Kouhei Nishikawa

Intermittent docetaxel therapy with estramustine for hormone-refractory prostate cancer in Japanese patients.

BackgroundWe evaluated the efficacy and toxicity of intermittent docetaxel (DCT) with estramustine (EM) for hormone-refractory prostate cancer (HRPC).MethodsFifteen patients were enrolled. They received injected DCT (70 mg/m2 body surface) on day 1 in association with oral EM 560 mg/day (days 1–5). Treatments were repeated every 3 weeks. Serum prostate-specific antigen (PSA) levels were categorized based on the first three courses. Patients exhibiting either a response or stable disease (SD) could have a holiday from treatment (intermittent schedule). The holiday continued until elevation of the PSA level from the nadir baseline level occurred three times. All patients were evaluated for toxicity and quality of life (QOL). Survival curves were established using Kaplan-Meier graphs.ResultsThe median number of courses of DCT/EM therapy was five (range, 3–12 courses). The response rate of the first cycle was 53%: 3 patients with complete response (CR), 5 patients with partial response (PR), 4 patients with SD, and 3 patients with disease progression. Eight patients were able to begin the second re-entry cycle. No patients showed a CR, 2 patients exhibited PR, 4 patients had SD, and the overall response rate was 25%. The survival rates were 93% at 1 year, and 26.1% at 2 years Grade 3–4 anemia was observed in 2 patients (13.3%), neutropenia in 11 (73.3%), and thrombocytopenia in 2 (13.3%). The QOL scale showed good QOL after 6 months, with improvement in the score for nausea and vomiting.ConclusionIntermittent DCT/EM therapy was well tolerated, and has the potential to prolong survival, with a high QOL, in patients with HRPC.

Low incidence of benign lesions in resected suspicious renal masses greater than 2 cm: Single-center experience from Japan

Objective:  To assess the incidence of benign renal lesions in our Japanese clinical experience with surgical resection.

Comparison of radical nephrectomy techniques in one center: Minimal incision portless endoscopic surgery versus laparoscopic surgery

This study was designed to assess the intraoperative and postoperative benefits of two techniques for treating renal cell carcinoma (portless endoscopic surgery with radical nephrectomy [PLES‐RN] and laparoscopic radical nephrectomy [LRN]) carried out at a single center. Radical nephrectomy with either PLES‐RN (14 cases) or LRN (15 cases) was carried out on 29 patients with cT1 renal cell carcinoma. There were no statistically significant between‐group differences in patient characteristics (except tumor side), operation time, and amount of blood loss (χ2 and Fishers test). No blood transfusions were required in either group. The mean incision length of PLES‐RN was not significantly longer than that of LRN. No minor or major complications resulted. From postoperative data, the first intake of fluid (P = 0.07) and food (P = 0.02) tended to be sooner in the PLES group than the LRN group. Postsurgically, white blood cell count and C‐reactive protein were not significantly different between the two groups. The added cost of disposable instruments needed in LRN was 111 570 Japanese yen (1115.7 United States dollars). Both techniques are optimal options for surgically treating early renal cell carcinoma. The comparison related to invasiveness between the two methods should be evaluated using a large number of cases focusing on the various aspects for the future.

A case of IgG4-positive plasma cell-rich tubulointerstitial nephritis in a kidney allograft mimicking IgG4-related kidney disease.

A 51‐year‐old woman received an ABO blood type‐incompatible renal transplant. She was administered rituximab and basiliximab and underwent plasma exchanges for induction therapy, followed by administration of tacrolimus, mycophenolate mofetil and methylprednisolone as maintenance immunosupression therapy. A planned renal biopsy 2 years after transplantation revealed infiltration of plasma cells in the renal interstitium, although there was no ‘storiform’ fibrosis surrounding these cells. There were also no findings of rejection, BK virus nephropathy, or atypical plasma cells. Immunohistochemical stainings showed a large number of IgG4‐positive plasma cells, most of which expressed kappa‐type light chains. A CT scan showed a mass at the renal hilum. The serum IgG4 level was high. Based on these findings, the patient was suspected of having IgG4‐related kidney disease. Nine months after the biopsy, her serum creatinine level increase to 1.56 mg/dL and the dose of methylprednisolone was therefore increased to 16 mg/day. Three months after this increase in steroid, a CT scan showed the hilum mass had disappeared. A follow‐up biopsy 5 months later showed that infiltration of plasma cells in the renal interstitium had decreased markedly, although focal and segmental severely fibrotic lesions with IgG4‐positive plasma cells were observed. Serum IgG4 levels decreased immediately after the increase in steroid dose and remained <100 mg/dL despite a reduction in methylprednisolone to 6 mg/day. Serum creatinine levels also remained stable at around 1.6 mg/dL. To our knowledge, this is the first report of IgG4‐positive plasma cell‐rich tubulointerstitial nephritis mimicking IgG4‐related kidney disease after kidney transplantation.

