The V89L polymorphism in the 5alpha-reductase type 2 gene and risk of prostate cancer.

5alpha-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5alpha-reductase activity are at increased risk for prostate cancer (CaP). A single nucleotide polymorphism of the 5alpha-reductase type 2 gene (SRD5A2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect of this polymorphism on the risk of prostate cancer in a prospective, nested, case-control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there was no significant association between AAG levels and V89L genotype. We also detected no significant association between risk for CaP and genotype [odds ratio: val/val = 1.0 (reference), leu/val = 0.96 (95% confidence interval, 0.76-1.20), and leu/ leu = 0.84 (95% confidence interval, 0.57-1.24)]. These data do not support a moderate to large effect of the SRD5A2 V89L polymorphism on plasma AAG levels or CaP risk in this predominantly Caucasian cohort, although a small effect cannot be completely excluded.

Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men.

In men over 30 years old, serum levels of testosterone (T) decrease with age. A shorter polymorphic CAG repeat length in exon 1 of the androgen receptor (AR) gene is associated with higher transcription activation by the AR. We determined the number of CAG repeats for 882 men aged between 40 and 70 years from the Massachusetts Male Aging Study (MMAS). MMAS is a population-based random sample survey of men for whom baseline (1987-1989, mean age 53+/-8 years) and follow-up (1995-1997, mean age 61+/-8 years) serum hormone levels were available. Multiple linear regression was used to determine if CAG repeat length would be predictive of hormone levels at follow-up. Hormone levels measured included T, free T, albumin-bound T, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG) and luteinizing hormone (LH). The CAG repeat length was significantly associated with T (P=0.041), albumin-bound T (P=0.025) and free T (P=0.003) when controlled for age, baseline hormone levels and anthropometrics. Follow-up levels of T decreased by 0.74%+/-0.36 per CAG repeat decrement. Likewise, the percentages of free and albumin-bound T decreased by 0.93%+/-0.31 and 0.71%+/-0.32 per CAG repeat decrement respectively. These results suggest that androgen levels may be modulated by AR genotype.

Ureteroarterial fistula: case report and review of the literature.

Ureteroarterial fistulae are rare. We report 2 cases of this clinical problem. Ureteroarterial fistulae can occur in association with prolonged ureteral stenting, radiation therapy, vascular pathology, and prior pelvic or vascular surgery. Identification of a fistula is often difficult and requires the physician to be highly alert and vigilant. Diagnostic and therapeutic options for a ureteroarterial fistula are discussed.

Survival characteristics of metastatic renal cell carcinoma patients treated with lymphokine-activated killer cells plus interleukin-2.

The immunologic manipulation of patients with metastatic renal cell carcinoma using lymphokine-activated killer (LAK) cells in conjunction with systemic interleukin-2 (IL-2) has been examined under conditions in which the life-threatening toxicities associated with IL-2 treatment have been virtually eliminated. We have examined tumor regression in vivo as well as the survival characteristics of 12 patients with metastatic renal cell carcinoma following immunotherapy. Five of 12 (42%) patients experienced tumor regression exceeding 50 percent following treatment. To determine if immunotherapy had influenced the length of survival, all patients were followed until the time of death. Previous studies have characterized the length of survival of metastatic renal cell cancer patients according to a combination of risk factors unique for each patient. In this model, patients were categorized into risk groups based on the number of risk factors. Survival was found to be dependent on risk factors such as performance status, time from initial diagnosis, number of metastatic sites, recent weight loss, and prior cytotoxic chemotherapy. On completion of the LAK cell immunotherapy protocol, patients were categorized as nonresponders or responders. In addition, they were assigned to risk groups based on their unique profile of risk factors at the time of entry into the protocol. Using this model, we found the median survival of nonresponders (23 months) to be no different from responders (24 months), p > 0.05. This was directly attributable to differences in risk factors which characterized members in these two response groups. However, the observed median survival of nonresponders following therapy was 1.9-fold longer than their projected survival based on the risk factors. Furthermore, the observed median survival of responders was 3.4-fold longer than projected from their risk factors. These results suggest that regardless of response status to therapy, cellular immunotherapy may play a role in mediating a significant palliative effect on the metabolic characteristics of these patients leading to extended survival.

Ureterorenoscopic approach to the symptomatic caliceal diverticulum.

PURPOSE: We evaluated ureterorenoscopy as a treatment approach to symptomatic caliceal diverticula. MATERIALS AND METHODS: Since 1989, 20 women and 6 men suffering from pain, recurrent urinary tract infections or urosepsis were treated using flexible ureterorenoscopy, balloon dilation or incision of the diverticular neck and subsequent intrarenal stone fragmentation when needed. RESULTS: Of 19 upper and middle caliceal diverticula 16 (84%) and 2 of 7 lower caliceal diverticula were successfully identified. The orifice to the diverticular cavity was dilated and the stone was fragmented. Of the patients 13 were treated as outpatients and 10 required a 1-night hospital stay. Of those patients in whom the diverticulum could be entered and the stone fragmented 100% were symptom-free at a mean followup of 39 months. One patient required repeat treatment to remove residual stone. CONCLUSIONS: Ureterorenoscopy produces minimal morbidity and is an effective treatment of upper and middle caliceal diverticula.

Cancer in relatives of survivors of childhood sarcoma.

Relatives of 88 long-term survivors of childhood sarcoma were examined for the familial cancer syndrome of sarcoma, breast cancer, and other neoplasms (Li-Fraumeni syndrome). Twenty-six of 402 close relatives developed cancer (expected, 23.8), including breast cancer in four mothers (expected, 3.1). Two sarcoma probands who developed second malignant tumors have multiple relatives with cancer and might have an inherited predisposition. An increased cancer risk and exceptional requirement for disease screening appear to be confined to first-degree relatives of a small fraction of children with sarcoma, notably probands with second cancers.

Evaluation of the contralateral breast. The role of biopsy at the time of treatment of primary breast cancer.

Ninety-five women who underwent blind contralateral breast biopsy during surgical treatment of a known breast cancer primary were studied prospectively. All biopsies were performed between 1981 and 1989. Patients with palpable or mammographic abnormalities prompting the contralateral biopsy were excluded so that the study sample included only truly blind contralateral biopsies. Only two infiltrating carcinomas were found, resulting in a positive biopsy rate of 2.1% for invasive disease. Three additional biopsies showed only lobular carcinoma in situ, a finding that usually does not alter clinical management. One patient with a negative contralateral biopsy developed invasive carcinoma in that breast within 2 years of the biopsy. The authors were unable to identify any subgroup of patients at increased risk of a positive contralateral biopsy. These results suggest that blind biopsy of the contralateral breast performed at the time of the initial treatment of breast carcinoma is not an efficient method of cancer detection. Alternative management strategies are discussed.