Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 47
1.
IJU Case Rep ; 7(2): 148-151, 2024 Mar.
Article En | MEDLINE | ID: mdl-38440696

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.

2.
IJU Case Rep ; 7(2): 177-180, 2024 Mar.
Article En | MEDLINE | ID: mdl-38440706

Introduction: Parenchymal renal rupture due to a ureteric calculus is extremely rare and an emergency. Case presentation: A 54-year-old man was brought to the emergency room with left back pain without trauma. Computed tomography showed left parenchymal renal rupture with an incompletely duplicated renal pelvis, ureter, and an 11-mm ureteric calculus in the ureterovesical junction. A ureteral stent was placed, and the patient was treated conservatively as his vital signs were stable. We performed transurethral lithotripsy after resolution of the perirenal hematoma. Conclusion: To best of our knowledge, this report is the first to present a case of parenchymal renal rupture due to a ureteric calculus in an incompletely duplicated renal pelvis and ureter. Ureteric calculus within an incompletely duplicated renal pelvis and ureter is at risk of parenchymal renal rupture. Therefore, the aggressive treatment of ureteric calculus could be important.

3.
IJU Case Rep ; 7(2): 157-160, 2024 Mar.
Article En | MEDLINE | ID: mdl-38440711

Introduction: Renal autotransplantation is considered a surgical procedure for extensive ureteral defects. Herein, we report a case of severe ureteral injury repaired by laparoscopic nephrectomy and renal autotransplantation with an iliac vein patch using bovine pericardium. Case presentation: A 56-year-old woman who had previously undergone gynecological surgery complained of right-sided abdominal pain. She was then later diagnosed with a right middle ureteral injury with a 5-cm long defect. We performed retroperitoneal laparoscopic nephrectomy and renal autotransplantation. As the iliac vein was fragile, venous patching using bovine pericardium was performed. The patient's renal function was well preserved after surgery. Conclusion: Laparoscopic nephrectomy and renal autotransplantation is an effective method for repairing severe ureteral injury with the preservation of renal function. A venous patch using bovine pericardium might be considered as a replacement for a fragile vein.

4.
IJU Case Rep ; 7(2): 131-135, 2024 Mar.
Article En | MEDLINE | ID: mdl-38440705

Introduction: Patients with translocation renal cell carcinoma (tRCC) have a poor prognosis without standardized treatment. Case presentation: The first case was of a 72-year-old woman who underwent robot-assisted partial nephrectomy for a left renal tumor and was pathologically diagnosed with tRCC. Recurrence was observed in the left retroperitoneal soft tissue. After treatment with avelumab-axitinib, continued progression-free survival was confirmed at the 90-week follow-up. The second case was of a 41-year-old woman referred to our hospital and presented with translocation renal cell carcinoma metastasis to a para-aortic lymph node. After treatment with avelumab-axitinib, continued progression-free survival was confirmed at the 43-week follow-up. Conclusion: The outcomes of these cases indicate that avelumab-axitinib therapy has a long-term antitumor effect in some patients with tRCC.

5.
Cancers (Basel) ; 16(3)2024 Jan 25.
Article En | MEDLINE | ID: mdl-38339274

The progression of prostate cancer (PCa) relies on the activation of the androgen receptor (AR) by androgens. Despite efforts to block this pathway through androgen deprivation therapy, resistance can occur through several mechanisms, including the abnormal activation of AR, resulting in castration-resistant PCa following the introduction of treatment. Mutations, amplifications, and splicing variants in AR-related genes have garnered attention in this regard. Furthermore, recent large-scale next-generation sequencing analysis has revealed the critical roles of AR and AR-related genes, as well as the DNA repair, PI3K, and cell cycle pathways, in the onset and progression of PCa. Moreover, research on epigenomics and microRNA has increasingly become popular; however, it has not translated into the development of effective therapeutic strategies. Additionally, treatments targeting homologous recombination repair mutations and the PI3K/Akt pathway have been developed and are increasingly accessible, and multiple clinical trials have investigated the efficacy of immune checkpoint inhibitors. In this comprehensive review, we outline the status of PCa research in genomics and briefly explore potential future developments in the field of epigenetic modifications and microRNAs.

