Real-world prostate-specific antigen response and progression to castration-resistant prostate cancer among men with metastatic castration-sensitive prostate cancer treated with apalutamide: a multi-institutional study in the Chu-shikoku Japan Urological Consortium.

BACKGROUND: Japanese men receiving apalutamide often experience skin-adverse events (AEs), possibly requiring treatment interruption or dose reduction. However, concerns have arisen regarding the impact of these adjustments on the efficacy of apalutamide. Our study evaluated the efficacy, safety, and persistence of apalutamide in men with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: We retrospectively reviewed the medical records of 108 men with mCSPC from 14 Japanese institutions. The primary outcomes were the efficacy of apalutamide: prostate-specific antigen (PSA) response (50%, 90% and < 0.2 decline) and progression to castration-resistant prostate cancer (CRPC). The secondary outcomes were the skin-AE and compliance of apalutamide. RESULTS: PSA50%, PSA90% and PSA < 0.2 declines were observed in 89.8, 84.3 and 65.7%, and the median time to CRPC progression was not reached. PSA < 0.2 decline and an initial full dose of apalutamide were significantly associated with a longer time to CRPC. The most common AE was skin-AE (50.9%), and there was no association between the occurrence of skin-AE and the time to CRPC (P = 0.72). The median apalutamide persistence was 29 months, which was longer in the initial full dose recipients than in the reduced dose recipients. The dosage is reduced in about 60% of patients within the first year of treatment in the initial full dose recipients. CONCLUSIONS: Our findings indicate the effectiveness of apalutamide in Japanese men with mCSPC, despite a substantial portion requiring dose reduction within a year among the initial full dose recipients.

Insulin receptor expression to predict resistance to axitinib and elucidation of the underlying molecular mechanism in metastatic renal cell carcinoma.

BACKGROUND: The study aimed to examine the significance of insulin receptor (INSR) expression in predicting resistance to axitinib in clear cell renal cell carcinoma (ccRCC). METHODS: Clinicopathological data were collected from 36 consecutive patients with metastatic RCC who received axitinib. Thirty-three primary tumours were obtained for immunohistochemistry. Patient-derived xenograft (PDX) models were created by transplanting primary tumours into immunodeficient mice, establishing axitinib-resistant PDX models. RCC cell lines were co-cultured with human renal glomerular endothelial cells (HGECs) treated with siRNA of INSR (HGEC-siINSR). Gene expression alteration was analysed using microarray. RESULTS: The patients with low INSR expression who received axitinib had a poorer outcome. Multivariate analysis showed that INSR expression was the independent predictor of progression-free survival. INSR expression decreased in axitinib-resistant PDX tumours. RCC cell lines showed upregulated interferon responses and highly increased interferon-ß levels by co-culturing with HGEC-siINSR. HGECs showed decreased INSR and increased interferon-ß after axitinib administration. RCC cell lines co-cultured with HGEC-siINSR showed high programmed death-ligand 1 (PD-L1) expression, which increased after interferon-ß administration. CONCLUSIONS: Decreased INSR in RCC could be a biomarker to predict axitinib resistance. Regarding the resistant mechanism, vascular endothelial cells with decreased INSR in RCC may secrete interferon-ß and induce PD-L1.

Comparison of robot-assisted partial nephrectomy with soft coagulation and double-layer technique for complex and non-complex tumors.

OBJECTIVES: To compare the postoperative outcomes of robot-assisted partial nephrectomy when only the inner layer is sutured (single-layer technique with soft coagulation) with those when sutures are placed in the inner and outer layers (double-layer technique) in patients with and without complex renal tumors. METHODS: This retrospective three-institution study included 371 patients with renal tumors who underwent robot-assisted partial nephrectomy with a double-layer technique or a single-layer technique with soft coagulation. Tumors that were cT1b, completely embedded, located in the renal portal, or had a RENAL score of ≥10 were considered complex. Relevant data were collected from hospital records. Propensity score matching was performed to minimize selection bias. RESULTS: Propensity score matching created 83 patient pairs with non-complex tumors and 32 with complex tumors. Regardless of tumor complexity, there was no significant difference in operation time, console time, warm ischemia time, positive surgical margin rate, or length of hospital stay between the double-layer and single-layer groups. Although Clavien-Dindo grade I-II urinomas not requiring intervention were significantly more common in the single-layer group regardless of tumor complexity, there was no significant between-group difference in the rate of decline in renal function or grade III-IV complications. CONCLUSION: Single-layer suturing with soft coagulation achieves renal function and perioperative outcomes comparable to those of double-layer suturing regardless of complexity.

