A case of complete response to avelumab plus axitinib combination therapy for metastatic clear cell renal cell carcinoma in a kidney undergoing dialysis.

Introduction: Combination therapies of immune checkpoint and tyrosine kinase inhibitors for end-stage kidney disease and patients on hemodialysis need careful consideration as few case reports provide suitable management decisions. Case presentation: A 70-year-old man who had undergone hemodialysis for 6 years due to nephrosclerosis. Avelumab plus axitinib combination therapy was performed for repeated lung metastasis, and a complete response was achieved without major side effects. Conclusion: A complete response was achieved after Ave plus Axi combination therapy for clear cell renal cell carcinoma in a patient undergoing dialysis. This suggests that Ave plus Axi combination therapy may be safe and effective for dialysis patients.

Geriatric 8 and Vulnerable Elders Survey-13 predict length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery.

INTRODUCTION: The Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) are established screening tools for assessing vulnerability in older patients. Here we investigated their usefulness as predictors of length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery. MATERIALS AND METHODS: This study included 643 patients who underwent urological surgery (74% were for malignancy) at our institute from 2017 to 2020. G8 and VES-13 scores were routinely recorded upon admission. These indices and other clinical data were obtained through chart review. The correlation between G8 group (high, >14; intermediate, 11-14; low, <11) or VES-13 group (normal, <3; high, ≥3) and length of total hospital stay (LOS), postoperative hospital stay (pLOS), and postoperative complications including delirium were analyzed. RESULTS: The median patient age was 69 years. A total of 44%, 45%, and 11% of patients were classified into high, intermediate, and low G8 groups, respectively, while 77% and 23% were classified into normal and high VES-13 groups, respectively. Univariate analyses revealed that low G8 scores were associated with prolonged LOS (vs. intermediate, odds ratio [OR] 2.87, P < 0.001; vs. high, OR 3.87, P < 0.001), prolonged pLOS (vs. intermediate, OR 2.37, P = 0.005; vs. high, OR 3.06, P < 0.001), and delirium (vs. intermediate, OR 3.23, P = 0.007; vs. high, OR 5.38, P < 0.001), and high VES-13 scores were associated with prolonged LOS (OR 2.85, P < 0.001), prolonged pLOS (OR 2.97, P < 0.001), and Clavien-Dindo grade ≥ 2 complications (OR 1.74, P = 0.044), and delirium (OR 3.18, P = 0.001). Furthermore, multivariate analyses revealed that low G8 and high VES-13 scores were independent factors which predicted prolonged LOS (low G8; vs. intermediate, OR 2.96, P < 0.001; vs. high, OR 3.94, P < 0.001; high VES-13; OR 2.98, P < 0.001) and prolonged pLOS (low G8; vs. intermediate, OR 2.41, P = 0.008; vs. high, OR 3.18, P = 0.002; high VES-13; OR 3.47, P < 0.001), respectively. DISCUSSION: The G8 and VES-13 may be effective tools for predicting prolonged LOS/pLOS and postoperative complications in Japanese patients who undergo urological surgery.

Cribriform pattern in prostate tissues: Predictor for intraductal carcinoma of the prostate based on biopsy and radical prostatectomy pathology.

Objectives: This study aims to investigate whether a cribriform pattern on prostate biopsy may be a factor in suspicion of intraductal carcinoma of the prostate after radical prostatectomy. Methods: This retrospective study assessed 100 men who underwent prostatectomy from 2015 to 2019. Participants were grouped as 76 patients with Gleason pattern 4 and 24 patients without this pattern. All 100 participants underwent retrograde radical prostatectomy and limited lymph node dissection. The same pathologist evaluated all specimens. The cribriform pattern was evaluated with haematoxylin and eosin counterstaining, and intraductal carcinoma of the prostate was evaluated with immunohistochemical analysis of cytokeratin 34ßE12. Results: Patients with intraductal carcinoma of the prostate on immunohistochemical analysis showed a significant tendency to relapse in the postoperative period, and those with the cribriform pattern on biopsy had a significant recurrence rate. In univariate and multivariate analyses, intraductal carcinoma of the prostate confirmed in biopsy tissue was an independent predictor of biochemical recurrence after prostatectomy. The rate of intraductal carcinoma of the prostate confirmation was 28% of cases with a cribriform pattern in biopsy tissue, which was increased to 62% in prostatectomy tissues. Conclusion: The cribriform pattern in the biopsy tissue may be a predictor for intraductal carcinoma of the prostate.

