Akinori Nukui

Serum PSA and Percent Free PSA Value Changes after Antibiotic Treatment

Introduction: An association between inflammatory foci in prostatic tissues and elevated serum prostate-specific antigen (PSA) levels has been a controversial issue. We studied the effects of antibiotics on elevated PSA levels to improve the diagnostic value of prostate cancer findings. Patients and Methods: Of 65 asymptomatic men with inconstant PSA elevation, 51 with laboratory signs of prostatitis received antibiotics instead of undergoing a prompt prostate biopsy. Asymptomatic prostatic inflammation was defined as the presence of >10 white blood cells/high-power field in the post-prostate massage urine. Follow-up measurements of PSA and percent free PSA values were obtained. Results: Approximately 30% of the patients had a treatment response, defined as PSA decrease >20% from baseline. The range of the variations of PSA and percent free PSA values, expressed as coefficient of variation, also decreased significantly. Moreover, antibiotic treatment lowered the extent of histological prostatic inflammation in some patients. Conclusions: Subclinical prostatic inflammation potentially contributes to an elevated PSA level and its variation among prostate cancer suspects. Watchful observation may be an optional tool for patients showing a significant PSA decrease following antibiotic treatment.

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.

Serum Anti–p53 Antibodies and p53 Protein Status in the Sera and Tumors from Bladder Cancer Patients

Objectives: The purpose of this study was to evaluate the association between the serum anti–p53 antibodies (Abs) status and the p53 protein status in the sera and tumors as well as clinical or pathological parameters in bladder cancer patients retrospectively.Methods: Serum samples from 100 patients with bladder cancer were assayed for anti–p53 Abs and p53 protein by enzyme–linked immunosorbent assay (ELISA). A monoclonal antibody DO7 was used for immunohistochemical staining of tumor p53 protein.Results: Prevalences of serum anti–p53 Abs, serum p53 protein and tumor p53 protein were 12, 1 and 63%, respectively. There was a significant correlation between serum anti–p53 Abs status and factors including tumor stage, tumor grade, and tumor p53 protein status. In the univariate analysis, tumor stage, tumor grade, serum anti–p53 Abs status, and tumor p53 protein status were significantly associated with an increased risk of death. Multivariate analysis showed that tumor stage was the only independent prognostic factor among the factors examined.Conclusions: The present study suggests that serum anti–p53 Abs had a limited value as a tumor marker in bladder cancer patients. Further studies to elucidate the mechanism of anti–p53 Abs production will be necessary for a better understanding of the immune status in bladder cancer patients.

Transplantation of ABO-Incompatible and Living Unrelated Donor–Recipient Combinations

INTRODUCTION According to the Japanese renal transplant registry 2005, 834 transplantations were performed using living donors. Among them 199 (23.9%) kidneys were donated from spouses (husband/wife) and 174 (20.9%) from ABO-incompatible donors. This study summarized our experience of ABO-incompatible and living unrelated, especially spousal kidney transplantation. PATIENTS AND METHODS We performed 44 cases of living donor kidney transplantation (LKT) between April 2003 and July 2007, including 14 (31.8%) from spouses (unrelated donor) who were divided into two groups: six patients (group 1; G1) from ABO-incompatible donors and eight patients (group 2; G2) from ABO-compatible donors. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were used for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. In all G1 patients plasmapheresis was performed to remove anti-AB antibodies prior to LKT, and splenectomy performed at the time of or before LKT. RESULTS Among G1, no patient died. Among G2, one patient died with a functioning graft due to a traumatic subdural hematoma. Graft survival rate was 100% in both groups. The incidence of acute rejection was 33.3% and 25.0% in G1 and G2, respectively. No patient experienced a lethal infectious complication. CONCLUSIONS Our results demonstrated that transplantation from an ABO-incompatible spousal donor was equivalent to transplantation from an ABO-compatible spousal donor. In response to the shortage of deceased donors, LKT between married couples and from ABO-incompatible donors will spread in Japan.

Strategic Hand Assistance for Effective and Safe Retroperitoneoscopic Live Donor Nephrectomy

Hand-assisted laparoscopic live donor nephrectomy has been widely applied, because it enables safe dissection of the renal vessels, reducing warm ischemia time (WIT) during rapid extraction of the kidney. In the method described in the current series, the hand-port device was placed after the kidney was mostly mobilized using a pure retroperitoneoscopic procedure. After placement of the hand port, the ureter was completely dissected by an open procedure. Finally, the renal vessels were dissected and transected under the hand-assisted retroperitoneoscopic procedure, and the kidney removed through the hand port. We performed 66 retroperitoneoscopic live donor nephrectomies, including 14 right-sided and 52 left-sided procedures, with this original method of hand assistance. The mean operative time, WIT, blood loss, and renal vein length were 246 +/- 43 minutes, 209 +/- 124 seconds, 202 +/- 180 mL, and 17.4 +/- 6.4 mm, respectively. Comparison of the operative data between the initial 30 cases and the recent 36 cases using the established method showed significant differences in blood loss and WIT that approached statistical significance. No delayed graft function was observed in the current series. The technical and functional outcomes were acceptable. The site and timing of hand assistance minimize the disadvantage of a small working space during the retroperitoneoscopic procedure, making surgery easier and safer.

Kidney transplantation in patients with long-term (more than 15 years) prior dialysis therapy.

