[A Case of Stauffer Syndrome-Like Findings Associated with Metastatic Renal Cell Cancer Improved by Molecular Targeted Therapy].

We report a case of Stauffer syndrome-like findings in a patient with metastatic renal carcinoma treated by surgery and molecular targeted therapy. The patient was a 58-year-old woman diagnosed with renal carcinoma with multiple metastases. She had hepatosplenomegaly and hepatic dysfunction with elevated serum liver enzyme and IL-6 levels. Treatment with temsirolimus and axitinib reduced the size of the local and metastatic tumors and simultaneously improved the hepatosplenomegaly. The local tumor was excised by laparoscopic nephrectomy, treated with axitinib and then with nivolumab. With the reduction in the metastatic tumor size, serum liver enzyme and IL-6 levels decreased. It was suggested that molecular targeted therapy is an effective treatment when the findings of metastatic renal cell carcinoma, are similar to those of Stauffer syndrome.

[A Cohort Study on the Prognosis of Patients with Urothelial Carcinoma Using the Miyazaki Urological Cancer Database (MUCD)].

Miyazaki Urological Cancer Database (MUCD) is a web-based database containing background, treatment, and prognosis of patients with prostate, renal, and urothelial cancers diagnosed in Miyazaki. We entered information on patients diagnosed with urothelial carcinoma from 2014 to 2018 at 4 of the 17 facilities that diagnose urothelial carcinoma in Miyazaki Prefecture. We analyzed the overall survival for bladder cancer and upper urinary tract cancer, and examined its correlation with the presence of symptoms, urine cytology, and clinical TNM classification. There were 487 patients with urothelial carcinoma, comprising 372 (76%) with bladder cancer and 115 (24%) with upper tract urinary cancer. In the bladder cancer group, 301 (81%) patients had symptomatic disease and 119 (32%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 248 (67%), 94 (26%), 19 (5%) and 11 (3%) patients, respectively. In the upper urinary tract cancers group, 89 (76%) had symptomatic disease and 41 (36%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 45 (39%), 37 (32%), 11 (10%) and 22 (19%) patients, respectively. The 3-year survival rates for bladder and upper urinary tract cancer were 83.4% and 67.8%, respectively. TNM classification (≤T1 vs ≥T2≥) was significantly associated with overall survival (bladder cancer : HR＝7.07, 95% CI＝3.13-16.0, p＜0.0001 ; upper tract urinary cancer : HR＝6.33, 95% CI＝2.13-18.8, p＝0.0009). The prognosis of patients with urothelial carcinoma diagnosed in multiple institutions could be evaluated using MUCD. The clinical T stage was significantly associated with overall survival in patients with bladder cancer and patients with upper urinary tract cancer.

[A Case of Neuroendcrine Carcinoma of the Prostate Diagnosed by Prostate Re-Biopsy during Hormonal Treatment and Effectively Treated by Multidisciplinary Therapy].

A 73-year-old Japanese man visited the urology clinic with the chief complaint of gross hematuria in June 2015. His prostate specific antigen (PSA) level was 146.7 ng/ml and he was diagnosed with prostate adenocarcinoma with a Gleason Score of 5+4. With bone metastasis in the right femur (cT3aN0M1), he was treated by orchiectomy and bicalutamide. He had gross hematuria in October 2017 and a prostate tumor was detected by computed tomography (CT) and magnetic resonance imaging without increasing PSA levels. Prostate re-biopsy showed prostate neuroendocrine carcinoma and local radiation therapy (74 Gy) was performed. Follow-up CT revealed a left adrenal tumor with a positive positron emission tomographic scan in October 2018. Under the diagnosis of metastatic neuroendocrine carcinoma, chemotherapy using cisplatinum and etoposide was performed. The tumor shrunk after five courses of treatment, followed by regrowth in April 2019. Radiation therapy (50 Gy) was added to the left adrenal tumor and it shrunk again. However, a left retroperitoneal tumor was detected in July 2019 and it was resected under laparoscopic surgery and diagnosed as metastatic neuroendocrine carcinoma. Since then, no recurrence has been observed.

Cyclooxygenase 2 genotypes influence prostate cancer susceptibility in Japanese Men.

This study aims to evaluate the relationship between the cyclooxygenase 2 (COX2) G1195A (rs689465) polymorphism and the risk of prostate cancer in a Japanese population and the associations between COX2 polymorphisms and clinicopathological characteristics, including Gleason grade and prostate-specific antigen (PSA) grade. We recruited 134 patients with prostate cancer and 86 healthy controls matched for age and smoking status. The COX2 G1195A polymorphism status was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. Genotype distributions (p = 0.028) and allelic frequencies (p = 0.014) differed significantly between prostate cancer and control groups in terms of the COX2 G1195A polymorphism (Pearson's χ (2) test). Logistic regression analysis of case and control outcomes showed an odds ratio between the GG and AA genotypes of 3.15 (95% confidence interval = 1.27-8.08, p = 0.014), indicating an increased risk of prostate cancer associated with the AA genotype. Subset analysis revealed no significant associations between this polymorphism and clinicopathological characteristics of prostate cancer. This study demonstrated a relationship between the COX2 G1195A variant and prostate cancer risk. This polymorphism may merit further investigation as a potential genomic marker for the early detection of prostate cancer. Our results support the hypothesis that rs689465 influences susceptibility to prostate cancer; however, prostate cancer progression was not associated with rs689465 in a Japanese population.