Primary diffuse large B cell lymphoma of the prostate in a patient with HIV infection.

Introduction: Primary prostate lymphomas are very rare; however, the incidence of malignant lymphoma is high among HIV-infected patients. Herein, we report a case of primary diffuse large B-cell lymphoma (DLBCL) of the prostate in an HIV-infected patient. Case presentation: A 47-year-old man presented with miction pain and back pain. Abdominal CT revealed a huge prostate mass extending to the left retroperitoneum. Serum sIL-2R level was abnormally high (2896 U/mL), whereas PSA level was normal. HIV antigen and antibody tests were positive. The patient was diagnosed with DLBCL after a prostate biopsy. Systemic treatments were administered; however, the tumor was refractory, and the patient died 9 months after diagnosis. Conclusion: Prostate malignant lymphomas are rare but should be considered in patients with enlarged prostates and normal PSA levels. It should be noted that HIV patients have a high incidence of malignant lymphomas.

Detection of anterior prostate cancer using a magnetic resonance imaging-transrectal ultrasound fusion biopsy in cases with initial biopsy and history of systematic biopsies.

Background: Prostate cancer in the anterior region may be missed on a transrectal systematic biopsy (SBx). Therefore, this study aimed to evaluate the performance of magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TBx) in detecting anterior region cancer in patients with a history of SBxs. Methods: Prostate biopsies were performed in 224 patients after multiparametric MRI, among whom 119 patients with prostate imaging reporting and data system (PI-RADS version 2) scores of 3 to 5 underwent MRI-TRUS fusion TBxs. Afterward, cancer detection rates (CDRs) and TBx-positive core regions were compared by categorizing patients into those with or without a history of SBxs. Results: Total CDR was 68.8% (44/64 cases) in the initial biopsy group (Initial-Bx group) and 47.3% (26/55 cases) in the previous-negative-systematic biopsy group (Pre-Neg-SBx group) (P = 0.018). Interestingly, both TBx- and SBx-core positive cases were more common in the Initial-Bx group than in the Pre-Neg-SBx group (Initial-Bx group: 75% [33/44 cases] vs. Pre-Neg-SBx group: 42.3% [11/26 cases], P = 0.006). However, only TBx-core positive cases were more common in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 11.4% [5/44 cases] vs. Pre-Neg-SBx group: 30.8% [8/26 cases], P = 0.043). In addition, the proportion of anterior lesions detected by TBx cores was higher in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 26.3% [10/38 cases] vs. Pre-Neg-SBx group: 52.6% [10/19 cases], P = 0.049). Conclusion: Using MRI-TRUS fusion TBx in the evaluation of previously negative SBx cases improved the detection rate of anterior lesions, which might have been missed in previous SBxs. Especially in patients with a history of SBxs mpMRI should be performed to screen for anterior lesions.

Complete response to perioperative treatment using nivolumab for metastatic renal cell carcinoma: A case report.

We report a case of 59-year-old woman who has multiple lung metastases with renal cell carcinoma (RCC). She received neoadjuvant therapy using nivolumab following sunitinib. Thereafter, we performed cytoreductive nephrectomy and subsequently administered nivolumab. We also found a high expression of PD-L1 in tumor cell and infiltration of lymphocytes with CD8 expression by immunohistochemistry. A complete response was achieved 4 months after surgery. A perioperative treatment using nivolumab might be useful treatment for metastatic RCC.