OBJECTIVE The number of kidney transplantations (KTx) among patients on long-term hemodialysis (HD) is increasing due to the donor shortage in Japan. We investigated the outcomes of KTx among long-term (more than 15 years) patients on HD. METHODS We performed 103 KTx between April 2003 and April 2010 including seven patients (one living and six deceased donor grafts), who had been treated with HD for more than 15 years (group 1) compared with 96 patients (94 living and two deceased donor grafts) treated for less than 15 years (group 2) before KTx. We examined the differences in patient and graft survivals and complication rates between the groups. RESULTS Acute rejection episodes (ARE) occurred in 2 (29%) group 1 and 22 (22%) group 2 subjects. Urinary tract infections were diagnosed in 1 (14%) group 1 versus 8 (8%) group 2 cases. The incidence of perioperative complications, such as delayed graft function, cytomegalovirus infection, and surgical complications was higher among group 1. The serum creatinine at 1 year after KTx was the same (1.3 mg/dL). The patient/graft survivals were 100%/100% at 1 and 3 years in group 1 versus 100%/100% at 1 and 99%/98% at 3 years in group 2. CONCLUSION The outcomes of KTx among long-term dialysis patients were similar to those in short-term dialysis patients.

Kidney transplantation of living unrelated donor-recipient combinations.

INTRODUCTION According to the Japanese renal transplant registry in 2009, there were 1123 living kidney transplantations (LKT), including 35% from spouses (husband/wife). Up to the present in Japan, biologically living unrelated donors (LURD) are most frequently spouses. This study summarized our experience with LURD, especially spousal, kidney transplantation. PATIENTS AND METHODS We performed 112 cases of LKT between April 2003 and March 2011, including 44 (39%) from spouses and two from other LURD. The other 66 cases received kidneys from living related donors (LRD). We divided the patients into two groups: 44 patients (group 1) received kidneys from spouses (LURD) and 66 (group 2) from LRD. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were prescribed for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. In ABO-incompatible LKT, plasmapheresis was performed to remove anti-AB antibodies prior to LKT; splenectomy or rituximab administration, at the time of or before LKT. RESULTS Among group 1, one patient died with a functioning graft and one lost her graft. Among group 2, one patient died with a functioning graft and one lost his graft. The incidences of an acute rejection episode were 31.8% and 24.2% in groups 1 and 2, respectively. There were three cases of antibody-mediated rejection in group 1. No patient experienced a lethal infectious complication. CONCLUSIONS Our results demonstrated that spousal LKT (LURD) was equivalent to LKT from LRD. In response to the shortage of deceased donors, LKT between married couples and from ABO-incompatible donors will spread in Japan.

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.

Kidney Transplantation of Living Unrelated and ABO-Incompatible Donor-Recipient Combinations

INTRODUCTION In Japan, ABO-incompatible (ABO-IC) living kidney transplantation (LKT) has been performed among more than 2000 patients between 1989 and 2010 seeking to compensate for the shortage of donor organs. In addition, many patients lack a genetically living related donor (LRD); therefore, volunteer spouses (unrelated, LURD) have been considered since about 1990. PATIENTS AND METHODS We performed 112 LKT between April 2003 and March 2011, including 44 (39%) spousal and two other LURD. The other 66 cases received LRD kidneys. We divided patients into two groups: 44 patients (group 1) received a kidney from a spouse (LURD) and 66 (group 2) from LRD. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were prescribed for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. For ABO-IC LKT, plasmapheresis was performed to remove anti-AB antibodies prior to LKT. Splenectomy was performed at the time of or before LKT. Since March 2010, rituximab administration was performed before transplantation instead of splenectomy. RESULTS Death-censored graft survival rates were 97.7% in group 1 and 98.5% in group 2, respectively. The incidences of acute rejection episodes were 31.8% and 24.2% in groups 1 and 2, respectively. There were three cases of antibody-mediated rejection in group 1. No patient experienced a lethal infectious complication. CONCLUSIONS Our results demonstrated that spousal LKT (LURD) was equivalent to LRD. In response to the shortage of deceased donors and genetically LRD, LKT between married couples or from ABO-IC donors will spread in Japan.

Clinical outcome and prognostic survival factors in patients with advanced renal cell carcinoma treated with very low-dose interleukin-2, interferon-α, and tegafur-uracil: a single-institution experience

BackgroundThe objective of the current study was to determine the efficacy and safety of very low-dose interleukin-2 (IL-2), interferon (IFN)-α, and tegafur-uracil for patients with unresectable renal cell carcinoma (RCC), metastatic RCC, or both. Clinical prognostic factors were also investigated.MethodsFifty consecutive patients underwent a 3-week treatment cycle of IL-2 (0.7 × 106 Japanese reference units [JRU])/person on days 1–3 weekly), IFN-α (3 × 106 international units/person, on days 1–5 weekly), and tegafururacil (300 mg/person daily).ResultsThe median follow-up after treatment initiation was 11.3 months. A median of three (range, 1–20) treatment cycles was administered. Of 47 eligible patients, 4 had a treatment response (3 complete responses and 1 partial response; objective response rate, 8.5%). The median progression-free and overall survivals were 8.3 months (95% confidence interval [CI], 5.5–10.9 months) and 38.8 months (95% CI, 27.8–49.7 months), respectively. Only 8 patients had grade III/IV toxicities. Two parameters, i.e., the absence of a previous nephrectomy and a low hemoglobin level, were identified as independent factors predictive of poor survival. Patients with low or intermediate risk (presence of none or one of the two prognostic factors) had a durable median survival exceeding 30 months. High-risk patients with both risk factors had rapid disease progression despite treatment.ConclusionWhile the effectiveness of this immunochemotherapy resulted in a limited antitumor response, low-and intermediate-risk patients with metastatic RCC seemed likely to have a survival benefit. Patient selection is essential to enhance treatment efficiency and avoid useless treatment for high-risk patients.