Bilateral long ureteral strictures were successfully replaced by ileum in inverse seven configuration: A case report.

INTRODUCTION AND IMPORTANCE: Ureteral stricture is a potential postoperative complication of pelvic surgery. Repair is performed in the intraoperative or postoperative phase for various reasons. Ileal reconstruction of ureter is considered for extensive and bilateral ureteral injuries. CASE PRESENTATION: A 44-year-old female presented to the hospital where she had undergone hysterectomy two months prior, with acute renal failure due to bilateral hydronephrosis. Radiological examination revealed bilateral distal ureteral stricture measuring 5 cm in length. After failed balloon-dilation, ileal reconstruction was successfully performed without perioperative complications; and she has remained free from hydronephrosis with normal renal function for four years. CLINICAL DISCUSSION: Ileal interposition can be used for reconstruction of long lengths or bilateral ureteral injuries. High success rates and low rates of complication have been reported, and the long-term outcome was also acceptable. Apparent ureteral injury was not observed in our case; however, narrowing of ureteral lumen due to submucosal and sub-adventitial edema was observed as a possible cause of strictures. Although, some minor occult injuries during hysterectomy, including thermal effect, ischemia or physical damage due to traction on the ureters were suggested, we were unable to conclusively determine the etiology. CONCLUSION: Ileal ureter replacement is a useful reconstruction, and the inverse seven configuration is suitable for long bilateral strictures of distal ureter.

Possible role of combined therapy targeting MET and pro-HGF activation for renal cell carcinoma: analysis by human HGF-producing SCID mice.

MET is a high-affinity receptor tyrosine kinase of HGF (hepatocyte growth factor). HGF is secreted as an inactive single-chain precursor (pro-HGF), which requires proteolytic activation for conversion to an active form. HGF activator inhibitor (HAI)-2 is a transmembrane Kunitz-type serine protease inhibitor, which inhibits all pro-HGF-activating enzymes. In RCC, increased expression of MET and decreased expression of HAI-2 were reported to be poor prognostic factors. In the current study, we tried to inhibit the growth of RCC cells by dual inhibition of both MET phosphorylation and pro-HGF-activation using MET inhibitor and HAI-2 overexpression. A transgenic mouse model which expressed human HGF (HGF mouse) was used for in vivo analysis to evaluate the HGF/MET signaling axis accurately. Initially, doxycycline-induced HAI-2 overexpression RCC cells (786-O-HAI2) were prepared. The cells were cultured with pro-HGF, and inhibitory effect of MET inhibitor (SCC244) and HAI-2 was evaluated by phosphorylation of MET and cell proliferation. Next, the cells were subcutaneously implanted to HGF mice and the growth inhibition was determined by SCC244 and HAI-2. Single use of each inhibitor showed significant inhibition in MET phosphorylation, migration and proliferation of 786-O-HAI2 cells; however, the strongest effect was observed by combined use of both inhibitors. Although in vivo analysis also showed apparent downregulation of MET phosphorylation and growth inhibition in combined treatment, statistical significance was not observed compared with single use of MET inhibitor. Combined treatment with MET-TKI and HAI-2 suggested to consider as a candidate for new strong therapy for RCC.

A case of von Hippel-Lindau disease with renal cell carcinoma treated by partial nephrectomy with pre- and post-surgical axitinib therapy.

von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary disease with benign and malignant tumors occurring in various organs including the kidneys. In patients with renal cell carcinoma (RCC) lesions in both kidneys, it is difficult to determine the treatment strategy. We report a case of VHL disease with RCC treated via partial nephrectomy after 6 months of axitinib therapy. Then, the patient continued to receive low-dose axitinib therapy without any signs of tumor progression for 3 years after surgery. Axitinib combined with surgery might be a treatment option for patients with VHL disease harboring bilateral RCC.

Expression of protease activating receptor-2 (PAR-2) is positively correlated with the recurrence of non-muscle invasive bladder cancer: an immunohistochemical analysis.

Background: Matriptase, which is a Type II transmembrane serine protease, has the potential to activate several growth factors, including pro-hepatocyte growth factor (HGF). A G protein-coupled transmembrane cell-surface receptor and a protease-activated receptor 2 (PAR-2) are also required for activation by matriptase. Activation of PAR-2 has been reported to induce the progression of various cancers. In a previous study, we evaluated the correlation between upregulation of MET phosphorylation with high matriptase expression and worse prognosis in patients with muscle invasive bladder cancer; however, expression of PAR-2, matriptase and MET in non-muscle invasive bladder cancer (NMIBC) has not been evaluated. Materials and methods: We retrospectively analyzed the expression of PAR-2, matriptase and MET using 55 paraffin-embedded specimens obtained from patients with NMIBC by immunohistochemistry. Results: MET was significantly expressed in high-grade urothelial carcinoma (UC) and pathological T1 cancers. High expression of PAR-2 was significantly associated with a worse recurrence rate in NMIBC. In subgroup analysis, the expression of PAR-2 was also correlated with high recurrence rate in low-grade UC. In addition, expression of matriptase tended to correlate with worse recurrence rate in high-grade UC. Conclusion: Increased expression of PAR-2 was significantly correlated with worse recurrence rate in patients with NMIBC. In addition, expression of matriptase also indicated a tendency toward recurrence in high-grade UC, suggesting an important role of matriptase-induced PAR-2 activation in NMIBC.