[A Case of Renal Pelvic Cancer with Acquired Hemophilia and Leukemoid Reaction].

A 71-year-old man was referred to us with a right renal mass that was discovered by computed tomography (CT) examination for acquired hemophilia and leukemoid reaction. He presented with persistent low-grade fever and purpura on the lower legs caused by acquired hemophilia. Contrastenhanced CT scan showed a right renal tumor 6.0×7.4 cm in diameterwith inhomogeneous enhancement. The result of his urine cytology was negative. After improvement of his coagulation by treatment with immunosuppressants and steroids, he underwent open nephrectomy. Histology of renal tissue revealed urothelial carcinoma (G3, pT4, N1). After surgery, his complete blood counts and coagulation improved without administration of immunosuppressants and steroids. Therefore, he was diagnosed with renal pelvic cancer with acquired hemophilia and leukemoid reaction.

The in vitro effect of a collagenolytic enzyme inhibitor on lesion development in root dentin.

PURPOSE: To evaluate the effects of a new active collagenase inhibitor, Pirocton Olamine (PO), on acid demineralization in dentin and to investigate possible mechanisms of the inhibitory effects. METHODS: Demineralized bovine dentin sections were cyclically exposed to one of the test solutions containing PO (0-0.33%) and NaF (0.07%) for 3 minutes, then to a Clostridium histolyticum (Ch-collagenase) collagenase solution for 16 hours and finally to an acetate buffer solution for 6 hours for further demineralization within a single day. This cyclic treatment was repeated three times for 3 days. Changes in the mineral loss and lesion depth were quantified by transverse microradiography, and the extent of the degradation by the collagenase in the collagen matrix was measured by microscopic observation after the completion of the 3-day cyclic treatments. Possible mechanisms of PO inhibitory effects on collagen matrix degradation were tested by incubating PO with one of the substances (Ch-collagenase, bovine tendon collagen pieces, zinc2+ (acetate) which is essential ion for collagenolytic activity) at 37 degrees C. Following 1 hour incubation, the incubated solutions were filtrated and PO concentrations (unbound to the substances) in the filtrates were spectroscopically measured. RESULTS: With increasing PO concentrations, the inhibition rates of collagen matrix degradation and the mineral loss were increased. Moreover, there was a positive statistical correlation between mineral loss and collagen matrix degradation, demonstrating that preservation of the collagen matrix would contribute to inhibiting acid demineralization. While the spectroscopic measurements indicated that PO possessed binding to these substances, PO exerted its inhibitory action primarily on the collagenolytic activity.

Association of a single-nucleotide polymorphism in the immunoglobulin mu-binding protein 2 gene with immunoglobulin A nephropathy.

Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis worldwide. The pathogenesis of IgA nephropathy is unknown, but it is certain that some genetic factors are involved in susceptibility to the disease. Employing a large-scale, case-control association study using gene-based single-nucleotide polymorphism (SNP) markers, we previously reported four candidate genes. We report here an additional significant association between IgA nephropathy and an SNP located in the gene encoding immunoglobulin micro-binding protein 2 (IGHMBP2) at chromosome 11q13.2-q13.4. The association (chi2 =17.1, p = 0.00003; odds ratio of 1.85 with 95% confidence interval of 1.39-2.50 in a dominant association model) was found using DNA from 465 affected individuals and 634 controls. The SNP (G34448A) caused an amino acid substitution from glutamine to lysine (E928K). As the gene product is involved in immunoglobulin-class switching and patients with the A allele revealed higher serum levels of IgA (p = 0.048), the amino acid change might influence a class switch to increase serum IgA levels, resulting in a higher risk of IgA nephropathy.

Association of single-nucleotide polymorphisms in the polymeric immunoglobulin receptor gene with immunoglobulin A nephropathy (IgAN) in Japanese patients.

