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.

[A Case of Prostate Adenocarcinoma Metastasis to the Bilateral Breasts].

A 67-year-old male came to our department with complaints of urinary retention and gross hematuria. The prostate specific antigen (PSA) level in the serum was elevated to 69.5 ng/ml. Thus a transperineal prostate biopsy was performed. The patient was diagnosed with prostate cancer, and lung and bone metastases were also revealed. Treatment for metastatic prostate cancer was performed for approximately 5 years with combined androgen blockade therapy followed by enzalutamide, docetaxel, estramustine, Ra-223 dichloride, estradiol, and then enzalutamide reintroduction. Thereafter, the patient presented with bilateral breast nodules and we referred him to our breast surgery department. Breast needle biopsy findings revealed breast metastasis from prostate cancer, that was not primary breast cancer. The patient underwent a bilateral mastectomy.

[A Case of Metachronous Bilateral Epididymal Tuberculosis after BCG Instillation Therapy].

Beginning in May 2016, an 83-year-old male underwent three transurethral resections for recurrent bladder cancer. In June 2017, following a positive urine cytology exam, a random biopsy of the bladder was performed. The histopathological findings revealed urothelial carcinoma, high grade, pTis. Treatment consisted of bacillus Calmette-Guerin (BCG) instillation. In February 2018, he complained of left scrotal swelling and pain ; and, was diagnosed with left epididymitis. However, based on resistance to the antibiotic agent, epididymal tuberculosis after BCG therapy was suspected and resection of the left testis and epididymis was performed. Histopathological findings revealed epididymal tuberculosis. Three months after the left orchiectomy, the patient complained of right scrotal swelling and pain. Based on antibiotic resistance and the positive findings of a urinary mycobacterium tuberculosis polymerase chain reaction assay, metachronous right epididymal tuberculosis was suspected and the patient underwent resection of the right epididymis. While the histopathological findings did not indicate tuberculosis, the urinary mycobacterium culture was positive. The patient was diagnosed with right epididymal tuberculosis and after surgery was administered an antituberculosis drug.

[TWO CASES OF FALSE POSITIVE 123I-MIBG SCINTIGRAPHY FINDINGS OF UPTAKE IN ADRENAL TUMORS].

Case 1 was a 71-year-old female who had been examined by her primary care physician for palpitation and hypertension. Urinary hormone test results revealed elevated urine metanephrine at 0.20 mg/day, urine normetanephrine at 0.45 mg/day and urine noradrenalin at 234.9 µg/day. 123I-MIBG scintigraphy showed uptake in the right suprarenal area, thus she was referred to our department because of pheochromocytoma. She underwent a laparoscopic right adrenalectomy and pathological results led to a diagnosis of adrenocortical adenoma. Case 2 was a 70-year-old female who had been examined at our hospital for hypertension. Blood hormone test results revealed elevated noradrenalin at 0.70 ng/ml. 123I-MIBG scintigraphy showed uptake in the left suprarenal area and she was referred to our department because of pheochromocytoma. She underwent a laparoscopic left adrenalectomy, thus pathological results showed no tumor lesion.

[A Case of Bilateral Renal Tumors, Renal Cell Carcinoma and IgG4- Related Retroperitoneal Fibrosis].

A 69-year-old man was referred to our hospital for a right renal pelvic tumor noted on a computed tomography (CT) scan at another hospital. Urine cytology was negative. Dynamic CT revealed a right renal pelvic tumor and, accidentally, a small left renal tumor enhanced in the arterial phase and washed out in the venous phase. No defect in the urinary tract was found on retrograde urography, and upper urinary cytology was negative. The patient's level of IgG4 was high, but other tumor markers were negative. We judged the right renal pelvic tumor to be an extrapelvic lesion, probably IgG4-related disease. We temporarily followed up the right renal pelvic tumor but performed retroperitoneal left partial nephrectomy for the small left renal tumor. Histopathology led to a diagnosis of clear cell renal cell carcinoma. Follow-up CT showed no change in the right renal pelvic tumor. We diagnosed the right renal tumor as IgG4-related disease and began steroid administration. After one monthof administration, the IgG4 value and the size of the tumor were reduced.

[Urothelial Carcinoma within a Calyceal Diverticulum Difficult to Distinguish from Cystic Renal Cell Carcinoma].

