Ákos Pap

Early diagnosis of pancreatobiliary duct malignancies by brush cytology and biopsy

Two hundred and five preoperative intraductal samplings (brushing and biopsy) were evaluated from 113 patients with biliary or Wirsung duct strictures. One hundred and three strictures could be specified by histology of the operative specimens, autopsy, or by the patients’ clinical course. Preoperative diagnostic efficacy depended on the tumor location (it was the best for ampullary and parapapillary tumors), but the average quantitative indices for sensitivity, absolute sensitivity, specificity, positive and negative predictive values, diagnostic accuracy of cytology were 53%, 20%, 100%, 100%, 25%, 59%, respectively. The same values for biopsy were 43%, 34%, 100%, 100%, 36% and 56%. These figures improved after simultaneous cytology and biopsy. Close cooperation with the endoscopist was necessary in cases of negative, inconclusive and dysplastic (27%) samples. Repetition of sampling improved the results by 8%. Among the 26 preoperative false negative cases, sampling-, technical- and interpretative errors occurred in 84%, 4% and 12%, respectively. Revision of samples revealed 4 malignant cases among the false negative cytologic brushings. Reclassification of specimens considering the latest criteria-primary and secondary malignant features, pancreatic intraepithelial neoplasia (PanINs), etc. - resulted in improvement of the diagnostic efficiency.

Histological evaluation of preoperative biopsies from ampulla Vateri

Frequency of the lesions of the papilla Vateri is increasing in Hungary because of epidemiological reasons. Over two years nearly 300 ampullary endoscopic biopsies were taken in our hospital. In 36 percent of the patients the papillary specimens demonstrated acute or chronic inflammation, in 44 percent adenoma, including 5 percent with severe dysplasia, in 5 percent adenomatous hyperplasia and in 7 percent adenomyosis or other benign tumors (2%) were found. Around 7 percent of the ampullary samples proved to be malignant, but only in 2.6 percent were the malignancy of intraampullary origin. Nearly 25 percent of biopsies were repeated once and 10 percent twice or more. Concordance of endoscopic and pathologic diagnoses was 69 percent on average but it increased to 83 percent after including repeated biopsies. In the adenomacarcinoma group the concordance was 90 percent. The sensitivity of the pathological diagnosis with forceps biopsy was only 77 percent, but it became at least 86 percent following papillectomy. In order to improve diagnostic reliability more extensive use of papillectomy is proposed with close cooperation between the endoscopist and pathologist.

Possible Role of Coxsackie-B Virus Infection in Pancreatitis

SummaryCoxsackie-B antibodies were examined in a study of 118 patients with acute and relapsing chronic pancreatitis. The rise in antibody titers was significant in 40 cases. Fourteen had acute, five relapsing acute, and 21 chronic pancreatitis. Among patients with acute pancreatitis, we detected infectious hepatitis in six cases. Two patients with persisting acute pancreatitis received levamisol as an immuneadjuvant, which promoted their recovery. It seems that Coxsackie-B virus can cause acute pancreatitis, and it can also worsen chronic pancreatitis.

Protein status in pancreatitis--transthyretin is a sensitive biomarker of malnutrition in acute and chronic pancreatitis.

Abstract Malnutrition may develop in acute pancreatitis (AP), accompanied by hypermetabolism and high nutritional requirements, and in chronic pancreatitis (CP). We measured the incidence of protein malnutrition in AP and CP by comparing different serum biomarkers of protein metabolism and inflammation. Thirty-five patients with acute (27 moderate, 8 severe), and 35 with chronic, pancreatitis were enrolled in the study. Serum transthyretin, albumin, transferrin and C-reactive protein (CRP) concentrations were measured in AP at admission, after 1 and 2 weeks of jejunal feeding, and in patients with CP at follow-up. In AP, at admission the transthyretin level was low in 74%, transferrin in 48%, and albumin in 29% of patients. In severe pancreatitis, transthyretin levels were significantly lower than in moderate forms (7.5±2.43 vs. 14.39±6.8 mg/dl, p<0.005). Transthyretin levels increased significantly after 2 weeks of jejunal feeding (p<0.05). In CP, transthyretin levels were decreased in 37%, transferrin in 27%, and albumin in 12% of patients. We found significantly lower transthyretin levels in alcohol-related CP than in other forms (18.5±8.3 vs. 30.2±5.7, p<0.01). Transthyretin correlated positively with albumin and transferrin and negatively with CRP. Transthyretin seems to be a sensitive biomarker of protein status and metabolic stress. Monitoring nutritional status through measurement of serum proteins is important for optimal treatment of AP and CP.

