G. Del Favero

Histological study of alcoholic, nonalcoholic, and obstructive chronic pancreatitis

Pancreatic tissue obtained from 26 patients with alcoholic chronic pancreatitis (ACP), nine patients with nonalcoholic idiopathic chronic pancreatitis (NAICP), and seven patients with obstructive chronic pancreatitis (OCP) was studied in an attempt to determine whether clinical or etiologic differences have a morphologic counterpart. Histologically it was easy to distinguish ACP from OCP occurring distal to an obstruction of the pancreatic duct. Nine patients with NAICP showed histological features similar to those found in ACP. Plugs and calcifications were found as frequently in NAICP as in ACP, suggesting that NAICP, whatever the etiology, is truly pancreatolithiasis, which leads to slowly progressive fibrosis and acinar atrophy in the obstructed pancreatic lobule. Nerve fibers were found to be more numerous in all disease categories. Inflammatory foci of lymphocytes associated with nerves were observed in 57 and 35% of cases with OCP and ACP, respectively, but only in one patient with NAICP. These findings may constitute a pathological basis for the existing clinical data showing that NAICP frequently runs a pain-free course.

Oxygen derived free radicals in patients with chronic pancreatic and other digestive diseases.

To ascertain modifications in the activation products derived from oxygen free radicals in patients with chronic pancreatic and extra-pancreatic diseases, lipid peroxide activity was measured in the sera of 40 control subjects, 28 patients with pancreatic cancer, 49 with chronic pancreatitis, and 53 with extra-pancreatic diseases. In 142 of the subjects, elastase 1, amylase, and pancreatic isoamylase activities were also determined. Increased lipid peroxide activities were found in some patients with both chronic pancreatic and extra-pancreatic diseases. Patients with chronic pancreatitis studied during relapse had higher activities of lipid peroxides than those without active disease. No difference was found between the values in patients with pancreatic cancer with liver metastases and those without. Correlations were found between lipid peroxides and both amylase and pancreatic isoamylase activities; no correlation was detected between lipid peroxides and elastase 1. In benign biliary tract disease a correlation was detected between lipid peroxides and alanine aminotransferase and alkaline phosphatase activities. In all patients, however, a correlation was found between alkaline phosphatase and lipid peroxide activities. It is concluded that activation of oxygen derived free radicals occurs in chronic pancreatic as well as in extra-pancreatic disease; it seems to reflect the degree of inflammation.

Insulin-like growth factor-I, interleukin-1 α and β in pancreatic cancer: role in tumor invasiveness and associated diabetes

SummaryWe evaluated levels of insulin-like growth factor-I and interleukin-1 α and β in patients with pancreatic cancer; the role of these substances in tumor spread and in hyperglycemia was also investigated. Thirty pancreatic cancer patients (21 with hyperglycemia) were compared with others with diseases causing hyperglycemia [liver cirrhosis (14 cases, 12 with hyperglycemia), chronic pancreatitis (20 cases, 12 with hyperglycemia), type I diabetes mellitus (13 cases, all hyperglycemic)]. Insulin-like growth factor-I was significantly reduced in patients with liver cirrhosis, probably due to a reduced hepatic capacity for synthesis. It was increased in 6 of 30 pancreatic cancer patients; in these subjects it was correlated with alanine aminotransferase and C-peptide, but not with tumor diameter or the presence of metastases. Interleukin-1α and β were both elevated in pancreatic cancer patients. The former was high, while the latter was low when liver metastases were present. Neither was related to glucose or C-peptide levels. In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis. Interleukin-1 α increased, while interleukin-1β decreased in pancreatic cancer patients with metastases, suggesting a different involvement of these two substances in pancreatic cancer spread.

