Masaaki Imanishi

Cancer risk after renal transplantation in Japan

Excess of cancer in patients receiving renal transplantation is well‐known in Western countries, but information in Japan remains limited. Our study examined whether excess risk is found in patients receiving renal transplantation in Japan. Between 1970 and 1995, 1155 males and 589 females underwent renal transplantation in 6 hospitals, and a total of 12,982 person‐years of observation was accumulated. Malignancies developed in 2.6% of patients; O/E ration was 2.78. Median interval from renal transplantation to tumor development was 58 months. The interval in the patients receiving medication with cyclosporine‐A (CyA) (median, 42.5 months) was significantly shorter than that with non‐CyA (median, 95.5 months). Median age at the diagnosis of malignancy was 40 years, which is much younger than that in the general population. Relative risk was highest in renal cancer, followed by thyroid cancer, malignant lymphoma and uterine cancer. A distribution of malignancies was different from that reported from Western countries. These findings showed the excess risk of malignancies in Japan with renal transplants, especially in male patients, similar to that observed in Western countries, though the types of malignancy were different. Int. J. Cancer 71:517‐520, 1997.

Immunofluorescent study on the interaction between collagen and calcium oxalate crystals in the renal tubules

The interaction of calcium oxalate crystals and renal tubular cells was studied. Rat renal collecting tubular cells were cultured and immunologically stained with anti-type-IV collagen antiserum (type-IV collagen exists in renal tubular basement membrane). When renal tubular cells and calcium oxalate crystals were mixed, clumps were formed. These clumps were examined by immunological staining with anti-type-IV collagen antiserum. In another series of experiments, calcium-containing crystals were found to be adsorbed onto mucous threads and cast-like materials, although no such adsorption was observed on squamous cells. These absorbed materials interacted with anti-type-IV collagen antiserum. These results suggest that collagen in the renal tubular basement membrane may act as matrix in urinary stone formation.

Characteristics and Usage of Different Ureteral Stent Catheters

Presuming that complications associated with ureteral stenting vary in type and occurrence depending on the material and cross-section of the stent, six types of stents immersed in 48 different preparations of artificial urine for 1 month to observe surface changes with a scanning electron microscope. As a result, there was less encrustation on the silicone material compared with other material types, probably due to the smoothness of the surface. This may be related with higher frequency of spontaneous removal or migration to the bladder of this catheter type. Because silicone catheters have softer and thicker walls with a narrow lumen, they may be appropriate for long-term stenting, but not for urinary drainage. In alkaline bacteriuria, struvite encrustation was observed on all stents. This reaction was especially intense with Towers peripheral stents, which had most irregular and uneven surfaces. In aseptic alkaline urine, calcium phosphate crystals partly covered with proteinaceous debris were noted on catheter surfaces. Although in some patients encrustation of uric acid occurred in the bladder portion of the stents, there was no uric acid encrustation in this experimental study.

Organ-specific unresponsiveness induced by intrathymic injection of donor bone marrow cells and a short course of immunosuppression in the rat heart transplantation model

Donor- and organ-specific unresponsiveness to Brown Norway (BN) heart allografts was achieved in Lewis (LEW) rats by giving intrathymic donor bone marrow cells (ITBMC) and immunosuppression at the time of transplantation. Antilymphocyte serum (ALS) (1 ml, days 0, 2, 4) extended graft survival to a median survival time (MST) of 29.5 days (n = 6), while ALS + ITBMC extended survival to over 120 days (n = 6). FK506 (1 mg/kg, days 0, 2, 4, 6, 8) too prolonged survival in the FK + ITBMC (n = 6; MST > 140 days) and FK (n = 5; MST > 140 days) groups. BN skin grafting provoked the rejection of long-surviving BN heart grafts in the FK group (n = 5; MST = 14 days), but did not do so in either the ALS + ITBMC (n = 2; MST > 100 days) or the FK + ITBMC (n = 4; MST > 93 days) groups. In the FK + ITBMC group, two of the rats which rejected BN skin grafts received a second BN heart, resulting in the graft being accepted indefinitely (> 100 days) without causing the rejection of the first BN heart grafts. These facts suggest that ITBMC and concurrent T cell depletion are decisive for induction of unresponsiveness by this protocol. BN and WF (Wistar Furth) skin grafts were eventually rejected in the LEW rats which accepted BN heart grafts. Persistent allogeneic chimerism was demonstrated in the graft and recipient spleen, suggesting that chimerism may be one of the possible mechanisms of unresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroid Carcinoma in a Case of Chronic Renal Failure on Dialysis

The combination of chronic renal failure plus parathyroid adenocarcinoma is very rare. A 53-year-old female had been on hemodialysis for chronic renal failure for 7 years. For 2 years she has had bilateral knee joint pain, hypercalcemia and an increased parathyroid hormone level. Swelling of parathyroid gland was diagnosed and it was excised. Histological examinations of the excised right lower parathyroid gland revealed adenocarcinoma and the left lower gland showed hyperplasia.

