Bile duct cancer 25 years after choledochoduodenostomy: a case report

We describe a 65-year-old man who had undergone choledochoduodenostomy (CDS) for choledocholithiasis 25 years prior to admission to our hospital for cholangitis. Abdominal sonography and computerized tomography (CT) scan revealed a tumor mass at the hilar region with bilateral intrahepatic duct dilatation. Upper gastrointestinal endoscopic examination indicated the site of the CDS. Biopsy was taken from the mucosa of the bile duct, and pathology revealed well-differentiated adenocarcinoma. CT scan and angiography further confirmed unresectable hilar bile duct cancer. Conservative treatment with intra-arterial chemotherapy was arranged. After briefly reviewing the hypothesized pathogenesis and radiographic diagnosis of this rare case, we recommend that chronic cholangitis consequent to CDS should be closely followed for late development of biliary tract malignancy.     

Chronic hepatitis with nonspecific histological changes. Is it a distinct variant of chronic hepatitis?

A longitudinal follow-up study has been undertaken in 62 patients with clinicopathologically verified chronic hepatitis with non-specific reactive histological changes (NSRH) in comparison with 28 patients with chronic persistent hepatitis (CPH), the clinical features of which are quite similar to NSRH. In contrast to the stationary and non-progressive course of CPH, 45.2% of patients with NSRH, either HBsAg positive or negative, ran a fluctuating course with moderate to marked elevation of SGPT (greater than 200 IU/l) In HBsAg-positive patients, only those positive for HBeAg and a few negative for both HBeAg and anti-HBe had fluctuating courses. In addition, patients with apparent clinical and biochemical changes could show histological features of chronic lobular hepatitis (CLH). A few developed chronic active hepatitis and/or cirrhosis on follow-up biopsy. It is concluded that NSRH is a form of chronic hepatitis different from CPH, but similar to or representing a phase of CLH. It is suggested that NSRH should be categorized as CLH in the classification of chronic hepatitis.     

The effect of recombinant human granulocyte macrophage colony- stimulating factor on neutrophil activation in patients with refractory carcinoma

Patients with refractory carcinoma were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by intravenous (IV) infusion. During the period of treatment, studies of polymorphonuclear leukocyte superoxide (O2-) release in response to formylmethionylleucylphenylalanine (fMLP) and phorbol myristate acetate (PMA) and studies of chemotaxis in response to fMLP and C5a were performed. We observed that patients receiving rhGM-CSF in vivo exhibited primed O2- release after stimulation both with fMLP and PMA. Chemotaxis, however, was not enhanced by the treatment. These data suggest that host defenses may be enhanced by this treatment and that rhGM-CSF may be a useful therapeutic adjunct in compromised patients.     

Clonal assay of mouse mast cell colonies in methylcellulose culture

When mouse marrow and spleen cells were cultured for over 12 days in methylcellulose containing media conditioned by pokeweed-mitogen- stimulated spleen cells, colonies containing mast cells and blast cells were observed. The characteristic morphology of the colonies and the time course of their development allowed in situ identification of the mast cell colonies. Identification of the mast cells was confirmed by metachromatic staining with toluidine blue and alcian blue, transmission electron microscopy, and by demonstration of the membrane receptors for IgE. Coculture studies with male and female marrow cells strongly indicated the single cell origin of individual colonies. Detailed cytologic analyses of mixed hemopoietic colonies and replating experiments of individual mixed hemopoietic and mast cell colonies clearly established the hemopoietic origin of mast cells. In replating experiments of individual mast cell colonies, those without blast cells did not yield secondary mast cell colonies. This result strongly indicated that morphologically recognizable mast cells have lost their self-renewing capabilities. The quantitative nature of the mast cell colony assay was supported by linearity studies and provides a method for studies of the progenitors of mouse mast cells.     