A propensity score matching study on robot-assisted radical cystectomy for older patients: comparison of intracorporeal ileal conduit and cutaneous ureterostomy.

BACKGROUND: Robot-assisted radical cystectomy (RARC) and intracorporeal urinary diversion are less invasive than conventional procedures. However, for older patients, cutaneous ureterostomy (CUS) may be preferred because urinary diversion using the intestine has a high incidence of perioperative complications and is highly invasive. The purpose of this study was to demonstrate the safety and efficacy of intracorporeal ileal conduit (ICIC) compared with CUS in patients aged 75 years or older who underwent RARC. METHODS: From October 2014 to December 2021, 82 patients aged 75 years or older who underwent RARC at Tokushima University Hospital, Tokushima Prefectural Central Hospital, or Ehime Prefectural Central Hospital were retrospectively reviewed. Of these, 52 and 25 patients who underwent ICIC and CUS, respectively, were included. After adjusting the patients' characteristics using propensity score-matching, surgical results and prognoses were retrospectively compared. The propensity score was based on age, Eastern Cooperative Oncology Group Performance Status Scale (ECOG-PS), American Society of Anesthesiologists physical status classification (ASA-PS), clinical tumor stage, and neoadjuvant chemotherapy. RESULTS: The median age was lower in the ICIC group compared with the CUS group, and the proportion of high-risk cases (ECOG-PS ≥ 2 or ASA-PS ≥ 3) did not differ. The median operation time was longer in the ICIC group, and estimated blood loss was higher, compared with the CUS group. There were no significant differences in the incidence of complications within the first 30 postoperative days, incidence of complications 30-90 days after surgery, 2-year overall survival, 2-year cancer-specific survival, and 2-year recurrence-free survival. The stent-free rate was significantly lower in the CUS group than that in the ICIC group. CONCLUSION: In older patients, the ICIC group showed non-inferior surgical and oncological outcomes compared with the CUS group. Urinary diversion following RARC in older patients should be carefully selected by considering not only the age but also the general condition (including comorbidities) of the patient.

Appropriate management reduces radiation exposure in daily urological practice.

OBJECTIVES: To identify and raise awareness of the radiation exposure of urologists due to X-ray fluoroscopic procedures in daily practice. METHODS: This was a single-center, cohort study of 30 consecutive patients who underwent periodic percutaneous or transurethral replacements of urinary tract catheters. A total of 55 replacements every 3 months with cases aligned were performed by a single urologist. The urologist's radiation exposure and the incident dose to patients per case were measured with thermoluminescent dosimeters. In the latter 3-month period, the pulse fluoroscopy condition was changed from 15 to 7.5 pulses per second, and collimation was added to the field of view. RESULTS: In the analysis of all patients, the use of a modified pulse rate and collimation did not affect the fluoroscopy time, but it did significantly reduce the air kerma and dose area product; in addition, with respect to the medical exposure dose during percutaneous catheter replacement, fluoroscopy time was longer, but air kerma and dose area product showed significant decreases. As with decreases in medical exposure of patients, the equivalent dose for eye lenses of the urologist decreased from 1.2 mSv in the first 3-month period to 0.2 mSv in the second 3-month period. Similarly, the exposure dose for the extremities also decreased significantly, from 33.9 mSv to 8.1 mSv. CONCLUSIONS: Urologists are exposed to non-negligible amounts of radiation due to fluoroscopy. Appropriate management such as modified pulse fluoroscopy condition and precautions are required.

[A Case of Pappilary Renal Cell Caircinoma which Responded Well to the Combination Therapy of Ipilimumab and Nivolumab --A CASE REPORT-].

We report a case of papillary renal cell carcinoma that responded well to the combination of ipilimumab and nivolumab. The patient was a 68-year-old male who was being followed up for a small left renal mass without treatment. Two years later, computed tomography (CT) showed enlarged cervical and para-aortic lymph nodes, and lymph node biopsy suggested metastases of the cancer. After resection of the renal tumor, we performed pararenal aortic lymph node biopsy, and we diagnosed the case as papillary renal cell carcinoma type 1 with lymph node metastasis. The combination of ipilimumab and nivolumab each metastatic site showed regression on CT. Since immune-related adverse events occurred during the therapy nivolumab was discontinued, but partial response of the metastases was maintained.

