Radiation therapy for increasing prostate-specific antigen levels after radical prostatectomy

Herein we present data on outcomes in patients with increasing prostate-specific antigen (PSA) levels treated with irradiation to the pelvis and/or prostatic bed after radical prostatectomy. Between 1988 and 1998, 92 patients who presented with increasing PSA levels after radical prostatectomy were treated with irradiation, 29 to the pelvis and prostatic bed and 63 to the prostatic bed only. The mean follow-up was 4 years for the 3D-CRT group and 6.5 years for the standard radiation therapy group. Criterion for biochemical failure was an increase in post irradiation PSA level on > or = 1 consecutive measurement. Patients were classified into 3 risk groups based on prognostic factors: pathologic tumor extent and stage, Gleason score, and PSA levels before irradiation. Acute and late morbidity was quantitatively evaluated in all patients. There was a close correlation between the preirradiation PSA level and the probability of 4-year biochemical failure-free survival (75% with PSA levels < or = 1 ng/mL, 30% with PSA levels of 1.1-2 ng/mL, and 20% with PSA levels > 2 ng/mL; P = 0.05). The 4-year chemical failure rate was 20% in the low/intermediate-risk group and 65% in the high-risk group (P = 0.36). In 20 patients in the low-PSA group (< or =1 ng/mL) receiving doses > 62 Gy, no biochemical failures have been detected in comparison to a 70% failure rate at 4 years in patients treated with lower doses (P = 0.15). In the higher-PSA groups, no impact of irradiation dose on outcome was noted (40%-60% incidence of failure at 3 years). Pelvic irradiation was associated with a trend toward decreased biochemical failure rate in the low-PSA group (70% vs. 0% at 4 years; P = 0.35), but not in the high-PSA group. Only 1 patient (1.5%) experienced clinical local recurrence in the prostatic bed and 2 patients (1.8%) had distant metastases. Treatment has been very well tolerated, with only 3 patients in the arc-rotation group experiencing grade 2 treatment toxicity. Prostate bed irradiation is an effective treatment in a significant proportion of patients who present with a biochemical failure after radical prostatectomy.     

Improvements in benign prostatic hyperplasia-specific quality of life with dutasteride,the novel dual 5alpha-reductase inhibitor

OBJECTIVES: To examine the effect of the dual-action 5alpha-reductase inhibitor dutasteride on benign prostatic hyperplasia (BPH)-specific health status, as measured by the BPH Impact Index (BII), and to identify baseline and treatment risk factors for those most bothered by their BPH symptoms at the end of the protocol. PATIENTS AND METHODS: Data were derived from three randomized, double-blind, placebo-controlled, 2-year studies conducted in 4325 men with lower urinary tract symptoms caused by benign prostatic enlargement. Each study comprised a 1-month single-blind placebo run-in period, followed by randomization to oral dutasteride 0.5 mg once daily or placebo for 2 years. Patients eligible for inclusion were consenting men aged >/= 50 years with moderate to severe symptoms (American Urological Symptom Index, AUA-SI, score >/= 12), a prostate volume of >/= 30 mL, a serum prostate-specific antigen (PSA) level of >/= 1.5 or < 10 ng/mL, and a maximum urinary flow rate (Qmax) of /= 5 (greatest symptomatic burden) treatment with dutasteride improved the scores by 2.41, while the scores in placebo-treated patients only improved by 1.64. Dutasteride-treated patients with a baseline BII score of < 5 (least symptom burden) had a clinically significant improvement in health status, while placebo-treated patients deteriorated. Regression analysis showed that men with a combination of a baseline BII item-3 score of 3 (bothered a lot) and a high symptom score (AUA-SI >/= 20) were more likely to be bothered by their symptoms at the end of the study. Men receiving placebo were also more likely to be bothered at the end of the study than were those receiving dutasteride. CONCLUSIONS: Dutasteride treatment is associated with clinically significant improvements in BII score, reflecting improvements in the quality of life of men with BPH. Taken together with previously reported improvements in prostate volume, lower urinary tract symptoms and urinary flow, and diminution of the risk of acute urinary retention and the need for BPH-related surgery, dutasteride offers demonstrable efficacy in the management of BPH.     

The effect of 4MA, a potent inhibitor of 5 alpha-reductase, on the growth of androgen-responsive human genitourinary tumors grown in athymic nude mice

The five alpha-reductase inhibitors are a newly developed family of compounds that block the intracellular conversion of testosterone (T) to dihydrotestosterone (DHT). 17-beta-N, N-Diethylcarbamoyl-4-methyl-4-aza-5-alpha-androstan-3-one (4MA), the most widely studied of these compounds, has been shown to inhibit the androgen-dependent growth of both normal animal tissues and of the Noble tumor, an experimental, hormone-responsive rat neoplasm. 4MA has been found to inhibit androgen-dependent growth without altering plasma levels of T or DHT. In the present study, we assessed the efficacy of 4MA in inhibiting the growth of PC-82 and R198, human androgen-responsive genitourinary malignancies. In the first experiment, 4MA was administered subcutaneously at a dose of 6 mg/kg/day to castrated and hormonally replaced groups of PC-82-bearing male athymic nude mice. 4MA therapy when compared to control therapy caused significant PC-82 growth inhibition in three different groups of hormonally replaced castrated mice: physiologic T-replaced (P less than .001), supraphysiologic T replaced (P less than .001), and supraphysiologic T and DHT replaced (P less than .001). There was no difference between the post therapy plasma levels of T or DHT in the control-treated and 4MA-treated mice. In the second experiment, the effect of 4MA (6 mg/kg/day S.Q.) was compared to that of castration and control therapy on the growth of R198. Both castration and 4MA therapy effectively inhibited R198 growth when compared to control therapy (P = .01 and .02, respectively), but there was no difference in the degree of growth inhibition seen with 4MA or castration (P = .45). Castration and 4MA-therapy significantly lowered plasma T levels when compared to control therapy; castration also significantly lowered plasma DHT levels, while 4MA and control therapy did not. These studies suggest that 4MA is effective in inhibiting the growth of human androgen-responsive tumors grown in athymic nude mice and that further studies with other 5 alpha-reductase inhibitors are indicated.     