Immunoglobulin A nephropathy (IgAN) is a primary glomerulonephritis of common incidence world-wide whose etiology and pathogenesis remain unresolved, although genetic factors are assumed to be involved in the development and progression of this disease. To identify genetic variations that might confer susceptibility to IgAN, we performed a case-control association study involving 389 Japanese IgAN patients and 465 controls. Genome-wide analysis of approximately 80,000 single-nucleotide polymorphisms (SNPs) identified a significant association between IgAN and six SNPs located in the PIGR (polymeric immuoglobulin receptor) gene at chromosome 1q31-q41. One of them, PIGR-17, caused an amino-acid substitution from alanine to valine at codon 580 (chi(2)=13.05, P=0.0003, odds ratio [OR] =1.59, 95% confidence interval [95% CI] =1.24-2.05); the OR of minor homozygotes to others was 2.71 (95% CI=1.31-5.61). Another SNP, PIGR-2, could affect promoter activity (chi(2)=11.95, P=0.00055, OR=1.60, 95% CI=1.22-2.08); the OR of minor homozygotes to others was 2.08 (95% CI=0.94-4.60). Pairwise analyses demonstrated that all six SNPs were in almost complete linkage disequilibrium. Biopsy specimens from IgAN patients were positively stained by antibody against the secretory component of PIGR, but corresponding tissues from non-IgAN patients were not. Our results suggest that a gene associated with susceptibility to IgAN lies within or close to the PIGR gene locus on chromosome 1q in the Japanese population.

Single-nucleotide polymorphisms in the class II region of the major histocompatibility complex in Japanese patients with immunoglobulin A nephropathy.

Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis of unknown etiology and pathogenesis. Immunogenetic studies have not conclusively indicated that human leukocyte antigen (HLA) is involved. As a first step in investigating a possible relationship between HLA class II genes and IgAN, we analyzed the extent of linkage disequilibrium (LD) in this region of chromosome 6p21.3 in a Japanese test population and found extended LD blocks within the class II locus. We designed a case-control association study of single-nucleotide polymorphisms (SNPs) in each of those LD blocks, and determined that SNPs located in the HLA- DRA gene were significantly associated with an increased risk of IgAN ( P = 0.000001, odds ratio = 1.91 [95% confidence interval 1.46-2.49]); SNPs in other LD blocks were not. Our data imply that some haplotype of the HLA- DRA locus has an important role in the development of IgAN in Japanese patients.

Association between single-nucleotide polymorphisms in selectin genes and immunoglobulin A nephropathy.

Although intensive efforts have been undertaken to elucidate the genetic background of immunoglobulin A nephropathy (IgAN), genetic factors associated with the pathogenesis of this disease are still not well understood. We designed a case-control association study that was based on linkage disequilibrium among single-nucleotide polymorphisms (SNPs) in the selectin gene cluster on chromosome 1q24-25, and we found two SNPs in the E-selectin gene (SELE8 and SELE13) and six SNPs in the L-selectin gene (SELL1, SELL4, SELL5, SELL6, SELL10, and SELL11) that were significantly associated with IgAN in Japanese patients. All eight SNPs were in almost complete linkage disequilibrium. SELE8 and SELL10 caused amino acid substitutions from His to Tyr and from Pro to Ser (chi2=9.02, P=.0026, odds ratio = 2.73 [95% confidence interval [CI] 1.38--5.38] for His-to-Tyr substitutions; chi2=17.4, P=.000031, odds ratio = 3.61 [95% CI 1.91--6.83] for Pro-to-Ser substitutions), and SELL1 could affect promoter activity of the L-selectin gene (chi2=19.5, P=.000010, odds ratio = 3.77 [95% CI 2.02--7.05]). The TGT haplotype at these three loci was associated significantly with IgAN (chi2=18.67, P=.000016, odds ratio = 1.88 [95% CI 1.41--2.51]). Our results suggest that these eight SNPs in selectin genes may be useful for screening populations susceptible to the IgAN phenotype that involves interstitial infiltration.