M.M. Oh

Combination therapy of testosterone enanthate and tadalafil on PDE5 inhibitor non-reponders with severe and intermediate testosterone deficiency

Several studies have suggested combination therapy with testosterone supplementation in patients not responding to PDE5 inhibitors. Considering the pathophysiological basis for testosterone supplementation, the present study aims to identify whether combination therapy allows persistence of treatment effect after testosterone discontinuation. Furthermore, we evaluated whether the degree of testosterone depletion affects treatment outcome from combination therapy. Hypogonadal patients (<350 ng dl−1) with erectile dysfunction who previously did not respond to PDE5 inhibitors were treated with testosterone enanthate injections and daily tadalafil. Patients were stratified into two groups depending on the level of testosterone deficiency, with 250 ng dl−1 as a reference point. Following testosterone supplementation (12 weeks) and combination therapy (12 weeks), patients with severe testosterone deficiency showed higher IIEF (International Index of Erectile Function) erectile function (EF) domain score (16.47±4.019 vs 12.36±4.051, P=0.001) and more patients responding satisfactorily to treatment by general assessment (57.9 vs 16.0%, P=0.009), despite reaching similar levels of serum total testosterone (602±169 ng dl−1 vs 698±165 ng dl−1, P=0.057). Testosterone supplementation was then discontinued and patients were maintained only on daily tadalafil (12 weeks). The severe depletion group maintained higher EF domain scores than baseline (13.06±3.38 vs 7.20±2.24, P=0.0004), despite testosterone levels returning to baseline. The results suggest that combination therapy was more beneficial to patients with severe testosterone depletion, possibly by improving underlying pathophysiology.

The effect of diet-induced insulin resistance on DNA methylation of the androgen receptor promoter in the penile cavernosal smooth muscle of mice

Population studies have suggested an association between diabetes and the symptoms of testosterone deficiency. Recently, the expression of the androgen receptor (AR) has been shown to be decreased in diabetic patients. Furthermore, diabetes has been shown to induce global methylation. In this study, we used an animal model to investigate whether diabetes results in increased methylation of the AR promoter and whether these changes are associated with the decreased expression of AR in penile cavernosal smooth muscle tissue. Twenty C57BL/6J mice were divided into two groups, receiving either high- (mature diabetic) or low- (mature control) caloric meals for 14 weeks. Another 10 mice were killed at 1 week (young control). Animals in the mature diabetic group showed decreased testosterone levels, although this was not statistically significant. In both control groups, no significant methylation was observed in the AR promoter region CpG island (-85 to +339). In the mature diabetic group, significant methylation was observed at +185 and +200 of the AR promoter. These changes were associated with increased homeostatic model assessment for insulin resistance (HOMA-IR) and decreased corpus cavernosal tissue mass and expression of AR mRNA and protein. We conclude that in these animals, insulin resistance increased the methylation of the GC-rich regions of the AR promoter, leading to decreased AR expression.

Treatment satisfaction with low-dose tamsulosin for symptomatic benign prostatic hyperplasia: results from a multicentre cross-sectional survey

Aims:  To evaluate the efficacy and treatment satisfaction with low‐dose (0.2 mg) tamsulosin in patients with symptomatic benign prostatic hyperplasia (BPH), and to investigate individual lower urinary tract symptoms according to treatment satisfaction.

Squamous cell carcinoma must be considered in patients with long standing upper ureteral stone and pyonephrosis

A 69-year-old male patient with chronic alcoholism presented with a history of swelling and pain of right upper abdomen for the recent 6 months. He complained of generalized weakness and weight loss in the past 3 months. There was no history of fever and hematuria but he had occasional right flank pain. Physical examination revealed moderate right costovertebral angle tenderness and right palpable abdominal mass. Routine hematology, biochemical tests and chest radiograph were normal. Urinalysis revealed microscopic hematuria and pyuria. Urine cytology was negative for malignancy. Ultrasonography of the abdomen showed severe hydronephrosis of the right kidney with hydronephrotic sac suggestive of pyonephrosis and dilatation of the right ureter. The left kidney was normal in size, shape and echogenicity. Computed tomography (CT) of abdomino-pelvis showed severe hydronephrosis filling the right abdominal cavity, thin parenchyma of the right kidney suggestive of non-functioning kidney, several calyceal stones (\10 mm) and one stone (22 mm) in the upper ureter. There was no ascites or lymphadenopathy (Fig. 1). The patient was scheduled for a right nephrectomy through a flank incision. On operation, a huge kidney measuring 27 9 20 9 15 cm was obtained. The whole kidney with pyonephrosis was a distended sac-like structure without any visible renal tissue. The cut surface showed multiple areas with necrotic tissue and multiple calculi (Fig. 2). The final pathology report showed invasive, poorly differentiated squamous cell carcinoma (5 9 2, 5 9 2 cm), several renal stones and a stone in the right upper ureter. The tumor extended to perinephric fat and all surgical margins were negative. There was no regional lymphatic invasion of the tumor and no distant metastasis (pathological stage T3N0M0) (Fig. 3). The patient had an uneventful postoperative course and was discharged on postoperative day 7 in stable condition. At 5-months follow-up visit after the surgery, he presented with pain of right shoulder and generalized weakness. Follow-up CT scan showed multiple metastases in the liver and spleen and metastatic lymphadenopathy in the aortocaval and retrocaval spaces. This pathology was not visible on the previous CT scan (Fig. 4). The patient received one course of chemotherapy but he expired 7 months after surgery. Primary malignant tumors of the renal pelvis are relatively rare and constitute approximately 8–14% of all the renal malignancies [1]. Of these, squamous cell carcinoma of the renal collecting system is rare, accounting for about 0.5–8% of the renal pelvic tumors [2, 3]. This rare malignancy is frequently associated with chronic pyelonephritis and renal stone formation. Other etiologic factors such as tuberculosis, immunosuppression with azathioprine, analgesic abuse with phenacetin, radiation therapy, chronic rejection in a transplant kidney and prior percutaneous nephrolithotomy have been associated with squamous cell carcinoma [4–7]. It is believed that chronic irritation leads to squamous metaplasia which may subsequently develop into squamous cell carcinoma [8]. Squamous cell carcinoma of the renal pelvis usually occurs in old people (50–70 years). Clinical presentation is similar to that of urothelial carcinoma, and a patient with this malignancy might present with flank or abdominal pain, microscopic or gross hematuria, fever, anorexia or cachexia, and a palpable B. k. Ham J. w. Kim J. h. Yoon M. Oh J. h. Bae H. s. Park D. g. Moon (&) Department of Urology, Korea University Institute for Regenerative Medicine, Korea University College of Medicine, 80, Guro-dong, Guro-gu, Seoul 152-703, Korea e-mail: dgmoon@korea.ac.kr