Trophic Effect of Cholecystokinin-Octapeptide in Man -A New Way in the Treatment of Chronic Pancreatitis?

The effect of 3-week CCK-OP treatment on test meal stimulated pancreatic secretion was investigated in chronic pancreatitis patients. One drop of a 1 mg/ml CCK-OP solution applied intranasally, three times daily during 3 weeks resulted in a significant increase in volume, trypsin, lipase and amylase secretion in response to the Lundh test meal. Augmentation of trypsin secretion was the most pronounced. Functional capacity of pancreatic enzyme secretion remained elevated for 3 months after treatment. Nearly all patients became symptom free during and for some time after treatment. The results were attributed to a trophic effect of CCK-OP on human pancreas.

Essential role of cholecystokinin in pancreatic regeneration after 60% distal resection in rats.

The essential role of cholecystokinin (CCK) in pancreatic regeneration after pancreatitis or resection has been supposed, but not yet clearly demonstrated. In rats, 6–8 weeks after 60% distal resection of the pancreas a gradual increase in pancreatic weight and contents of DNA, protein, trypsin, chymotrypsin and amylase, occurred (there was no increase in lipase); Pancreatic regeneration stopped thereafter. Nonparallel increases in enzyme values were similar to those seen after CCK administration. Indeed, basal CCK levels increased significantly by the 6th week and declined thereafter. A one month S.C. administration of CCK-octapeptide (CCK-8) (3 × 300 ng/kg/d) accelerated regeneration in the first month, but it had almost no effect during the second or third postoperative months. A two week S.C. administration of a specific CCK antagonist, CR 1409 (3 × 4 mg/kg/d) totally prevented regeneration by the fifth and sixth weeks, but did not diminish pancreatic weight or DNA and protein contents during the first two weeks. Alcohol administration (12 g/kg/d) reduced CCK release and prevented pancreatic regeneration during the three-month experimental period. These data indicate that CCK has an essential role in pancreatic regeneration and that the deleterious effect of alcohol on regeneration involves inhibition of CCK release.

Alcohol-induced chronic pancreatitis in rats after temporary occlusion of biliopancreatic ducts with ethibloc

Chronic obstructive pancreatitis-like histological and biochemical alterations were provoked in male Wistar rats with Ethibloc occlusion of the common bile duct and the main pancreatic ducts. After the disappearance of the glue from the ducts, a gradual and almost total recovery was demonstrated during a 2-month observation period. About 12 g/kg of alcohol (20% vol/vol) given daily by gastric intubation and ad libitum intake inhibited the recovery of pancreatic weight and enzyme contents in the occluded rats, and within a 2-month period chronic calcifying-type pancreatitis became evident with some signs of remaining obstructive pancreatitis-like lesions. Cessation of alcohol administration after 2 months resulted in a recovery of pancreatic weight and enzyme contents, although morphological regeneration was less pronounced and calcification remained visible in some rats. A 50% raw soy flour diet provoked some further changes in the proportion of enzymes without any supplementary increases of pancreatic weight and protein content. This animal model of chronic pancreatitis demonstrates that chronic obstructive and calcifying pancreatitis can appear together and earlier if the etiological factors act in combination. Suppression of pancreatic regeneration by alcohol seems to be necessary to maintain chronic pancreatitis-like lesions and to develop calcification.

Time-course of changes in pancreatic size and enzyme composition in rats during starvation

SummaryThe effect of starvation for 3, 5, or 7 d on body weight, fat stores, pancreatic weight, and enzyme composition was studied in 300 g rats and was compared with a. 3-d fast in 200 g rats. In the 300 g animals, fasting led to a gradual hypotrophy of the pancreas with a marked, continuous decrease in amylase content. Pancreatic lipase, trypsinogen, chymotrypsinogen, proelastase, and secretory trypsin inhibitor contents increased temporarily, but by d 7, they declined to about the initial values. This decline in enzyme levels coincided with the exhaustion of fat stores. The decrease in amylase content could be related to decreases in circulating insulin levels, whereas the temporary increase in lipase content may be owing to changes in plasma free fatty acid concentrations. In 200 g rats, starvation for 3 d led to exhaustion of fat stores that was accompanied by greater losses of pancreatic weight, protein, and amylase contents. In addition, the levels of trypsinogen and chymotrypsinogen decreased and lipase was unchanged. These findings indicate that during starvation, changes in pancreatic secretory enzymes are time-dependent and vary with the age, body weight, and/or adipose tissue mass of the rats.

