Neuroendocrine tumors diagnosed at the Antonio Cardarelli hospital (Naples, Italy) between 2006-2009: a single-institution analysis.

Neuroendocrine tumors (NETs) are rare, with an incidence of about 5 per 100,000 inhabitants. As no study on NETs has ever been specifically conducted on the population of Campania, we performed a retrospective analysis of all newly diagnosed NETs at the Antonio Cardarelli hospital between 2006-2009. A search of the registry of the Pathology Department of the Antonio Cardarelli hospital was carried out to retrieve available data on all newly diagnosed NET cases. Two hundred and ninety-nine NET tumors were diagnosed at our Institution from January, 2006 to December, 2009. Globally, 121 patients (40% of the population) had a lung NET, while 92 patients (30% of the population) presented a GEP-NET. The most common primary tumor site varied by sex, with female patients being more likely to have a primary NET in the lung, breast or colon, and male patients being more likely to have a primary tumor in the lung. Also, twenty-three cases of breast NETs were identified, and clinical information regarding therapy and response was available for 22 patients. Our study represents a pioneering effort to provide the medical community in Campania with basic information on a large number of patients with different types of NETs. The Antonio Cardarelli hospital could greatly benefit from cooperation with other hospitals in order to become a highly specialized center for NETs in the region and Southern Italy.

Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels.

BACKGROUND & AIMS: Some patients with serum hepatitis C virus (HCV) have persistently normal aminotransferase (ALT) levels and are affected by cirrhosis. This study prospectively evaluated progression of the disease in a group of anti-HCV-positive patients with persistently normal ALT levels. METHODS: Thirty-seven subjects were studied. Each subject underwent liver biopsy at baseline and after 5 years of follow-up. At baseline, serum samples were tested for genotypes and HCV RNA load. ALT levels and serum HCV RNA were tested every other month and every 6 months, respectively. Patients with increased ALT were discharged from the study and treated with IFN. Five years after the end of IFN therapy, a liver biopsy was performed. RESULTS: Liver biopsy at baseline showed chronic hepatitis in 34 patients and normal histology in 3 patients, 2 of whom were negative for HCV RNA and 1 positive. HCV genotypes were distributed as follows: 2a, 56%; 1b, 41%; and 1a, 3%. At the end of 7-year follow-up, 73% of the patients still had normal ALT values. Liver histology after 5 years was comparable to that observed at entry to study. CONCLUSIONS: Most patients with persistently normal ALT serum levels have very mild chronic hepatitis. However, healthy anti-HCV-positive subjects exist. In patients with HCV-related chronic hepatitis associated with persistently normal ALT levels, the grade of disease activity does not increase over years and progression to cirrhosis is slow or absent.

Non-ulcer dyspepsia and Helicobacter pylori in type 2 diabetic patients: association with autonomic neuropathy.

Diabetic patients often suffer from symptoms arising from the gastrointestinal tract. Several factors are considered responsible for these alterations, including abnormalities of gastric motility. Recently Helicobacter pylori (HP) has been identified in a relevant aliquot of subjects with or without gastrointestinal abnormalities, but only scarce and controversial data are available on the prevalence of HP and the association between HP and chronic gastritis or peptic ulcer in diabetic patients. In addition, the possible association between alterations of gastric motility induced by autonomic neuropathy (AN) and the presence of HP has never been evaluated in diabetic subjects. In this study we document the presence of HP in the gastric biopsies of 73% out of a series of 29 patients affected by type 2 diabetes and non-ulcer dyspepsia (3 with oesophagitis, 10 with gastritis, 7 with bulbar duodenitis, and 9 with a normal endoscopy), with a significantly higher prevalence (P < 0.01) in subjects with AN (74%) than in subjects without AN (26%). Two other tests have been compared with the histological evidence of HP (used as golden standard), i.e. the urease test (CP-test) and the assay of anti-HP G-immunoglobulins, both of which were positive in a significantly (P < 0.01) higher percentage of neuropathic patients in comparison with non-neuropathic patients. The sensitivity and the specificity of the CP-test were 96% and 100%, respectively. Similarly, both the sensitivity and the specificity of the assay of IgG HP-Ab were 100%. Since patients affected by non-ulcer dyspepsia and NIDDM complicated by autonomic neuropathy are under a higher risk to be carriers of HP than non-neuropathic or non-diabetic patients. The assay of serum IgG HP-Ab could be used as a screening method, thus avoiding the more expensive and time-consuming endoscopy.

Regional distribution of transforming growth factor-alpha and epidermal growth factor in normal and portal hypertensive gastric mucosa in humans.

This study was designed to evaluate the concentration and the regional distribution of TGF-alpha and EGF in normal and portal hypertensive human gastric mucosa. To this end we measured by RIA the gastric and duodenal concentration of TGF-alpha and EGF in subjects with chronic hepatitis, who had normal gastric endoscopic appearance, and in patients with liver cirrhosis with and without congestive gastropathy. Our results show that TGF-alpha concentration is significantly higher than EGF concentration in both the stomach and duodenum. No significant regional differences in the distribution of the two peptides were found. Moreover, the gastroduodenal tissue levels of TGF-alpha were comparable in subjects with and without hypertensive gastropathy. EGF gastric concentration was not altered in patients with congestive gastropathy. However, EGF duodenal tissue levels were significantly lower in patients with liver cirrhosis than in noncirrhotic subjects. We speculate that the higher level of TGF-alpha in the gastroduodenal mucosa may support the hypothesis that TGF-alpha and not EGF is the major physiological ligand for TGF-alpha/EGF receptor in the intact gut. Furthermore, the lower duodenal concentration of EGF in cirrhotics might partially explain the increased susceptibility of cirrhotic patients to duodenal ulcer.

