Longer preserved urethral length in robot-assisted radical prostatectomy significantly contributes to post-operative urinary continence recovery.

Objectives: To assess the relationship between the surgical procedure of robot-assisted radical prostatectomy (RARP) and urinary continence recovery by reviewing the video database. Methods: Video and data about men diagnosed with prostate cancer and underwent RARP were extracted and reviewed. Preserved urethral length (PUL) was semi-quantitatively measured using the lateral width of a 16-Fr urethral balloon catheter while cutting the urethra on a video screen. In addition, by reviewing intraoperative RARP video database, other surgical skill outcomes were also collected. Kaplan-Meier analysis with log-rank test was used to compare the urinary continence recovery rate, stratified by the PUL. Univariate and multivariate analyses were performed using the Cox proportional hazards model, and p-values of <0.05 were considered significant. Results: The number of patients included in this study was 213. In univariate analysis, a PUL of ≥16 mm, a body mass index of <23.1 kg/m2 and a resected prostate volume of <44.3 g were statistically significant factors that influenced urinary continence recovery [hazard ratio (HR) 1.58, p = 0.036; HR 0.67, p = 0.021; and HR 0.58, p = 0.005, respectively]. Those factors also remained statistically significant in the multivariate analysis (HR 1.87, p = 0.022; HR 0.54, p = 0.001; and HR 0.57, p = 0.005, respectively). One year post-operatively, the recovery rate from urinary continence was 79.0% for patients with a PUL of ≥16 mm and 66.5% for patients with a PUL of <16 mm. Conclusion: These results suggest that patients with longer PUL in RARP have a significantly higher rate of post-operative urinary continence recovery.

The cutoff value of transitional zone index predicting the efficacy of dutasteride on subjective symptoms in patients with benign prostate hyperplasia.

OBJECTIVES: We investigated the efficacy of dutasteride add-on therapy to α-1 adrenoceptor antagonists in patients with benign prostate hyperplasia (BPH) in relation to the transitional zone index (TZI) and evaluated the cutoff value of TZI that predicted improvements of subjective symptoms at 6 months. METHODS: Male BPH patients with prostate volume (PV) ≥ 30 mL receiving dutasteride 0.5 mg/d for 6 months as add-on therapy along with α-1 adrenoceptor antagonists were enrolled. PV, transitional zone volume (TZV), TZI, International Prostate Symptom Score (IPSS), and uroflowmetry parameters before and at 6 months with dutasteride add-on treatment were evaluated. RESULTS: Eighty-three patients were included. The changes of total IPSS, IPSS voiding subscore, IPSS quality of life score, and voided volume were significantly correlated with TZI. Among baseline parameters, TZV and TZI were significantly associated with the changes of total IPSS in univariate analysis, and only TZI remained as an independent predictive factor for improving total IPSS in multivariate analysis (odds ratio -8.3, P = .048). The cutoff point of TZI for predicting an improvement of the total IPSS by 6 points or more was 0.67 (area under the curve 0.71, sensitivity 0.62, specificity 0.79). CONCLUSIONS: A higher TZI was significantly associated with improvement of subjective symptoms but not uroflowmetric findings for BPH patients with 6 months of dutasteride add-on therapy along with α-1 adrenoceptor antagonists, and the predictive value of TZI for effective dutasteride add-on therapy was higher than 0.67. BPH patients using α-1 adrenoceptor antagonists with a TZI higher than 0.67 can be good candidates for add-on dutasteride therapy.

Natural history of asymptomatic renal artery pseudoaneurysm after robot-assisted partial nephrectomy.