[Two Cases of Robot-Assisted Total Pelvic Exenteration and Intracorporeal Ileal Conduit for Locally Advanced Rectal Cancer].

We describe two cases of locally advanced rectal cancer (LARC) treated with robot-assisted total pelvic exenteration (Ra-TPE) and intracorporeal ileal conduit (ICIC). The first case was in a 71-year-old man with LARC (RbP, T4bN2bM0, cStage IIIc). He was started on bevacizumab+S-1/oxaliplatin therapy in July 2019. In April 2020, he developed Fournier's gangrene due to subcutaneous penetration of rectal cancer. Emergency drainage and colostomy were performed simultaneously, and a percutaneous vesical fistula was created. In May 2020, Ra-TPE and ICIC were performed. Histopathological analysis revealed moderately differentiated tubular adenocarcinoma (ypT3N0, RM0). At postoperative 9 months, thoracoscopic right upper lobectomy was performed for a right metastatic lung tumor. At present, ie, at postoperative 12 months, the patient has been free of recurrence and metastasis, with a carcinoembryonic antigen (CEA) level of 1.4 ng/ml and carcinoma antigen (CA) 19-9 level of 11 U/ml. The second case was in a 61-year-old man with fistula-associated anal cancer (PRb, T4N3M1b, cStage IVb). In April 2019, he was started on FOLFOXIRI+cetuximab therapy. In August 2020, Ra-TPE, ICIC, and transperineal total mesenteric excision were performed. Histopathological analysis revealed adenocarcinoma (ypT4N0, RM0). At postoperative 11 months, thoracoscopic left lower lobectomy was performed for a left metastatic lung tumor. At present, ie, at postoperative 12 months, the patient remains free of recurrence and metastasis, with a CEA level of 7.3 ng/ml and CA19-9 level of 12 U/ml. Ra-TPE, which allows transperineal removal of a specimen, can be performed as a minimally invasive surgery in combination with ICIC.

[A Case of Robot-Assisted Radical Cystoprostatectomy for Locally Advanced Prostate Cancer with Bladder Infiltration].

While robot-assisted radical cystoprostatectomy (RARC) for locally advanced prostate cancer (LAPC) may sometimes prove to be excessive treatment, it can significantly reduce the risk of positive surgical margins and lower urinary tract obstruction in some cases. Here, we report a case of LAPC treated with RARC in a patient with right hydronephrosis due to bladder infiltration and left hypoplastic kidney. A 71-year-old man presented with frequent urination in August 2019. Prostate-specific antigen (PSA) level was 8.633 ng/ml, and magnetic resonance imaging led to the suspicion that the prostate cancer extended beyond the prostate capsule without distant metastasis. Prostatic biopsy revealed Gleason score 10 (5＋5) adenocarcinoma in 8 out of 8 specimens. We diagnosed left hypoplastic kidney and LAPC with right hydronephrosis due to bladder infiltration. We performed percutaneous right nephrostomy and started neoadjuvant hormone therapy. RARC and intracorporeal ileal conduit were performed in March 2020. The prostate was adherent to the anterior surface of the rectum and was difficult to remove. At present, five months after the surgery, the patient remains free of recurrence and metastasis with PSA level ＜0.003 ng/ml. RARC for LAPC with bladder infiltration can be an effective therapeutic strategy in some cases.

[A Case of Desmoid Tumor Initially Diagnosed as a Metastasis from Renal Cell Carcinoma --A CASE REPORT-].

We report a case of desmoid tumor that was initially diagnosed as metastasis from renal cell carcinoma. A follow-up computed tomographic (CT) scan after nephrectomy for renal cell carcinoma in a 64-year-old man revealed a right retroperitoneal tumor 3.5 cm in diameter. Though the CT density of the tumor was similar to that of muscles, we first suspected metastasis from renal cell carcinoma or other cancer because the tumor growth was relatively fast. We resected the tumor. The pathological diagnosis was desmoid type fibromatosis. We also review six cases of desmoid tumors after nephrectomy for renal cell carcinoma reported in Japan. Careful followup is required for the patients with desmoid tumors because of frequent recurrence.

[A Case of Pelvic Organ Prolapse and Bladder Diverticulum Surgically Treated at the Same Time].

