Study objectives: Esophageal carcinosarcoma is a rare malignant lesion of the esophagus. Its clinical and pathological characteristics, as well as factors influencing prognosis, are still controversial. Aim of this study was to evaluate the management and prognosis of esophageal carcinosarcoma.

Patients treated with alpha-2a interferon for chronic hepatitis C may produce anti-interferon antibodies whose effect, if any, on the individual response to therapy has not been fully clarified. The prevalence and kinetics of anti-interferon, including those of neutralizing type, have been studied in 60 patients with chronic hepatitis C enrolled in a randomized controlled trial of recombinant alpha-2a interferon. Thirty patients received interferon while 30 were untreated controls. Two different methods, an enzyme immunoassay and an antiviral neutralization bioassay, were used and serial serum samples from each patient were analyzed. Enzyme immunoassay-positive anti-interferon appeared in 60.7% of treated patients within 6 months of therapy; antiviral neutralization bioassay-positive anti-interferon appeared in 52.9% of these enzyme immunoassay-positive patients, and was associated with high enzyme immunoassay reactivity and long-term persistence. Anti-interferon was detected in 75% of patients showing no response to interferon. Antibodies were also detected in three out of six patients who showed alanine aminotransferase normalization persisting up to the end of treatment and in 8 out of 14 patients who showed an initial marked reduction or even normalization of alanine aminotransferase, followed by reactivation of liver damage during treatment. Interestingly, patients who became anti-interferon positive before complete alanine aminotransferase normalization later showed reactivation of liver damage independently of interferon dose reduction, while patients who became positive for anti-interferon after complete alanine aminotransferase normalization either did not reactivate or did so only after interferon dose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis C virus is the most frequent cause of chronic non-A, non-B hepatitis, and the antibodies to structural and nonstructural proteins encoded by viral genome have been suggested to be markers of ongoing HCV infection. We studied the behavior of these antibodies during interferon therapy in 18 patients with chronic hepatitis C and also during a follow-up period of at least four years. A significant decrease of anti-HCV titer was found only in patients who had shown positive response to therapy and all of them were anti-HCV negative at the end of follow-up. Analysis by recombinant immunoblotting assay showed that only anti-c100 were affected by interferon therapy, whereas anti-c22 and anti-c33 were not modified. Using polymerase chain reaction to detect small amounts of HCV genome in serum, we could confirm that the behavior of HCV-RNA during and after interferon therapy is similar to that of anti-HCV and the loss of anti-c100 seems to be closely related to HCV-RNA disappearance from serum. Our patients with chronic hepatitis C were found to be of type 1b and 2, according to the recent score of Simmonds, and the clearance of serum HCV-RNA during treatment and its sustained negative status are closely related to genotype 2 and to long-term positive response to interferon.

BACKGROUND:The "in vivo" interplay between hepatitis B virus (HBV) and hepatitis C virus (HCV) both in terms of replication activity and cytopathic effect on liver cells is poorly understood. The aim of the study was to investigate their reciprocal influence in patients with HBV and HCV coinfection.METHODS:HBV and HCV genomic sequences in the serum and liver of 55 patients with chronic liver disease who were positive for anti-HCV and for markers of HBV were studied.RESULTS:Twenty-five hepatitis B surface antigen-positive patients, without markers of hepatitis D virus (HDV) infection, showed an inverse relation between seropositivity for HCV RNA and for HBV DNA (P < 0.001). HCV genomic sequences were detected in the liver of all patients positive for HBV DNA but negative for HCV RNA in serum. The biochemical activity and the histological severity of liver disease were lower in HCV RNA-positive/HBV DNA-negative patients, compared with HCV RNA (serum)-negative/HBV DNA-positive cases (P < 0.005). Nine of 10 patients with concurrent HDV infection were negative for serum and liver HCV RNA. None of 20 hepatitis B surface antigen-negative/HCV RNA-positive patients with antibodies to HBV had HBV DNA detectable in serum or liver.CONCLUSIONS:Our findings indicate a reciprocal inverse relation between HBV and HCV replication. Patients positive for antibody to HCV with antibodies to HBV usually have no evidence of HBV DNA persistence in the liver.

Eighty-eight consecutive hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, heterosexual patients of Caucasian origin presenting with chronic hepatitis were followed for 1 to 15 years (mean, 5.4 years). During the study period, 45 (51%) patients cleared HBeAg and hepatitis B virus-deoxyribonucleic acid from serum and were followed for 53 +/- 29 months (mean +/- SD) after seroconversion to antibody to hepatitis B e antigen. All patients manifested biochemical improvement. During follow-up, 10 (22%) of the 45 patients experienced spontaneous reactivation of hepatitis B replication with reappearance of serum hepatitis B virus-deoxyribonucleic acid and, in 4 patients, of hepatitis B e antigen. All patients then showed biochemical exacerbation of disease. These serologic events were transient, lasting an average of 12 months, in 8 (80%) patients. All patients were asymptomatic or minimally symptomatic. Histologic findings of liver tissue from 7 patients showed progression from chronic active hepatitis to active cirrhosis in 2 (28%) patients, while in the remaining 6 cases histology remained unchanged or improved from chronic active to chronic persistent hepatitis. These data indicate that spontaneous reactivation of hepatitis B infection occurs in heterosexual patients with chronic hepatitis B and this event is usually transient and asymptomatic, although in some patients it may be the major cause of progressive hepatic damage.

