Incidence of postoperative cytomegalovirus and BK-polyoma virus infections and graft loss in ABO-incompatible renal transplant recipients: a multicenter retrospective study.

OBJECTIVES: The current study aimed to examine the incidence of perioperative infections and graft viability in ABO-compatible and ABO-incompatible renal transplant recipients. METHODS: We included 643 living donor renal transplant recipients registered in the Michinoku Renal Transplant Network from 1998 to 2021. Patients were divided into the ABO-compatible and ABO-incompatible kidney transplantation groups. We compared the characteristics of the two groups and evaluated the incidence of postoperative viral infections (cytomegalovirus and BK virus), graft loss-free survival, and overall survival between the two groups. RESULTS: Of 643 patients, 485 (75%) and 158 (25%) were ABO-compatible and ABO-incompatible renal transplant recipients, respectively. Postoperative viral infections, rituximab use, and plasma exchange were significantly more common in ABO-incompatible than in ABO-compatible transplant recipients. However, there were no significant differences in terms of other background characteristics. The ABO-incompatible group was more likely to develop viral infections than the ABO-compatible group. Graft loss-free survival and overall survival did not significantly differ between the two groups. According to the multivariate Cox regression analysis, ABO compatibility was not significantly associated with graft loss-free survival and overall survival. CONCLUSION: Although the incidence of postoperative viral infections in ABO-incompatible renal transplant recipients increased, there was no significant difference in terms of rejection events, graft loss-free survival, and overall survival.

Impact of timing of rejection episode on cardiovascular events in living donor kidney transplantation: a multicenter retrospective study.

BACKGROUND: Cardiovascular diseases are still highly prevalent after kidney transplantation. However, little is known about the impact of the timing of rejection episodes on cardiovascular disease. The study aimed to analyze the influence of the timing of rejection episodes on cardiovascular events in recipients of living donor kidney transplantation. METHODS: We studied 572 living donor kidney transplant recipients from the Michinoku Renal Transplant Network (MRTN), which includes 6 centers in the Tohoku region of Japan. Fine-Gray proportional hazards regression analysis with time-dependent variables was used to assess the effect of rejection episode on cardiovascular events. Recipients were divided into three groups: those without rejection (non-rejection, 370 patients), rejection within 6 months after transplantation (early rejection, 99 patients), and rejection after 6 months (late rejection, 103 patients). The effect of timing on cardiovascular events was evaluated using Fine-Gray proportional hazards regression analysis. RESULTS: During a median follow-up of 77 months, 70 patients experienced cardiovascular events. Rejection episodes were significantly associated with cardiovascular events (hazard ratio [HR]: 2.08, 95% confidence interval [CI]: 1.26-3.43, P = 0.004), along with age and dialysis vintage. The 5-year cumulative incidence of cardiovascular events was significantly higher in the late rejection group than in the early rejection group (15% vs. 3.3%, P = 0.021). However, no significant difference in 5-year cumulative cardiovascular event incidence was observed between the early rejection and non-rejection groups. Late rejection was significantly associated with cardiovascular events (HR: 2.40, 95% CI: 1.38-4.18, P = 0.002), whereas early rejection was not significantly correlated with cardiovascular event risk (HR: 1.18, P = 0.670). CONCLUSIONS: Rejections occurring more than 6 months after transplantation is significantly associated with risk of cardiovascular events. TRIAL REGISTRATION NUMBER: 2019-099-1, date of registration; 3 Dec. 2019, retrospectively registered.

Real-world outcomes and risk stratification in patients with metastatic castration-sensitive prostate cancer treated with upfront abiraterone acetate and docetaxel.

PURPOSE: We assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies. METHODS: The medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted. RESULTS: A total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34-0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33-1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42-2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups. CONCLUSIONS: Upfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.

Real-world survival outcomes of adding docetaxel or abiraterone in patients with high-volume metastatic castration-sensitive prostate cancer: historically controlled, propensity score matched comparison with androgen deprivation therapy.