A 64-year-old man visited our hospital because of right renal cyst and microscopic hematuria which was found in a medical checkup. Contrast computed tomography (CT) and contrast magnetic resonance imaging (MRI) suggested cystic renal cell carcinoma. A laparoscopic nephrectomy was performed, and the surgical specimens showed urothelial carcinoma within the calyceal diverticulum. At a later date, ureterectomy was performed. The surgical specimens had no malignant findings. There has been no recurrence. To our knowledge only 10 cases of urothelial carcinoma within the calyceal diverticulum have beenreported inJapan. A few cases have beenreported overseas.

[Urethrocutaneous Fistula Caused by a Vesical Foreign Body in an Adolescent Boy : A Case Report].

In daily medical practice, we occasionally encounter patients with a foreign body in the urinary bladder. However, the identification of such a foreign body in an adolescent and the occurrence of an urethrocutaneous fistula caused by the foreign body are extremely rare. Only two cases have been reported previously. Herein we present a case of a foreign body in the urinary bladder and an urethrocutaneous fistula in a young patient. A 14-year-old boy with fever, left scrotal pain and urinary incontinence was referred to our department. Intravenous pyelography and micturition cystourethrography findings revealed a vesical foreign body and an urethrocutaneous fistula. He mentioned that he had inserted two dozen magnets into the urethra for masturbation one year previously. As the foreign bodies were spherical small magnets, we performed transurethral surgery and successfully removed the magnets. His postoperative course was uneventful and he was discharged from our department on the seventh day after surgery. Three months following surgery, the fistula had closed spontaneously.

[A Case Report : Primary Urothelial Carcinoma of the Prostate Producing Interleukin-6 Detected from a Fever].

A 72-year-old man visited a hospital because of a fever and fatigue. His fever persisted and computed tomography revealed a tumor of the prostate. The patient was referred to our hospital with a suspicion of prostate cancer. The blood test showed increased serum C-reactive protein (CRP) level without any infectious findings. Tumor markers including prostate specific antigen were within the normal range and urine cytology was negative. Prostate needle biopsy revealed urothelial carcinoma. No tumor was detected in other areas of the urinary tract. Therefore we diagnosed the patient with primary urothelial carcinoma of the prostate, cT3N0M0. Serum interleukin-6 (IL-6) elevated up to 68 ng/ml. We were not able to detect any metastatic lesions and performed radical cystoprostatectomy and ileal conduit. Serum CRP and IL-6 levels decreased and the fever declined. There has been no relapse 52 months after the surgery.

[Vesical Perforation Caused by a Foreign Body : A Case Report --A Clinical Review of 41 Cases in Japan-].

In daily medical practice, we occasionally encounter a foreign body present in the urinary bladder. However, the occurrence of vesical perforation caused by a foreign body is rare. A 53-year-old man with vesical pain and macrohematuria was referred to our department because of the presence of a foreign body in his urinary bladder. He seemed to have inserted the foreign body from the urethra during use of a stimulant drug according to his story. Cystoscopy revealed that the plastic foreign body had a few barbs and had penetrated the bladder through the left lateral wall. On performing computed tomography, we did not detect any injuries to other organs or hematoma formation. Therefore, we performed elective suprapubic cystostomy and removed the plastic foreign body. The patient's postoperative course was favorable, and he left our department on the sixth day after surgery.

[A Case of Clear Cell Adenocarcinoma Arising from a Female Urethral Diverticulum].

Adenocarcinoma arising from the female urethral diverticulum is very rare, as only about 100 cases have been reported worldwide. An 82-year-old woman presented with asymptomatic macrohematuria. A transvaginal examination revealed a firm circular mass on the anterior vaginal wall. Cystourethroscopy showed a urethral tumor, which was determined to be clear cell adenocarcinoma after transurethral resection of the urethral tumor. However, we could not resect all of the tumor, so anterior pelvic exenteration and ileal conduit urinary diversion were performed. The final pathological diagnosis was clear cell adenocarcinoma arising from the urethral diverticulum. However multiple lymph node metastases appeared 10 months after surgery. The patient refused additional therapy and died 23 months after surgery.

[A CASE REPORT: LITHIASIS OF THE LEFT ECTOPIC PELVIC KIDNEY].

We report a case of lithiasis of the left ectopic pelvic kidney. A 70-year-old man was admitted to our department for left lower back pain. He has been aware of gross hematuria since three or four years before. Computed tomography demonstrated the left ectopic pelvic kidney with a 16-mm stone and a 5-mm stone in the renal pelvis which was accompanied by hydronephrosis. Ten days later, the renal pelvic stones moved to the renal calices and the symptoms disappeared. Though a pyeloureteral junction obstruction was not evident, renogram showed a obstruction pattern of the left kidney. He had been followed up for six years, then the stone was impacted in the renal pelvis and hydronephrosis worsened. Open pyelolithotomy was performed. His clinical course was uneventful and no evidence of recurrence has been observed.

