Pioglitazone induces hypoxia-inducible factor 1 activation in human renal proximal tubular epithelial cell line HK-2.

We previously reported that fatty acid-bearing albumin but not fatty acid-depleted albumin induces hypoxia-inducible factor-1 (HIF-1) activation in human renal proximal tubular epithelial cell line HK-2. Then, an increase in mRNA expression of peroxisome proliferator-activated receptor gamma (PPARγ) was observed on treatment with fatty acid-bearing albumin but not fatty acid-depleted albumin. The aim of this study was to determine whether a PPARγ agonist, pioglitazone, induces HIF-1 activation or not. Treatment with pioglitazone induced HIF-1α mRNA as well as PPARγ mRNA expression in a concentration dependent manner. In addition, pioglitazone increased HIF-1 target genes such as the mRNAs of glucose transporter 1 (GLUT1) and breast cancer resistance protein (BCRP/ABCG2), in a concentration-dependent manner. Consistent with the increases in GLUT1 and ABCG2 mRNAs, protein expression of GLUT1 and BCRP was increased by pioglitazone. In addition, GLUT inhibitor phloretin-sensitive D-[3H]glucose uptake activity and BCRP inhibitor Ko143-sensitive accumulation of Hoecsht33342, a BCRP substrate, were significantly enhanced by treatment with pioglitazone. These findings suggest that PPARγ activation by pioglitazone leads to HIF-1 protein expression induction followed by changes in HIF-1 target gene expression and protein product activity.

[KIDNEY-SPARING SEGMENTAL URETERECTOMY WITH TRANSURETHRAL BLADDER CUFF EXCISION FOR DISTAL URETERAL CARCINOMA].

(Introduction and objectives) Radical nephroureterectomy with complete distal ureterectomy is the standard therapy for upper tract urothelial malignancy. Segmental ureterectomy with ueteroneocytostomy is an alternative for distal ureteral carcinoma. We describe extravesical complete distal ureterectomy combined by transurethral bladder cuff excision with frozen-section analysis. (Patient and methods) Since December 2008, 11 patients (median age 77 year old, male 10, female 1, right 10, left 1) with solitary distal ureteral carcinoma who had mild hydronephrosis of ipsilateral kidney remaining renal function on enhanced CT. Under general anesthesia, the patient was placed in lithotomy position, rigid cystoscopy was inserted into the bladder. Cold punch biopsy of 4 sites of bladder mucosa 5 mm away from ureteral orifice (12, 3, 6, 9 o'clock) was carried out and sent to frozen-section analysis. Use resectoscopy with needle-type electrode, incise the bladder mucosa along the biopsy sites circumferentially and incise submucosa tissue around the ureteral orifice deeply enough to detach intramural ureter. Then lower abdominal midline incision was made. After entering the retroperitoneal space, the ureter was dissected and ureteral margin was sent to frozen-section analysis. The distal ureter was dissected until the margin of bladder mucosa incised by transurethrally. After ascertainment of no cancer cell in the frozen-section, close the defect in the bladder. Then the ureter was re-implanted into the bladder by extravesical approach. (Results) Median estimate blood loss was 150 ml (40-350 ml) and median operative time was 258 min (170-317 min.). No patients in our series required a blood transfusion. The mean tumor size was 20+/- 4.4 mm. Pathological T stage was Ta 3, T1 3, T2 2 and T3 3. No positive surgical margin was noted. Mean serum creatinine before and 1 month after surgery was 1.05+/- 0.21 mg/dl and 089+/- 0.13 mg/dl. Mean eGFR before and 1 month after surgery was 54.1+/- 11.4 and 63.4+/- 8.4. Median followup was 35 months (range 4 to 93). Although there were two patients who died from distant metastatic disease, no patients have encountered cancer recurrence in the remained ipsilateral upper urinary tract. (Conclusions) Segmental ureterectomy combined by transurethral bladder cuff excision with frozen-section analysis could perform complete resection of distal ureteral carcinoma and preserve ipsilateral renal function. This technique is feasible for patients with distal ureteral carcinoma as an optional treatment. Better preservation of renal function can lead to increased tolerance of cisplatin-based adjuvant or salvage chemotherapy.

[A case of Bellini duct carcinoma with giant hydronephrosis].

We report a case of Bellini duct carcinoma with giant hydronephrosis. A 56-year-old man was referred with the chief complaint of gross hematuria. The intravenous pyelography showed a huge right renal contour and non-functioning kidney. The abdominal computed tomographic scan and magnetic resonance imaging demonstrated giant hydronephrosis. Percutaneous urinary cytology obtained in the direct pyelography was class V. Right total nephro-ureterectomy was performed. Punctured fluid volume was 1,010 ml during the operation. Histological and immunohistochemical analysis revealed the collecting duct carcinoma of the kidney. Three months later, multiple bone metastases had appeared. He was treated by the combination chemotherapy of gemcitabine and paclitaxel, but lung and liver metastases developed. The patient died of cancer 12 months later. This case was considered to be Bellini's duct carcinoma as its features had poor prognosis and image findings infiltrating from medulla to cortex with the total enlargement of the kidney. To our knowledge there has been no case found like these atypical imaging findings.