal retrograde pancreatography, 32 (84.2%) presented with morphologic features consistent with chronic pancreatitis by EUS. During follow-up (median 18 months, range 6-25 months) chronic pancreatitis was confirmed by repeat endoscopic retrograde pancreatography in 22 of these 32 patients (68.8%). On the basis of these follow-up data, the sensitivities of EUS and endoscopic retrograde pancreatography at the time of the first examination were, respectively, 100% and 80.7% (p0.001).EUS detects chronic pancreatitis in all cases if endoscopic retrograde pancreatography was suggestive for chronic pancreatitis. However, EUS is more sensitive than endoscopic retrograde pancreatography in the detection of early morphologic changes of chronic pancreatitis in patients with abdominal pain and a history of chronic and continued ingestion of alcohol.

Aims: To compare the diagnostic value of endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) in the differentiation of malignant from benign masses in the pancreatic head. Methods: Within 14 months 95 prospective patients with masses in the pancreatic head were assigned for preoperative EUS and ERCP. Both procedures were performed and recorded according to a standardized protocol. Based on intraoperative findings and histology, 50 patients (53%) suffered from malignant and 45 patients (47%) from benign (inflammatory) tumors. Results: Success rates were 96% for EUS and 95% for ERCP. The overall results for EUS and ERCP to predict malignant masses were, respectively: sensitivity 78 and 81%, specificity 93 and 88%, positive predictive value 93 and 89%, negative predictive value 78 and 80%, and diagnostic accuracy 85 and 84%. When EUS and ERCP were taken together, the sensitivity was 92% (specificity 85%), but the diagnostic accuracy (89%) was not significantly enhanced. The results for EUS to diagnose lymph node metastases preoperatively were: sensitivity 55%, specificity 91%, positive predictive value 69%, negative predictive value 84%, and accuracy 81%. Conclusions: EUS and ERCP have similar diagnostic accuracies to separate malignant from benign masses in the pancreatic head. Combination of both procedures is not superior to the use of one modality alone. Abnormal lymph nodes visualized on EUS in patients with inflammatory masses in the pancreatic head due to chronic pancreatitis should be interpreted cautiously.

Es wird die Sekretionsreserve des exokrinen Pankreas bestimmt: Nach hormonaler Stimulation wird die Sekretion von Bikarbonat und verschiedenen Pankreasenzymen gemessen (s. Abbildung).

Das in der Abbildung dargestellte Prinzip der antroduodenalen Manometrie ist ahnlich dem der Osophagusmanometrie: Durch Druckmessung an verschiedenen Punkten in Magen und Duodenum konnen die Peristaltik und die Koordination des jeweiligen Darmabschnitts beurteilt werden. Messungen konnen nur in tubularen Systemen erfolgen, nicht in Hohlorganen (Magenfundus und -korpus entziehen sich der manometrischen Diagnostik!)

An verschiedenen Punkten in Magen und Speiserohre werden nach einem vorgegebenen Ablauf simultan die intraluminalen Drucke gemessen. Aus den Messdaten konnen Ruckschlusse auf die Peristaltikabfolge und die Koordination des tubularen Osophagus sowie der angrenzenden Sphinkteren gezogen werden.

Triple therapy with a proton-pump inhibitor (PPI) in combination with metronidazole and clarithromycin is the method of choice for eradication of Helicobacter pylori. Failures have been primarily blamed on the development of resistance to clarithromycin. The present study investigated the prevalence and clinical significance of resistance to clarithromycin and metronidazole in determining therapeutic success of both triple therapy as a primary eradication method and high-dose dual therapy in non-responders.On the basis of prior therapy, H. pylori-positive patients were assigned to one of two groups in the present prospective study. Group A (n = 93) included patients who had not undergone any prior eradication treatment, whereas group B (n = 15) consisted of patients who had received clarithromycin but in whom eradication had been unsuccessful. All patients underwent endoscopy with biopsy for bacterial culture and resistance studies. Patients in group A were treated with a 7-day regimen of pantoprazole (40 mg twice daily), metronidazole (500 mg twice daily), and clarithromycin (250 mg twice daily), whereas those in group B received omeprazole (40 mg three times a day) and amoxycillin (1000 mg three times a day ) for 14 days. Success of the eradication treatment was ascertained by means of the 13C urea breath test.In group A resistance to clarithromycin and metronidazole was identified in 3 patients (4.9%) and in 14 patients (22.9%), respectively. Eradication proved successful in 78 of 84 patients (92.6%) followed up. Two of the 3 patients with primary clarithromycin resistance and 1 of the 14 patients with metronidazole resistance did not respond to treatment. In group B isolated or combined resistance to clarithromycin was found in seven patients, whereas another four showed isolated resistance to metronidazole. Eradication proved successful in 10 of 13 controlled patients (76.9%) followed up, and only 2 patients reported severe side effects.Determination of antibiotic resistance before initiating therapy is not necessary, since primary resistance to clarithromycin is rare. The Italian triple therapy remains a highly effective primary therapeutic method. Further, routine determination of resistance in non-responders also seems to be superfluous because high-dose dual therapy is an effective and well-tolerated second-line therapy regardless of the patients' resistance status.