We report a case of bladder diverticulum presumably caused by lower urinary tract dysfunction due to pelvic organ prolapse (POP) simultaneously treated with transurethral coagulation (TUC) of the bladder diverticulum and laparoscopic sacrocolpopexy (LSC). A literature search showed this is the first report of bladder diverticulum and POP surgically treated at the same time. A 71-year-old woman was referred to our hospital for the treatment of cystocele. She had both storage and voiding symptoms. She had a POPQ stage III cystocele and stage I uterine prolapse. Ultrasonography and computed tomographic scan showed a large volume of residual urine along with a bladder diverticulum. Since urodynamic studies revealed a low compliance bladder and obstruction, we opined that the lower urinary tract symptoms were induced by the cystocele. TUC of the bladder diverticulum and LSC were performed at the same time. After the operation, clean intermittent catheterization (CIC) was needed once a day for one month. Gradually, residual urine decreased and CIC became unnecessary. The bladder diverticulum disappeared, and there has been no recurrence of POP.

[Mucinous Tubular and Spindle Cell Carcinoma in a Patient on Hemodialysis : A Case Report].

Although patients on long-term hemodialysis frequently develop renal cell carcinoma, mucinous tubular and spindle cell carcinoma (MTSCC) is rare in incidence. Here, we report a case of MTSCC occurring in a patient under hemodialysis. The patient was a 72-year-old man with end stage renal failure due to diabetic nephropathy. Hemodialysis was initiated in 2003. He presented with macrohematuria. Contrastenhanced computed tomography (CT) revealed a right renal tumor. Laparoscopic right nephrectomy was performed accordingly in June 2017. Pathologically, the tumor was diagnosed as MTSCC. Six months after the surgery, the patient remains free of recurrence and metastasis. Here we review the characteristics of 5 MTSCC cases in patients on hemodialysis reported in Japan.

[One-Step Laparoscopic Surgery for Two Regions : Pelvi-Ureteric Junction Obstruction and Mid Ureteral Obstruction Due to Umbilical Ligament].

The patient first presented with left flank pain at the age of 15. Computed tomography (CT) and ultrasonography performed at that time revealed left hydronephrosis and hydroureter. Mid-ureteral obstruction was suspected,and he underwent balloon catheter dilation of the mid-ureteral obstruction. Hydronephrosis,hydroureter and flank pain improved after surgery. However,at 21 years of age,he again presented with left flank pain. CT and ultrasonography revealed pelvi-ureteric junction obstruction and mid-ureteral obstruction. The suspected cause of the mid-ureteral obstruction was the umbilical ligament. Renal scintigraphy showed an obstructive pattern in the left kidney,with 52% split renal function. He thus underwent laparoscopic pyeloplasty and end-to-end anastomosis of the mid-ureter with the one-step approach. No intra- or postoperative complications occurred,and the D-J stent was removed 6 weeks after surgery. At 12 months after surgery,he has had no recurrent flank pain and left renal function is normal.

[ROBOT-ASSISTED RADICAL PROSTATECTOMY FOR MEN AGE 75 AND OLDER].

(Objectives) Surgical treatment prostate cancer in elderly patients is controversial. However, robot-assisted radical prostatectomy (RARP) is a less invasive procedure than conventional surgery. Therefore, we perform RARP for elderly patients whose general condition is good (Performance status ≤1). The aim of this study is to evaluate surgical, oncological and functional outcomes for RARP in men age 75 and older. (Patients and methods) From July 2013 to April 2016, 300 patients underwent RARP at our institution. They were divided into two groups: an older patient group (≥75 years) and a younger patient group (<75 years). Treatment outcomes for each group, including surgical, oncological and functional outcomes, were compared. (Results) There were no statistically significant differences in surgical outcomes with the exception of nerve sparing rates (older patients: 5.9% vs. younger patients: 17.7%, P=0.0192). Importantly, intra- and postoperative complication rates were similar in both groups (minor complication: 7.4% vs. 3.9%, P=0.322, major complication: 0.0% vs. 2.2%, P=0.592). Regarding oncological outcomes, including positive surgical margin rate and PSA failure (PSA>0.2 ng/ml) at 12 months after surgery, no significant differences existed. Lastly, functional outcomes between the groups, including continence (≤1 pads/day) at 12 months after surgery, had no significant differences. (Conclusions) Our data suggests that RARP can be performed safely for men age 75 and older, and can become a good option for older patients with prostate cancer.

