Histological features of donor grafts for orthotopic liver transplantation.
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Biomedical subjects
Publications and source records attributed to R Naccarato.
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Hepatic fibroplasia seems to play an important role in the course of primary liver cancer (PLC) since, for instance, encapsulated and fibrolamellar hepatocellular carcinomas show a definitely better prognosis. In this study, serum procollagen III amino-terminal peptide (PIIIP) levels, which reflect synthesis and release of procollagen type III, were measured with the aim of assessing hepatic fibrogenesis in PLC patients and determining whether serum PIIIP levels play a diagnostic or prognostic role in PLC. Twenty-five patients with PLC, 74 patients with cirrhosis and 38 healthy volunteers were studied. Serum PIIIP levels were determined by a radioimmunoassay (RIA) method. In PLC patients PIIIP serum levels were significantly higher than those of controls and cirrhotic patients (P less than 0.001 and P less than 0.01 respectively) but an analysis of individual values showed an important overlap between PLC and cirrhosis. No correlation was found between serum PIIIP levels and tumour histology, presence or absence of cirrhosis, Child status, possible aetiology of the disease, indices of hepatocellular inflammation, cholestasis and synthesis, or tumour markers. On the contrary, serum PIIIP levels correlated with tumour gross pattern (z = 3, P less than 0.001) and, inversely, with survival (r = 0.659, P less than 0.01), patients with serum PIIIP over 25 ng/mL showing a significantly worse prognosis. These data confirm that hepatic fibroplasia plays an important, but not yet fully understood, role in the course of PLC. From the clinical point of view, PIIIP determination does not add to the differential diagnosis between PLC and cirrhosis but helps to identify patients with larger liver replacements and worse prognoses.
Liver abnormalities seem a very rare association in Turner's syndrome, only reported in a few anecdotal cases. We report the clinical and morphological findings in 3 patients who presented with cholestasis. One of them had a definite diagnosis of primary sclerosing cholangitis, in whom the natural history was complicated by the development of two distinct tumors. A review of the few cases described in the literature and our own case reports support the hypothesis that liver disease in Turner's syndrome may have a variety of expressions including cholestasis.
The role of neurotensin as a physiologic regulator of exocrine pancreatic secretion is known, but the hormone has only recently been recognized as important mitogen in vitro for human cancer cells. The aim of this study was to evaluate the variations of serum levels of neurotensin in pancreatic cancer. We studied 58 patients: 13 control subjects, 20 pancreatic cancer patients, 11 chronic pancreatitis patients, and 14 cases of extrapancreatic disease. No differences were found between serum values of neurotensin in pancreatic cancer and control subjects or extrapancreatic disease. Significantly higher values were detected in chronic pancreatitis than in pancreatic cancer patients (P < 0.04). In chronic pancreatitis patients, the serum levels of neurotensin were correlated with serum amylase (r = 0.95, P < 0.01). Lower levels of neurotensin were found in stage IV pancreatic cancer than in stages I-II (t = 1.82, P < 0.04) and in grade II than in grade I (t = 2.21, P < 0.02). Significant correlations were found between serum levels of neurotensin and two indices of nutrition: albumin (r = 0.60, P < 0.05) and the percentage reduction in body weight (Z = 2.20, P < 0.02). No correlations were found between serum levels of the hormone and size of the neoplasm or the survival of patients. We can conclude that the serum variations of neurotensin do not seem to be related to the progression of human pancreatic cancer. The variation of serum levels of the hormone may be linked to a poor nutritional status of the patient.
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.
The proto-oncogene c-jun is involved in cell proliferation and Ki-67 antigen permits determination of the proportion of proliferating tumour cells. The expression of c-jun and Ki-67 in pancreatic cancer and their relation with tumour histological features and patients survival were evaluated. Specimens were obtained as follows: 14 pancreatic cancer from patients radically operated, 8 liver metastases from subjects submitted to palliation, 5 normal pancreas from organs donors and 5 chronic pancreatitis. Ki-67 and c-jun were studied by immunohistochemistry. The percentage of tumour cells stained for c-jun was increased in 11/14 cases. A high c-jun expression was more frequently found in liver metastases than in pancreatic cancer tissue (p=0.031). The frequency of high c-jun expression was more elevated in short-term as compared to long-term survivors (Fisher's exact test, p=0.031 and log-rank, p=0.03). The percentage of tumour positive cells for Ki-67 showed a mean value of 12.8% in primary pancreatic cancer and was lower than in the liver metastases (32.5%) (p=0.029). Significantly lower values were found in long-term (6.5%) as compared to the short-term survivors (18.1%) (p=0.032 and log-rank, p=0.006). A positive relation was demonstrated with stage (p<0.05), lymph node state (p=0.045) and perineural invasion (p=0.0001). In the multivariate analysis the Ki-67 staining was the most important determinant of long-term survival (p=0.005). c-jun and Ki-67 are overexpressed in pancreatic carcinoma, but only Ki-67 is a strong predictive factor.
