Extramammary Paget's disease of the scrotum associated with hepatocellular carcinoma.

Extramammary Paget's disease (EMPD) is a rare cutaneous carcinoma of epidermal origin. The diagnosis is frequently delayed, and the disease tends to be associated with an underlying adnexal or internal malignancy. There have been several reports of EMPD associated with carcinoma of the bladder, prostate, kidney, and colon. The association of hepatocellular carcinoma (HCC) with EMPD appears to be exceedingly rare; to our knowledge, it has been reported only once in the English literature. Herein, we report an unusual case of EMPD of the scrotum associated with HCC. EMPD was diagnosed 1 year after the appearance of an erythematous plaque, and HCC was noted 19 months after the diagnosis of EMPD. From our experience and literature review, in patients with nonspecific skin lesions that are unresponsive to conventional treatment, EMPD should be considered and skin biopsy performed. Long-term follow-up is needed to watch for the appearance of adnexal carcinoma or internal malignancy.

Dysregulated apoptosis through the intrinsic pathway in the internal spermatic vein of patients with varicocele.

BACKGROUND/PURPOSE: Apoptosis plays a critical role in various physiological processes. Varicocele is the most common cause of male infertility in adults. The dilated and thickened wall of the internal spermatic vein (ISV) in varicocele is considered similar to that in varicose veins. We investigated apoptotic protein expression in the ISV of varicocele, including Bcl-2, Fas, caspase-8 and caspase-9, to determine the intrinsic or extrinsic pathway. METHODS: The study group consisted of 10 patients with grade 3 left varicocele. The control group consisted of 10 patients with left indirect inguinal hernia. A 1-cm section of ISV was resected, using left inguinal incision, from each patient in both groups. The ISV sections were used to detect the mediators that regulate the intrinsic (Bcl-2 and caspase-9) and extrinsic (Fas and caspase-8) apoptotic pathways, by immunoblotting and immunohistochemical staining. Results were analyzed using Student's t tests. RESULTS: Bcl-2, Fas, caspase-8 and caspase-9 immunoblots from both groups revealed a single band. The relative intensities of the Bcl-2 and caspase-9 protein bands differed significantly between the varicocele and control groups. Thickening of the smooth muscle layer of the ISV was found in patients with varicocele compared with the control group. Bcl-2 overexpression and downregulation of caspase-9 expression were noted in the varicocele group. There was no significant difference in Fas or caspase-8 expression in either group. CONCLUSION: We showed overexpression of Bcl-2 and downregulation of caspase-9 expression in the ISV under hypoxic stress. This indicated dysregulated apoptosis through the intrinsic pathway in the ISV of patients with varicocele. To the best of our knowledge, this is the first study of the apoptotic pathway in the human ISV. Additional studies are needed to establish whether adjunctive hyperbaric oxygen therapy reduces the recurrence rate after varicocelectomy.

Cadmium concentration and metallothionein expression in prostate cancer and benign prostatic hyperplasia of humans.

BACKGROUND/PURPOSE: Cadmium (Cd) causes various genitourinary disorders and is a carcinogen for prostate cancer. Metallothionein (MT) is a protein that detoxifies heavy metals. We evaluated changes in Cd concentration and MT expression in human prostate cancer (CaP) and benign prostatic hyperplasia (BPH). Our goal was to clarify the relationship between Cd concentration and MT expression in prostatic diseases. METHODS: The experimental group consisted of 18 patients who underwent radical prostatectomy for CaP. The control group consisted of 35 patients who underwent transurethral resection of the prostate for BPH. Tissue samples were acquired from the gross tumor site and from resected chips. We determined Cd concentration by atomic absorption, MT expression by immunoblotting, and immunohistochemical staining. The significance of between-group differences for these outcomes was analyzed using Student's t tests. RESULTS: There was no statistically significant difference in Cd concentration between the CaP and BPH groups. Immunoblots from both groups revealed a single band. The relative intensity of the MT band was 0.58 +/- 0.09 in the BPH group and 0.17 +/- 0.03 in the CaP group. MT expression in patients with BPH was 3.4-fold higher than in those with CaP. CONCLUSION: MT may bind heavy metals and protect patients from CaP. Additional studies are needed to reveal the factors that influence the expression of MT in prostate epithelial cells, and to analyze the free and compound forms of Cd at the same time.

Chronic renal failure rats are highly sensitive to aristolochic acids, which are nephrotoxic and carcinogenic agents.

Aristolochic acid (AA), a component of some Chinese herbal medicines, may cause Chinese Herbs Nephropathy (CHN) and multi-systemic tumors by the formation of AA-DNA adducts. In this study, we established an animal model to further characterize the mechanisms of AA-induced diseases. Our results indicated that AA significantly inhibited rat growth in terms of weight gain. By measuring the serum creatinine levels, AA resulted in considerable damage to the rat renal system, not only for those in which chronic renal failure (CRF) was induced but also for normal healthy rats. Mutation-specific polymerase chain reaction (PCR) and XbaI restriction fragment length polymorphism (RFLP) revealed the CAA-->CTA transversion mutation at codon 61 of the H-ras proto-oncogene from the stomach tissues of CRF rats fed with AA, but not from other tissues of rats in the same experimental group. In addition, no such mutations were found in the tissues of CRF rats without AA treatment or healthy rats fed with AA. Our results strongly demonstrated that AA was in fact nephrotoxic and carcinogenic, especially to those CRF rats.