Increased levels of oxidized glutathione in CD4+ lymphocytes associated with disturbed intracellular redox balance in human immunodeficiency virus type 1 infection

We investigated the intracellular glutathione redox status in isolated lymphocyte subpopulations and monocytes in patients with human immunodeficiency virus type 1 (HIV-1) infection and in healthy controls. CD4+ lymphocytes from HIV-1-infected patients were primarily characterized by a substantial increase in oxidized glutathione levels and a considerable decrease in the ratio of reduced to total glutathione, in most cases below 0.5 in patients with symptomatic HIV-1 infection, rather than decreased levels of reduced glutathione. The increase in oxidized glutathione was strongly correlated with low numbers of CD4+ lymphocytes in peripheral blood and impaired stimulated interleukin-2 production and proliferation in peripheral blood mononuclear cells, which is compatible with an immunopathogenic role for these redox disturbances. The HIV-1-infected patients with the most advanced clinical and immunologic disease were also characterized by an increase in levels of reduced glutathione in monocytes, suggesting that the glutathione redox cycle may be differentially regulated in CD4+ lymphocytes and monocytes. We could not confirm previous reports suggesting cysteine deficiency as a major cause of disturbed glutathione homeostasis during HIV-1 infection. The demonstrated glutathione abnormalities were correlated with raised serum levels of tumor necrosis factor alpha. These findings suggest that a therapeutical approach, which can restore the glutathione redox dysbalance in CD4+ lymphocytes and decrease the inflammatory stress, may be worthwhile exploring in HIV-1 infection.     

Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection

BACKGROUND & AIMS: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance is a rare event in patients with chronic hepatitis B virus infection. The aim of this study was to clarify the controversy on long-term prognosis following spontaneous HBsAg seroclearance using a large series of patients. METHODS: A total of 218 patients (172 men and 46 women) who had undergone spontaneous HBsAg seroclearance were followed up for 12-179 months (median, 61.7 months; mean, 63.4 +/- 38.5 months) with liver biochemistry, serology, measurement of alpha-fetoprotein level, and abdominal ultrasonography every 6 months or every 3 months for the 29 patients who had developed cirrhosis at the time of HBsAg seroclearance. RESULTS: Of the 189 patients who were noncirrhotic at the time of HBsAg clearance, 3 (1.6%) developed cirrhosis, 2 (1.1%) developed hepatocellular carcinoma (HCC), and 1 died of HCC. These complications all developed in patients with concurrent hepatitis C virus or hepatitis delta virus infection (P < 0.001). The prognosis of the noncirrhotic patients without concurrent infection was significantly better than that of the matched control group (elevation of alanine aminotransferase level, 11.6% vs. 0%, P < 0.001; development of cirrhosis/HCC, 4% vs. 0%, P = 0.004). In contrast, of the 29 patients who had developed liver cirrhosis, 4 (13.8%) had hepatic decompensation and one died of HCC. CONCLUSIONS: The prognosis following spontaneous HBsAg seroclearance is excellent, except in patients with cirrhosis or those with concurrent hepatitis C virus or hepatitis delta virus infection.     

Biochemical correlates of the differential sensitivity of subtypes of human leukemia to deoxyadenosine and deoxycoformycin

Leukemic cells incubated in vitro with 2'-deoxyadenosine (dAdo) plus an inhibitor of adenosine deaminase, 2'-deoxy-coformycin (DCF), show different metabolic responses depending on the histologic and immunologic type of the leukemia. Leukemic cells were obtained from 54 patients with acute lymphoblastic leukemia (ALL), 9 with myeloid or nonlymphoblastic leukemia, 3 with chronic lymphocytic leukemia (CLL), and 3 with lymphoma. There was a wide variation in the LD50, the concentration of dAdo that caused 50% inhibition of the incorporation of 3H-thymidine into cells in the presence of 20 microM DCF. T-cell leukemia specimens were much more sensitive to dAdo than were specimens of pre-B-ALL and null-ALL. In leukemic cells that had been incubated with 14C-dAdo plus DCF, a good correlation was observed between the LD50 and the ratio of 14C-deoxyATP to ATP (correlation coefficient for the fit to a hyperbola = 0.853). The accumulation of deoxyATP by the leukemic cell specimens was correlated best with the activity of ecto- ATPase, less well with cytoplasmic 5'-nucleotidase and deoxyadenosine kinase, and poorly with adenosine deaminase and ecto-5'-nucleotidase. The clinical response to DCF therapy of a patient with T-ALL and another with pre-B-ALL was consistent with the in vitro metabolic response of their cells to DCF and dAdo.