Diabetes mellitus is a frequent complication in chronic pancreatitis (CP) that occurs with progressive atrophy of the gland. Ammann and coworkers have shown in their large population of patients with chronic-calcifying pancreatitis that the incidence of diabetes mellitus goes in parallel with exocrine insufficiency and pancreatic calcifications. In patients with noncalcifying chronic pancreatitis, the incidence of impaired glucose tolerance and of overt diabetes is lower. In the majority of patients, the time between diagnosis of chronic pancreatitis and onset of pancreatic diabetes ranges from 7 to 15 years [1–3].

The present study was undertaken to investigate postprandial responses of cholecystokinin (CCK) and pancreatic polypeptide (PP) and their interrelationship in patients with diabetes mellitus (DM) with and without autonomic neuropathy (AN). Twenty-two patients with DM (seven with AN and 15 without AN) and 14 age-matched healthy controls were studied. AN was diagnosed according to several tests of cardiovascular autonomic function. CCK and PP plasma levels were measured by specific radioimmunoassays before and at several time points after the oral administration of a test meal. Basal CCK plasma levels in DM patients were normal, whereas basal PP plasma levels were increased (139 +/- 18 vs 72 +/- 7 pg/ml; P < 0.01). Integrated postprandial CCK response was increased in DM patients (208 +/- 27 vs 110 +/- 14 pmol/liter/2 hr; P < 0.05), mainly due to the patients with AN. Postprandial PP response was increased in DM patients without AN (37,273 +/- 5241 vs 13,418 +/- 3299 pg/ml/2 hr; P < 0.001) but not in those with AN (8887 +/- 3461 pg/ml/2 hr). Moreover, PP response was closely (P < 0.002) correlated with the degree of AN. A direct and linear correlation between postprandial CCK and PP responses was found in healthy controls (r = 0.78; P < 0.005) but not in DM patients. We conclude that the CCK response to a meal is increased in diabetic patients with AN, whereas the PP response is increased only with an intact autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to investigate the relationship between postprandial release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in healthy subjects and patients with chronic pancreatitis (CP). 14 patients with CP and 14 age-matched healthy subjects were studied. Diagnosis of CP was confirmed by standardized imaging modalities (ERCP and CT). Exocrine pancreatic function was assessed in all 28 subjects using the pancreolauryl serum test (PLT). An oral test meal was administered to stimulate endogenous hormone release. Plasma samples were taken before and at several time points after the test meal. CCK and PP plasma levels were measured by specific radioimmunoassays. Basal CCK and PP plasma levels were not different between patients with CP and controls, and were not correlated in either group. However, a direct linear correlation between integrated postprandial release of CCK and PP was found in healthy subjects (r = 0.74, P < 0.005). This postprandial coupling was not evident in patients with CP (r = 0.16; n.s.). Peak fluorescein serum concentration in patients with CP and steatorrhea (SCP) (n = 6) was < 2.5 micrograms/ml, and CCK and PP responses to the meal were significantly impaired (CCK response = 61 +/- 14 pmol/l/120 min in SCP vs. 110 +/- 14 in controls, P < 0.05; PP response = 3920 +/- 1773 pg/ml/120 min in SCP vs. 13418 +/- 3299 in controls, P < 0.05). In patients with mild/moderate exocrine insufficiency, CCK and PP responses varied greatly and were not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to determine whether obese patients have different rates of solid and liquid gastric emptying compared to healthy controls. Twenty-four obese patients (7 males, 17 females) were investigated prior to dietary restriction. The patients had a weight excess above ideal weight ranging from 25% to 216% (mean weight 118.1 ± 6.5 kg). The control group consisted of 8 healthy subjects (4 males, 4 females), within 10% of the ideal weight. The solid phase of the test meal consisted of 40 g bread, 30 g ham, 10 g margarine, and two scrambled eggs labeled with 99mTc. For the liquid phase, 200 ml orange juice was labeled with 201Tl. Three-minute counts of both tracers were taken for 106 min using a large field-of-view gamma camera. In obese patients, a significantly shortened lag phase for the emptying of solids was observed (27.0 ± 3.3 versus 38.4 ± 4.1 min; P < 0.05). Half-emptying time (105.9 ± 6.7 versus 100.7 ± 5.7 min), emptying rate (0.60 ± 0.04 versus 0.71 ± 0.07%/min), and total emptying of solids (49.4 ± 3.6 versus 50.5 ± 5.0%) were not different from controls. Obese subjects had a trend to slowed liquid emptying (half-time 82.7 ± 4.8 versus 69.9 ± 6.9 min; emptying rate 0.59 ± 0.03 versus 0.65 ± 0.03%/min; total emptying 59.8 ± 2.9 versus 66.0 ± 3.3 %), but this was not statistically significant. There was no correlation between weight or body surface area and rate of solid or liquid gastric emptying. It is concluded that no relevant disturbance in gastric emptying is related to the pathogenesis of obesity.