PURPOSE: This study investigated the impact of treatment intensification with upfront docetaxel (DOC) or abiraterone (ABI) plus prednisolone on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) by comparing it with androgen deprivation therapy (ADT) monotherapy or combined androgen blockade (CAB) using propensity score matching (PSM). METHODS: Outcomes from 278 CHAARTED high-volume patients receiving upfront DOC (92 patients) or upfront ABI (186 patients) were compared to those from 354 patients receiving ADT or CAB. PSM was conducted to assess castration-resistant prostate cancer-free survival (CRPCFS) and overall survival (OS). RESULTS: After PSM, patient distributions between the three groups were well balanced. After 1:1 PSM, patients receiving upfront ABI had significantly better CRPCFS than those receiving ADT/CAB or upfront DOC [hazard ratio (HR) 0.39; 95% CI 0.27-0.56 vs. HR 0.50; 95% CI 0.30-0.82, respectively]. No significant difference in CRPCFS was observed between the upfront DOC and ADT/CAB groups (HR 0.75; 95% CI 0.50-1.12). Patients receiving upfront DOC and upfront ABI had significantly better OS than those receiving ADT/CAB (HR 0.54; 95% CI 0.0.30-0.98 vs. HR 0.49; 95% CI 0.29-0.84, respectively). However, no significant difference in OS was observed between upfront ABI and upfront DOC (hazard ratio 0.84; 95% CI 0.34-2.06). CONCLUSION: The comparison of real-world retrospective cohorts showed that treatment intensification with upfront DOC or upfront ABI promoted better OS compared to ADT alone or CAB in patients with high-volume mCSPC after PSM. However, no difference in OS was observed between upfront DOC and upfront ABI.

Short-term outcomes of risk-adapted upfront docetaxel administration in patients with metastatic hormone-sensitive prostate cancer: a multicenter prospective study in Japan.

We conducted a risk-adapted upfront docetaxel (DOC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Here, we reported an interim analysis of the study. The study enrolled 68 patients with newly diagnosed mHSPC between 2016 and 2018. According to the presence of visceral metastasis, an EOD score ≥ 3, or prostate-specific antigen (PSA) level at 3 months of ≥ 1 ng/mL, patients were divided into low- and high-risk groups. Patients were treated with androgen deprivation therapy (ADT) with or without bicalutamide; those in the high-risk group received upfront treatment involving six cycles of DOC (70 mg/m2). Short-term treatment effect, adverse events, and quality of life (QOL) were evaluated. Fifty (73.5%) were classified in the high-risk group, and 46 (67%) received upfront ADT + DOC. In the ADT + DOC group, 43.5% (20/46) patients achieved a PSA level ≤ 0.2 ng/mL. PSA nadir and time to PSA nadir were 0.291 ng/mL and 288 days, respectively. In the ADT + DOC group, 76.1% (35/42) patients had adverse events (AEs) of grade ≥ 3. During a median follow-up of 18.5 months, 36.4% (8/22) patients in the ADT group and 43.5% (20/46) in the ADT + DOC group had CRPC. Two QOL scores including the physical status and appetite loss at 6 months significantly worsened in the ADT + DOC group but was resolved by 12 months. Upfront DOC achieved high PSA responses without long-term QOL deterioration. However, the short-term outcomes were limited. Longer follow-up is needed to determine the survival advantage.

Inhibition of the RANK/RANKL signaling with osteoprotegerin prevents castration-induced acceleration of bone metastasis in castration-insensitive prostate cancer.

Androgen deprivation therapy (ADT) for patients with metastatic or locally advanced prostate cancer reduces bone mineral density by stimulating receptor activator of nuclear factor kappa-B (RANK) signaling in osteoclasts. The involvement of the RANK/RANKL signaling in ADT-induced acceleration of bone metastasis in castration-insensitive prostate cancer was examined in a murine model using osteoprotegerin (OPG). Male Balb/c nude mice were divided into three groups: the non-castration, castration, and castration + OPG groups. PC-3M-luc-C6 was injected into the left ventricle of the mice. Recombinant OPG was injected intravenously twice weekly in the castration + OPG group. In-vivo imaging system (IVIS®) determined that the prevalence and photon counts of bone metastasis in the castration group were significantly higher than that in the non-castration and castration + OPG groups. The mean number of RANKL-positive osteoblasts and the mean serum RANKL level in the castration group were significantly higher than those in the non-castration group. RANKL-enhanced activation of osteoclasts was attenuated in the castration + OPG group. These results suggest that the mechanisms of RANK/RANKL signaling are involved in the ADT-induced acceleration of bone metastasis in castration-insensitive prostate cancer.

[Outcome of Resection of Inferior Vena Cava Superior to the Renal Vein in Renal Cell Carcinoma with Vena Caval Tumor Thrombus].