Efficacy and safety of treatment with low-dose Fluvastatin in hypercholesterolemic renal transplant recipients

HYPERCHOLESTEROLEMIA is one of the major risk factors for long-term patient survival of renal transplant recipients maintained with cyclosporin (CYA). When combined with CYA, HMG-CoA reductase inhibitors (HMG-CoARIs, statins) are known to induce rhabdomyolysis through the elevation of plasma statin concentration, and they also affect CYA trough level. The purpose of this study was to investigate the efficacy and safety of antihypercholesterolemic agent fluvastatin (FLU) at a low dose in recipients treated with CYA.

Clinical Outcome of Small Renal Cell Carcinoma after Delayed Surgery versus Immediate Surgery

Background: This study was undertaken to investigate the growth rate and clinical outcome of patients with a small renal mass (SRM) after delayed surgery versus immediate surgery. Methods: We reviewed the clinical records of 328 patients with SRM ≦ 4cm at diagnosis, who underwent delayed or immediate surgical intervention from January 2000 to December 2011. Radiographic evaluation using CT scan and MRI were performed at least every 6 months and the tumor size was determined at least twice in the delayed surgery group. Results: A total of 292 RCC patients with pT1aN0M0 were identified; among them, 32 patients had been managed with delayed surgery intervention. No statistically significant difference was observed in overall survival rate (OSR) and cancer recurrence-free rate (CRFR). But cancer-specific survival rate (CSSR) was significantly lower in the delayed surgery group (p=0.0002). Conclusions: The overall survival rate of delayed surgery was not inferior compared with that after immediate surgery. Delayed surgery intervention for SRMs is a treatment option in the current study.

Zoledronic acid combined with androgen-deprivation therapy may prolong time to castration-resistant prostate cancer in hormone-naïve metastatic prostate cancer patients – A propensity scoring approach

Objective To clarify the oncological benefit of zoledronic acid for hormone-naïve metastatic prostate cancer, patient outcome of androgen deprivation therapy with zoledronic acid (ADT + Z) and androgen deprivation therapy alone (ADT) was compared. Methods Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade (goserelin and bicalutamide) with zoledronic acid (4 mg every 4 weeks for 24 months). A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts (both from ADT + Z and from historical control cohorts who had undergone ADT alone), and patient outcomes were compared. Results Patients with ADT + Z had significantly longer time to progression (TTP) than those with ADT (median TTP; 24.2 vs. 14.0 months, p = 0.0092), while no significant difference of overall survival between two groups (p = 0.1502). Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor (HR: 1.724, 95% CI: 1.06–2.86, p = 0.0297). Conclusion Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.

Intravesical Bacillus Calmette-Guerin Therapy for Grade 3 Non-Muscle Invasive Bladder Cancer: Results of Six or Eight Successive Instillations

Background: Bacillus Calmette-Guerin (BCG) instillation has been considered to be the most effective method of treatment for non-muscle invasive bladder cancer. The objective of the study was to evaluate the efficacy of between 6 and 8 intravesical BCG instillations after transurethral resection of bladder tumor (TUR-Bt) for Grade 3 nonmuscle invasive bladder cancer. Methods: Between January 2000 and December 2007, a total of 68 cases (58 males and 10 females) with nonmuscle invasive bladder cancer (pTa-1 G3, without carcinoma in situ) were used in the study. After TUR-Bt, patients were divided into a non-infusion group (group A) and BCG (Tokyo 172 strain BCG, 80 mg in 40 ml saline or Connaught BCG, 81 mg in 40 ml saline) infusion groups administered weekly for 6 (group B) and 8 weeks (group C). Recurrence rates were used as endpoints for this study. Also, a single variable and multivariable analysis in a T classification (Ta or T1), tumor multiplicity, tumor size (diameter) and presence or absence of concomitant carcinoma in situ was conducted. Results: In group A, one-year recurrence free survival was 59.1%, and three-year recurrence free survival was 45.2%. In group B, one-year recurrence free survival was 63.6%, and three-year recurrence free survival was 53%. In group C, one-year recurrence free survival was 81%, and three-year recurrence free survival was 72%. Conclusion: This study showed that there may be an increased advantage from adjuvant treatment therapy consisting of 8 weekly intravesical administrations of BCG following TUR-Bt for patients suffering from grade 3 non-muscle invasive bladder cancer.