We compared the circadian patterns of pancreatic and biliary secretions in fasting rats. For this purpose, indwelling plastic catheters were placed in 10 male Wistar rats (300-320 g) for the collection of biliary and pancreatic secretions. After small samples were taken for analysis, pancreatic and biliary secretions were recirculated into the duodenum by an additional connecting system. The rats were adapted to an inverse night-day cycle by artificial light during the night (8 pm-8am) and by darkroom housing at daytime (8 am -8 pm ). During a 24-h fasting period, samples of bile (100 μL) and pancreatic juice (20 μL) were taken every hour for determination of the following parameters: pancreatic and biliary flow rate, protein, amylase, lipase, trypsin, and bile acid output. Peak pancreatic flow rate (1.96 ± 0.05 mL/h-kg) was achieved toward the end of the dark period at 7 pm. A significant increase of pancreatic secretion could be achieved merely by turning the lights off, a significant decrease by turning the lights on. Similar circadian patterns were found for pancreatic protein, amylase, and lipase output with peak secretions at 7 PM. An increase of nearly 5x was found between minimal (15.64 ± 0.65 mg/h-kg) and maximal (72.43 ± 2.83 mg/h-kg) pan-creatic protein output. The amplitude was highest for amylase; peak amylase output (13740 ± 832 U/h-kg) was about 18-fold above minimal output (758 ± 44.3 U/h-kg). Conversely, the peak of trypsin concentration in pancreatic juice (1095 ± 17.8 U/mL) occurred during the light period when flow rates were lowest. Circadian patterns of biliary vol flow rate and bile acid output were also present, with peak secretions after 4 and 5 h of the dark phase, respectively (9.22 ± 0.31 mL/h-kg; 440 ± 9,53 μmol/h-kg). No acute alterations in biliary secretion resulted from turning the lights on or off. We conclude that pancreatic and biliary secretions are nonparallel in fasting rats and that distinct mechanisms are likely to be involved in the regulation of these different circadian patterns.

Vitamin B12 malabsorption was reported earlier to occur in patients with exocrine pancreatic insufficiency, and pancreatic extracts were shown to improve the absorption of vitamin B12. We investigated serum levels of vitamin B12 and serum folate in patients with chronic pancreatitis and different degrees of pancreatic insufficiency. 137 patients (84 males, 53 females, age 34-72 years) with chronic pancreatitis (C.P.) were included in the study. 123 of 137 (89.8%) patients had a pathologic pancreatic function test result, classified into mild (n = 24), moderate (n = 61) or severe (n = 38) insufficiency. The normal range of serum vitamin B12 and folic acid was established in 58 healthy controls and was found to be 190-1020 pg/ml for serum vitamin B12 and 2.4-16.1 ng/ml for folic acid. 7 patients (5.7%) with C.P. had vitamin B12 serum levels below 190 pg/ml; 4 of these had severe and 3 had mild or moderate exocrine pancreatic insufficiency. However there was no overall correlation between the degree of pancreatic insufficiency and vitamin B12 values. Serum levels of Vitamin B12 were 512 +/- 48 pg/ml in mild, 493 +/- 52 pg/ml in moderate and 428 +/- 45 pg/ml in severe exocrine insufficiency. Serum folic acid below 2.4 ng/ml were present in 5 patients (3.6%). Folic acid serum levels were 8.34 +/- 0.76 ng/ml in mild, 6.34 +/- 0.52 ng/ml in moderate and 7.45 +/- 0.53 ng/ml in severe exocrine insufficiency. We conclude that vitamin B12 deficiency is a rare finding in chronic pancreatitis and does not strictly depend on the degree of exocrine pancreatic insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyrotropin-releasing hormone (TRH) has been shown to be scattered throughout the gastrointestinal tract. High concentrations of TRH are reported in the pancreas of animals and humans. The present study was designed to investigate the pattern of pancreatic adaptation following chronic TRH administration in rats. Ten male Wistar rats were injected daily at 8.00 and 16.00 h with TRH (total dose of 6 mg/kg of body weight/day) via a chronic gastric fistula. Ten pair-fed control animals were injected with a saline solution. After 10 days, the rats were killed after an overnight fast; pancreatic wet weight, DNA, protein, amylase, trypsin, and lipase content were determined. Blood TRH levels were measured using a specific RIA (TRH antiserum K2B7, normal range of 30-80 fmol/ml). TRH increased pancreatic wet weight (+70%, p less than 0.01), DNA content (+83%, p less than 0.01), and protein content (+42%, p less than 0.05). Pancreatic enzyme concentrations (U/mg of DNA) were decreased (amylase, -81%; trypsin, -47%; lipase, -59%, p less than 0.01). Absolute rates of amylase discharge (U/mg of DNA) in vitro were reduced in TRH-treated rats (p less than 0.01) but the relative amount of basal and stimulated amylase discharge (% of total) was not influenced by TRH. Blood TRH levels were significantly increased (324 +/- 53 vs. 48 +/- 6 fmol/ml, p less than 0.01) 12 h after the last TRH administration. These data indicate that chronic TRH administration in rats induces pancreatic hyperplasia but decreases the pancreatic concentration of digestive enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)