[Penile Tuberculosis : A Case Report].

A 66-year-old man presented with a chief complaint of glans penis pain, induration, and discharge of pus. He was prescribed a course of antibiotics, but the condition persisted despite treatment. Thus, we differrentially diagnosed the patient with penile tuberculosis and pyoderma gangrenosum, and performed a biopsy of the penis. The biopsy result was thickening of the horny layer epidermis with only a foreign body granuloma composed of inflammatory cells, and did not lead to a definitive diagnosis. Thoraca-abdominal computed tomography revealed axillary lymphadenopathy with necrosis. Suspecting tuberculosis lymphadenitis, we performed T-spot and QuantiFERONtests. The result was T-spot negative and QuantiFERONpositive, so we diagnosed the patient with penile tuberculosis, and started antituberculosis medication. In about half a year after the start of treatment the symptoms subsided, and lymphadenopathy showed reduction.

MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma.

BACKGROUND: Extracellular vesicles are lipid bilayer vesicles containing protein, messengerRNA and microRNA. Cancer cell-derived extracellular vesicles may be diagnostic and therapeutic targets. We extracted extracellular vesicles from urine of urothelial carcinoma patients and the control group to identify cancer-specific microRNAs in urinary extracellular vesicles as new biomarkers. MATERIALS AND METHODS: microRNA from urinary extracellular vesicles extracted from 6 urothelial carcinoma patients and 3 healthy volunteers was analyzed. We verified candidate microRNAs in an independent cohort of 60 urinary extracellular vesicles samples. To normalize the microRNA expression level in extracellular vesicles, we examined the following in extracellular vesicles: protein concentration, CD9 intensity, amounts of whole miRNAs, RNA U6B small nuclear expression and the creatinine concentration of original urine correlating with the counts of extracted extracellular vesicles measured by the NanoSight™ system. RESULTS: From the microarray results 5 microRNAs overexpressed in urinary extracellular vesicles of urothelial carcinoma patients were identified. Creatinine concentration of original urine correlated most with particle counts of extracellular vesicles, indicating that creatinine could be a new tool for normalizing microRNA expression. MiR-21-5p was the most potent biomarker in urinary extracellular vesicles (sensitivity, 75.0%; specificity, 95.8%) and was also overexpressed in urinary extracellular vesicles from urothelial carcinoma patients with negative urine cytology. For the subgroup with negative urine cytology, the sensitivity was 75.0% and specificity was 95.8%. CONCLUSION: MiR-21-5p in urinary extracellular vesicles could be a new biomarker of urothelial carcinoma, especially for urothelial carcinoma patients with negative urine cytology.

HIV-associated cystic lesions of the parotid gland.

We present two cases of an HIV-associated parotid gland cyst. One case was a 36-year-old HIV infected woman. She was diagnosed with HIV infection and presented with slowly enlarged parotid gland cysts together with elevation of HIV viral RNA copies/mL in her serum. She was performed parotid gland biopsy under the general anesthesia. The histopathologic analysis revealed negative HIV p24-antigen in her parotid gland tissue. The other case was a 43-year-old man found his parotid gland swelling shortly after highly active antiretroviral therapy (HAART). He was diagnosed with HIV infection 2 years previously. He had started HAART several days before. He showed exceeding elevation of IgE in his serum. We treated him with medication using anti-histamic drugs for his cyst. A computed tomography scan revealed a complete response of his parotid gland cyst 4 weeks after the medication. His serum IgE level was decreased to half of the level before the medication. These findings suggested that the parotid gland swelling associated with HIV was due to various factors including immune reconstitution inflammatory syndrome (IRIS). In case such a parotid gland swelling, we could avoid invasive treatments.

[Solitary Fibrous Tumor in the Retroperitoneum : A Case Report].

A 55-year-old man was diagnosed with an abdominal tumor and referred to our department. Abdominal contrast-enhanced computed tomography revealed a 15-cm tumor in the retroperitoneum. The inferior vena cava was compressed ventrally, the right ureter laterally, and the right kidney toward the head. Part of the tumor was situated on the dorsal side of the abdominal aorta. A preoperative diagnosis of neurogenic tumor or a type of sarcoma was made. We performed en bloc resection of the tumor. The right kidney was also resected. We exfoliated between the tumor and inferior vena cava without temporary interruption. The final diagnosis was a solitary fibrous tumor. The patient received no adjuvant therapy. Neither recurrence nor metastasis has been detected for 8 months postoperatively.

