Radio-frequency ablation of hepatocellular carcinoma before liver transplantation: a histologic and 'TUNEL' study.

BACKGROUND: Radio-frequency ablation (RFA) is an increasingly used treatment modality for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation (OLTX). The current study evaluates the effectiveness of RFA in this setting based on evaluation of total cell death in explanted native livers. DESIGN: We evaluated 36 tumors from 35 patients with RFA-treated HCC who underwent OLTX at our center between 1998 and 2002. Native livers from OLTX were extensively sampled for histologic evaluation. For each HCC, an estimate ratio of necrotic tumor areas was calculated based on hematoxylin and eosin (H&E) sections. In tumors with 10% or more residual viable areas, Tdt-mediated UTP nick-end labeling (TUNEL) was further performed to assess apoptosis in the morphologically 'viable' areas. A final 'tumor cell death' (TCD) ratio was recalculated for each HCC to include areas of apoptosis identified by TUNEL. RESULTS: Based on H&E evaluation, 22/36 (61.1%) HCC revealed > or = 90% necrosis including 12/36 HCC (33.3%) showing no evidence of residual viable tumor. The overall median tumor necrosis was 79%. When TUNEL findings were added, 26/36 (72.2%) HCC revealed > or = 90% TCD including 14/36 HCC (38.8%) showing complete TCD (median TCD of 88.4%). None of our patients died of HCC while awaiting OLTX. Longer RFA-to-transplant time appears to be associated with a higher TCD rate (median of 154.5 days in patients with less than 90% TCD vs 326 days for patients with > or = 90% TCD; P = 0.019). There was no significant correlation between tumor grade or pre-RFA size of the tumors and TCD rate in RFA-treated HCC (P = 0.11). CONCLUSION: Extensive TCD (88.4% median) can be obtained using RFA for HCC in patients awaiting OLTX. Our TUNEL findings suggest that RFA-induced cell injury could be associated with apoptosis.

Randomized double-blind prospective trial to evaluate the effects of sargramostim versus placebo in a moderate-dose fluorouracil, doxorubicin, and cyclophosphamide adjuvant chemotherapy program for stage II and III breast cancer.

PURPOSE: To determine the effects of sargramostim (recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) on the incidence, duration, and complications of myelosuppression after moderate-dose fluorouracil, doxorubicin, cyclophosphamide (FAC) adjuvant chemotherapy in patients with node-positive breast cancer. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled study, 142 women with stage II and III breast cancer were to receive four 21-day cycles of chemotherapy that consisted of fluorouracil 600 mg/ m2 intravenously (IV), doxorubicin 60 mg/m2 IV, and cyclophosphamide 750 mg/m2 IV on day 1, followed by placebo or GM-CSF 250 micrograms/m2/d daily subcutaneously (SC) on days 3 through 15. All patients received prophylactic ciprofloxacin by mouth when the absolute neutrophil count (ANC) was less than 1,000/microL. RESULTS: Eighty-six percent of GM-CSF patients (n = 62) and 96% of placebo patients (n = 69) completed four assessable cycles of treatment on study. Overall, the median duration of severe neutropenia (ANC < 500/microL) was 2.8 days with GM-CSF and 6.8 days with placebo (P < .001); the duration of ANC less than 1,000/microL was 6.0 versus 9.1 days, respectively (P < .001). Hospitalizations for febrile neutropenia were uncommon in either group: GM-CSF, six; placebo, eight. The only other difference in hematologic toxicity was grade 3/4 thrombocytopenia observed with greater frequency in GM-CSF patients than placebo patients in cycles 3 and 4. GM-CSF increased mean the FAC dose-intensity among patients who completed two or more cycles (P < .001). GM-CSF was generally well tolerated and associated with more injection-site reactions, but less mucositis than placebo. There were no deaths on study. CONCLUSION: GM-CSF significantly enhanced ANC recovery after FAC chemotherapy; it decreased the incidence and duration of associated neutropenia and moderately increased the dose-intensity of adjuvant chemotherapy. Whether these effects will ultimately translate into improved long-term outcome remains to be determined.

Acceptance of isoniazid preventive therapy by health care workers after tuberculin skin test conversion.

OBJECTIVE: To examine health care workers' (HCWs') acceptance of and adherence to isoniazid preventive therapy in the setting of a comprehensive tuberculin skin-testing program. DESIGN: Descriptive case series. SETTING: University-affiliated inner-city public hospital in Atlanta, Ga. PARTICIPANTS: A total of 125 HCWs (91 hospital employees and 34 house staff or medical students [the physician group]) who had a positive tuberculin skin test between July 1992 and January 1994 and were offered isoniazid preventive therapy. INTERVENTIONS: Health care workers with a recent tuberculin skin test conversion were required to have a chest x-ray performed and see a physician and were encouraged but not required to undergo preventive therapy. MAIN OUTCOME MEASURES: Acceptance and initiation of preventive therapy with isoniazid by HCWs, completion of at least 6 months of preventive therapy, and differences between the employee and physician groups. RESULTS: All 125 HCWs with a recent positive tuberculin skin test had a chest radiograph performed, 123 (98.4%) saw a physician, and 105 (84%) initiated preventive therapy. Sixty-nine (66%) of the 105off HCWs who initiated preventive therapy (55% of the 125 total) completed at least 6 months of isoniazid therapy. More of the physician group than of the employee group completed preventive therapy (25 of 34 [74%] vs 44 of 91 [48%], respectively; P<.01). Of the 36 HCWs who started but did not complete preventive therapy, 12 discontinued therapy because of an adverse drug effect and 24 were nonadherent. CONCLUSIONS: Acceptance of tuberculosis preventive therapy by HCWs was high in the setting of a comprehensive tuberculin skin-testing program, and completion of therapy was much higher in the physician group than in previously reported series.