Surgical management with radical nephrectomy and thrombectomy has often been performed in renal cell carcinoma (RCC) with tumor thrombus infiltrating the inferior vena cava (IVC). We retrospectively reviewed the outcomes of IVC resection without venous reconstruction in patients with RCC and IVC thrombus at our institution. Eight patients with right RCC underwent radical nephrectomy and IVC resection superior to the level of the renal vein without venous reconstruction from August 2005 to February 2015. Thoracotomy, liver mobilization, and extracorporeal circulation were performed based on the IVC thrombus level. We assessed surgical outcomes, perioperative complications, and survival. At presentation, four patients had level IIIa IVC thrombus, three had level IIIb IVC thrombus, and one had level IV IVC thrombus. Perioperative imaging showed that three of the four patients who underwent neoadjuvant molecular targeting therapy achieved down-staging of the tumor thrombus level. The median operative time was 406 min, and the median estimated blood loss was 3,135 ml. With regard to IVC resectionassociated perioperative complications, one patient needed extracorporeal circulation with IVC ligation and Pringle maneuver owing to low blood pressure. Another patient underwent temporary hemodialysis for 8 days after surgery. There were no perioperative deaths, and none of the patients required permanent hemodialysis. Three patients survived the mean observation period of 25 months, including one patient with no recurrence. Three patients achieved long-term survival of more than 2 years. IVC resection without venous reconstruction may be a feasible option for patients with RCC and IVC tumor thrombus. Further study is needed to determine the most appropriate candidates for this procedure.

Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been used as standard therapy for patients with advanced renal cell carcinoma (RCC). However, information on factors predicting response to treatment with TKIs is lacking. This study aimed to assess the association between initial tumor size, involved organs, pre-treatment C-reactive protein (CRP) levels, and reduction in tumor size in patients with clear cell RCC (CCRCC) treated with sunitinib. METHODS: Patients with advanced CCRCC with target lesions with a maximum diameter ≥ 10 mm treated with sunitinib were evaluated. The tumor diameter representing the best overall response was designated as the post-treatment tumor diameter. RESULTS: A total of 179 lesions in 38 patients were analyzed. Organ-specific analysis demonstrated that pre-treatment diameter of lung metastatic lesions had a moderate inverse association with percent reduction in post-treatment tumor diameter (R = 0.341). Lung lesions showed significantly greater percent reductions in diameter than liver and kidney lesions (P = 0.007 and 0.002, respectively). Furthermore, based on a CRP cut-off level of 2.0 mg/dl, mean tumor size reduction was significantly greater in patients with low CRP levels than in patients with high CRP levels in lesions with diameters < 20 mm (P = 0.002). CRP level had no effect on mean size reduction in lesions with a diameter ≥ 20 mm. CONCLUSIONS: Patients with CCRCC with smaller lung metastatic lesions and lower CRP levels may achieve greater percent reductions in tumor size with sunitinib therapy than patients with extra-pulmonary lesions, large lung lesions, and/or higher CRP levels.

Laparoendoscopic single-site plus one trocar donor nephrectomy using the GelPort: initial clinical experience.

OBJECTIVE: To achieve better cosmesis, less invasiveness, and less morbidity in donor nephrectomy without using specialized instruments, which is usually required in the laparoendoscopic single-site (LESS) procedure, we performed laparoendoscopic plus one trocar donor nephrectomy (LEPODN). METHODS: From October 2010 to December 2011, 20 living renal transplantation donors underwent the LEPODN procedure. Their mean age, body mass index (BMI), and preoperative creatinine clearance were 55.7 years, 23.2, and 118.4 mg/min, respectively. The GelPort laparoscopic system was inserted through a 5-6 cm pararectal incision at the umbilicus level. A subcostal 5-mm right-hand working trocar was placed under the left costal arch. The graft kidney was extracted using a retrieval bag. A 5-mm diameter drain was placed via a right-hand working trocar. Operative data of LEPODN were retrospectively compared to those of standard laparoscopic donor nephrectomy (standard-LDN, n = 27) previously performed at our hospital. RESULTS: The procedure was technically successful in all 20 patients. The mean operative time in the LEPODN group was significantly shorter than that in the standard-LDN group (229.1 vs 249.8 minutes, P = .033). Mean blood loss and warm ischemic time in the LEPODN group were 39.4 mL and 272.4 seconds, respectively. The mean serum creatinine concentrations of the recipients 7 and 30 days after operation were 1.57 and 1.13 mg/dL, respectively. These results were not significantly different from those in the standard-LDN group. CONCLUSION: The LEPODN procedure was feasible and performed without specialized instruments by surgeons experienced in only standard laparoscopic nephrectomy.

