Impact of Tumor Grade Distribution on Genetic Alterations in Clear Cell Renal Cell Carcinoma and Prostate Cancer.

BACKGROUND/AIM: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. PATIENTS AND METHODS: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. RESULTS: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. CONCLUSION: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments.

Derivative Chromosome 3 Loss from t(3;6)(q12;q14) Followed by Differential VHL Mutations Underlie Multifocal ccRCC.

BACKGROUND/AIM: The Von Hippel-Lindau (VHL) gene encodes a protein (pVHL) that plays an important role in proteasome degradation of hypoxia inducible factor α (HIFα) through E3 activation. Accumulation of HIFα by loss of functional pVHL promotes tumorigenesis, thus, VHL has tumor suppressor gene capability in clear cell renal cell carcinoma (ccRCC). VHL is the most frequently mutated gene in ccRCC. The complete loss of VHL is mainly achieved by loss of chromosome 3p, which has a VHL coding region in combination with mutation or hypermethylation of the remaining copy of VHL. Given the risk of constitutional chromosome 3 translocation for RCC, it is important to detect the translocation and understand the mechanism underlying the development of multifocal ccRCC. CASE REPORT: A 67-year-old female patient diagnosed with multifocal RCC underwent robot-assisted partial nephrectomy (RAPN) for three kidney tumors. A cancer gene panel test using next generation sequencing (NGS) detected differential VHL mutations (c.533T>G; p.L178R, c.465_466insTA; p.T157Ifs*3, c.343C>A; p.H115N), while VHL mutation was not detected in peripheral blood DNA. A tendency toward copy number loss of genes on der(3) was also detected in all tumors, but not in the germline one. A karyotype analysis revealed a germline translocation between 3 and 6, t(3;6)(q12;q14). CONCLUSION: Chromosome 3 translocation and loss of derivative chromosome containing 3p and subsequent somatic differential VHL mutations in this case strongly support the previously proposed three-step model to explain the development of familial conventional ccRCC.

[A Case of Metastasis of Gastric Cancer to the Bladder].

A 62-year-old woman was diagnosed with peritoneal dissemination of gastric cancer and was treated with anticancer drugs. Eleven months after the start of the treatment, follow-up computed tomography newly showed thickening of the bladder wall and left hydronephrosis even though the chemotherapy reduced peritoneal dissemination. Therefore, she was referred to our hospital for further evaluation. Cystoscopy and magnetic resonance imaging showed the tumor arising from the bladder neck to trigone. A few days later, she was admitted to our hospital because of bladder tamponade. Transurethral coagulation was carried out, and we resected part of the bladder tumor for pathological examination at the same time. As the pathological features of the bladder tumor were similar to those of the primary stomach cancer and peritoneal dissemination, the diagnosis of the bladder tumor was metastatic gastric adenocarcinoma. She died three months after visiting our hospital.

Intensity-modulated radiation therapy for elderly patients (aged ≥75 years) with localized prostate cancer: Comparison with younger patients (aged <75 years).

The aim of the present study was to evaluate the efficacy and safety of intensity-modulated radiation therapy (IMRT) for elderly patients with prostate cancer (age ≥75 years) compared with younger patients (<75 years). The numbers of patients enrolled into the elderly and younger groups were 238 and 853, respectively. More than half of the patients in the elderly group were high-risk, and the total risk of the elderly group was higher than that of younger group. The median follow-up periods for the elderly and younger groups were 42 (range, 2-108) and 49 (range, 2-120) months, respectively. All patients were treated with IMRT at a dose of 74-78 Gy with or without androgen-deprivation therapy. The biochemical failure-free rates (BFFRs) at 3-year follow-up for the elderly and younger groups were 93.3 and 95.7%, respectively; there was no significant difference between the 2 groups in regard to the BFFR. The clinical failure-free rates (CFFR) at 3-year follow-up for the elderly and younger groups was 95.8 and 98.5%, respectively; the 2 groups did not differ significantly in regard to the CFFR. The cumulative incidence rates of gastrointestinal toxicity (grade ≥2) and genitourinary toxicity (grade ≥2) at 3-year follow-up were 10.5 and 1.3%, respectively; there was no significant difference between the elderly and younger groups. It was concluded that in prostate cancer patients aged 75 years or older, IMRT has a treatment effect equivalent to that in patients <75 years old; adverse events are also comparable.