6.
J Mol Diagn ; 26(4): 278-291, 2024 Apr.
Article En | MEDLINE | ID: mdl-38301868

The aim of this study was to evaluate the clinical validity of monitoring urine pellet DNA (upDNA) of bladder cancer (BC) by digital PCR (dPCR) as a biomarker for early recurrence prediction, treatment efficacy evaluation, and no-recurrence corroboration. Tumor panel sequencing was first performed to select patient-unique somatic mutations to monitor both upDNA and circulating tumor DNA (ctDNA) by dPCR. For longitudinal monitoring using upDNA as well as plasma ctDNA, an average of 7.2 (range, 2 to 12) time points per case were performed with the dPCR assay for 32 previously treated and untreated patients with BC. Clinical recurrence based on imaging and urine cytology was compared using upDNA variant allele frequency (VAF) dynamics. A continuous increasing trend of upDNA VAF ≥1% was considered to indicate molecular recurrence. Most (30/32; 93.8%) cases showed at least one traceable somatic mutation. In 5 of 7 cases (71.4%) with clinical recurrence, upDNA VAF >1% was detected 7 to 15 months earlier than the imaging diagnosis. The upDNA VAF remained high after initial treatment for locally recurrent cases. The clinical validity of upDNA monitoring was confirmed with the observation that 26 of 30 cases (86.7%) were traceable. Local recurrences were not indicated by ctDNA alone. The results support the clinical validity of upDNA monitoring in the management of recurrent BC.


Circulating Tumor DNA , Urinary Bladder Neoplasms , Humans , Mutation , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/genetics , Circulating Tumor DNA/genetics , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/genetics , Biomarkers, Tumor/genetics
7.
Sci Rep ; 14(1): 1442, 2024 01 16.
Article En | MEDLINE | ID: mdl-38228697

The prognosis for patients who achieve a pathologic complete response in bladder cancer is excellent, but the association between their prognosis and the tumor microenvironment is unclear. We investigated the tumor immune microenvironment of those with pathological complete response after platinum-based neoadjuvant chemotherapy for cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. Our retrospective study included 12 patients with pathological complete response who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. We assessed the density of several immune cell types in pretreatment and posttreatment tissues via multiplex fluorescence immunohistochemical analysis. The median age was 67 years; 10 patients were male. Nine (75%) and 3 (25%) patients were cT2 and cT3, respectively. The 5-year progression-free and overall survivals were 90% and 100%, respectively. The densities of regulatory T cells (Treg; CD3+CD4+FoxP3+ cell) were significantly decreased and almost disappeared in the tumor microenvironment of posttreatment tissue compared with pretreatment tissue. Other immune cells, such as effector T cells or M2 macrophages, were not significantly changed between posttreatment and pretreatment tissues. In pathological complete response, Tregs in the tumor immune microenvironment were significantly decreased after platinum-based chemotherapy for muscle-invasive bladder cancer. The temporary arresting of immune response in the tumor microenvironment may reflect a favorable prognosis due to the decrease of Tregs with tumor shrinkage and improve the host tumor immune response.


T-Lymphocytes, Regulatory , Urinary Bladder Neoplasms , Humans , Male , Aged , Female , T-Lymphocytes, Regulatory/pathology , Retrospective Studies , Neoadjuvant Therapy , Neoplasm Staging , Urinary Bladder Neoplasms/pathology , Cystectomy , Pathologic Complete Response , Immunity , Muscles/pathology , Neoplasm Invasiveness/pathology , Tumor Microenvironment
8.
IJU Case Rep ; 7(1): 26-29, 2024 Jan.
Article En | MEDLINE | ID: mdl-38173460

Introduction: There are few reports of pelvic hematoma after prostatic urethral lift. Here, we report two cases of pelvic hematoma in Japan. Case presentation: The first case was a 71-year-old man with benign prostatic hyperplasia who underwent prostatic urethral lift. Although the procedure was uneventful, he experienced lower abdominal pain the day after the operation. CT revealed a hematoma in the right pelvis; however, it was manageable with conservative treatment. The second case was a 68-year-old man. The procedure was uneventful; however, 6 days after the operation, a subcutaneous hematoma appeared in the lower abdomen. CT revealed a hematoma in the left pelvis. We then performed pelvic hematoma removal surgery. Conclusions: Pelvic hematomas after PUL may requires attention, particularly in men with the narrow pelvises. Appropriate compression of the prostate and a high lithotomy position procedure could effectively avoid the occurrence of pelvic hematomas.