Comparison of surgical stress in patients undergoing open versus laparoscopic radical prostatectomy by measuring perioperative serum cytokine levels.

PURPOSE: We evaluated the perioperative serum levels of inflammatory cytokines in patients with prostate cancer (PCa) treated with open or laparoscopic radical prostatectomy (RP) and assessed the surgical stress based on the cytokine levels in addition to conventional clinical stress markers after surgery. PATIENTS AND METHODS: One hundred sixty-five patients who received RP for clinically localized PCa were enrolled. Serum levels of interleukin (IL)-10, IL-6, tumor necrosis factor-α, IL-1ß, IL-8, and IL-12p70 were quantitatively measured using a multiplex bead array at three time points (i.e., before the operation [pre-OP], immediately after the operation [post-OP], and on postoperative Day 1 [POD1]). The perioperative changes in serum stress markers, including cytokines, were compared between patients who underwent open and laparoscopic RP, and the predictors for high levels of postoperative cytokines were assessed. RESULTS: The median age and estimated blood loss were significantly lower in the laparoscopic RP group than in the open RP group (P=.003 and P<.01, respectively). In all patients, body temperature, white blood cell count, and serum IL-10 and IL-6 levels were significantly higher at post-OP and POD1 than at pre-OP. Patients who underwent laparoscopic RP had significantly lower levels of serum IL-10, IL-6, and IL-1ß at post-OP and POD1 than those who underwent open RP. Multivariate regression analyses showed that the surgical group (open versus laparoscopic) was an independent influencing factor on the levels of serum IL-6 and IL-10 at POD1 (P=.031 and P<.004, respectively) among various clinical perioperative parameters. CONCLUSIONS: Several inflammatory cytokines, particularly IL-6 and IL-10, are potential surgical stress markers in patients with PCa treated with RP. Based on cytokine production, our data support the view that laparoscopic RP is less invasive than open RP.

Hyperuricemia at 1 year after renal transplantation, its prevalence, associated factors, and graft survival.

BACKGROUND: The present study investigated the prevalence and predictors for the development of hyperuricemia within 1 year after transplantation and their associations with genetic polymorphisms and graft outcome in patients taking tacrolimus and mycophenolate mofetil. METHODS: One hundred twenty-one renal allograft recipients transplanted between January 2001 and March 2009 were studied. Patients with serum uric acid concentrations above 7.0 mg/dL within 1 year after transplantation were defined as having hyperuricemia, and all were treated with allopurinol. Genetic polymorphisms of nitric oxide synthase, angiotensin-converting enzyme, methylenetetrahydrofolate reductase, and 3 uric acid transporters were examined. RESULTS: At 1 year after transplantation, 46 (38%) recipients developed hyperuricemia. Male gender, higher body mass index, long-term pretransplantation dialysis, and hypertension were associated with the development of hyperuricemia. The estimated glomerular filtration rate (eGFR) at 1 year after transplantation was lower in the patients with hyperuricemia than in those without. There were no differences in graft survival between the two groups. The pharmacokinetics of tacrolimus and mycophenolic acid and 6 polymorphisms were not associated with hyperuricemia. In the multivariate analysis, male gender, long-term pretransplantation dialysis (>36 months), and eGFR (<60 mL/min) were independently associated with the development of hyperuricemia. CONCLUSION: The incidence of hyperuricemia in our cohort was 38%. Male gender and long-term pretransplantation dialysis were predictors for the development of hyperuricemia. The eGFR was lower in patients with hyperuricemia, but graft survival did not differ between the patients with hyperuricemia treated with alloprinol and those without hyperuricemia. We could not define the significance of the pharmacokinetics of immunosuppressants and genetic risk factors for hyperuricemia.

Comparison of the clinical outcome and systemic inflammatory marker levels between retroperitoneal and transperitoneal laparoscopic donor nephrectomy.