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The proto-oncogene c-jun is involved in cellular proliferation by interfering with signals that lead to cellular differentiation. Moreover the induction of metalloproteinase gene appears to utilise the c-jun oncogene as intracellular messenger. The aims of this study were to evaluate a) the expression of c-jun oncogene in pancreatic cancer b) its relation with tumor histological features. Surgical specimens of pancreatic cancer were collected from 22 patients radically operated upon, and from 11 submitted to palliation. As a control group, 5 specimens of normal pancreas and 5 specimens of chronic pancreatitis were studied. C-jun staining was graded as follows: (-) positive cells < 10%, (+) from 10 to 30%, (+2), from 30 to 60%, (+3) from 60 to 90%. Glucagon and somatostatin staining was graded counting the positive cells of total numer of Langherans islet cells counted. c-Jun expression (low: < 30% and high: > 30%) was related to stage, architectural and cytological grading, vascular, lymph nodal, perineural invasion. Normal pancreas and chronic pancreatitis tissues appear to express the c-jun protein in less than 10% of ductal cells. The percentage of tumor cells stained for c-jun is increased as compared to the control group in 28/33 cases: in 13 (46%) it ranges from 10 to 30%; in 10 (36%) from 30 to 60% and in 5 (18%) from 60 to 90%. The frequency of high or low c-jun expression is not different in relation to the histological features of tumor. Moreover, c-jun protein is present in 40% of cells of Langherans islets in normal pancreas, chronic pancreatitis and pancreatic cancer. The Langherans islet cells stained for c-jun exhibit also a positivity for glucagon. In conclusion; a) in pancreatic cancer, the expression of c-jun is increased in tumour cells in majority of cases as compared to the control group, b) a c-jun positivity is also found in alpha cells with a pattern not different from control group, but the relation between the alpha cells and c-jun production is unknown, c) c-jun expression does not vary in relation to histological findings.
BACKGROUND/AIMS: Patients with chronic cholestasis, particularly those with associated cirrhosis, are susceptible to infectious complications. From animal models it has been postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMNL) function by impeding chemotaxis, phagocytosis and superoxide release, which are necessary for an adequate immune response. The aim of this study was to evaluate neutrophil activity in the production of oxygen-derived free radicals in chronic cholestatic liver diseases. METHODOLOGY: The following groups were included in the study: 27 primary biliary cirrhosis (PBC) patients, 12 primary sclerosing cholangitis (PSC) patients, and 3 control groups (29 healthy subjects, 19 patients with HCV-related cirrhosis and 23 ulcerative colitis (UC) patients). Peripheral neutrophils were isolated from heparinized blood samples and PMNL activity was measured by free radical production, using a chemiluminometer, after stimulation with fMLP, PMA and Zymosan. The effect of liver disease severity and degree of cholestasis on PMNL function was also evaluated. RESULTS: Both PBC and PSC patients exhibited a normal PMNL activity compared to healthy subjects after the three stimuli used. In PBC patients only (but not in PSC patients), the histological stage of the disease seems to positively influence ROS production. Stage IV PBC patients showed a significantly higher PMNL activity compared to HCV-related cirrhotic patients. PSC patients failed to show any difference according to the association with UC. CONCLUSIONS: The increased susceptibility to bacterial infections in patients with chronic cholestatic liver disease is not related to an impaired PMNL activity. However, our findings may support the influence of biohumoral factors (cytokines?) on PMNL activation.
Being informed is not only a patient's right, it is also important in order to improve compliance and management. Apart from verbal consultations, informative material is often produced without prior analysis of what patients consider important to know. Patient information needs were defined in order to plan future educational programmes. A 44-item questionnaire was given to 100 Inflammatory Bowel Disease (IBD) out-patients (50 Crohn's Disease (CD) and 50 Ulcerative Colitis (UC). Sixty-two per cent of those with UC and 78% of those with CD consider themselves insufficiently informed about their disease. CU and CD patients indicated different priorities concerning areas where further information is requested: CD patient needs were aetiology, diet, symptoms, history, new treatments, risks deriving from treatment, cancer risk and consequences on work. UC patients indicated a different priority order: risk of cancer, new treatments, symptoms, psychological and diet factors and aetiology. The media preferred by patients were: specifically prepared books (73%), video-cassettes (20%) and leaflets (25%). Ninety per cent think that educational material prepared according to their needs could be very useful; however 35% think that knowledge of the possible severity of their disease might increase their anxiety.
The need to change the methods of teaching medical students has become self-evident in the past two decades, and strategies for revision are indicated in the new course curriculum, Tabella XVIII. A modern teaching method is the problem-based learning (PBL) method, which has already been adopted by over 100 medical schools throughout the world. This method can also be a satisfactory tool for teaching gastroenterology to undergraduate students, and its implementation requires only a few resources that are available in most universities. The theoretical principles of the method are illustrated and practical suggestions are given to set up a course in gastroenterology using this method.