Metastatic epithelioid angiomyolipoma treated with everolimus in a patient receiving hemodialysis: A case report.

INTRODUCTION: A patient undergoing hemodialysis and being treated with everolimus for metastatic epithelioid angiomyolipoma has never been described in the literature, to our knowledge. CASE PRESENTATION: A 53-year-old woman who had undergone trans-arterial embolization for epithelioid angiomyolipoma was referred with a chief complaint about right knee pain. Hemodialysis had been started after the embolization. Needle biopsy specimens of tumors obtained from behind the right kidney and in the right femur were diagnosed as epithelioid angiomyolipoma metastases. The patient underwent treatment with everolimus and achieved a partial response after 6 months of treatment without serious adverse events. CONCLUSION: Everolimus might be effective for patients with metastatic epithelioid angiomyolipoma who are undergoing hemodialysis.

Treatment outcomes and late toxicities of intensity-modulated radiation therapy for 1091 Japanese patients with localized prostate cancer.

AIM: This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer. BACKGROUND: A total of 1091 patients with localized prostate cancer were recruited between March 2006 and July 2014. The patients were stratified into low- (n = 205 [18.8%]), intermediate- (n = 450 [41.2%]), high- (n = 345 [31.6%]), and very high-risk (n = 91 [8.3%]) groups according to the National Comprehensive Cancer Network classification. All patients were irradiated via IMRT at a dose of 74-78 Gy with or without androgen-deprivation therapy. The mean follow-up period was 50 months (range, 2-120 months). RESULTS: The biochemical failure-free rate (BFFR), the clinical failure-free rate, and the overall survival rate at the 5-year follow-up for all patients was 91.3%, 96.2%, and 99.1%, respectively. In univariate analysis, the prostate-specific antigen (PSA) levels (≤20 vs. >20 ng/ml) were significantly correlated with BFFR. A trend toward higher BFFR was noted in patients with a Gleason score (GS) of ≤7 than in patients with GS ≥8. In multivariate analysis, only PSA (≤20 vs. >20 ng/ml) was significantly correlated with BFFR. The cumulative incidence rate of gastrointestinal and genitourinary toxicity (≥grade 2) at the 5-year follow-up was 11.4% and 4.3%, respectively. CONCLUSIONS: The findings of this study indicate that IMRT is well tolerated and is associated with both good long-term tumor control and excellent outcomes in patients with localized prostate cancer.

Does intensity-modulated radiation therapy (IMRT) alter prostate size? Magnetic resonance imaging evaluation of patients undergoing IMRT alone.

AIM: To assess the changes in prostate size in patients with prostate cancer undergoing intensity-modulated radiation therapy (IMRT). BACKGROUND: The effect of size change produced by IMRT is not well known. MATERIALS AND METHODS: We enrolled 72 patients who received IMRT alone without androgen-deprivation therapy and underwent magnetic resonance imaging (MRI) examination before and after IMRT. The diameter of the entire prostate in the anterior-posterior (P-AP) and left-right (P-LR) directions was measured. The transitional zone diameter in the anterior-posterior (T-AP) and left-right (T-LR) directions was also measured. RESULTS: The average relative P-AP values at 3, 6, 12, 24, and 36 months after IMRT compared to the pre-IMRT value were 0.94, 0.90, 0.89, 0.89, and 0.90, respectively; the average relative P-LR values were 0.93, 0.92, 0.91, 0.91, and 0.90, respectively. The average P-AP and P-LR decreased by approximately 10% during the 12 months post-IMRT, and remained unchanged thereafter. The average relative T-AP values at 3, 6, 12, 24, and 36 months after IMRT compared to the pre-IMRT value were 0.93, 0.88, 0.91, 0.87, and 0.89, respectively; the average relative T-LR values were 0.96, 0.90, 0.91, 0.87, and 0.88, respectively. The average T-AP and T-LR also decreased by approximately 10% during the 12 months post-IMRT, and remained unchanged thereafter. At 12 months after IMRT, the average relative T-AP was significantly lower in patients with recurrence than in those without recurrence. CONCLUSIONS: The average prostate diameter decreased by approximately 10% during the 12 months after IMRT; thereafter remained unchanged.