[MICROCYSTIC VARIANT OF UROTHELIAL CARCINOMA IN URINARY BLADDER: A CASE REPORT].

In the present report, we describe a patient with microcystic variant of urothelial carcinoma in urinary bladder. In March 2016, a 71-year-old man presented with bladder tumors found incidentally by ultrasonography. Cystoscopy and contrast-enhanced computed tomography (CT) revealed multiple invasive tumor of posterior wall, with a maximum diameter of 33 mm. Transurethral resection (TUR) of bladder tumors was performed. Pathological diagnosis was urothelial carcinoma, high grade, T2 or more. Invasive urothelial carcinoma was diagnosed and laparoscopic radical cystectomy with orthotopic neobladder was performed accordingly in April 2016. Pathological findings indicated a diagnosis of microcystic variant of urothelial carcinoma. At present, six months after surgery, the patient remains free of recurrence and metastasis. Here we review the characteristics of 4 microcystic variant of urothelial carcinoma cases reported in Japan.

[Two Cases of Overwhelming Post-Splenectomy Infection].

In this report, we describe two cases of overwhelming post-splenectomy infection (OPSI). The first case was in a 70-year-old man who received a splenectomy in 2012 due to pancytopenia induced by hepatic cirrhosis. He presented with fever and fatigue. A blood test and abdominal ultrasonography were performed. However, these examinations did not indicate any abnormal findings. He unexpectedly suffered from septic shock and acute renal failure the following day. Treatment consisted of mechanical ventilation, broad-spectrum antibiotics and continuous hemodiafiltration. Despite intensive treatment, he died 3 days after the initial visit. The second case was in a 55-year-old man with end-stage renal failure who started hemodialysis in 2004 and received a splenectomy in 2005 because of splenic artery aneurysm rupture. He presented with headache and nausea. A blood test indicated bacterial infection. We suspected OPSI and treated him with broad-spectrum antibiotics, continuous hemodiafiltration and mechanical ventilation. Despite treatment, his general condition gradually deteriorated, and he died 15 days after the initial visit. In view of the high mortality rate, prevention through vaccination and provision of proper information regarding OPSI is important.

[Port-Site Metastasis of Urothelial Carcinoma after Laparoscopic Nephroureterectomy: A Case Report].

The patient was a 70-year-old woman with a chief complaint of right hydronephrosis and hydroureter detected by ultrasound by a local doctor. She came to our hospital in January, 2014 for further examination. Because a tumor was discovered in her right upper ureter by computed tomography (CT) and retrograde pyelography, a right laparoscopic nephroureterectomy was perfomed on the suspicion of a right ureter carcinoma (clinical stage T2 N0M0). The pathological examination showed urothelial carcinoma, grade 3, pT3. She was followed up carefully without adjuvant chemotherapy. At 10 months postoperatively, a subcutaneous tumor was found at the port-site by CT, and she underwent surgical resection of the subcutaneous tumor. Pathological diagnosis was urothelial carcinoma, and was confimed to be portsite metastasis of urothelial carcinoma. She received three courses of gemcitabine and carboplatin chemotherapy therapy from November, 2014. She has been followed up without signs of recurrence.

[Renal arteriovenous fistula with a vein aneurysm: a case report].

A 54-year-old woman presented with abdominal distension. Her medical history was unremarkable. Contrast-enhanced computed tomography (CT) revealed a left renal arteriovenous fistula and a large vein aneurysm, and she was diagnosed with aneurismal-type renal arteriovenous fistula. She was successfully treated with transcatheter arterial embolization using steel coils. Although she had pulmonary embolism as a serious post-operative complication, she recovered with anticoagulant therapy using heparin and warfarin. A contrast-enhanced CT scan performed 6 months after transcatheter arterial embolization did not show recanalization.

[Gangrene of the penis due to strangulation by a rubber band: a case report].

We report a case of strangulation of the penis by a rubber band. A 79-year-old man placed a rubber band tightly around the corona of his glans penis in order to prevent urinary incontinence. After five days, he was taken to our hospital in an ambulance for high temperature and general malaise. We found the rubber band and removed it immediately. Gangrene of the penis continued and he did not recover from sepsis, so we performed partial penectomy. After the operation, he completely recovered. Penile strangulation using a soft constricting object such as a rubber band might result in severe complications and we should be careful.