Renal tubular sodium handling was evaluated in 27 non-azotemic cirrhotic patients with ascites and positive sodium balance and in 17 controls after at least 5 days of a constant sodium intake using the lithium clearance as an index of fluid delivery to the distal tubule. Plasma renin activity and plasma aldosterone were also evaluated. Sodium fractional excretion, filtered sodium load, absolute sodium distal delivery, lithium fractional excretion and absolute distal sodium reabsorption were significantly lower in cirrhotics than in controls (0.58 +/- 0.11 vs. 1.29 +/- 0.12%, P less than 0.001; 12529 +/- 677 vs. 15707 +/- 796 microEq min-1 1.73 m-2 BSA, P less than 0.005; 2384 +/- 135.2 vs. 3685 +/- 219.3 microEq min-1 1.73 m-2 BSA, P less than 0.001; 19.5 +/- 1.0 vs. 24.2 +/- 1.3%, P less than 0.01; 2299 +/- 127 vs. 3485 +/- 214 microEq min-1 1.73 m-2 BSA, P less than 0.001, respectively). A correlation was found between lithium clearance and sodium clearance only in cirrhotic patients (r = 0.62; P less than 0.01). Distal sodium reabsorption evaluated as a per cent of filtered sodium load was lower in cirrhotics than in controls (19.1 +/- 1.0 vs. 22.4 +/- 1.2%, P less than 0.05) while distal sodium reabsorption evaluated as a per cent of sodium distal delivery was higher in cirrhotics than in controls (96.7 +/- 0.4 vs. 94.4 +/- 0.5%, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Out of 1,338 esophageal carcinomas observed from 1980 to 1987, 171 were clinically staged as early cancers. 150 of 171 patients underwent esophagectomy, and an early cancer was pathologically confirmed in 61. Hospital mortality was 3.3% (2 of 61). The 5-year survival rate of mucosal (n = 10) and submucosal (n = 51) tumors was 100 and 33%, respectively. Neoplastic recurrence was detected in 9 patients, all of whom were operated on for a submucosal tumor. We think that mucosal tumors can be cured with surgical resection, whereas submucosal cancers may need a multimodality treatment. During the last 3 years of the study, 10 patients with a clinical diagnosis of early cancer who were not candidates for surgery underwent endoscopic laser therapy: until now, no patients died with neoplastic recurrence.

In a group of 10 patients with cirrhosis, protal hypertension, and previous gastro-intestinal bleedings, hepatic plasma flow, indocyanine green clearance and intrinsic hepatic clearance were determined before and during i.v. infusion of somatostatin (7.5 micrograms/min). The same study protocol was performed in a further seven patients with cirrhosis infused with placebo. All these parameters were significantly decreased by the drug (p less than 0.05; less than 0.01; less than 0.01, respectively) mean decrease being 12, 9 and 8%, respectively, while no significant change occurred in the placebo-infused patients. These data indicate that somatostatin infused at a dose of 7.5 micrograms/min in cirrhotics provokes a slight decrease in hepatic plasma flow and in liver metabolic activity. This effect may contribute to further decrease hepatic removal of harmful substances and may increase systemic concentration of drugs metabolized by the liver.

The beta 2-microglobulin plasma level is often high in patients suffering from cirrhosis. Many authors believe this to be due to an increased production, provided that the creatinine level is in the normal range. In the present study, alterations in the plasma level and production of beta 2-microglobulin were investigated in patients with liver cirrhosis without overt renal failure. 62 patients, 48 men and 14 women, suffering from liver cirrhosis were examined. The glomerular filtration rate (GFR) and plasma beta 2-microglobulin were measured in all patients and in 16 controls. As beta 2-microglobulin is freely filtered by glomeruli and its extrarenal catabolism is negligible, the beta 2-microglobulin filtration rate was calculated as the product of the beta 2-microglobulin plasma level times the GFR. In steady state conditions, the beta 2-microglobulin filtration rate may be used as an indirect index of beta 2-microglobulin production. The beta 2-microglobulin plasma level was high in 26 patients; however, only 12 of them showed a definite rise in beta 2-microglobulin production, as shown by an increased beta 2-microglobulin filtration rate. The 14 patients with high beta 2-microglobulin plasma levels without high beta 2-microglobulin filtration rates obviously showed a decreased GFR; however, creatinine was not increased because of its small sensitivity as an index of renal function. A linear correlation was found between IgG and the beta 2-microglobulin filtration rate (r = 052; p less than 0.02), not between IgG and the beta 2-microglobulin plasma level. The other indices of liver damage were not related to the beta 2-microglobulin filtration rate of plasma level.