A pretreatment nomogram predicting recurrence- and progression-free survival for nonmuscle invasive bladder cancer in Japanese patients.

PURPOSE: Our aim was to provide nomograms that allow urologists to easily calculate a nonmuscle invasive bladder cancer patient's risk of recurrence and progression. MATERIALS AND METHODS: We retrospectively analyzed 800 nonmuscle invasive bladder cancer patients newly diagnosed between 1991 and 2001 from the Gifu urothelial cancer registry program. We developed the nomogram using the original 500 patients and validated it using the remaining 300 patients. The prognostic factors of recurrence and progression were identified by multivariate analysis in 500 patients. RESULTS: In the multivariate analysis, tumor number, shape, grade, and intravesical instillation were associated with recurrence-free survival. Tumor shape and grade were associated with progression-free survival. Six factors for recurrence and three factors for progression were used to make the nomogram. Using the original 500 patients who were modeled for the nomogram, the areas under the receiver operating characteristic curves (AUCs) were calculated to be 0.61 for recurrence and 0.71 for progression. To validate nomogram performance, we applied an additional 300 patients to the nomograms. The AUCs were 0.57 for recurrence and 0.67 for progression. CONCLUSIONS: The nomograms that have been developed can be used to predict the probability of recurrence and progression of nonmuscle invasive bladder cancer.

[Clinical usefulness of chlormadinone acetate as an alternative antiandrogen therapy for prostate cancer relapse after combined androgen blockade therapy].

We prospectively studied the usefulness of chlormadinone acetate (CMA) as an alternative therapy for prostate cancer relapse after combined androgen blockade (CAB) therapy. Sixteen patients with relapsed prostate cancer after treatment with CAB, including surgical or medical castration and nonsteroidal antiandrogens, 80 mg bicalutamide daily or 375 mg flutamide daily, were enrolled. After discontinuing the antiandrogen for evaluating the patient for the antiandrogen withdrawal syndrome, we administered 100 mg CMA daily as alternative antiandrogen and estimated its effect. Four patients showed a > or = 50% decline in prostate-specific antigen (PSA) levels and another 4 patients showed a < 50% decline in PSA levels but residual 8 patients showed no decline in PSA levels. In 8 patients with a decline in PSA levels, the median duration of alternative CMA therapy was 11.4 months. Patients with a PSA level of < 1 ng/ml at the start of CMA therapy showed the tendency of decline in PSA levels. In contrast, patients with a nadir PSA level of > or = 0.2 ng/ml during pretreatment showed no effectiveness of the alternative CMA therapy. The alternative CMA therapy may be useful in a part of patients with prostate cancer relapse after CAB therapy.

[Case of urachal cancer treated by neoadjuvant chemotherapy with FOLFOX4 (oxaliplatin, 5-FU and leukovolin)].

A 52-year-old woman was referred to our hospital for treatment of urachal cancer. She complained of supurapubic dull pain and gross hematuria. Computed tomography and magnetic resonance imaging showed a non-papillary sessile tumor, which was located on the dome of the bladder and invaded the small intestine. The tumor was diagnosed as Sheldon's stage IIIC urachal cancer. After three courses of neoadjuvant chemotherapy with FOLFOX4 (oxaliplatin, 5-FU and leukovolin), the tumor was reduced from 7 x 6 cm to 5.5 x 5 cm in size. Consequently, the patient underwent an en-bloc resection of the urachal tumor with the dome of the bladder and the parts of the ileum invaded by the tumor. One course of adjuvant chemotherapy (FOLFOX4) was performed. Surgical specimen revealed histologically well differentiated squamous carcinoma and invasion to the propria of the ileum. The surgical margins were negative for the cancer. For 1.5 years after the surgery, no local recurrence or distant metastasis has been observed.

Prognostic value of the co-expression of carbonic anhydrase IX and vascular endothelial growth factor in patients with clear cell renal cell carcinoma.

