Hepatocellular carcinoma presenting as pyogenic liver abscess: characteristics, diagnosis, and management

We performed a 17-year retrospective analysis of 10 cases of hepatocellular carcinoma presenting as pyogenic liver abscess. Spontaneous tumor necrosis and biliary obstruction caused by tumor thrombi, superimposed with bacterial infection, were the two major pathogeneses. Exact diagnosis of the underlying hepatocellular carcinoma was made for five of the 10 patients before management was attempted. Main clinical manifestations included fever, chills, right-upper-quadrant pain, malaise, anorexia, jaundice, and hepatomegaly. Characteristics such as middle age and male sex, seropositivity for hepatitis B and/or hepatitis C, chronic liver disease, unexplained anemia, marked weight loss, and a severely inversed albumin/globulin ratio raise suspicions about the underlying hepatocellular carcinoma. Management strategies included percutaneous drainage (n = 3), surgical drainage (n = 4), and hepatectomy (n = 3) in addition to administration of parenteral antibiotics in all cases. The prognosis was dismal, with a mean survival of 3.5 months (range, 8 days to 6 months).     

Evidence for involvement of ventral tegmental area cyclic AMP systems in behavioral sensitization to psychostimulants

The present study investigated the role of ventral tegmental area (VTA) cyclic AMP (cAMP) systems in the behavioral sensitivity to psychostimulants in male Sprague-Dawley rats. Bilateral microinjections of cholera toxin (CTX) into the VTA (50-500 ng/500 nl/side) dose-dependently sensitized animals to the locomotor stimulant effects of systemic d-amphetamine, cocaine and apomorphine, but were without effects on morphine-induced locomotion 24 hr after microinjection. The CTX-induced behavioral sensitization to amphetamine was even greater 72 hr after microinjection, but was no longer present 14 days after intra-VTA CTX pretreatment. Coadministration of the cAMP-dependent protein kinase inhibitor H8 into the VTA blocked CTX-induced sensitization to amphetamine, suggesting that the sensitization is dependent on phosphorylation events in the VTA mediated by cAMP-dependent protein kinase. Pretreatment with CTX did not enhance amphetamine-induced dopamine release in the nucleus accumbens relative to saline controls 24 hr after microinjection. A single bilateral injection of d-amphetamine into the VTA (5 micrograms/side) produced a significant sensitization to systemic amphetamine challenge 72 hr later, and this effect was also blocked by coadministration of H8 into the VTA. These results extend previous studies which have established the importance of the VTA in the development of behavioral sensitization and suggest that cAMP systems may play a crucial role in this neuroadaptive process.     

Regulation of classic and alternative bile acid synthesis in hypercholesterolemic rabbits: effects of cholesterol feeding and bile acid depletion

The effect of cholesterol feeding (3 g/day) on bile acid synthesis was examined in 10 New Zealand white rabbits (NZW), 8 Watanabe heterozygous and 10 homozygous rabbits with partial and complete deficiencies of LDL receptors. After 10 days of cholesterol feeding, bile fistulas were constructed and bile acid pool sizes were measured. Cholesterol feeding increased plasma and hepatic cholesterol levels in all rabbit groups. Baseline bile acid pool sizes were smaller (P < 0.01) in heterozygotes (139 +/- 3 mg) and homozygotes (124 +/- 30 mg) than NZW rabbits (254 +/- 44 mg). After feeding cholesterol, bile acid pool sizes doubled with increased cholic acid synthesis in NZW and, to a lesser extent, in Watanabe heterozygous rabbits but not in homozygotes. Baseline cholesterol 7alpha-hydroxylase activity in NZW and heterozygotes declined 69% and 53% (P < 0.001), respectively, after cholesterol feeding. Sterol 27-hydroxylase activity reflecting alternative bile acid synthesis increased 66% (P < 0.01) in NZW and 37% in Watanabe heterozygotes but not in homozygotes after feeding cholesterol. Bile fistula drainage stimulated cholesterol 7alpha-hydroxylase activity but not sterol 27-hydroxylase activity in all three rabbit groups. These results demonstrated that dietary cholesterol increased hepatic sterol 27-hydroxylase activity and alternative bile acid synthesis to expand the bile acid pool and inhibited cholesterol 7alpha-hydroxylase in NZW and in Watanabe heterozygous rabbits but not in homozygotes with absent hepatic LDL receptor function. Thus, in rabbits, sterol 27-hydroxylase is up-regulated by the increased hepatic cholesterol that enters the liver via LDL receptors whereas cholesterol 7alpha-hydroxylase is controlled by the circulating hepatic bile acid flux.     