BACKGROUND: The impact of liver disease and medical complications on quality of life (QOL) and psychological distress before and after liver transplantation (LT) is a matter of growing interest. METHODS: In a longitudinal prospective study, perceived QOL (LEIPAD Quality of Life test) and psychological distress (Brief Symptom Inventory, BSI) were assessed in 25 cirrhotic patients when they were listed for LT and 1, 3, 6 and 12 months after LT. Patients were also evaluated for medical complications and blood levels of immunosuppressive agents. RESULTS: Overall QOL and psychological distress improved significantly and rapidly in most domains from the first month and up to a year after LT. Medical complications and immunosuppressive agents did not correlate with any changes in QOL and psychological distress after LT. When patients were divided according to liver disease etiology: 1. HCV patients listed for LT had worse QOL levels than the group of patients as a whole or the alcoholic liver disease (ALD) patients; 2. HCV patients reported a significant improvement in QOL only 6 and 12 months after LT, and still suffered more psychological distress 12 months after surgery; 3. in ALD patients, overall QOL and psychological distress improved significantly at all follow-up points after LT; 4. HCV patients reported a worse QOL and greater psychological distress 1 and 3 months after LT than the group as a whole or the ALD patients (p < 0.05). CONCLUSIONS: Liver transplantation improves QOL and psychological distress in most recipients, but not in the early stages after LT in patients transplanted for HCV cirrhosis.
To contribute to a better understanding of the role of leukotrienes in inflammatory conditions of the upper gastrointestinal tract, leukotriene B4 (LTB4) levels were measured by specific radioimmunoassay in extracts of mucosal biopsies from the stomach and duodenum of control subjects and of patients with gastritis, benign gastric ulcer and duodenal ulcer. The control mucosa contained measurable levels of LTB4. Levels were 20% higher in gastritis than in controls and the lowest levels were found in the patients with no bile reflux. LTB4 levels were more than 3 times higher in duodenal ulcer (p less than 0.025) than in controls, whereas gastric ulcer margins had very low levels. No clear relationship was found between LTB4 levels and the drugs used in treatment. While these data do not explain the role of LTB4, they suggest that LTB4 may be an important mediator of the inflammation accompanying or leading to development of duodenal ulcer.
A comparative seroepidemiological study (1979 vs 1989) on HAV infection, was carried out in children and adolescents from North-East Italy. Anti-HAV was tested in 850 subjects 6 to 8 years of age and the results were compared to those observed in 1979, in 462 subjects of the same age range and from the same geographical area. Overall anti-HAV prevalence was 1.9% (ranging from 0.5 to 5.2) in 1989 vs 32.5% (ranging from 7.8 to 70.7) in 1979. This dramatic decline of HAV infection in children and adolescents reflects the improved sanitation standard of our country but, on the other hand, indicates that the number of non-immune adults is increasing, with a higher risk of symptomatic infection in the near future.
Hepatitis B infection was endemic in Italy and household transmission has been considered to be the main mode of HBV spread. Prevalence of HBsAg positive subjects was therefore higher in children than in adults. Serum samples from 500 children (aged 6-15 year) without overt liver disease were tested for HBV serum markers in 1979. Serological evidence of HBV infection was present in 16% of the subjects. To verify a possible decline of HBV infection we designed a seroepidemiological study in school children from the same town. Three classes of age (6 yrs, 10 yrs, 14 yrs) were selected. Children were recruited from those attending primary and secondary schools using a systematic cluster sampling. After parents' informed consent sera were collected in May 1989. All were tested for anti-HBc: anti-HBc + ve sera were then tested for HBsAg and anti-HBs (EIA Abbott Lab., Chicago, Ill. USA). Of the 1635 children one was HBsAg positive and 21 were positive for any HBV marker. Both the prevalence of HBsAg and that of any HBV marker were significantly lower (p less than 0.001) in 1989 when compared to the corresponding age-class of 1979.
The University of Wisconsin solution discovered in 1987 by Belzer and associates, has dramatically changed the logistics associated with liver transplantation. The extension of hypothermic preservation time has mode at possible: a) to operate in a semi-elective situation, rather than urgent; b) to improve patient selection and to be able to admit them from distant locations, and c) to reduce postoperative complications with a better quality of organ preservation. In the present work we illustrate the pathophysiological background and the rationale behind the various chemical constituents included in the new solution, emphasizing the antiedemogenic effect. Furthermore we report some experimental data on the role of energy level (ATP) and intracellular pH in the monitoring of liver preservation. Together with the improvements of surgical technique and immunosuppression, the new solution of the University of Wisconsin represents a fundamental step in the development of organ transplantation.