This study aimed to investigate whether the expression of carbonic anhydrase IX (CAIX) is associated with the expression of vascular endothelial growth factor (VEGF) and whether the co-expression of the two correlates with survival outcome in clear cell renal cell carcinoma (ccRCC). The expression of CAIX and VEGF was evaluated immunohistochemically in 122 paraffin-embedded ccRCC specimens. The clinical significance of these markers in relation to disease-specific survival (DSS) was analyzed. Patients with a low expression of CAIX had a significantly worse prognoses than those with a high expression (p=0.0005). Inversely, patients with a high expression of VEGF had a significantly worse prognoses than the patients with a low expression (p=0.0030). Furthermore, CAIX expression significantly stratified the DSS of patients with high-stage (p=0.0001), high-grade (p=0.0392), low-grade (p=0.0273), metastasis (p=0.0034), no metastasis (p=0.0303) and ECOG-PS=0 (p=0.0003). VEGF expression significantly predicted the survival of patients with low-grade (p=0.0003), high-stage (p=0.0401) and ECOG-PS=0 (p=0.0063). A multivariate Cox regression analysis showed that tumor stage (p=0.0054), metastasis (p=0.0193), ECOG-PS (p=0.0065) and CAIX expression (p=0.0001) were independent prognostic factors of DSS. Since CAIX and VEGF expression correlated inversely (p=0.0032), the prognostic value of the co-expression of CAIX-VEGF was evaluated. Multivariate analysis revealed that the co-expression was an independent prognostic factor of DSS (p=0.0002). In addition, the co-expression was able to stratify DSS into three risk groups: high-risk, intermediate-risk and low-risk (p<0.0001). In patients with ccRCC, CAIX and VEGF expression correlated inversely. Independent expression of CAIX and a co-expression of CAIX-VEGF were found to be independent predictors of DSS. Furthermore, the co-expression data for CAIX-VEGF provide more accurate prognostic information than the individual data. This information may be useful for survival prediction and risk stratification of patients with ccRCC.

The potential role of prebiopsy magnetic resonance imaging combined with prostate-specific antigen density in the detection of prostate cancer.

AIM: Two-thirds of patients with a gray-zone prostate-specific antigen (PSA) level undergo unnecessary biopsy. Sensitivity is not yet sufficient to permit the use of modified PSA parameters or magnetic resonance (MR) imaging alone for prostate cancer screening. Thus, we evaluated the combination of MR imaging and PSA density (PSAD) for specificity and sensitivity. METHODS: During the period April 2004 through March 2006, 185 patients with a PSA level of 4.0-10.0 ng/mL underwent MR imaging and transrectal ultrasonography-guided 8-core biopsy (systemic sextant biopsy of the peripheral zone plus two cores of transition zone). All MR images were interpreted prospectively by two radiologists. An image was considered positive for prostate cancer if any feature indicated a cancerous lesion. Receiver operating characteristic (ROC) curves were used to compare the usefulness of the PSA level, PSAD and PSA transitional zone density (PSATZ) for the detection of prostate cancer. RESULTS: Of the 185 patients, 62 had prostate cancer. Sensitivity and specificity of the axial T2-weighted MR imaging findings for cancer detection were 79.0% and 59.4%, respectively. The area under the ROC curve was 0.590 for the PSA level, 0.718 for PSAD and 0.695 for PSATZ. MR imaging findings and PSAD were shown by multivariate analysis to be statistically significant independent predictors of prostate cancer (P < 0.001). With a PSAD cut-off value of 0.111, sensitivity was 96.8%, but specificity was 19.5%. Combining MR imaging findings with PSAD increased the specificity to 40% and retained 95% sensitivity. CONCLUSION: MR imaging findings combined with PSAD provide high sensitivity and improve the specificity for the early detection of prostate cancer.

Anterior urethral valve in the fossa navicularis presenting as a split urinary stream in a child.

An anterior urethral valve is uncommon compared to a posterior urethral valve as a cause of lower obstructive uropathy. Furthermore, an anterior urethral valve in the fossa navicularis is extremely rare. We describe the case in a 6-year-old boy who presented with a split urinary stream. Endoscopy revealed an anterior urethral valve in the fossa navicularis, and we successfully incised the valve with a hook knife. We should consider the possibility of an anterior urethral valve in any child with an abnormal urinary stream.

Transcatheter arterial embolization with N-butyl-2-cyanoacrylate (Hystoacryl) in two treatments for huge renal arteriovenous malformation.

We report a case of huge renal arteriovenous malformation treated with superselective endovascular embolization in two treatments using N-butyl-2-cyanoacrylate (Hystoacryl).

[Clinical evaluation of our first 50 laparoscopic adrenalectomies].