BACKGROUND: We assessed the natural history of renal artery pseudoaneurysm (RAP) after robot-assisted partial nephrectomy (RAPN). METHODS: From May 2016 to September 2020, 106 patients underwent RAPN for renal tumors at our institution. Among 100 patients, excluding 6 who were ineligible for contrast-enhanced computed tomography (CE-CT), 4 underwent renal artery selective embolization (RAE), of which 2 cases were emergency RAE within 7 days after RAPN and the other 2 were prophylactic RAE 8 or more days after RAPN. In 98 patients examined for the clinical course of asymptomatic RAP managed by surveillance, excluding the 2 who underwent emergency RAE, routine CE-CT was performed at 7 days, 1 month and 3 months after RAPN. Factors influencing the occurrence of RAP among these 98 patients, including the 2 who underwent emergency RAE and excluding the 2 who underwent prophylactic RAE, were analyzed by logistic regression analysis. RESULTS: Median [interquartile range (IOR), range] observation period, age, radiographic tumor size, and maximum diameter of RAP were 20.8 (23.9, 3.0-57.6) months, 63 (18, 22-84) years, 23 (11, 9-48) mm, and 6.6 (5.2, 3.0-16.0) mm, respectively. CE-CT detected 28 RAPs in 23 (23.0%) of 100 patients by 7 days after RAPN and routine CE-CT detected 25 RAPs in 21 (21.4%) of 98 patients excluding 2 who underwent emergency RAE at 7 days after RAPN. RAP was diagnosed by routine CE-CT in 21 (21.4%), 1 (1.0%), and 0 (0%) patients at 7 days, 1 month, and 3 months after RAPN, respectively. In univariate analysis, age [odds ratio (OR) 0.144: 69-84 vs. 22-56 years old, P=0.0179], R.E.N.A.L [radius (tumor size as maximal diameter), exophytic/endophytic properties of tumor, nearness of tumor deepest portion to collecting system or sinus, anterior/posterior descriptor and location relative to polar line] nephrometry score (OR 1.374, P=0.0382), warm ischemic time (OR 1.085, P=0.0393), and renorrhaphy time (OR 1.055, P=0.0408) were significantly associated with the occurrence of RAP. In multivariate analysis, only age (OR 0.124, P=0.0148) was a significant factor. CONCLUSIONS: Asymptomatic RAP up to 15 mm in diameter resolved spontaneously 3 months after RAPN. Young age (under 56 years) may be a factor in the development of RAP.

Mechanism of hypertensive crisis during energy device ablation of the adrenal gland: An experimental animal study.

OBJECTIVE: To elucidate the mechanism of hypertensive crisis during energy device ablation of the adrenal gland. METHODS: Electrocoagulation on the adrenal glands of six pigs was carried out with the same energy device (VIO300D) using four methods: (i) monopolar coagulation; (ii) monopolar soft coagulation using IO-advanced ball-type electrodes; (iii) bipolar soft coagulation by pinching; and (iv) bipolar soft coagulation by non-pinching (surface contact) using Bipolar forceps Premium. After electrocoagulation for 5 s, blood pressure and pulse changes were monitored, and adrenal hormones were measured from a central vein. The adrenal glands were removed, and the degree of tissue damage was scored histologically. RESULTS: Hypertensive crisis occurred with electrocoagulation of the adrenal gland by the monopolar coagulation, monopolar soft coagulation and bipolar soft coagulation pinching methods. Blood pressure did not change with the bipolar soft coagulation non-pinching method. Pathologically, tissue damage to the adrenal medulla was associated with elevated blood pressure and adrenaline and noradrenaline release. CONCLUSIONS: Hypertensive crisis caused by energy device ablation to the adrenal gland is caused by the release of catecholamines due to heat damage to the adrenal medulla rather than the type of energy device. Proper use of an energy device that does not cause thermal degeneration of the medulla is required to prevent hypertensive crisis.

Questionnaire survey assessing seasonal changes in lower urinary tract symptoms in men with benign prostate hyperplasia.

OBJECTIVE: A prospective questionnaire survey was conducted for patients with benign prostatic hyperplasia (BPH) to clarify seasonal changes in the lower urinary tract symptoms (LUTS). MATERIAL AND METHODS: Male patients receiving α1-adrenoreceptor antagonists for BPH were enrolled. They answered the International Prostate Symptom Score (IPSS) questionnaire, and an unvalidated questionnaire that consisted of 10 questions assessing variations in the urinary stream (voiding symptoms) and urinary frequency (storage symptoms), depending upon the seasons or the patients' subjective sensations of warm and cold in last one year. RESULTS: A total of 412 participants answered IPSS and our unvalidated questionnaire. Of the 412 participants, 36.7% and 59.0% realized seasonal variations in urinary stream and frequency, respectively. Among patients perceiving seasonal urinary stream and urinary frequency changes (n=151 and n=243, respectively), significantly more patients realized weaker urinary stream, 59.8% (107/179) in winter compared with 26.2% (47/179) in summer, and increased urinary frequency, 69.8% (199/285) in winter compared with 20.7% (59/285) in summer (p<0.0001 and p<0.0001, respectively). Even in summer, when feeling cold, 34.7% and 56.3% realized a weaker urinary stream and an increased urinary frequency, and even in winter, when feeling warm, 53.4% and 69.4% realized a stronger urinary stream and a decreased urinary frequency. Those with seasonal stream changes showed a significantly higher IPSS total, voiding and post-voiding scores than those without, and those with seasonal frequency changes showed significantly higher IPSS total, storage, voiding, and post-voiding scores. CONCLUSION: Our results revealed seasonal changes and feeling of hot and cold were associated with subjective changes of LUTS in BPH patients.