9.
Eur Urol Oncol ; 7(3): 625-632, 2024 Jun.
Article En | MEDLINE | ID: mdl-38296736

BACKGROUND: Androgen deprivation therapy (ADT), administered alone, as combined androgen blockade (CAB) or as ADT plus androgen receptor signalling inhibitors (ARSIs) or ADT plus docetaxel, is the standard treatment for metastatic hormone-naïve prostate cancer (mHNPC) in Japanese real-world practice. OBJECTIVE: To investigate treatment patterns and clinical outcomes in LATITUDE criteria high-risk mHNPC. DESIGN, SETTING, AND PARTICIPANTS: The longitudinal, multicentre, J-ROCK registry study enrolled patients initiating ADT in Japan after May 2019, and categorised them as cohort 1 (ADT or CAB) or cohort 2 (ADT plus ARSIs or docetaxel). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate-specific antigen (PSA) response, progression-free survival (PFS), time to castrate-resistant prostate cancer (CRPC), overall survival (OS), and safety were evaluated. PFS, time to CRPC, and OS were estimated via the Kaplan-Meier method and between-cohort comparisons via multivariate Cox regression models. RESULTS AND LIMITATIONS: In total, 974 patients were included (cohort 1: 38.1%, cohort 2: 61.9%). CAB was preferred (67.4%) to ADT alone in cohort 1, and abiraterone acetate plus prednisolone was used most frequently in cohort 2 (59.4%). The proportion of patients with ≥50%/≥90% PSA decline or who achieved PSA ≤0.2/≤0.1 ng/ml tended to be higher in cohort 2. PFS (adjusted hazard ratio 0.42; 95% confidence interval [CI] 0.31-0.55), time to CRPC (0.28; 95% CI 0.23-0.36), and OS (0.54; 95% CI 0.35-0.82) were longer in cohort 2. In cohorts 1 and 2, adverse drug reactions of special interest (ADRSIs) occurred in 1.3% and 15.1%, and fatal adverse events occurred in 1.9% and 1.7%, respectively. Limitations included nonrandomised design, varying time since marketing authorisation for ARSIs, and limited safety assessments. CONCLUSIONS: ADT plus ARSIs or docetaxel was used more frequently to treat high-risk mHNPC than standard ADT/CAB and was associated with more favourable clinical outcomes. Although ADRSIs were reported more in cohort 2, the safety profile was considered tolerable. PATIENT SUMMARY: Although many treatment options are available for high-risk metastatic prostate cancer, there are limited reports on real-world clinical experience with different therapies outside of the clinical trial setting. In this study, we compared clinical and safety outcomes with different treatment regimens, using a large series of patients with high-risk metastatic hormone-naïve prostate cancer across Japan. We found that androgen deprivation therapy in combination with newer androgen receptor signalling inhibitors resulted in improved response compared with androgen deprivation therapy alone or in combination with a first-generation antiandrogen.


Androgen Antagonists , Prostatic Neoplasms , Male , Humans , Aged , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/mortality , Treatment Outcome , Androgen Antagonists/therapeutic use , Middle Aged , Time Factors , Longitudinal Studies , Neoplasm Metastasis , Aged, 80 and over , Japan
10.
Cancer Sci ; 115(2): 529-539, 2024 Feb.
Article En | MEDLINE | ID: mdl-38083992

Biomarkers that could detect the postoperative recurrence of upper tract urothelial carcinoma (UTUC) have not been established. In this prospective study, we aim to evaluate the utility of individualized circulating tumor DNA (ctDNA) monitoring using digital PCR (dPCR) as a tumor recurrence biomarker for UTUC in the perioperative period. Twenty-three patients who underwent radical nephroureterectomy (RNU) were included. In each patient, whole exome sequencing by next-generation sequencing and TERT promoter sequencing of tumor DNA were carried out. Case-specific gene mutations were selected from sequencing analysis to examine ctDNA by dPCR analysis. We also prospectively collected plasma and urine ctDNA from each patient. The longitudinal variant allele frequencies of ctDNA during the perioperative period were plotted. Case-specific gene mutations were detected in 22 cases (96%) from ctDNA in the preoperative samples. Frequently detected genes were TERT (39%), FGFR3 (26%), TP53 (22%), and HRAS (13%). In all cases, we obtained plasma and urine samples for 241 time points and undertook individualized ctDNA monitoring for 2 years after RNU. Ten patients with intravesical recurrence had case-specific ctDNA detected in urine at the time of recurrence. The mean lead time of urinary ctDNA in intravesical recurrence was 60 days (range, 0-202 days). Two patients with distal metastasis had case-specific ctDNA in plasma at the time of metastasis. In UTUC, tumor-specific gene mutations can be monitored postoperatively as ctDNA in plasma and urine. Individualized ctDNA might be a minimally invasive biomarker for the early detection of postoperative recurrence.


