Taro Kubo

Hand–Foot Skin Reaction is Associated with the Clinical Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Sorafenib

BACKGROUND To elucidate whether Hand-Foot skin reaction could become a biomarker of clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib, we retrospectively examined the association between the Hand-Foot skin reaction and the clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib. METHODS Thirty-six Japanese metastatic renal cell carcinoma patients treated with sorafenib were enrolled and divided into the groups with or without Hand-Foot skin reaction. Patient characteristics, best tumor response, progression-free survival and adverse events were investigated and compared between these two groups. RESULTS A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients was observed at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification, and with Eastern Cooperative Oncology Group Performance Status of one or less, prior nephrectomy, higher hemoglobin, lower lactate dehydrogenase and lower C-reactive protein. The mean best tumor response was significantly better in the group with Hand-Foot skin reaction (-16.7%) than that in the group without it (17.9%; P < 0.001). The median progression-free survival was significantly longer in the group with Hand-Foot skin reaction (4.6 months) than that in the group without it (1.5 months; P = 0.002). In multivariate analysis, only Hand-Foot skin reaction was shown to be a predictive factor of progression-free survival (hazard ratio 0.312, P = 0.010). CONCLUSIONS A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients emerged at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification and was significantly associated with best tumor response and progression-free survival, suggesting that Hand-Foot skin reaction might be an independent predictive factor for clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib.

Transurethral incision of congenital obstructive lesions in the posterior urethra in boys and its effect on urinary incontinence and urodynamic study.

Study Type – Therapy (case series)
Level of Evidence 4

Early prediction of cisplatin-induced nephrotoxicity by urinary vanin-1 in patients with urothelial carcinoma.

Cisplatin is a widely used anticancer drug, but its nephrotoxicity is a serious problem. To examine whether the novel biomarker, urinary vanin-1, could predict reduction in renal function after dosing of cisplatin. We conducted a prospective single-center pilot study of 24 patients with urothelial carcinoma who received cisplatin-based chemotherapy between 2012 and 2015. The primary outcome was a 20% or greater decline in estimated glomerular filtration rate (eGFR) from baseline within the first 6days of cisplatin. Urine concentration of creatinine, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and NAG (N-acetyl-β-d-glucosaminidase) as well as vanin-1 were measured during the perioperative period. During 6days after cisplatin, 37.5% (9/24) of patients showed more than 20% decline in eGFR (baseline, 68.8±11.1mL/min/1.73m(2); on day 6, 51.0±2.5mL/min/1.73m(2)) and this reduction persisted until day 10. Urinary vanin-1, but not KIM-1, NGAL and NAG, significantly elevated early on day 3 after cisplatin, which preceded the elevation of serum creatinine on day 6. Sensitivity and specificity of a cutoff point of urinary vanin-1 (9.31ng/mg Cr) on day 3 were calculated to be 66.7% (95% CI: 0.30-0.93) and 83.3% (95% CI: 0.52-0.97), respectively, for predicting 20% decline in eGFR during 6days after cisplatin. These data suggest that urinary vanin-1 is an early predictive biomarker for decline in eGFR in patients with urothelial carcinoma after dosing of cisplatin.

Docetaxel with or without estramustine for estramustine refractory castration-resistant prostate cancer: a single institution experience

BackgroundThe significance of combination of docetaxel (DTX) with estramustine phosphate (EMP) in castration-resistant prostate cancer (CRPC) patients remains unclear. In this study, we aimed to retrospectively evaluate the efficacy and toxicity of DTX with or without EMP and to elucidate the significance of DTX and EMP combination therapy in Japanese EMP-refractory CRPC patients.MethodsTo compare the efficacy and toxicity of DTX and EMP, we divided CRPC patients, who were confirmed to be resistant to EMP, into the following two groups: group D (n = 28), which included patients treated with DTX (60 mg/m2, once in every four weeks) alone, and group DE (n = 33), which included patients treated with a combination of DTX (60 mg/m2, once in every four weeks) and EMP (twice daily oral administration at 280 mg).ResultsProstate specific antigen (PSA) response (> 50% decline in PSA) was observed in six patients (21%) in group D and eight patients (24%) in group DE. The median time to progression (TTP) was 12.0 months and 6.2 months and the median overall survival (OS) was 26.4 months and 24.3 months in group D and DE, respectively. There was no statistical difference between the two groups in terms of PSA response, TTP, and OS. The incidence of adverse events of grade 3/4 was low in both the groups, and there was no statistical difference between the two groups.ConclusionsAlthough treatment with DTX at 60 mg/m2 was effective and highly tolerated in EMP-refractory Japanese CRPC patients, the DTX and EMP combination therapy might not exhibit any survival benefit for CRPC patients.