The efficacy of axitinib as a first-line treatment for metastatic renal cell carcinoma.

AIM: To evaluate predictive factors which associated with oncological outcomes to first-line axitinib for metastatic renal cell carcinoma (mRCC). METHODS: A retrospective chart review was conducted patients who had been treated with axitinib as first-line therapy for the treatment of mRCC from September 2013 to February 2018. Axitinib was given by single daily oral administration at a dose of 10 mg, which was reduced according to adverse events (AEs). We investigated progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and AEs. RESULTS: Thirty-eight mRCC patients were enrolled. The median follow-up duration of axitinib treatment was 11.3 months (range = 1.0-56.9). ORR was 28.9%. Median PFS and OS was 12.8, and 17.9 months, respectively. In univariate analysis, baseline lactate dehydrogenase (LDH), neutrophil, corrected calcium (Ca), platelets (Plt) and time from diagnosis were selected as potential predictive factors. Multivariate Cox's proportional hazards model analysis showed that the number of risk factors were associated with PFS (P = 0.03) and OS (P = 0.02). CONCLUSION: Baseline LDH, neutrophil, Ca, Plt and time from diagnosis are predictive factors for both PFS and OS in first-line treatment with axitinib for metastatic renal cell carcinoma.

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era.

OBJECTIVES: The efficacy and safety of sunitinib versus sorafenib in patients with advanced renal cell carcinoma with renal impairment remains poorly documented. PATIENTS AND METHODS: We assessed the efficacy and safety of sunitinib and sorafenib in patients with advanced renal cell carcinoma with an estimated glomerular filtration rate of 15-60 mL/min/1.73 m2 by reviewing the medical records of patients treated at Jichi Medical University Hospital, Japan, between May 2008 and August 2016. RESULTS: Twenty-seven patients were treated with sunitinib and 14 with sorafenib. Median progression-free survival in sunitinib- and sorafenib-treated patients was comparable, at 6.6 vs 5.8 months, respectively (HR, 1.618; 95% CI, 0.689-3.798; P = 0.2691). Median overall survival was also comparable, at 65.9 vs 58.0 months (HR, 0.985; 95% CI, 0.389-2.479; P = 0.9748). Grade 3 or higher adverse events were significantly more frequent in the sunitinib-treated than sorafenib-treated patients (P = 0.0357). Compared to pre-treatment values, estimated glomerular filtration rate at the discontinuation of treatment was not decreased in either group. In contrast, estimated glomerular filtration rate was decreased on long-term treatment, particularly in previously nephrectomized patients. CONCLUSIONS: Sunitinib and sorafenib had similar efficacy in patients with advanced renal cell carcinoma and severe renal impairment. Although renal function was not markedly impaired in either group, close attention to decreased renal function may be necessary in previously nephrectomized patients on long-term treatment.

Primary carcinosarcoma of the ureteropelvic junction associated with ureteral duplication: A case report.

RATIONALE: Primary carcinosarcoma of the upper urinary tract is rare. Ureteral duplication is one of the most common urinary tract malformations. Additionally, the association between ureteral duplication and malignancy is unknown. To the best of our knowledge, no cases of malignant tumors diagnosed as carcinosarcoma with ureteral duplication have been reported. We herein report the case of a patient with carcinosarcoma of the ureteropelvic junction associated with incomplete ureteral duplication. PATIENT CONCERNS: A 60-year-old Japanese woman presented with painless gross hematuria. She had a history of total hysterectomy and chemotherapy for endometrioid carcinoma 5 years before. She had no history of occupational chemical exposure. DIAGNOSES: Radiographic imaging revealed right incomplete ureteral duplication, hydronephrosis, and a polypoid tumor in the ureteropelvic junction of the lower moiety of the right kidney. Urine cytology showed a small amount of degenerated atypical epithelial and nonepithelial cells. The transureteral biopsy specimen showed dysplastic urothelial cells and atypical myoid spindle cells. These findings were indefinite for malignancy. INTERVENTIONS: The patient underwent right nephroureterectomy. Pathological examination of the resected tumor showed a biphasic neoplasm composed of carcinomatous and sarcomatous components. The sarcomatous component was immunohistochemically positive for vimentin, desmin, h-caldesmon, and α-SMA and negative for pancytokeratin (AE1/AE3), low molecular weight cytokeratin (CAM 5.2), EMA, E-cadherin, GATA3, uroplakin 2, and p63. Based on these findings, we diagnosed the tumor as carcinosarcoma. OUTCOMES: The postoperative course was uneventful. No additional therapy was administered. The patient has remained alive without recurrence for 21 months since surgery. LESSONS: Carcinosarcoma can arise from ureteral duplication. Although the majority of carcinosarcomas of the upper urinary tract are diagnosed at an advanced stage and have a poor prognosis, some can have a less aggressive course. Further studies are needed to determine the association between ureteral duplication and malignancy.