We performed 50 laparoscopic adrenalectomies during the period from 1998 through 2003. We report our experience and the outcomes of this procedure, which has become a standard surgery for adrenal tumors. In most cases, the transperitoneal approach was used. In 48 cases, laparoscopic adrenalectomy was performed successfully. However, in two cases, the operation was converted to an open procedure because of bleeding. As our experience with laparoscopic adrenalectomy increased, operation time decreased. Laparoscopic adrenalectomy should be used more widely in the future.

[Extra-adrenal pheochromocytoma (paraganglioma) of the urinary bladder without typical symptoms: a case report].

A 33-year-old female patient was admitted to our department with bladder tumor. It was detected by a magnetic resonance imaging (MRI) in an examination for hysteromyoma. She had neither hypertention, gross hematuria nor the classic symptoms of cathecholamine excess during micturition. The diameter of the tumor was 33 mm. Cystoscopic examination showed a submucosal tumor in the left anterior wall of the bladder. Percutaneous needle biopsy was performed. Biopsy specimens revealed as a pheochromocytoma. 131 I-MIBG scintigraphy showed abnormal accumulation in the bladder, and no abnormal accumulation in the other lesion. Endocrinologic examination disclosed increased levels of serum and urinary noradrenalin. On May 18, 2005, partial cystectomy was performed. The catecholamine levels normalized after partial cystectomy. The patient has been followed up for 9 months and shown no recurrence.

[A case of ruptured renal artery aneurysm treated effectively by endovascular embolization].

Previously, renal arterial aneurysms were thought to be extremely uncommon. However, these lesions are now being detected more frequently as incidental findings on computed tomography (CT) and magnetic resonance imaging (MRI). The incidence of ruptured renal artery aneurysms is very low. A 58-year-old man presented to a physician complaining of left flank pain and was diagnosed as having a left kidney stone. Abdominal CT scan demonstrated a mass in the left renal pelvis. The mass measured 40mm in diameter and showed calcification. The patient was referred to our hospital 5 days after the first attack. Left renal mass was diagnosed as renal aneurysm based on clinical signs and perirenal findings on CT. Emergent endvascular embolization was performed. The postoperative course was uneventful. Hypertension improved after embolization.

[Analysis of factors affecting reccurence and prognosis of superficial bladder cancer--study of 800 patients--].

PURPOSE: The purpose of the present paper was to evaluate clinical factors responsible for recurrence and prognosis of superficial bladder cancer. SUBJECTS AND METHOD: We reviewed date from 800 patients who were initially treated between 1991 and 2000. Recurrent and prognostic factors were examined with univariate and multivariate analysis. Kaplan-Meier Method and log rank test were used for comparing the significance of recurrence free curve and survival curve. Cox's proportional hazard model was used for univariate and multivariate analysis. A 5% level of significance was used for all statistical testing. RESULTS: Of 800 cases 282 patients (35.2%) had recurrence and 27 patients (3.4%) were died in during follow up. Progression was defined as the development of muscle invasion or metastasis, progression were noted on 10 metastasis cases and 16 muscle invasion cases. Univariate analysis revealed that tumor numbers, shape, size, stage and grade were significant recurrent and prognostic factors. Multivariate analysis revealed that tumor numbers (P<0.0001), shape (P = 0.066) and size (P = 0.0178) were significant recurrent factors, and tumor shape (P = 0.0422), size (P = 0.0140) and stage (P = 0.0330) were significant prognostic factors. Of 272 recurrent cases, univariate analysis revealed that tumor shape, stage and grade were significant prognostic factors, and multivariate analysis revealed that tumor shape (P = 0.0164) and stage (P = 0.0017) were significant prognostic factors. CONCLUSION: We conclude that tumor numbers, shape and size are predictive value in recurrence and tumor shape, size and stage are predictive value in prognosis, and when recurrent case, tumor shape and stage are predictive value.

Successful management of lower pole moiety ureteropelvic junction obstruction in a partially duplicated collecting system using retrograde endoureteropyelotomy with the Holmium:YAG laser.

A patient with lower pole moiety ureteropelvic junction obstruction in a partially duplicated collecting system was managed successfully by retrograde endoureteropyelotomy using a Holmium:YAG laser. To our knowledge, we report the first case of this entity managed successfully by retrograde endoureteropyelotomy without a percutaneous approach.