A giant chromophobe renal cell carcinoma exceeding 10 kg

Chromophobe renal cell carcinoma (CRCC) is a rare histological entity of RCC. We herein report a case of giant CRCC (tumor weight: 11 500 g) that could be removed surgically en bloc. A 55-year-old man presented with low-grade fever, general malaise and respiratory disturbance probably due to an abdominal mass. His bodyweight was 81 kg, and his maximum abdominal girth was 110 cm. Blood tests showed high inflammatory reactions (white blood cell count, 16 400/ mm; C-reactive protein, 31.1 mg/dL) and high lactate dehydrogenase level (6692 mU/mL). Abdominal computed tomography (Fig. 1a) and magnetic resonance imaging showed that the left kidney had lost its original form and a giant mass extended from directly below the diaphragm into the pelvis, crossing the midline. Renal cell carcinoma (RCC) without metastasis, or xantogranulomatous pyelonephritis were suspected. After treatment with antibiotics, his general condition and inflammatory reactions improved. As the mass was mobile and his performance status was good, left radical nephrectomy was performed after renal artery embolization to reduce the intraoperative bleeding. The surgical procedure was as follows. After making median and left oblique incisions of the abdomen to explore the abdominal cavity, the descending colon was moved to the right side.As adhesion of the tumor was mild and the renal vessels could be readily found, the tumor could be removed surgically en bloc. This tumor measured 35 ¥ 18 ¥ 19 cm in size and 11 500 g in weight. The surgery took 5 h and 2 min, and the blood loss was 3250 mL. Histopathologically, the case was diagnosed as CRCC (mixed variant) pT2 (TNM 1997) (Fig. 1b). Postoperatively, his bodyweight was 69 kg and his maximum abdominal girth had improved to 89 cm. There has been no recurrence so far (20 months after surgery) without adjuvant therapy. The main characteristics of CRCC are generally its low stage as compared to clear cell carcinoma and good prognosis (5-year survival rate: 78 to 100%). However, the CRCC patients with large tumor size or high pT stage, metastasis to liver, sarcomatoid change or papillary RCC and microscopic necrosis reportedly have a poorer prognosis. Nevertheless, although the tumor size was too large with necrosis in the present case, it had a favorable course without recurrence, probably due to its low pT stage. However, there has been no definition of ‘giant’in previous reports on giant renal tumors, and any tumor exceeding 20 cm in diameter was considered as giant. As far as we could find in the published reports, the tumor size of the largest CRCC was 30 cm in diameter (unknown weight). Furthermore, the largest tumor in or around the kidney (including RCC, sarcoma, oncocytoma, angiomyolipoma, and cystic nephroma) was sarcoma around the kidney (tumor size: 40 ¥ 34 ¥ 13 cm; weight: 8500 g). As the tumor in our present case weighed more than any of the previously reported renal tumors, it seems to be the largest in the world. Even though this tumor was so large, there are cases, including the present one, that have a favorable course, and therefore the indication for radical nephrectomy should be considered case-by-case.

The changes of urethral morphology recognized in voiding cystourethrography after endoscopic transurethral incision for posterior urethral valve in boys with intractable daytime urinary incontinence and nocturnal enuresis

PurposeEndoscopic transurethral incision (TUI) of posterior urethral valve (PUV) can improve daytime urinary incontinence (DUI) and nocturnal enuresis (NE). However, the underlying mechanism has not been elucidated. In this study, we retrospectively examined the mobility of the urethra before and after TUI by measuring the urethral angle with voiding cystourethrography (VCUG), to clarify the effects of TUI on the morphology of the urethra during voiding.MethodsBetween July 2010 and December 2014, 29 boys with intractable DUI and/or NE were diagnosed as PUV and underwent endoscopic TUI. VCUG during voiding phase was performed at sequential radiographic spot images (1 image per second) at a 45° angle in oblique standing position. The point at which the angle of the urethra was the smallest during urination was regarded as the minimum urethral angle. The maximum urethral angle during early voiding phase was compared with the minimum urethral angle, and the percentage by which this angle changed was calculated as the flexion rate. Then changes in minimum urethral angle and flexion rate were analyzed before and 3–4 months after TUI.ResultsAfter TUI, the minimum urethral angle on VCUG became more obtuse (before vs. after TUI, respectively: 112.7 vs. 124.5°, p < 0.001), the flexion rate decreased (before vs. after TUI, respectively: 11.8 vs. 4.1%, p < 0.001).ConclusionsThis study demonstrated a significant difference in the degree of change. The findings may contribute to understanding of the mechanism of improvement in symptoms after TUI in patients with PUV.