Extra‐hepatic cholestasis determines a reversible increase of glycoproteic tumour markers in benign and malignant diseases

Abstract. This study was performed in order to assess the relative role of cholestasis in increasing some serum glycoproteic markers of malignancy (CA 19–9, TPA, CEA). 30 Patients with benign and 16 with malignant extra‐hepatic cholestasis were studied on admission (stage A) and after the operative or spontaneous resolution of the cholestatic picture (stage B). CA 19–9 and TPA were found to be lower in stage B than in stage A benign diseases. A similar behaviour was found in malignant diseases, although findings were significant only for CA 19.9. In neither of the patient groups was CEA found to present a significant trend. Extra‐hepatic cholestasis appears able to increase per se serum glycoproteic markers in benign diseases, with variations proportional to the severity of the clinical picture. The same considerations can apply to malignancies, even if in these situations the production of tumour markers by the neoplastic growth should also be considered. We should therefore be cautious in assessing the diagnostic usefulness of new tumour markers when cholestasis is present.

Tumor markers in the diagnosis, monitoring and therapy of pancreatic cancer : state of the art

The present review focuses on the utility of serum tumor markers in screening, diagnosis, prognosis and monitoring of pancreatic cancer. Serum determination of all tumor markers studied offers no help in screening or early diagnosis of pancreatic cancer. For diagnosis, blood group-related antigens, in particular CA 19-9, are considered the best indicators of this neoplasm. However, as occurs with other glycoproteic tumor markers, the circulating levels of CA 19-9 are significantly influenced by jaundice, probably because its liver metabolism is reduced. Therefore, the finding of elevated CA 19-9 levels in jaundiced patients has to be evaluated with caution. Since pancreatic cancer recurrences are not susceptible to treatment, the clinical role of widespread use of tumor marker determination in follow-up programs is limited and calls for a critical evaluation.

Role of proctography in severe constipation

As referred to in the literature, patients complaining of constipation may have a spastic or, in the case of chronic straining, weak pelvic floor. Twenty-two severely constipated patients who did not improve after a high fiber diet were submitted to whole gut transit time (TT), proctographic, and anorectal manometric studies. A control group consisting of five subjects for TT, five subjects for proctogram, and ten subjects for manometry was also studied. Transit time was delayed (P< 0.001) in all patients. Manometry in the constipated group showed a high rectal threshold (64.1vs.17.1 ml of air,P< 0.01), but no other significant difference. Proctograms in 10 of 22 patients (Group A) showed no differences in the anorectal angle (ARA) and in its distance from the pubococcygeal line (DLPC) in respect to the control group; 12 of 22 patients (Group B) had a paradoxical closure of the ARA at straining in respect to resting position (101.2†vs.120.1†), and a higher DLPC than Group A and the control group in all positions studied. There was no difference in TT for rectal stasis of radiopaque markers between the two pathologic groups. Patients in Group B were older than patients in Group A (55.3vs.42.9 years,P<0.05). In conclusion, proctograms showed alterations of the pelvic floor, but there was no correlation between proctographic data and rectal or colonic stasis of the radiopaque markers, or clinic severity of constipation, but a correlation between ages did exist.

Serum elastase 1 in chronic pancreatic disease

SummaryElastase 1 and immunoreactive trypsin were assessed by a RIA technique in the sera of 29 control subjects, 24 pancreatic cancer patients, 22 patients with chronic pancreatitis and 31 with extra-pancreatic diseases to ascertain and compare their usefulness in chronic pancreatic disease diagnosis. Increased levels of elastase 1 were detected in 60.9% of pancreatic cancer and in 61.1% of chronic pancreatitis patients; low values were found in only two subjects with pancreatic disease. A close correlation between the two enzymes was found in patients suffering from pancreatic cancer and chronic pancreatitis. These data suggest that serum elastase 1, as well as immunoreactive trypsin, is of limited value in chronic pancreatic disease diagnosis; increased levels of the two enzymes always occur simultaneously; low immunoreactive trypsin values together with normal elastase 1 serum levels are detectable in a number of patients with chronic pancreatitis and severe exocrine insufficiency.

Computed tomography in predicting gall stone solubility: a prospective trial.