Finger taps and constipation are closely related to symptoms of overactive bladder in male patients with Parkinson's disease.

OBJECTIVES: To assess which motor and non-motor symptoms are closely related to overactive bladder severity in male patients with Parkinson's disease. METHODS: A total of 160 male patients (mean age 71.4 ± 8.2 years) diagnosed with Parkinson's disease were included in the present study at Osaka University and affiliated hospitals. The severity of Parkinson's disease was classified as stage 3, 4 or 5 based on the Hoehn and Yahr staging system. Disease duration was 8.9 ± 5.1 years. Age, seven items from the Unified Parkinson's Disease Rating Scale motor section part III and three non-motor symptoms were assessed by multivariate analysis for their impact on the overactive bladder symptom score, a specific questionnaire for overactive bladder. RESULTS: Overactive bladder symptom score was significantly higher in the group with severe motor symptoms related to finger taps and gait than in the group with mild motor symptoms related to these two factors. Furthermore, overactive bladder symptom score of patients with erectile dysfunction and constipation was significantly higher than that in patients without these symptoms. Multivariate analysis identified only finger taps and constipation as factors independently associated with overactive bladder symptom score. CONCLUSIONS: Although a study on a larger scale is required to further assess the association of Parkinson's disease symptoms with overactive bladder symptom score, information on finger taps and severity of constipation should be obtained when assessing urological patients with Parkinson's disease.

[A case of bronchogenic cyst treated as retroperitoneal tumor].

A 66-year-old man presented with a retroperitoneal mass found in a routine medical examination. He had no complaints and no medical history. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a cystic mass in the retroperitoneal space, attached to the left crus of the diaphragm, 5.5 cm in size. Retroperitoneal cystic tumor was diagnosed, and transperitoneal tumor resection was performed. Pathological findings revealed a cyst wall lined with ciliated epithelium and cartilage, diagnosed as a retroperitoneal bronchogenic cyst. The patient was in good health at 12 months after the surgery with no evidence of recurrence.

Diversity in protein profiles of individual calcium oxalate kidney stones.

Calcium oxalate kidney stones contain low amounts of proteins, some of which have been implicated in progression or prevention of kidney stone formation. To gain insights into the pathophysiology of urolithiasis, we have characterized protein components of calcium oxalate kidney stones by proteomic approaches. Proteins extracted from kidney stones showed highly heterogeneous migration patterns in gel electrophoresis as reported. This was likely to be mainly due to proteolytic degradation and protein-protein crosslinking of Tamm-Horsfall protein and prothrombin. Protein profiles of calcium oxalate kidney stones were obtained by in-solution protease digestion followed by nanoLC-MALDI-tandem mass spectrometry, which resulted in identification of a total of 92 proteins in stones from 9 urolithiasis patients. Further analysis showed that protein species and their relative amounts were highly variable among individual stones. Although proteins such as prothrombin, osteopontin, calgranulin A and calgranulin B were found in most stones tested, some samples had high contents of prothrombin and osteopontin, while others had high contents of calgranulins. In addition, calgranulin-rich stones had various neutrophil-enriched proteins such as myeloperoxidase and lactotransferrin. These proteomic profiles of individual kidney stones suggest that multiple systems composed of different groups of proteins including leucocyte-derived ones are differently involved in pathogenesis of individual kidney stones depending on situations.

Low serum free testosterone level is associated with carotid intima-media thickness in middle-aged Japanese men.

In the present study, we measured carotid artery intima-media thickness (CIMT) and assessed several metabolic factors in middle-aged healthy Japanese men to clarify the relation between testosterone and atherosclerosis. The study comprised 176 male employees aged ≥40 years who visited Osaka University Healthcare Center for their annual health examinations. Serum total testosterone (TT) concentration was measured using radioimmunoassay (RIA) and serum free testosterone concentration was measured using analog ligand RIA (aFT). A multivariate model adjusted for age, body mass index, mean arterial pressure and treatment for hypertension demonstrated a significant association between aFT and CIMT. Even after adjustment for other clinically relevant factors, the significant association between aFT and CIMT was not attenuated. After adjustment for all other clinically relevant factors, both univariate and multivariate models ascertained the stepwise association that a level of aFT of ≤10.0 pg/mL was significantly associated with CIMT. However, the association between TT and CIMT was not significant in either univariate or multivariate models. We conclude that our finding showing that low serum aFT level is an influencing and independent risk factor for CIMT is of value in the clinical setting because no other studies, to our knowledge, have conducted multivariate analyses using the various metabolic factors included in the present analyses.