Remarkable improvement of diabetic nephropathy in transplanted allograft after kidney transplantation.

Although glomerular damage caused by diabetic nephropathy was thought to be irre-versible, in recent years, there have been reports on improvement in glomerular damage with strict glycemic control. However, few reports are available on the pathologic course after renal transplantation of donor-derived grafts with findings of diabetic nephropathy. A 53-year-old woman underwent an ABO blood-type compatible living-donor renal transplant. The recipient had no history of diabetes, and fasting blood glucose and hemo-globin A1c (HbA1c) levels were both normal. The donor was a 57-year-old male who had received treatment for type 2 diabetes mellitus for 10 years. Transplant renal biopsy performed 1 h after revascularization showed mesangial matrix expansion and arterial hyalinosis due to diabetic nephropathy. The blood glucose level was within the normal range after transplantation. Mesangial matrix expansion and arterial hyalinosis disap-peared in allograft biopsy samples 7 years after transplantation. We observed significant improvement in the pathological findings of donor-derived diabetic nephropathy after renal transplantation in the subsequent follow-ups.

The hybrid CL-SP-D molecule has the potential to regulate xenogeneic rejection by human neutrophils more efficiently than CD47.

OBJECTIVE: Innate immunity plays a vital role in xenotransplantation. A CD47 molecule, binding to the SIRPα expressed on monocyte/macrophage cells, can suppress cytotoxicity. Particularly, the SIRPα contains ITIM, which delivers a negative signal. Our previous study demonstrated that the binding between CL-P1 and surfactant protein-D hybrid (CL-SP-D) with SIRPα regulates macrophages' phagocytic activity. In this study, we examined the effects of human CD47 and CL-SP-D expression on the inhibition of xenograft rejection by neutrophils in swine endothelial cells (SECs). METHODS: We first examined SIRPα expression on HL-60 cells, a neutrophil-like cell line, and neutrophils isolated from peripheral blood. CD47-expressing SECs or CL-SP-D-expressing SECs were generated through plasmid transfection. Subsequently, these SECs were co-cultured with HL-60 cells or neutrophils. After co-culture, the degree of cytotoxicity was calculated using the WST-8 assay. The suppressive function of CL-SP-D on neutrophils was subsequently examined, and the results were compared with those of CD47 using naïve SECs as controls. Additionally, we assessed ROS production and neutrophil NETosis. RESULTS: In initial experiments, the expression of SIRPα on HL-60 and neutrophils was confirmed. Exposure to CL-SP-D significantly suppressed the cytotoxicity in HL-60 (p = 0.0038) and neutrophils (p = 0.00003). Furthermore, engagement with CD47 showed a suppressive effect on neutrophils obtained from peripheral blood (p = 0.0236) but not on HL-60 (p = 0.4244). The results of the ROS assays also indicated a significant downregulation of SEC by CD47 (p = 0.0077) or CL-SP-D (p = 0.0018). Additionally, the suppression of NETosis was confirmed (p = 0.0125) in neutrophils co-cultured with S/CL-SP-D. CONCLUSION: These results indicate that CL-SP-D is highly effective on neutrophils in xenogeneic rejection. Furthermore, CL-SP-D was more effective than CD47 at inhibiting neutrophil-mediated xenograft rejection.

Determination of enzalutamide long-term safety and efficacy for castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy: a multicenter prospective DELC study.

BACKGROUND: Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide. METHODS: The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. RESULTS: The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. CONCLUSIONS: In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.

Pre-treatment metastatic growth rate is associated with clinical outcome in patients with metastatic renal cell carcinoma treated with nivolumab.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been approved for the treatment of metastatic renal cell carcinoma (mRCC). However, the response rate is still limited, and it is urgent to pursue novel and concise markers of responses to ICIs that allow the determination of clinical benefits. Recently, it was reported that the metastatic growth rate (MGR) is an independent factor associated with clinical outcome for anticancer therapy in some types of cancer. METHODS: We investigated pre-treatment MGR before starting nivolumab for mRCC patients between September 2016 to October 2019. In addition, we examined clinicopathological factors including MGR and analyzed the correlation between pre-treatment MGR and clinical efficacy of nivolumab. RESULTS: Of all patients, the median age was 63 years (range, 42-81), and the median observation period was 13.6 months (range, 1.7-40.3). Twenty-three patients and sixteen patients were classified as the low and the high MGR group, respectively, with the cutoff value of 2.2 mm/month. Progression-free survival (PFS) and overall survival (OS) were significantly better in patients in the low MGR group (p = 0.005 and p = 0.01). Importantly, in multivariate analysis, only the high MGR was significantly associated with a decrease of PFS (Hazard ratio (HR): 2.69, p = 0.03) and OS (HR: 5.27, p = 0.02). CONCLUSIONS: Pre-treatment MGR may serve as the simple and valid indicator obtained from imaging studies, and the prominent surrogate marker associated with OS and PFS in mRCC patients treated with nivolumab.