This prospective study was undertaken to evaluate the correlation between densitometric values of gall stones assessed by computed tomography and the success rate of litholytic therapy in 28 patients eligible for oral treatment. A densitometric study of the stones was performed in all patients before treatment. A cut off point of 60 Hounsfield units (HU) was chosen to divide the subjects into two groups--group 1, 14 patients with low density stones (less than 60 HU) and group 2, 14 patients with high density stones (greater than 60 HU). All patients were treated with ursodeoxycholic acid (8-10 mg/kg/day) for 12 months and followed up by ultrasound. In group 1, dissolution was complete in 50% of the patients and partial in a further 20%. In group 2 patients, complete dissolution was not observed but 33% showed partial dissolution. The number of patients with total dissolution at 12 months was significantly higher in group 1 compared with group 2 (p less than 0.02). These results suggest that computed tomography can be used to select patients with a better likelihood of successful stone dissolution after bile acid therapy.

The effect of aging on oro-cecal transit time in normal subjects and patients with gallstone disease

To ascertain whether aging and/or cholelithiasis can influence oro- cecal transit time (OCTT), we studied a total of 70 subjects, i.e., 10 healthy young adult controls, 22 healthy elderly controls, 18 elderly cholelithiasis patients and 20 elderly subjects with a history of cholecystectomy for gallstones. OCTT was measured by means of the hydrogen breath test after administering a liquid meal of 10 g of lactulose in 200 mL of water, and collecting exhaled breath samples every 10 minutes for 200 minutes. Of all subjects in the group of patients with a history of cholecystectomy, 6/20 were non- hydrogen producers, and therefore were not included in the study. The OCTT was found to be significantly longer in healthy elderly controls, than in healthy young adult controls; the elderly subjects who had undergone cholecystectomy had a longer OCTT than the healthy elderly controls, while no difference was detected when compared to elderly patients with gallstones. In conclusion, OCTT seems to increase in healthy aging. Cholecystectomy also increases OCTT in the elderly, suggesting a link between intestinal motility and the biliary tract which may be of pathophysiological significance. (Aging Clin. Exp. Res. 7: 234–237, 1995)

Alterations in bilirubin metabolism during extra- and intrahepatic cholestasis

SummaryThis study was performed to investigate modifications in the serum bilirubin forms, hepatobiliary enzymes, and some glycoproteic substances in patients during the course of extrahepatic cholestasis (stage A) and following its clinical resolution (stage B). The series consisted of 16 patients 11 had main bile duct stones; two, benign stenosis of the main bile duct; and three, main bile duct cancer. Cholestasis resolved spontaneously in one case, under endoscopy in two, and following surgery in 13. Five patients with liver cirrhosis and a picture of intrahepatic cholestasis following anesthesia were also investigated. Serum bilirubin forms were measured using van den Berghs method and the alkaline methanolysis-HPLC procedure; the mono- and di-conjugated forms were considered together in the overall evaluation of the results. The hepatobiliary enzymes (ALP, GGT, and AST) were increased at stage A and significantly decreased at stage B. Similar patterns were observed in total (TB), unconjugated (UB), and conjugated bilirubin (CB) and in the percentage of CB out of TB (% CB). In the majority of patients, % CB at stage B was lower than at stage, whereas in subjects with a high initial UB value, a different % CB pattern was observed. The direct bilirubin percentage (% DB), on the other hand, had a different pattern, and the variations between stages A and B were not significant. The pathophysiological bilirubin pattern was similar in patients with intrahepatic cholestasis. At stage A, in a number of patients the levels of glycoproteic substances (CA 19-9, TPA and ferritin) were raised, but at stage B they tended to decrease towards the normal range. Correlations were found between CA 19-9 or TPA variations and cholestasis indicators. It may be concluded that our HPLC technique may reveal differences in the behavior of the bilirubin pigments that cannot be detected with van den Berghs method, even in the presence of similar TB variations. The increase in the glycoproteic substances considered may express an impairment in their metabolic (largely hepatic) clearance, as occurs in the cholestatic setting.