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-ß-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.

Tumor Thrombus of Renal Cell Carcinoma Extending Into the Inferior Vena Cava, Ovarian Vein, and Ureter Treated With Neoadjuvant Axitinib.

Ureter tumor thrombus (TT) of renal cell carcinoma (RCC) is quite rare, although RCC-TT in the inferior vena cava (IVC) is not uncommon. We report the first case of RCC-TT extending into the IVC and ovarian vein as well as the ureter. Neoadjuvant axitinib shrank both the primary tumor and TT, making radical nephrectomy less invasive, particularly by downleveling the IVC-TT. Pathological examination of the primary tumor, IVC-TT, and ureter TT showed clear cell carcinoma with extensive necrosis. Although the role of neoadjuvant axitinib in RCC remains unclear, the present case suggests that neoadjuvant axitinib is clinically beneficial for RCC-TT.

Influence of genetic polymorphisms of multidrug and toxin extrusion protein 1 on its mRNA expression in peripheral blood cells.

This study aimed to determine the effect of multidrug and toxin extrusion protein 1 (MATE1) genetic variants on its transcript expression in peripheral blood cells. Consistent with previous in vitro findings, MATE1 mRNA levels were significantly higher in subjects carrying rs2453579, but not rs2252281, compared to those without either of these promoter variants. In addition, the mRNA levels did not differ between subjects with both variants and those with neither allele. Thus, this study reveals that the influence of MATE1 genetic variants on its mRNA expression can be detected in vivo using peripheral blood.

Association of decreased mRNA expression of multidrug and toxin extrusion protein 1 in peripheral blood cells with the development of flutamide-induced liver injury.

PURPOSE: The anti-prostate cancer drug flutamide occasionally causes hepatotoxicity, and predictive biomarkers of flutamide-induced liver injury (FILI) are needed to improve safety of this drug. The aim of this prospective study was to identify such a biomarker by analyzing peripheral blood samples from patients before flutamide therapy. METHODS: Blood samples were obtained from 52 patients with prostate cancer before flutamide therapy. FILI was defined as treatment-related elevation of the serum concentration of aspartate or alanine aminotransferase to more than twice the upper limit of the reference range. The patients were monitored for at least 6 months regarding FILI. Microarray and quantitative real-time PCR analyses were conducted to compare gene expression profiles between the groups with and without FILI. RESULTS: Seventeen patients developed FILI. Microarray analysis of the training set in 15 patients detected 11 annotated genes showing >twofold expression changes between the groups (p < 0.005). Quantitative PCR analysis of both the training set and validation set confirmed that mRNA levels of multidrug and toxin extrusion protein 1 (MATE1 or SLC47A1, encoded by 1 of the 11 genes) were significantly lower in patients with FILI. A small experiment on mice (three per group) showed that Mate1 knockout mice had an elevated serum concentration of 4-nitro-3-(trifluoromethyl)phenylamine, a major metabolite of flutamide, 2 h after administration of the drug, suggesting that Mate1 could affect the pharmacokinetics of flutamide. CONCLUSIONS: The MATE1 mRNA level in peripheral blood is a possible negative predictive biomarker of FILI.

Approach via a small retroperitoneal anterior subcostal incision in the supine position for gasless laparoendoscopic single-port radical nephrectomy: initial experience of 42 patients.