BACKGROUND AND PURPOSE: Whether the retroperitoneal approach (RA) or the transperitoneal approach (TA) for performing laparoscopic donor nephrectomy (LDN) in kidney transplant donors is less invasive is unclear. In this study, we compared the clinical outcome and systemic inflammatory marker levels between RA and TA to assess surgical invasiveness. PATIENTS AND METHODS: We enrolled 105 donors (RA: 41, TA: 64) who underwent LDN in our hospital. Evaluation of both approaches included comparison of conventional clinical parameters and preoperative, immediate postoperative, and 1-day postoperative levels of the following circulating inflammatory cytokines: Tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-8, IL-10, and IL-12p70. RESULTS: The frequency of right nephrectomy being performed was significantly lower in the TA than in the RA group (3/64 vs 12/41, P<0.001). Other clinical parameters in the TA group, including the frequency of surgical complications and incidence of delayed graft function, were comparable to those in the RA group. Immediate and 1-day postoperative mean serum IL-6 levels were significantly higher in the RA than in the TA group (P=0.023 and 0.044, respectively). The 1-day postoperative mean serum IL-10 level was also significantly higher in the RA than in the TA group (P=0.041). Meanwhile, the mean serum IL-6 and IL-10 levels were not associated with surgical duration or estimated intraoperative blood loss. CONCLUSIONS: Conventional clinical parameters related to surgical invasiveness were comparable in both approaches, thus indicating that both LDN approaches were similar and equally effective as minimally invasive procedures. The clinical significance of the higher postoperative mean serum IL-6 and IL-10 levels in the RA group remains to be clarified in a future study.

Short-term clinicopathological outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade, followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with high-risk localized prostate cancer.

BACKGROUND: To assess the outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with a high risk of localized prostate cancer (PCa). METHODS: Complete androgen blockade followed by 6 cycles of docetaxel (30 mg/m2) with estramustine phosphate (560 mg) were given to 18 PCa patients before radical prostatectomy. Subsequently, the clinical and pathological outcomes were analyzed. RESULTS: No patients had severe adverse events during chemohormonal therapy, and hence they were treated with radical prostatectomy. Two patients (11.1%) achieved pathological complete response. Surgical margins were negative in all patients. At a median follow-up of 18 months, 14 patients (77.8%) were disease-free without PSA recurrence. All 4 patients with PSA recurrence had pathologic T3b or T4 disease and 3 of these 4 patients had pathologic N1 disease. CONCLUSION: We found that neoadjuvant chemohormonal therapy with complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy was safe, feasible, and associated with favorable pathological outcomes in patients with a high risk of localized PCa.

Outcome, clinical prognostic factors and genetic predictors of adverse reactions of intermittent combination chemotherapy with docetaxel, estramustine phosphate and carboplatin for castration-resistant prostate cancer.

OBJECTIVES: Docetaxel-based chemotherapy is effective in patients with castration-resistant prostate cancer (CRPC). This phase II study assessed the outcome and predictive factors for prognosis and toxicity following intermittent chemotherapy with docetaxel, estramustine phosphate, and carboplatin (DEC) in patients with CRPC. METHODS: Thirty-five patients were treated with a DEC regimen that consisted of a 28-day cycle of drugs as follows: docetaxel (60 mg/m(2) on day 1), carboplatin (AUC 5 on day 1) and estramustine phosphate (560 mg daily). Treatment was continued intermittently. The end point was to test the effect of DEC on the response rate and overall survival (OS). Statistical correlations between the outcomes and predictive factors, including clinical parameters and 8 single-nucleotide polymorphisms (SNPs) related to drug metabolism, were assessed. RESULTS: Prostate-specific antigen levels decreased by more than 30% in 65.7% of the patients. The median OS following DEC was 17.8 months, and the median total time of chemotherapy holiday was 7.7 months (range 1.7-35.8). On multivariate analysis, serum lactate dehydrogenase (LDH) was an independent prognostic factor for OS (p = 0.007). On SNP analysis, patients carrying the TT genotype of the ABCB1 C3435T polymorphism showed a significantly more severe leukocytopenia during the first cycle of DEC therapy compared to patients with the CC + CT genotype (p = 0.036). CONCLUSION: Combination chemotherapy with DEC has a potential effect on CRPC with acceptable toxicity. Serum LDH may be a promising predictor of prognosis, and the ABCB1 C3435T polymorphism may be a genetic predictor of the severity of leukocytopenia in patients with CRPC treated with DEC.

Antitumor effect of sunitinib against skeletal metastatic renal cell carcinoma through inhibition of osteoclast function.