Multimodal therapy including robot-assisted radical cystoprostatectomy for locally advanced prostate cancer with bladder and ureteral invasion: A case report.

Introduction: It remains unclear whether robot-assisted radical cystoprostatectomy for locally advanced prostate cancer represents excessive treatment. Case presentation: A 58-year-old man presented with urinary retention and renal failure. Prostate-specific antigen level was 38.07 ng/mL and computed tomography scans revealed bilateral hydronephrosis due to prostate enlargement. Prostate biopsy revealed a Gleason score of 5 + 5 adenocarcinoma, and bilateral hydronephrosis persisted even after urethral catheter placement. We diagnosed locally advanced prostate cancer with bladder and ureteral invasion. Percutaneous bilateral nephrostomy was performed, and neoadjuvant hormone therapy was initiated. Four months after the start of hormone therapy, robot-assisted radical cystoprostatectomy and an intracorporeal ileal conduit were performed, followed by adjuvant radiation therapy for lymph node metastasis. Seven months after the surgery, the patient was free of disease with prostate-specific antigen level <0.03 ng/mL. Conclusion: Robot-assisted radical cystoprostatectomy can be an effective multimodal therapy for locally advanced prostate cancer with bladder and ureteral invasion by locally advanced prostate cancer.

[OUTCOMES OF BLADDER CANCER IN NONAGENARIANS].

(Objectives) We evaluated the chronological change in the number and proportion of elderly patients with bladder cancer. We also retrospectively investigated the clinical outcomes of bladder cancer in patients of ≥90 years of age. (Patients and methods) We evaluated the chronological change in the number and proportion of patients of ≥90 years of age who were clinically diagnosed with bladder cancer and who underwent transurethral resection of a bladder tumor (TUR-BT) at our hospital between 2008 and 2018. We also assessed the clinicopathological factors, perioperative outcomes, and clinical outcomes in bladder cancer patients of ≥90 years of age. (Results) The number and proportion of bladder cancer patients of ≥90 years of age increased with time. A total of 39 patients of ≥90 years of age underwent TUR-BT at our hospital, among whom 22 were diagnosed with primary bladder cancer. The median age was 91 years. No grade ≥III complications were observed after TUR-BT. Two out of 6 with pT1 disease underwent second TUR-BT. Two out of 7 with pT1 disease or carcinoma in situ received intravesical BCG therapy. Six deaths were observed during the study period, 2 of which were due to bladder cancer. At 1 and 3 years after TUR-BT, the overall survival rates of the 22 patients were 80.4% and 68.9%, respectively. (Conclusions) The number and proportion of elderly patients with bladder cancer increased with time. The current standard of care including second TUR-BT and intravesical BCG therapy for high-risk non-muscle invasive bladder cancer was underutilized in nonagenarians.

Clinical Efficacy of Intravenous Immunoglobulin for BK Polyomavirus-Associated Nephropathy After Living Kidney Transplantation.

PURPOSE: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is one of the most difficult infections to be treated after kidney transplantation. Although patients with BKPyVAN usually received a reduction of immunosuppressive agents, the majority of these patients undergo the loss of the graft kidney without any effective treatment afterward. Therefore, development of more effective therapy for BKPyVAN is eagerly expected. PATIENTS AND METHODS: Among patients who underwent a kidney transplantation between January 2016 and April 2019 at our hospital, there were five cases of BKPyVAN. After the initial diagnosis, all patients discontinued administration of mycophenolate mofetil (MMF), which was not enough to diminish decoy cells in urine cytology test. Therefore, all patients received additional intravenous immunoglobulin (IVIG) (100 mg/kg/day) therapy for five days and were evaluated for the therapeutic effect of IVIG with immunohistochemical examination using re-biopsy samples of the graft kidney. RESULTS: After IVIG therapy, 2 cases showed negative decoy cells in urine and 3 cases showed a drastic decrease of plasma BK virus load. Importantly, simian virus (SV) 40 large T antigens diminished after IVIG administration in all cases, which degraded polyomavirus nephropathy classification. CONCLUSION: Although it is difficult to treat BKPyVAN after kidney transplant, IVIG therapy was considered to a promising treatment to improve severity of BKPyVAN especially in cases that dose reduction of immunosuppressive agents was ineffective.