Aggressive diagnosis and treatment for posterior urethral valve as an etiology for vesicoureteral reflux or urge incontinence in children

Vesicoureteral reflux (VUR) is one of the most common diseases in pediatric urology and classified into primary and secondary VUR. Although posterior urethral valve (PUV) is well known as a cause of the secondary VUR, it is controversial that minor urethral deformity recognized in voiding cystourethrography represents mild end of PUV spectrum and contributes to the secondary VUR. We have been studying for these ten years congenital urethral obstructive lesions with special attention to its urethrographic and endoscopic morphology as well as therapeutic response with transurethral incision. Our conclusion to date is that congenital obstructive lesion in the postero-membranous urethra is exclusively PUV (types 1 and 3) and that severity of obstruction depends on broad spectrum of morphological features recognized in PUV. Endoscopic diagnostic criteria for PUV are being consolidated.

Acute Kidney Injury Associated with Renal Cell Carcinoma Complicated by Renal Vein and Inferior Vena Cava Involvement.

Acute kidney injury (AKI) is caused by diverse pathologies, although it may occasionally result from concurrent renal efflux disturbances. We herein describe a case of AKI in a patient complicated by renal cell carcinoma (RCC) with renal vein and inferior vena cava (IVC) involvement. A neoplastic thrombus which disrupted the blood flow in the renal vein appeared to play a role in the rapid decline in the renal function. Such a scenario has rarely been mentioned in the previous literature describing the cases of RCC complicated by AKI. Concerns regarding the diagnostic and therapeutic strategies for RCC are also discussed.

The Endoscopic Morphological Features of Congenital Posterior Urethral Obstructions in Boys with Refractory Daytime Urinary Incontinence and Nocturnal Enuresis

Purpose This study aims to evaluate the endoscopic morphological features of congenital posterior urethral obstructions in boys with refractory daytime urinary incontinence and/or nocturnal enuresis. Patients and Methods A total of 54 consecutive patients underwent endoscopy and were diagnosed with a posterior urethral valve (PUV) (types 1-4). PUV type 1 was classified as severe, moderate, or mild. A transurethral incision (TUI) was mainly performed for anterior wall lesions of the PUV. Voiding cystourethrography and pressure flow studies (PFS) were performed before and 3 to 4 months after TUI. Clinical symptoms were evaluated 6 months after TUI, and outcomes were assessed according to PFS waveform pattern groups (synergic pattern [SP] and dyssynergic pattern [DP]). Results All patients had PUV type 1 and/or 3 (i.e., n = 34 type 1, 7 type 3, and 13 types 1 and 3). There were severe (n = 1), moderate (n = 21), and mild (n = 25) cases of PUV type 1. According to PFS, SP and DP were present in 43 and 11 patients, respectively. TUI was effective in the SP group and symptoms improved in 77.4 and 69.3% of patients with daytime incontinence and nocturnal enuresis, respectively. Almost no effect was observed in the DP group. A significant decrease in the detrusor pressure was observed at maximum flow rate using PFS in the SP group. Conclusions PUV type 1 encompassed lesions with a spectrum of obstructions ranging from severe to mild, with mild types whose main obstructive lesion existed at the anterior wall of urethra occurring most frequently in boys with refractory daytime urinary incontinence and/or nocturnal enuresis.

The impact of preserved Klotho gene expression on antioxidative stress activity in healthy kidney

Klotho, which was originally identified as an antiaging gene, forms a complex with fibroblast growth factor 23 receptor in the kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho, including antiaging effects such as protection from various types of cellular stress, have been shown; however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and antioxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. The nitrotyrosine expression level in the kidney was evaluated in these animal models. Expression levels of Klotho gene were positively correlated with the p53 gene and antioxidant enzyme genes such as catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function or pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for catalase, PRDX3, and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The preservation of Klotho gene expression might induce the antioxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition, including age, renal function, and histological findings.