Carcinoma, Transitional Cell , Circulating Tumor DNA , Urinary Bladder Neoplasms , Humans , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/surgery , Circulating Tumor DNA/genetics , Prospective Studies , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Biomarkers , Biomarkers, Tumor/genetics
11.
Int J Urol ; 31(3): 259-264, 2024 Mar.
Article En | MEDLINE | ID: mdl-38041218

OBJECTIVES: Nocturnal polyuria (NP) is one of the causes of nocturia that impairs quality of life. It is necessary to consider that NP is latent when the initial treatment for nocturia is unsatisfactory. Therefore, it is important to establish a treatment for NP based on the pathophysiology. We have previously reported the relationship between NP and fluctuation in blood pressure. The present study aimed to investigate the association between NP and 24-h blood pressure fluctuations in a multicenter prospective study. METHODS: This study included male patients with lower urinary tract symptoms. We categorized the patients into the nonnocturnal polyuria (non-NP) group (≤0.33) and the NP group (>0.33) based on the nocturnal polyuria index from the frequency volume chart. We measured the 24-h diurnal blood pressure and compared the two groups. RESULTS: Among 90 patients, 46 in the non-NP group and 44 in the NP group were included. There was no significant difference in the systolic and diastolic blood pressure during waking time between the two groups; however, the degree of systolic blood pressure reduction during sleep time in the NP group was significantly less than that in the non-NP group (p = 0.039). In the multivariate analysis, systolic BP during sleep was significantly associated with NP (OR 0.970, p = 0.028). CONCLUSION: NP is associated with inadequate nocturnal blood pressure reduction in males, suggesting that reduction in nocturnal blood pressure may lead to improvement in nocturia.


Lower Urinary Tract Symptoms , Nocturia , Humans , Male , Nocturia/epidemiology , Nocturia/etiology , Nocturia/diagnosis , Polyuria/complications , Prospective Studies , Blood Pressure , Quality of Life
12.
Jpn J Clin Oncol ; 54(4): 489-497, 2024 Apr 06.
Article En | MEDLINE | ID: mdl-38157885

OBJECTIVE: The companion diagnosis for olaparib, a poly (ADP-ribose) polymerase inhibitor for prostate cancer, aims to detect BRCA1/2 gene variants. In clinical practice, the frequency of germline BRCA1/2 variants in patients receiving castration-resistant prostate cancer treatment is unknown. We aimed to evaluate the prevalence of germline BRCA1/2 variants and their relationship to prognosis and treatment efficacy in castration-resistant prostate cancer. METHODS: Between June 2021 and 2023, 92 patients receiving castration-resistant prostate cancer treatment were examined for germline BRCA1/2 variants using BRACAnalysis CDx®. Furthermore, the associations between BRCA1/2 pathogenic variants and clinical outcomes were assessed. RESULTS: Of the 92 patients referred for genetic testing, 6 (6.5%) carried germline pathogenic variants in BRCA1/2. The BRCA2 variant was the most frequent (n = 5), followed by BRCA1 variant (n = 1). Among the five variants in BRCA2, the p.Asp427Thrfs*3 variant was identified for the first time in prostate cancer. Overall survival from castration-resistant prostate cancer for patients with BRCA1/2 variants was significantly shorter than for patients without BRCA1/2 variants (P = 0.043). Progression-free survival of androgen receptor signaling inhibitors for patients with BRCA1/2 variants was significantly shorter than for those without (P = 0.003). Progression-free survival of taxane chemotherapy was significantly shorter in patients with BRCA1/2 variants than in those without (P = 0.0149). CONCLUSIONS: In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer.