Preventing the nosocomial transmission of tuberculosis.

OBJECTIVE: To study the efficacy of expanded tuberculosis infection control measures consisting primarily of administrative controls. DESIGN: Descriptive case series. SETTING: University-affiliated, inner-city hospital. INTERVENTIONS: Introduction of expanded tuberculosis infection control measures (including an expanded respiratory isolation policy). MEASUREMENTS: The number of tuberculosis exposure episodes and skin test conversion rates of health care workers were measured before and after implementation of expanded infection control measures. Tuberculosis exposure episodes (the number of patients who were not placed in respiratory isolation at admission but who subsequently had a diagnosis of acid-fast bacilli smear-positive pulmonary tuberculosis during that admission or within 2 weeks of discharge) were compared for two time periods: the 8 months before and the 28 months after implementation of infection control measures. Tuberculin skin test conversion rates among health care workers were evaluated during a 2.5-year period. RESULTS: After expanded infection control measures were implemented, the number of tuberculosis exposure episodes decreased from 4.4 per month (35 episodes among 103 patient admissions for potentially infectious tuberculosis over 8 months) to 0.6 per month (18 episodes among 358 patient admissions for smear-positive pulmonary tuberculosis over 28 months) (odds ratio, 9.72; 95% CI, 4.99 to 19.25 [P < 0.001]). The cumulative number of days per month that potentially infectious patients with tuberculosis were not in isolation decreased from 35.4 to 3.3 (P < 0.001). A concomitant decrease in tuberculin skin test conversion rates in health care workers was seen; 6-month tuberculin skin test conversion rates decreased steadily from 3.3% (118 conversions in 3579 health care workers; 1/92 to 6/92), 1.7%, 1.4%, 0.6%, to 0.4% (23 conversions in 5153 workers [1/94 to 6/94]) (P < 0.001). CONCLUSIONS: Infection control measures effectively prevented nosocomial transmission of tuberculosis to health care workers. Administrative controls appear to be the most important component of a tuberculosis infection control program and should be the first focus of such a program, especially at public hospitals, where resources are most likely to be limited.

Bladder leiomyosarcoma: a review of 10 cases with 5-year followup.

Of 10 patients with leiomyosarcoma of the bladder followed for a minimum of 5 years 4 remain free of disease at 5, 6, 6 and 9 years, respectively, following partial cystectomy. An additional patient who was treated sequentially by radiation, radical cystectomy and chemoimmunotherapy survived for 10 years before death of metastatic disease. Wide surgical extirpation (partial or radical cystectomy) remains the curative treatment of choice.

Behavioral effects of phosphatidylserine in the aged Fischer 344 rat: amelioration of passive avoidance deficits without changes in psychomotor task performance.

A series of studies was conducted to evaluate the effects of phosphatidylserine (PS) in aged Fischer 344 rats. No effects were observed in any of four psychomotor tasks in which aged rats normally show deficits, nor on measures of shock sensitivity. However, significant dose-related effects on retention of passive avoidance were observed when PS was given both 30 min prior to training and retention. Further, in a second experiment similar positive effects were observed when PS was given only 30 min prior to training, as well as only 5 min following training. These results suggest that one effect of PS may include an ability to enhance neural events involved in the encoding or consolidation of new information into memory.

Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat.

The nucleus basalis magnocellularis (NBM) is the name given to a group of cholinesterase-reactive neurons in the ventromedial corner of the globus pallidus of the rat. This cell group appears to be the major extrinsic source of cortical acetylcholine and is believed to be homologous to the nucleus basalis of Meynert in primates. The excitotoxin ibotenic acid (2.4 micrograms/0.4 microliter) was infused bilaterally into the ventromedial globus pallidus. These lesions depleted frontal cortical choline acetyltransferase (CAT) by a third. Neurotoxic lesions of the dorsolateral globus pallidus did not affect cortical CAT activity. Neither lesion affected the rats' performance on a battery of psychomotor tasks or on tests of shock sensitivity. Rats with NBM lesions were mildly impaired in the acquisition of a one-way active avoidance response, but did not differ from the other groups on extinction of the task. The NBM lesioned rats exhibited a severe deficit in the retention of a passive avoidance response. This effect was visible both 24 hours and one hour after training. Experimental controls suggested that the poor performance of the NBM lesioned rats involves a deficit in learning and/or memory of the training trial. Lesions of the dorsolateral globus pallidus also produced an impairment of passive avoidance retention, but this impairment was not as severe as that following NBM lesions. These results are discussed as they relate to the behavioral role of cholinergic innervation of the cortex, and the development of animal models for disorders involving cortical cholinergic deficiencies, including senile dementia of the Alzheimer's type.

Nongranulomatous septic vasculitis due to miliary tuberculosis. A pitfall in diagnosis for the pathologist.

A 38-year-old patient with chronic alcoholism was on chemotherapy for acute myelomonocytic leukemia and developed purpuric and erythematous papules. Skin biopsy showed a vasculitis. Subsequent autopsy revealed disseminated tuberculosis with a poor cellular response. This case calls attention to the lack of tuberculoid granulomatous reaction is anergic patients and to the need of pathologists to suspect tuberculosis when necrotizing vasculitis in the skin is encountered in a patient with decreased immunological competence.