We investigated the inhibitory effect of sunitinib, a newly approved multitargeted tyrosine kinase inhibitor, against the progression of renal cell cancer (RCC) bone metastases in vivo. In vitro cell proliferation was determined using the MTS assay. To investigate the inhibitory effects of sunitinib in vivo, we established luciferase-labeled ACHN(Luc) cells derived from papillary RCC. Mice in which ACHN(Luc) cells had been transplanted into the left ventricle to establish bone metastases were treated orally with 40 mg/kg/day sunitinib or vehicle control for 3 weeks. Growth of the cancer cells was monitored using an in vivo imaging system. In addition, 16 patients with metastatic RCC were treated with sunitinib, and serum and urine levels of amino-terminal telopeptide (NTx) were measured as markers of bone resorption. Sunitinib did not inhibit the growth of RCC cells in vitro at clinically or experimentally achievable serum levels (100 nM-1 µM). To investigate the inhibitory effect of sunitinib in vivo, we established luciferase-labeled human RCC cells (ACHN(Luc) ). Sunitinib prevented the growth of ACHN(Luc) RCC cells in the bone metastatic mouse model. The number of osteoclasts in sunitinib-treated mice was significantly less than that in control mice. Serum and urine levels of NTx in patients with metastatic RCC declined significantly during the first 4 weeks of sunitinib treatment (p = 0.027). Sunitinib is a potent anticancer agent for RCC bone metastases, at least for papillary RCC.

What is the most preferred wound site for laparoscopic donor nephrectomy?: a questionnaire assessment.

INTRODUCTION: Although specimen extraction site selection for laparoscopic donor nephrectomy (LDN) is relatively flexible and is mostly selected by surgeons from the patient's standpoint, the patient's request may differ from the medical worker's recommendation. The cosmetic aspect may also differ with age, gender, and the extent of medical knowledge. We performed an unsigned questionnaire assessment of individual preferences for LDN wound sites. MATERIALS AND METHODS: Between August 2007 and October 2008, we surveyed LDN wound site preferences among 148 physicians, 263 nurses, and 266 outpatients of urology at Akita University Hospital. They were questioned for their age, gender, occupation (medical worker or not), and for the most preferred surgical wound site among the following: A, lower vertical midline: B, upper vertical midline: C, anterior subcostal: D, Pfannenstiel: E, Gibson: and F, subcostal flank. The valid response rate was 93.5% (677/724). RESULTS: Wound sites preferred (ranked in descending order) were F (48.3%), D (25.6%), E (10.5%), A (9.0%), C (5.2%), and B (1.4%). The subcostal flank incision was the most preferred in almost all the categories. Second preferences were Pfannenstiel incisions in women and incisions on the lower abdomen in men. Overall, flank and lower abdominal incisions tended to be preferred, and mid and upper abdominal incisions tended to be avoided. Medical workers selected the subcostal flank and Pfannenstiel incisions more frequently than outpatients. With increasing age, the selection rates of the Gibson and the lower vertical midline incisions increased, whereas the subcostal flank and the Pfannenstiel incisions decreased. CONCLUSIONS: The subcostal flank was the most preferred LDN sites. Age, gender, and the extent of medical knowledge may influence the individual preferences for LDN wound sites.

Combination therapy consisting of gemcitabine, carboplatin, and docetaxel as an active treatment for advanced urothelial carcinoma.

BACKGROUND: To evaluate the efficacy and toxicity of a combination chemotherapy consisting of gemcitabine, carboplatin, and docetaxel (GCD) in patients with advanced urothelial carcinoma (UC) as a phase II trial. MATERIALS AND METHODS: Patients with metastatic or locally advanced unresectable UC were eligible for this trial. All enrolled patients were considered to be "unfit" for cisplatin-based chemotherapy, or to have methotrexate, vinblastine, doxorubicin, cisplatin (MVAC)-refractory UC. The chemotherapy regimen consisted of gemcitabine 1000 mg/m(2) on days 1 and 8, and carboplatin (with a target area under the curve of 5) and docetaxel 70 mg/m(2) on day 1; this was repeated every 21 days. RESULTS: Thirty-five patients were enrolled, with a median age of 68 years. A total of 89 cycles were administered (median, 2 cycles). Major toxicities were Grade 3/4 neutropenia in 28 (80.0%) patients and Grade 3/4 thrombocytopenia in 18 (51.5%). An objective response rate (ORR) was 11 of 21 patients (52.4%), including a complete response in 1 (4.8%). The median overall survival (OS) was 13.1 months (1-year survival rate, 60%) and the median progression-free survival (PFS) was 5.0 months. Among 16 patients who had previously received MVAC, the ORR, the median PFS, the median OS and 1-year survival rate was 56.3%, 5.0 months, 12.6 months and 54%, respectively. CONCLUSIONS: GCD chemotherapy is active and well tolerated as a first- or second-line therapy for patients with advanced UC. Response rate, duration and survival did not differ between those with and without a history of MVAC treatment.