Antineoplastic Agents , Prostatic Neoplasms, Castration-Resistant , Male , Humans , BRCA1 Protein/genetics , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/pathology , BRCA2 Protein/genetics , Receptors, Androgen/therapeutic use , Prevalence , Japan/epidemiology , Antineoplastic Agents/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Taxoids/therapeutic use , Germ Cells
13.
Ther Apher Dial ; 2023 Dec 12.
Article En | MEDLINE | ID: mdl-38087844

INTRODUCTION: We aimed to determine whether unfractionated heparin (UH) and low molecular weight heparin (LH) contribute to aberrant carnitine metabolism in patients receiving hemodialysis. METHODS: The rate of increase in serum free fatty acids (FFAs) and the ratio of acylcarnitine to free carnitine (AC/FC) from before to after hemodialysis were determined in patients receiving UH and LH. Additionally, the effect of switching patients to UH from LH was examined. RESULTS: AC/FC was significantly higher in the UH group. In addition, serum FFAs in that group increased to 0.825 ± 0.270 after dialysis from 0.172 ± 0.160 before dialysis, showing a positive correlation with AC/FC. Furthermore, AC/FC was observed to be significantly higher in patients who were switched to UH from LH at 3 months after the change. CONCLUSION: Compared with UH, LH has a lesser effect on lipid metabolism, suggesting that it also has a lesser effect on carnitine metabolism.

14.
Int J Mol Sci ; 24(24)2023 Dec 07.
Article En | MEDLINE | ID: mdl-38139039

The human mitochondrial genome (mtDNA) is a circular DNA molecule with a length of 16.6 kb, which contains a total of 37 genes. Somatic mtDNA mutations accumulate with age and environmental exposure, and some types of mtDNA variants may play a role in carcinogenesis. Recent studies observed mtDNA variants not only in kidney tumors but also in adjacent kidney tissues, and mtDNA dysfunction results in kidney injury, including chronic kidney disease (CKD). To investigate whether a relationship exists between heteroplasmic mtDNA variants and kidney function, we performed ultra-deep sequencing (30,000×) based on long-range PCR of DNA from 77 non-tumor kidney tissues of kidney cancer patients with CKD (stages G1 to G5). In total, this analysis detected 697 single-nucleotide variants (SNVs) and 504 indels as heteroplasmic (0.5% ≤ variant allele frequency (VAF) < 95%), and the total number of detected SNVs/indels did not differ between CKD stages. However, the number of deleterious low-level heteroplasmic variants (pathogenic missense, nonsense, frameshift and tRNA) significantly increased with CKD progression (p < 0.01). In addition, mtDNA copy numbers (mtDNA-CNs) decreased with CKD progression (p < 0.001). This study demonstrates that mtDNA damage, which affects mitochondrial genes, may be involved in reductions in mitochondrial mass and associated with CKD progression and kidney dysfunction.


Carcinoma, Renal Cell , Genome, Mitochondrial , Kidney Neoplasms , Renal Insufficiency, Chronic , Humans , DNA, Mitochondrial/genetics , Heteroplasmy , DNA Copy Number Variations , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Renal Insufficiency, Chronic/genetics
15.
Front Oncol ; 13: 1274494, 2023.
Article En | MEDLINE | ID: mdl-38023224

We report the case of a 68-year-old man who developed a sigmoidorectal fistula after marked response to enfortumab vedotin for advanced bladder cancer. The patient had undergone radical cystectomy with ileal conduit after neoadjuvant chemotherapy. Six months after surgery, local recurrence in the pelvic cavity and multiple lung metastases were found, and the patient was administered pembrolizumab as second-line therapy. Due to worsening local recurrence and suspected invasion of the sigmoid colon and rectum, enfortumab vedotin was initiated as third-line therapy and comprehensive genomic profiling was simultaneously performed. Enfortumab vedotin was remarkably effective, the lung metastases disappeared, and the local recurrent lesion shrank in volume although a sigmoidorectal fistula was found to form through the tumor cavity. Immunohistochemical analysis of the tumor specimens exhibited increased nectin-4 expression. This rare case of metastatic bladder cancer with sigmoidorectal fistula associated with effective enfortumab vedotin therapy suggests that nectin-4 expression and comprehensive genomic profiling might be useful in predicting treatment response to enfortumab vedotin.

16.
IJU Case Rep ; 6(6): 349-352, 2023 Nov.
Article En | MEDLINE | ID: mdl-37928301

Introduction: Most congenital ureteral strictures occur at the ureteropelvic or ureterovesical junction in children. Mid-ureteral stricture is very rare and can cause congenital hydronephrosis. Only a few studies have reported on coexisting mid-ureteral stricture with ipsilateral atrophic kidney in young adults. Case presentation: A 16-year-old girl presented with repeated urinary tract infection. Computed tomography revealed a right atrophic kidney and hydroureter. Retrograde pyelography showed a mid-ureteral stricture. Laparoscopic nephroureterectomy was performed, and histological examination revealed mid-ureteral stricture with hyperplasia of the fibrous connective tissue and an atrophic kidney. Conclusion: Mid-ureteral stricture in a young adult is extremely rare. Appropriate imaging studies including retrograde pyelography are necessary for accurate diagnosis of mid-ureteral stricture.