The epidemiology of pseudallescheriasis complicating transplantation: nosocomial and community-acquired infection

The epidemiology of two cases of pseudallescheriasis in organ transplant patients are described and the disease in that population is reviewed. Disseminated hospital-acquired infection occurred in a liver transplant recipient and was fatal despite therapy with miconazole. A heart transplant recipient developed localized disease following soil contamination of soft tissue trauma which was cured with surgical resection and miconazole therapy. Itraconazole showed in vitro activity against Pseudallescheria boydii and should be evaluated in pseudallescheriasis. P. boydii infections are important complications of transplantation and should be considered in the differential diagnosis of community-acquired as well as nosocomial fungal infections in this population.     

Water, acidosis, and experimental pyelonephritis

The effect of water restriction and ammonium chloride acidosis on the course of Escherichia coli pyelonephritis was determined in the nonobstructed kidney of the rat. To alter the chemical composition of the renal medulla, water intake was reduced in rats to one-half the normal daily intake. Water restriction increased the incidence of coliform pyelonephritis. Systemic acidosis, produced by giving a 300 mM solution of ammonium chloride, increased urinary osmolality to values comparable to water restriction and also predisposed to pyelonephritis. However, when rats were fed the same solution of ammonium chloride but were allowed access to tap water ad lib., urinary osmolality values were comparable to those observed in normal animals, and susceptibility to pyelonephritis was reduced or eliminated despite a degree of systemic acidosis similar to that observed in rats fed ammonium chloride solution without access to tap water. These results suggest that water diuresis may overcome the inactivation of complement produced by ammonium chloride acidosis and that renal medullary hypertonicity, produced by either water restriction or ammonium chloride acidosis, is a major determinant of this tissue's unique susceptibility to infection.     

Efficacy of UK-109496, a new azole antifungal agent, in an experimental model of invasive aspergillosis.

The efficacy of UK-109496, a new azole antifungal agent, was evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Oral therapy with UK-109496 at a dosage of 10 or 15 mg/kg of body weight every 8 h was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls. UK-109496 eliminated mortality and also reduced the tissue burden of Aspergillus fumigatus 10- to 100-fold in liver and kidney tissues and to a lesser degree in lung tissue, and at the higher dose, no viable organisms were recovered from brain tissue from these animals. Both dosages of UK-109496 decreased or eliminated circulating antigen. The half-life of UK-109496 in rabbits was 2.5 to 3 h, and no accumulation of drug was seen even after 15 doses in either uninfected or infected animals. Thus, UK-109496 shows activity in this rabbit model of invasive aspergillosis. Additional studies are needed to determine the potential of the drug for use in the treatment of this infection.     

Change in neoadjuvant chemotherapy could alter the prognosis of patients with pancreatic adenocarcinoma: A case report

BACKGROUNDNeoadjuvant treatment has become a standard of care for borderline or locally advanced pancreatic cancer and is increasingly considered even for up-front resectable disease. The aim of this article is to present the case of a 62-year-old patient with locally advanced pancreatic adenocarcinoma who was successfully treated with gemcitabine plus nab-paclitaxel after the failure of the first line treatment.CASE SUMMARYComputerized tomography scan and magnetic resonance imaging demonstrated a nodular lesion of ill-defined limits in the body of the pancreas, measuring approximately 4.2 cm × 2.7 cm, with an infiltrative aspect. The tumor had contact with the superior mesenteric vein, splenomesenteric junction and the proximal segment of the splenic artery, causing focal reduction of its lumens. Due to vascular involvement, neoadjuvant chemotherapy treatment with eight cycles of “folinic acid, 5-fluorouracil, irinotecan and oxaliplatine” (FOLFIRINOX) were performed. At the end of the cycles, surgery was performed, but the procedure was interrupted due to finding of lesions suspected of metastasis. Gemcitabine plus nab-paclitaxel was then successfully used for neoadjuvant treatment with subsequent R0 surgical resection.CONCLUSIONGemcitabine plus nab-paclitaxel may be effective as an alternative regimen when FOLFIRINOX fails as the first line of treatment, suggesting the need for further studies to identify which patients would benefit from each type of therapeutic approach.     

Synergism of Oxacillin and Gentamicin Against Enterococci

Strains of enterococci isolated from 34 patients were studied for susceptibility to oxacillin and gentamicin alone and in combination. The minimal bactericidal concentrations of oxacillin and gentamicin for these strains ranged from 16 to 250 mug/ml (median 32 mug/ml) for oxacillin and 12 to 48 mug/ml (median 24 mug/ml) for gentamicin. The minimal bactericidal concentration of oxacillin for 50% of strains in the presence of 12, 6, 3, and 1.5 mug of gentamicin per ml, respectively, was 2, 8, 16, and 32 mug/ml. The combination of oxacillin and gentamicin at clinically attainable serum levels was synergistically bactericidal against 27/34 (80%) of these strains using strict criteria. This report reconfirms the original observation that antibiotics which affect the synthesis of bacterial cell walls combine synergistically with aminoglycosides against enterococci. This is so even though enterococci are far more resistant to oxacillin than to penicillin or ampicillin. In addition, this report suggests that the combination of oxacillin and gentamicin administered in the usual dosages includes enterococci in its bactericidal spectrum.