Renal resistive index in experimental partial and complete ureteral obstruction

RATIONALE AND OBJECTIVES: Recent clinical work suggests that the Doppler resistive index (RI) may be useful in distinguishing obstructive from nonobstructive hydronephrosis. We evaluated the usefulness of the RI in a rabbit model of hydronephrosis. METHODS: Unilateral partial ureteral obstruction was produced in nine rabbits and complete obstruction in another nine. Three sham operations were performed, and these animals served as control subjects. The RI was measured in all kidneys before and 6 hr after surgery and on days 1, 4, and 7 postoperatively. The RI and the difference in RI (delta RI) between the obstructed and normal kidney were evaluated over time using a two-way analysis of variance. The intravenous urography and Whitaker tests served as gold standards. RESULTS: Hydronephrosis was observed on sonograms in all obstructed kidneys. Comparing groups, there was no significant difference in mean RI or delta RI between the three groups at any time point. Looking at individual groups over time, there was no significant change in mean delta RI, whereas the change in mean RI was significantly elevated above baseline only in the complete obstruction group at 6 hr (p = .002) and on days 4 (p = .008) and 7 (p = .006). In evaluating varying thresholds of RI and delta RI, we could not consistently discriminate between normal and obstructed kidneys. CONCLUSION: Although complete obstruction caused a significant increase in RI, partial obstruction failed to do so. RI and delta RI values proved to be insensitive predictors of obstruction in this rabbit model.     

Increased living donor volunteer rates with a formal recipient family education program

As part of our ongoing studies to characterize molecular alterations in a well-defined series of surgically resected esophageal cancers, we examined the expression of 2 ras-regulated genes, whose products (osteopontin and cathepsin L) previously were shown to be associated with tumor invasion and metastasis. RNA was extracted from primary esophageal tumors (adenocarcinomas, 19; squamous-cell carcinomas, 6) and matched histologically normal esophageal mucosa from the distant resection margin. Northern analysis was used to quantitate RNA, relative to an 18S rRNA control, and immunohistochemistry to assess the tissue distribution of osteopontin. In addition, H-, K- and N-ras mutations were studied in the same tissues using PCR and hybridization with allele (mutant)-specific oligonucleotide probes. We demonstrated a K-ras mutation (codon 12, GTT) in one esophageal adenocarcinoma. The ras-regulated gene osteopontin was over-expressed in 100% of squamous-cell carcinomas and in 58% of adenocarcinomas relative to matched normal esophageal mucosa. Patterns of immunoreactivity for osteopontin protein also varied between squamous-cell carcinomas (tumor cell staining) and adenocarcinomas (predominantly tumor-infiltrating macrophages). Expression of cathepsin L also varied with esophageal tumor histology, with over-expression in 58% of primary esophageal adenocarcinomas and 33% of squamous-cell cancers.     

Phase I and pharmacological study of CI-980, a novel synthetic antimicrotubule agent

CI-980 (NSC 613862) is one of a novel class of 1,2-dihydropyrido[3, 4-b]pyrazines that inhibits tubulin polymerization, presumably by binding to the colchicine binding site of tubulin. In a Phase I and pharmacological study, 16 patients with advanced solid neoplasms were treated with CI-980 on a continuous 72-h infusion schedule at doses ranging from 3.0-5.4 mg/m2/day every 3 weeks. High rates of central nervous system (CNS) toxicity and neutropenia occurred in both minimally and heavily pretreated patients who were treated with CI-980 doses above 3.75 mg/m2/day, which is the maximum tolerated dose and the recommended dose for additional evaluations. CNS effects, characterized by neurocortical, mood, and cerebellar manifestations, were generally observed toward the end of the infusion and immediately posttreatment and usually resolved within 48 h after the completion of treatment. Toxicity was mild to modest at the 3.75 mg/m2/day dose level. Neither clinical nor pharmacological risk factors that may predispose patients to the development of CNS effects were evident. Although no objective antineoplastic activity was observed in this Phase I study, CI-980 steady-state plasma concentrations achieved at the recommended dose of 3.75 mg/m2/day (mean +/- SE, 5.74 +/- 0.54 nM) approached and exceeded concentrations that have been associated with significant activity in preclinical studies, indicating that additional disease-directed evaluations of CI-980 may be warranted.     

Decreased transforming growth factor beta type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression

Two cases of cavitary lung cancer with pulmonary aspergillosis were experienced. Case 1 was a 45-year-old male. Chest X-ray and Chest CT revealed a round shadow in the thin-wall cavity of the upper lobe of the right lung. Upper lobectomy of the right lung was performed. Histologically large cell carcinoma was found to invade the entire cavity wall, and aspergillus was not detected in the intracavitary space. Case 2 was a 75-year-old male. Chest X-ray and Chest CT revealed a round shadow in the thin-wall cavity of the upper lobe S1 + 2 of the left lung. As a result of upper lobectomy of the left lung and S6 partial resection, large cell carcinoma was found to invade the entire cavity wall, and aspergillus was not detected in the intracavitary space. Only 19 cases including ours are reported about cases of lung cancer complicated by pulmonary aspergillosis at the same site in Japan. The mechanism of aspergillus infection had not been clarified in the discussions of the reported literature and nothing characteristic could be pointed out in our cases except for the assumption that the presence of cancer was a factor triggering Aspergillus implantation.