Gemcitabine and capecitabine chemotherapy in Japanese patients with immunotherapy‐resistant renal cell carcinoma

The objective of this study was to evaluate the efficacy and toxicity of combined gemcitabine and capecitabine (Gca) chemotherapy in patients with advanced renal cell cancer after immunotherapy failure. Nine patients were enrolled in this trial. Gemcitabine (1000 mg/m2) was injected on days 1 and 8, followed by oral administration of capecitabine (1660 mg/m2) on days 1–14. The response rate was 11%, with a partial response in one patient (11%), stable disease in five patients (56%) and disease progression in three patients (33%). Grade 3–4 neutropenia was observed in one patient (11%) and thrombocytopenia in two patients (22%). The quality of life (QOL) questionnaire scales showed no significant changes induced by chemotherapy. The median progression‐free survival was 4 months with an overall 1‐year survival rate of 78%. Gemcitabine and capecitabine chemotherapy can be safely administered as second‐line therapy in renal cell cancer patients, maintaining QOL baseline parameters.

Usefulness of Monitoring Cell-Mediated Immunity for Predicting Post–Kidney Transplantation Viral Infection

BACKGROUND Monitoring cell-mediated immunity (CMI) can be used to estimate the risk of viral infections in kidney transplant recipients. The Immuknow (IMK) assay measures CD4(+) T-cell adenosine triphosphate activity, assesses patient CMI status, and assists clinicians in determining the risk of viral infection. METHODS We retrospectively analyzed 224 IMK values in 39 kidney transplant recipients at our institution from April 2012 to January 2013. We analyzed the relationship between IMK value and viral infection during the early and late post-transplantation periods. Multiple regression analyses were performed, to determine which factors impacted the results of the IMK assay. RESULTS Eight patients developed viral infections, including BK virus, cytomegalovirus, herpes simplex, and shingles. Five infections occurred in the early post-transplantation period (<50 d) and 3 in the late period (>120 d). The IMK levels in patients who developed an infection in the early period were within normal limits; however, those in the late period were significantly lower than 200 ng/mL (421.0 ± 062.6 for early vs 153.7 ± 72.7 for late; P = .02). Our multiple regression analyses indicated that peripheral white blood cell and neutrophil counts affected IMK values (P = .03 and P = .02, respectively). CONCLUSIONS The IMK assay is a useful test for identifying patients at risk for post-transplantation viral infections in the late transplant period.

Manserin as a novel histochemical neuroendocrine marker in prostate cancer.

OBJECTIVES To investigate the presence of manserin in human prostate cancers and to correlate manserin expression with pathologic outcomes and progression-free survival. METHODS Eighty-seven patients with recent prostate cancer were classified into 4 groups based on Gleason score, and manserin immunohistochemistry was correlated with Gleason sum grade. To investigate the validity of manserin as a prognostic factor, the Cox proportional hazards regression model was performed on 48 patients in our cohort with T3 or T4 prostate cancer who were initially treated with androgen deprivation therapy. RESULTS The manserin-positive rates of patients with Gleason sums of 6, 7, 8, and ≥9 were 0%, 20.0%, 35.0%, and 48.1%, respectively. Manserin-positive rates were positively correlated with Gleason sums (P = 0.0001). Median times to cancer progression in groups with (n = 8) and without (n = 40) manserin expression were 8 months and 28 months, respectively (P = 0.01). Univariate Cox analysis revealed that manserin expression, clinical stage T4, and high Gleason sum were significantly associated with progression. Multivariate analysis revealed that only 2 factors, manserin expression (hazard ratio (HR) 4.99, P = 0.01) and clinical stage T4 (HR 4.77, P = 0.03), were independent risk factors for progression. CONCLUSIONS This is the first report of manserin expression in human prostate cancers. Manserin may serve as a marker of prostate cancer progression.