BACKGROUND: Gasless laparoendoscopic single-port surgery (GasLESS) for radical nephrectomy (GasLESSRN) in the flank position is a minimally invasive treatment option for patients with T1-3 renal cell carcinoma (RCC). However, RCC patients considered suitable for supine positioning rather than flank positioning for radical nephrectomy are occasionally encountered. This study evaluated the safety and feasibility of approach via a small retroperitoneal anterior subcostal incision (RASI) in the supine position for GasLESSRN (RASI-GasLESSRN) on the basis of our initial experience. METHODS: RASI-GasLESSRN was performed on 42 patients with RCC or suspected RCC from 2011-2013. The RASI, which was 6 cm long in principle, was made parallel to the tip of the rib from the lateral border of rectus abdominis muscle toward the flank in the supine position. The specimen was extracted via the RASI using a retrieval device. All procedures were performed retroperitoneally under flexible endoscopy with reusable instruments and without carbon dioxide insufflation or insertion of hands into the operative field. RESULTS: RASI-GasLESSRN was successfully performed in all patients without complications. The mean incision length was 6.3 cm, mean operative time was 198 minutes, and mean blood loss was 284 mL. All 42 patients were classified as Clavien grade I. The mean times to oral feeding and walking were 1.1 and 2 days, respectively. The mean number of postoperative days required for patients to be dischargeable was 3.7 days. CONCLUSIONS: The approach via a small RASI in the supine position for GasLESSRN is a safe and feasible technique. RASI-GasLESSRN in the supine position is an alternative minimally invasive treatment option, especially for RCC patients considered suitable for supine positioning.

External validation of risk classification in patients with docetaxel-treated castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) patients have poor prognoses, and docetaxel (DTX) is among the few treatment options. An accurate risk classification to identify CRPC patient groups for which DTX would be effective is urgently warranted. The Armstrong risk classification (ARC), which classifies CRPC patients into 3 groups, is superior; however, its usefulness remains unclear, and further external validation is required before clinical use. This study aimed to examine the clinical significance of the ARC through external validation in DTX-treated Japanese CRPC patients. METHODS: CRPC patients who received 2 or more DTX cycles were selected for this study. Patients were classified into good-, intermediate-, and poor-risk groups according to the ARC. Prostate-specific antigen (PSA) responses and overall survival (OS) were calculated and compared between the risk groups. A multivariate analysis was performed to clarify the relationship between the ARC and major patient characteristics. RESULTS: Seventy-eight CRPC patients met the inclusion criteria. Median PSA levels at DTX initiation was 20 ng/mL. Good-, intermediate-, and poor-risk groups comprised 51 (65%), 17 (22%), and 10 (13%) patients, respectively. PSA response rates ≥ 30% and ≥ 50% were 33%, 41%, and 30%, and 18%, 41%, and 20% in the good-, intermediate-, and poor-risk groups, respectivcixely, with no significant differences (p = 0.133 and 0.797, respectively). The median OS in the good-, intermediate-, and poor-risk groups were statistically significant (p < 0.001) at 30.1, 14.2, and 5.7 months, respectively. A multivariate analysis revealed that the ARC and PSA doubling time were independent prognostic factors. CONCLUSIONS: Most of CRPC patients were classified into good-risk group according to the ARC and the ARC could predict prognosis in DTX-treated CRPC patients. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) number, UMIN000011969.

Nocturia Quality-of-Life questionnaire is a useful tool to predict nocturia and a risk of falling in Japanese outpatients: a cross-sectional survey.

OBJECTIVES: To evaluate the Japanese version of the Nocturia Quality-of-Life questionnaire for prediction of night-time voiding and risk of falling. METHODS: A survey was carried out from October 2008 to June 2009 in outpatients at 15 general hospitals and 80 general clinics in Tochigi, Japan, using the Nocturia Quality-of-Life questionnaire, overactive bladder symptom score and self-administered questionnaires on night-time symptoms (awakening, number of voids, incontinence and falling). RESULTS: The survey was completed by 2494 participants (1154 men, 1208 women; mean age 63.2 ± 15.1 years). Overactive bladder was diagnosed in 625 participants (25.1%) according to the Japanese overactive bladder guideline using overactive bladder symptom score. Awakening during sleep was reported by 80.1% of the participants, and 70.4% awakened to go to the toilet. The mean Nocturia Quality-of-Life score was 86.8 ± 16.9. The Nocturia Quality-of-Life score was lower in patients with overactive bladder, benign prostatic hyperplasia, diabetes, hypertension and cardiovascular diseases. The Nocturia Quality-of-Life score was significantly decreased in patients with night-time symptoms (P < 0.001). Nocturia Quality-of-Life scores and those for subdomains were correlated with overactive bladder symptom score. Nocturia Quality-of-Life ≤90 had 63.1% sensitivity and 78.6% specificity in indicating night-time voiding more than twice, and Nocturia Quality-of-Life questionnaire ≤80 had 70.2% sensitivity and 79.5% specificity in indicating the probability of falling at least once. Logistic analysis showed that 10-year increase in age and overactive bladder in all participants were significant risk factors for Nocturia Quality-of-Life ≤90. CONCLUSIONS: The Nocturia Quality-of-Life questionnaire represents a useful tool to predict nocturia and risk of falling in Japanese patients.