Stimulated Gastrointestinal Hormone Release and Gallbladder Contraction During Continuous Jejunal Feeding in Patients with Pancreatic Pseudocyst Is Inhibited by Octreotide

SummaryBackground. Continuous enteral feeding, the old-new therapeutic modality in the treatment of patients with acute pancreatitis and those with complications is considered to bypass the cephalic, the gastric, and (at least in part) the intestinal phase of pancreatic secretion. The aim of this study was to test the GI hormonal changes and gallbladder motility during CJF in patients with pancreatic pseudocysts following acute pancreatitis, with or without octreotide pretreatment.Patients and Methods. In 15 patients with pancreatic pseudocysts, an 8-French (8F) nasojejunal catheter was positioned into the jejunum distal to the ligament of Treitz during duodenoscopy. On test d 1, blood samples were taken for CCK, gastrin, insulin-like immunoreactivity (IRI), glucagon, and glucose measurements prior to and at 20, 40, 60, and 120 min following jejunal saline infusion at a rate of 2 mL/min. The gallbladder volumes were determined simultaneously by ultrasonography. On test d 2, CJF (175 kcal/h) was started by the same route and at the same infusion rate. Analogous measurements were performed as indicated above. On test d 3, 100 µg of octreotide was administered subcutaneously and the previous procedure was repeated. The plasma level of CCK and glucagon and the serum levels of IRI and gastrin were determined by bioassay and radioimmunoassay (RIA), respectively.Results. Significant changes in hormone levels were not observed during jejunal saline perfusion. However, the levels of CCK (5.7±0.9 pmol), gastrin (10.6±1.3 pmol/L), IRI (27.2±5.8 µIU/mL), glucagon (322.8±32.4 pg/mL), and glucose (5.8±1.0 mmol/L) were significantly increased at 20 min during CJF vs the saline controls (2.0±0.3 pmol, 6.8±1.1 pmol/L, 7.8±0.4 µIU/mL, 172.8±33.4 pg/mL, and 4.5±0.5 mmol/L, respectively) and remained elevated at 40, 60, and 120 min. Octreotide pretreatment eliminated the increases in CCK, gastrin, IRI, and glucagon levels observed during CJF alone. The significant decrease in gallbladder volume during CJF was also prevented by octreotide pretreatment. Conclusion. Continuous jejunal feeding (CJF) elicited significant increases in gastrointestinal (GI) regulatory hormone (cholecystokinin [CCK], gastrin, IRI, and glucagon) levels and evoked a consecutive gallbladder contraction. These biological responses are eliminated by octreotide pretreatment. Further clinical studies are needed to assess the eventual therapeutic effect of octreotide during CJF in patients with pancreatic pseudocyst.

Pancreatic trophism in experimental liver cirrhosis

SummaryPancreatic trophism and pancreatic enzyme composition, and plasma levels of cholecystokinin, insulin, glucagon, and glucose in liver cirrhosis induced by chronic thioacetamide administration (0.02% in the drinking water for 12 mo) were studied in rats. Advanced liver cirrhosis was evident in all thioacetamide-treated rats. The weight of the pancreas and its contents of DNA, protein, trypsinogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor, and amylase were significantly increased as compared to the controls. The pancreatic secretory enzyme content changes showed a nonparallelism, characteristic of a cholecystokinin effect. Light and electron microscopy revealed a normal pancreatic architecture. Bioassayed plasma cholecystokinin levels in both fed and 24-h-fasted cirrhotic rats were significantly higher than in the corresponding controls. The plasma glucose, insulin, and glucagon levels demonstrated hypoglycemic tendencies with a glucagon predominance. These findings indicate that advanced liver cirrhosis in the rat is accompanied by pancreatic hypertrophy and hyperplasia, which might be attributed, at least in part, to elevated circulating cholecystokinin levels.