Immune Response following Liver Transplantation Compared to Kidney Transplantation: Usefulness of Monitoring Peripheral Blood CD4+ Adenosine Triphosphate Activity and Cytochrome P450 3A5 Genotype Assay

Seventy living donor liver transplantation (LDLT) and 39 kidney transplantation (KT) patients were randomly screened by using the peripheral blood CD4+ adenosine triphosphate activity (ATP) assay (IMK assay). The patients were divided into 2 groups in each organ transplantation with low IMK ATP level (<225 ng/mL) or high (>225) (LT-L: n = 23, KT-L: n = 19, LT-H: n = 47, and KT-H: n = 20, resp.). The incidence of bacterial and/or viral infection was significantly higher in LT-L group than in LT-H group (74.0 versus 8.5%: P < 0.001). Occurrence of total viral infection in KT-L was also significantly higher than that in KT-H (36.8 versus 10%: P = 0.046). The sensitivity and specificity of the IMK assay for identifying risk of infection was 0.810 and 0.878 in LDLT patients and 0.727 and 0.607 in KT patients. The percentage of LDLT patients with cytochrome P450 3A5 (CYP3A5) *1/*1 or *1/*3 genotype (expressors) was significantly higher in LT-L group than in LT-H group (53.8 versus 20.7%: P = 0.032). In both LDLT and KT patients, the IMK assay can be useful for monitoring immunological aspects of bacterial and/or viral infection. CYP3A5 expressors in LT-L group are related to postoperative infections.

The Impact of the Preoperative Serum Albumin Level and Postoperative C-Reactive Protein Nadir on the Survival of Patients with Non-Metastatic Renal Cell Carcinoma with Vessel Thrombus after Nephrectomy

Purpose: To evaluate the predictors for survival in non-metastatic renal cell carcinoma (non-mRCC) associated with tumor thrombus following surgical resection. Patients and Methods: Between February 1983 and December 2009, a total of 40 patients with a diagnosis of non-mRCC (23 with pT3a pN0M0, 15 with pT3b pN0M0 and 2 patients with pT3c pN0M0) were enrolled. Various preoperative and postoperative parameters were assessed as prognostic factors. Results: In the multivariate analysis, a low level of preoperative albumin less than 35 g/l [hazard ratio (HR) 8.06] and high postoperative C-reactive protein (CRP): CRP nadir greater than 2 mg/l (HR 1.78) were identified significant risk factors for cause-specific survival. For the risk of progression-free survival, 3 factors proved to be significant independent predictors: a low preoperative albumin (HR 25.5), a high postoperative CRP nadir (HR 18.71) and low preoperative hemoglobin (HR 17.4). In 24 cases with the high preoperative CRP (> 2 mg/l), the progression-free survival rates in the low postoperative CRP nadir group achieved a significant better survival rate than the high CRP nadir group after nephrectomy (p = 0.048). Conclusion: In non-mRCC with tumor thrombus after surgical resection, a low preoperative albumin level and an elevated postoperative CRP nadir were significant independent predictors of survival.

Mood Status and Quality of Life in Kidney Recipients after Transplantation

BACKGROUND Kidney transplantation is performed as a useful treatment to improve the quality of life (QOL) of patients with end-stage renal failure; however, the correlation between mood status and QOL among recipients post-kidney transplantation have yet to be clarified. METHODS Sixty-eight post-kidney transplantation patients who visited our institution between March and December 2016 were enrolled in this study. The QOL of the participants as measured by the Short Form-36 Health Survey Version 2 (SF-36v2) questionnaire was compared to results gathered from hemodialysis patients in a previous study. To identify the factors associated with QOL, a multiple regression analysis was performed, including some physical, mental, and socioeconomic characteristics as well as the Profile of Mood States as independent variables. RESULTS The QOL of the transplantation group was significantly higher for all 8 subscales of SF-36v2 compared to the hemodialysis group. Among the factors, greater age and higher Confusion levels were related to lower physical QOL. In addition, higher Vigor and lower Fatigue levels were related to higher mental QOL, while the condition of having an occupation was related to higher role/social QOL. CONCLUSION The QOL of recipients after kidney transplantation was better than that of hemodialysis patients. It is important to pay attention to mood status, especially confusion and fatigue, in order to maintain and improve the QOL of the recipient after kidney transplantation. Kidney transplantation can be a beneficial treatment not only physically but also psychologically and socially.