Prevalence of hepatitis C virus infection in the household contacts of patients with HCV-related chronic liver disease.

It is still controversial whether the familial environment plays a role in the diffusion of HCV infection. The aim of this study was to evaluate the prevalence of anti-HCV positivity in the household contacts of patients with HCV-related chronic hepatitis. Nearly all the household contacts of 113 subjects with anti-HCV+ chronic hepatitis (100/113 spouses and 260/290 children) were investigated. Anti-HCV was determined by means of ELISA II and was confirmed by RIBA II. Anti-HCV positivity was found in 27% of the spouses and in 1.9% of the children. Prevalence of anti-HCV positivity in spouses correlated positively with the duration of the marital status. Seventeen/32 (53.1%) of anti-HCV-positive subjects were found to have chronic hepatitis. This study indicates that intrafamilial diffusion of HCV infection is mostly accounted for by horizontal, in particular spouse to spouse, transmission and that spouse to spouse transmission of HCV infection correlates positively with the duration of marital status.

Gastric endoscopic features in patients with liver cirrhosis: correlation with esophageal varices, intra-variceal pressure, and liver dysfunction.

This study was aimed at evaluating the gastric endoscopic features in patients with liver cirrhosis and at assessing whether endoscopic findings correlated with the severity of portal hypertension and of the underlying liver disease. We studied 394 cirrhotic patients and 110 controls. Prevalence of a mosaic-like pattern of the gastric mucosa was significantly higher in cirrhotics than controls (80.5 vs. 0.9%; p < 0.001). Red spots of the gastric mucosa were found in 8.1% of cirrhotic patients and in none of the control subjects. Erosions and petechiae were found in 14.5 and 5.4% of the control population, but their prevalence was significantly higher in cirrhotics (28.7 and 12.7%, respectively; p < 0.05). Severity of the mosaic-like pattern as well as the presence of red spots were closely related to the size and hemorrhagic risk of esophageal varices and to the presence of fundic varices. Also, severe mosaic-like patterns were found more frequently in patients with severe impairment of liver function, as assessed by the Child-Pugh's criteria. Furthermore, the mosaic-like pattern was more severe in cirrhotic patients with a higher degree of portal hypertension as indirectly assessed by measurement of esophageal intravariceal pressure. In conclusion, (1) a mosaic-like pattern and red spots of the gastric mucosa are the only specific signs of congestive gastropathy in liver cirrhosis, and (2) the severity of the mosaic-like pattern correlates with the severity of liver dysfunction and of portal hypertension.

Recombinant human interferon alpha-2a therapy for chronic hepatitis C with or without cirrhosis: comparison of 3 or 6 MU for 1 year.

The aim of this study was to compare the effects of two different therapeutical regimens of IFN alpha-2a in patients with HCV related chronic liver disease. Eighty one patients with HCV chronic hepatitis with or without cirrhosis entered the study; 42 and 39 patients were treated with 3 or 6 MU IFN, respectively. The results show that: 1) 25/39 (64.1%) patients treated with 6 MU and 21/42 (50.0%) patients treated with 3 MU had a complete response defined as a decline in serum ALT levels to the normal range during therapy; 2) complete response to 6 MU treatment was observed independently of the presence or absence of cirrhosis; in the 3 MU group, a complete response was observed in 31.6% of patients with CAH + cirrhosis as compared with 68.2% of those with CAH alone (p < 0.03); and 3) at 1 year after the end of the treatment we observed persistent ALT normalization in 40.6% and 28.2% of patients treated with 6 or 3 MU, respectively, and absence, of HCV viraemia (HCV-RNA) in 7/10 patients with CAH and in 2/7 patients with CAH + cirrhosis, mostly in patients treated with 6 MU. In conclusion, 6 MU IFN dose is more effective than 3 MU in reducing disease activity in HCV chronic hepatitis, specially in patients with CAH + cirrhosis.

Effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients.

This study was undertaken to evaluate the effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients. Sixteen cirrhotics were randomly assigned to metoclopramide (10 mg i.v.) or saline. Metoclopramide significantly decreased transmural variceal pressure (15.7% decrease, p less than 0.05 vs. basal value). In order to evaluate if the metoclopramide-induced drop in transmural variceal pressure was due to an effect on portal haemodynamics, we also measured, by means of real time and pulsed Doppler ultrasonography, portal vein diameter, mean velocity of portal flow, and portal venous flow. No significant change was observed before and after metoclopramide. In conclusion, metoclopramide, which increases lower oesophageal sphincter pressure, significantly decreases transmural variceal pressure in cirrhotic patients. However, it does not have any effect on portal haemodynamics.

Role of delta infection in the progression to chronicity of acute HBsAg positive hepatitis.

A previous study of 159 consecutive cases of HBsAg+ acute viral hepatitis, observed from the onset of disease and seen between May 1977 and May 1980, revealed a higher frequency of evolution to chronicity in the region of Naples than that reported for other areas. This suggested that environmental factors might influence the chronically rate. We investigated 125 HBsAg+ acute hepatitis cases for whom sera were available: 35 patients who remained HBsAg+ at the two-year control (28 chronic hepatitis and 7 healthy carriers) and 90 who recovered and seroconverted HBsAg---- anti-HBs during follow-up. At the onset of disease, all patients who cleared HBsAg showed IgM anti-HBc positivity and 48 were also HBeAg positive; no patient was anti-delta positive. On the contrary of the 28 chronic cases only 7 were IgM anti-HBc+ (6 under 13 years old), while 21 were IgM anti-HBc- but anti-delta+. This study demonstrates that not all HBsAg+ acute hepatitis cases are due to HBV and that in our area, superinfection by the delta agent is responsible for most cases of chronic HBsAg positive hepatitis.