Primary perirenal angiosarcoma: A preoperative diagnostic challenge.

Angiosarcoma arising in the retroperitoneal space is rare. We report a case of perirenal angiosarcoma presenting preoperative diagnostic difficulties. A 49-year-old man was referred to our department with left kidney mass. Specimens of CT-guided percutaneous needle biopsy of the mass did not contain any atypical cells suggestive of malignancy. A CT scan 6 months after embolization of the tumor revealed growth of the mass and two space-occupying lesions appearing in the liver. Laparoscopic resection of the left kidney with perirenal mass and one of the liver lesions was performed. Histopathological findings confirmed a diagnosis of perirenal angiosarcoma with hepatic metastases.

Malignancy With Immunosuppression After Renal Transplantation: A Competing Risk Analysis.

OBJECTIVES: This study analyzed clinical characteristics of renal transplant recipients who developed malignancy with immunosuppression after transplantation by applying a competing risk analysis to reduce the effects of competing events. METHODS: All patients who underwent renal transplantation at our institution from 1973 to 2017 were included in this analysis. All data were collected from patient medical records and retrospectively analyzed. The cumulative incidence of malignancy before allograft loss and its risk factors were calculated by a competing risk analysis, the Gray test, and the Fine-Gray proportional hazard model. RESULTS: Of the 596 recipients, 78 developed malignancies. The mean age at transplantation was 38.5 ± 13.1 years. The median time from transplantation to the initial malignancy was 147.0 (5.2-407.3) months. The most common initial malignancy was skin cancer (21.8%), followed by posttransplant lymphoproliferative disease (14.1%). The cumulative incidence of malignancy at 20 years was 16.2% according to a competing risk analysis, whereas the conventional Kaplan-Meier method estimated the cumulative incidence at 20 years to be 25.6%. Increasing age at transplantation was significantly associated with the incidence of malignancy (P = .0091). Overall 10-year survival rates of recipients with and without malignancy were 81.7% and 88.5%, respectively (P < .001). CONCLUSIONS: Results of time-to-event analysis must be interpreted with caution in situations with competing events when estimating the cumulative incidence of malignancy with immunosuppression after renal transplantation. Renal transplant recipients with increasing age should be more carefully monitored as a high-risk population for developing malignancies.

Keratinizing Squamous Metaplasia of the Urinary Bladder With White Hair-like Structures.

A 74-year-old woman presented to the urology clinic with a protruding mass in her urinary bladder detected by ultrasonography. She had no symptoms. Cystoscopy revealed a 1-cm lesion with a lock of 1-cm-long white hair-like structures on the right side of the bladder. White plaques were also noted covering some areas of the bladder. Transurethral resection of the lesion and biopsy of the white plaques were performed. Pathological examination confirmed a diagnosis of keratinizing squamous metaplasia of the bladder with no evidence of malignancy.

[AN ADULT MALE CASE OF CRYPTORCHIDISM CONCOMITANT WITH HYPOGONADOTROPIC HYPOGONADISM WHO UNDERWENT hCG THERAPY AND SHOWED A SPONTANEOUS DESCENT OF THE TESTIS].

A 32-year-old Japanese man was referred to our hospital with a chief complaint of the delayed puberty with having been aware of it since he was in his teens. Physical examination demonstrated the small penis, the impalpable left testis, and the atrophic right testis in the scrotum. Abdominal magnetic resonance imaging showed the left testis of 8 mm in the external inguinal ring. Endocrinological blood tests revealed that testosterone and luteinizing hormone were 0.34 ng/mL and 1 mIU/mL, respectively, leading to a diagnosis of the left cryptorchidism with hypogonadotropic hypogonadism. The hCG therapy was initiated, resulting in the increased volume and spontaneous descent into the scrotum of the left testis after 6 months of the treatment. The hCG therapy could be an alternative treatment for surgery for cryptorchidism with hypogonadism in adults.