[Primary retroperitoneal carcinoid tumor associated with multiple endcrine neoplasia (men) type 1: a case report].

We report an extremely rare case of a 69-year-old man having a retroperitoneal carcinoid tumor associated with multiple endocrine neoplasia (MEN) type 1. The patient whose son and daughter were previously diagnosed with MEN type 1 was admitted to the Department of Endocrinology at our hospital for evaluation of this disorder. Computed tomography (CT) and ultrasonography revealed a parathyroid and retroperitoneal tumor (43 mm x 34 mm). The patient did not consent to surgical management of the tumor; however three years later, a follow-up CT revealed tumor enlargement (55 mm x 50 mm). We were unable to rule out a malignancy, and subsequently resected the tumor. A pathological diagnosis of retroperitoneal carcinoid was made. No local recurrence or metastasis have been observed for 21 months.

Two survivin polymorphisms are cooperatively associated with bladder cancer susceptibility.

Abnormal survivin expression has been reported to be involved in many types of cancer. A single-nucleotide polymorphism (SNP), C-31G, located in the promoter region of survivin reportedly may alter the mRNA level, while the significance of the nonsynonymous SNP A9194G in exon 4 has not yet been clarified. Here, the association between the two survivin SNPs and bladder cancer susceptibility and progression was investigated in 235 patients with bladder cancer and 346 healthy controls. Regarding the C-31G SNP, subjects with the CC genotype had a significantly higher risk of bladder cancer compared to those with the GG + CG genotype [odds ratio (OR) = 1.85, p = 0.001]. Regarding the A9194G SNP, the presence of the G allele was associated with a significantly reduced risk with a gene dosage effect (OR = 0.69, p = 0.002). Using the C-A haplotype as a reference, the G-G haplotype was associated with a significantly lower risk (OR = 0.11, p = 0.00006), indicating the cooperative effect of the two SNPs. Immunohistological evaluation of surgical specimens showed that cancer cells of the C-31G CC genotype had significantly higher nuclear survivin expression than those of the C-31G GG + CG genotype. With reverse transcriptase-polymerase chain reaction analysis, a significantly higher survivin mRNA expression level was observed in surgical specimens with an increase in the number of the C-31G C allele (p = 0.016). These results indicate that the two SNPs have a significant and cooperative influence on bladder cancer susceptibility.

Relationship between bone mineral density and androgen-deprivation therapy in Japanese prostate cancer patients.

OBJECTIVES: To examine Japanese patients who had received androgen-deprivation therapy (ADT) for longer periods, as it is known that ADT of patients with prostate cancer reduces their bone mineral density (BMD). However, our previous cross-sectional study revealed that short-term ADT (average, 23.5 months) does not significantly increase the prevalence of osteoporosis in Japanese patients. METHODS: The subjects consisted of 201 native Japanese patients with prostate cancer. They comprised 113 ADT-treated and 88 hormone-naive patients. Lumbar spine, total hip, and femoral neck BMDs were measured by dual-energy x-ray absorptiometry and expressed in standard deviation units relative to the scores of young adult men (T-score) or age-matched men (Z-score). Serum levels of bone metabolism markers were also measured. RESULTS: The ADT-treated patients had significantly lower BMD values, T-scores, and even Z-scores than the hormone-naive patients (P <.001). For patients who were hormone-naive, ADT-treated for less than 2 years, and ADT-treated for more than 2 years, the osteoporosis prevalence was 4.5% (4/88), 12.1% (4/33), and 10.8% (4/37), respectively. The ADT-treated patients had significantly higher serum amino-terminal telopeptide levels than the hormone-naive patients (P = .014), but significantly lower serum carboxy-terminal telopeptide of type-I collagen levels than the ADT-treated patients with bone metastasis (P <.001). CONCLUSIONS: Our cross-sectional study confirmed that both ADT-treated and hormone-naive Japanese patients with prostate cancer have low rates of osteoporosis. These findings are different from those of studies in western countries. Genetic and hormonal or other environmental factors may result in population differences in the characteristics of prostate cancer and BMD.