17.
Hinyokika Kiyo ; 69(8): 227-232, 2023 Aug.
Article Ja | MEDLINE | ID: mdl-37667600

A 73-year-old man with renal cell carcinoma underwent a left-sided open radical nephrectomy at our center. The pathological diagnosis was Fuhrman Grade 2, stage pT3a, clear cell renal cell carcinoma. A follow-up computed tomography (CT) scan revealed lung metastases 9 months after the surgery. The patient was started on ipilimumab with nivolumab combination therapy; however, after two cycles of administration, he developed arthralgia and swelling of the knee. Furthermore, he developed diarrhea almost simultaneously, resulting in the interruption of the ipilimumab plus nivolumab treatment. We diagnosed arthritis and colitis with immune-related adverse events (irAE) and initiated steroid therapy with rehabilitation. His condition improved dramatically, and nivolumab treatment could be resumed after 3 months of treatment interruption.


Arthritis , Carcinoma, Renal Cell , Colitis , Kidney Neoplasms , Male , Humans , Aged , Carcinoma, Renal Cell/drug therapy , Ipilimumab/adverse effects , Nivolumab/adverse effects , Kidney Neoplasms/drug therapy , Colitis/chemically induced
18.
Cancer Diagn Progn ; 3(1): 124-129, 2023.
Article En | MEDLINE | ID: mdl-36632579

BACKGROUND/AIM: Surgical treatment of renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is associated with high morbidity and mortality rates, therefore presurgical systemic therapies are required in order to improve the safety and feasibility of the surgical procedure by decreasing the thrombus level and burden. The efficacy of presurgical combination therapy of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) for advanced renal cell carcinoma with IVC thrombus remains unclear. CASE REPORT: We report a case of a 69-year-old male with cT3bN0M0 locally advanced RCC. We successfully performed a less invasive nephrectomy with thrombectomy, because nivolumab plus cabozantinib administration remarkably reduced the primary tumor and IVC thrombus, resulting in complete pathological response, as assessed with perioperative immunohistochemistry. CONCLUSION: To the best of our knowledge, this is the first report showing that nephrectomy could be safely performed for RCC with IVC thrombus after presurgical nivolumab plus cabozantinib therapy, leading to pathological complete response.

19.
Hum Mol Genet ; 32(2): 290-303, 2023 01 06.
Article En | MEDLINE | ID: mdl-35981075

Patients with end-stage renal disease (ESRD) or receiving dialysis have a much higher risk for renal cell carcinoma (RCC), but carcinogenic mechanisms and genomic features remain little explored and undefined. This study's goal was to identify the genomic features of ESRD RCC and characterize them for associations with tumor histology and dialysis exposure. In this study, we obtained 33 RCCs, with various histological subtypes, that developed in ESRD patients receiving dialysis and performed whole-genome sequencing and transcriptome analyses. Driver events, copy-number alteration (CNA) analysis and mutational signature profiling were performed using an analysis pipeline that integrated data from germline and somatic SNVs, Indels and structural variants as well as CNAs, while transcriptome data were analyzed for differentially expressed genes and through gene set enrichment analysis. ESRD related clear cell RCCs' driver genes and mutations mirrored those in sporadic ccRCCs. Longer dialysis periods significantly correlated with a rare mutational signature SBS23, whose etiology is unknown, and increased mitochondrial copy number. All acquired cystic disease (ACD)-RCCs, which developed specifically in ESRD patients, showed chromosome 16q amplification. Gene expression analysis suggests similarity between certain ACD-RCCs and papillary RCCs and in TCGA papillary RCCs with chromosome 16 gain identified enrichment for genes related to DNA repair, as well as pathways related to reactive oxygen species, oxidative phosphorylation and targets of Myc. This analysis suggests that ESRD or dialysis could induce types of cellular stress that impact some specific types of genomic damage leading to oncogenesis.


Carcinoma, Renal Cell , Kidney Failure, Chronic , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Renal Dialysis/adverse effects , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/pathology , Genomics
20.
Prostate Int ; 11(4): 212-217, 2023 Dec.
Article En | MEDLINE | ID: mdl-38196555

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.

...