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.

Changes in peripheral blood immune cells: their prognostic significance in metastatic renal cell carcinoma patients treated with molecular targeted therapy.

Recently, novel molecular targeted agents markedly changed the treatment of renal cell carcinoma (RCC), with promising results. However, there is little understanding of how these agents affect immune cell populations in RCC, an immunogenic tumor. Therefore, we investigated the changes in the peripheral blood immune cells in 58 RCC patients during the first 4 weeks of treatment with sorafenib, sunitinib, everolimus, or temsirolimus and evaluated whether these changes were associated with clinical outcomes. The immunological parameters were the proportion of type-1 (Th1) and type-2 (Th2) T cells, regulatory T cells (Treg), mature dendritic cells, and the neutrophil-to-lymphocyte ratio (NLR). The changes in these immune cells varied with the agents and the clinical response, dichotomized by the median progression-free survival (PFS) time (PFS-short or PFS-long). A significant decrease in the Th1/Th2 ratio was seen after sunitinib treatment only in the PFS-short group, suggesting a shift toward Th2 that down-regulates host immunity. The NLRs indicative of the balance between host immunity and cancer-related inflammation were consistently lower in the PFS-long group than in the PFS-short group, suggesting that lower NLR is associated with better clinical response. Only sunitinib decreased NLR remarkably regardless of PFS status, which may favor anti-tumor immunity. When patients were dichotomized by the cutoff values, Th1/Th2 ratio was not associated with PFS in any targeted therapy, while lower pre-treatment NLR was associated with longer PFS in each targeted therapy. In addition, in RCC patients given sequential targeted therapy, those with a lower baseline NLR survived significantly longer compared with the counterparts. Moreover, those whose baseline NLR was sustained low during the initial therapy survived the longest. Our results suggest the diverse changes in host immune cells in RCC patients during targeted therapy. The changes in NLR during the early phase of targeted therapy may be a powerful discriminator of who will benefit from the subsequent treatment.

Involvement of magnitude of ambient temperature change in nonspecific effect in perceived placebo effect on lower urinary tract symptoms: study on switching of naftopidil in patients with benign prostatic hyperplasia.

PURPOSE: To determine if switching from one brand of the α1-adrenoceptor antagonist naftopidil (Avishot™) to another brand (Flivas™) under the same conditions causes the same changes in lower urinary tract symptoms (LUTS) and quality of life (QOL) as the perceived placebo effect, and if ambient temperature as a nonspecific factor is related to those changes in benign prostatic hyperplasia (BPH) patients. PATIENTS AND METHODS: A retrospective study was carried out on 217 BPH patients who had received Avishot™ for more than 6 months and then were switched to Flivas™ at the same dose and timing. The two drugs contain the same principal ingredient and display the same pharmacokinetic properties. The International Prostate Symptom Score (IPSS), QOL score, and average monthly ambient temperature at the patients' residence area from the Automated Meteorological Data Acquisition System in Japan were used for the evaluation. RESULTS: A significant change in urinary storage symptoms (P = 0.006), and especially in nighttime frequency (P< 0.001), was observed by switching drugs, suggesting the perceived placebo effect. There was significant improvement of daytime frequency (P< 0.05), nighttime frequency (P< 0.001), storage symptoms (P< 0.001), and total IPSS (P< 0.05) when the magnitude of ambient temperature change from before and 3 months after switching drugs was higher than 10°C, while no significant improvement was noted in any of the parameters examined when the same was lower than 10°C. CONCLUSION: The present study showed the nonspecific effect of magnitude of ambient temperature change was involved in the perceived placebo effect on LUTS, especially on storage symptoms, by switching drugs. The nonspecific effect on LUTS with BPH needs to be considered when evaluating subjective treatment efficacy of drugs for LUTS with BPH in routine clinical practice. The present study supports the lifestyle advice "avoid exposing the lower body to cold temperature" or "keep warm when it is cold" for LUTS with BPH.