Real-world treatment outcomes of patients with penile cancer in the Kyushu-Okinawa area of Japan in the pre-guideline era.

OBJECTIVES: To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. METHODS: We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. RESULTS: A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26 months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter ≥ 30 mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status ≥ 1, cT ≥ 3, cN ≥ 2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN ≥ 2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P = 0.0002), Eastern Cooperative Oncology Group performance status ≥ 1 (4.42; 1.79-10.9; P = 0.0012) and cT ≥ 3 (3.34; 1.11-10.1; P = 0.0319) were identified as independent prognostic factors. CONCLUSIONS: The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN ≥ 2, Eastern Cooperative Oncology Group performance status ≥ 1 and cT ≥ 3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.

Cellular and physical microenvironments regulate the aggressiveness and sunitinib chemosensitivity of clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most predominant type of kidney cancer in adults and is responsible for approximately 85% of clinical cases. The tumor-specific microenvironment includes both cellular and physical factors, and it regulates the homeostasis and function of cancer cells. Perirenal adipose tissue and tumor-associated macrophages are the major cellular components of the RCC microenvironment. The RCC microvasculature network generates interstitial fluid flow, which is the movement of fluid through the extracellular compartments of tissues. This fluid flow is a specific physical characteristic of the microenvironment of RCC. We hypothesized that there may be an interaction between the cellular and physical microenvironments and that these two factors may play an important role in regulating the behavior of RCC. To elucidate the effects of adipose tissue, macrophages, and fluid flow stimulation on RCC and to investigate the relationships between these factors, we used a collagen gel culture method to generate cancer-stroma interactions and a gyratory shaker to create fluid flow stimulation. Adipose-related cells, monocytes, and fluid flow influenced the proliferative potential and invasive capacity of RCC cells. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by both fluid flow and cellular interactions between RCC and adipose tissue fragments or macrophages. Fluid flow stimulation synergistically enhanced the anti-proliferative effect of sunitinib on RCC cells, but macrophages abolished the synergistic anti-proliferative effect related to fluid flow stimulation. In conclusion, we established a reconstructed model to investigate the cellular and physical microenvironments of RCC in vitro. Our alternative culture model may provide a promising tool for further therapeutic investigations into many types of cancer. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Long-term outcomes of Blocksom vesicostomy for elderly patients with chronic urinary retention.

PURPOSE: To report on the long-term outcomes of vesicostomy in elderly patients with chronic urinary retention. MATERIALS AND METHODS: We conducted a study of 16 elderly patients with chronic urinary retention who underwent Blocksom vesicostomy between April 2010 and March 2021. Postoperative follow-up was conducted every 3 months to check for abnormal findings, such as stoma outlet obstruction, infection, bleeding, bladder prolapse, and bladder stones. The incidence of these findings and the time until they occurred, as well as the rate of achieving a catheter-free status and the time until catheter reinsertion, were then calculated using the Kaplan-Meier curve. RESULTS: The mean age (±standard deviation) of patients whose cases were observed was 78.6 (±7.8) years; the oldest patient was 87 years of age. The study population included 14 male patients and 2 female patients, with a higher number of males. The causes of urinary retention included neurogenic bladder in 12 patients (including patients with 3 spinal cord injury), advanced prostate cancer in 2 patients, and iatrogenic urethral stricture in 2 patients. The average follow-up period was 55.7 months. During follow-up, 14 patients (87.5% of the total) achieved a catheter-free status under conditions that required no additional treatment. Complications were observed in 6 cases (37.5%); among them, two cases required reoperation. All complications were observed within 2 years after surgery. CONCLUSION: Blocksom vesicostomy may become a viable option in the treatment of elderly patients with chronic urinary retention whose symptoms do not improve with medical therapy.

Surveillance of urachal abscess in the Kyushu-Okinawa area of Japan.

OBJECTIVE: To report a multicenter experience with the management of urachal abscess treatment in Japan. METHODS: This was a retrospective study of 263 cases of urachal abscess managed at 12 university hospitals in the Kyushu-Okinawa region over a 10-year period. Age, sex, abscess size, clinical symptoms, type of urachal remnants, and treatment were collected and analyzed. RESULTS: The average age was 29.8 ± 18.1 years, with males accounting for approximately two-thirds of the study population. The average abscess size was 1.7 cm (range 0-11 cm). The most common presenting symptom was umbilical secretion (66%), followed by abdominal pain (46%). A total of 127 patients (48.3%) were treated with antibiotics alone, whereas 136 patients (51.7%) received surgical treatment. The surgical approach was laparotomy in 75 patients (61.0%) and laparoscopic surgery in 48 patients (39.0%). Regarding the type of urachal remnant, the urachus sinus (180 patients) accounted for 68.4% of the total. CONCLUSIONS: To our knowledge, this study represents the first report on urachal abscess treatment in Japan. Our data show that the clinical symptoms might vary depending on the type of urachus remnant. It should be noted that gross hematuria, a characteristic symptom of urachal cancer, is rare in patients with urachal abscess.

Risk Factors for Uroseptic Shock in Patients with Urolithiasis-Related Acute Pyelonephritis.

OBJECTIVES: To analyze the risk factors of uroseptic shock induced by calculous acute pyelonephritis (APN). METHODS: This study included 69 patients (41 were women and 28 were men) who were admitted to our hospital for APN treatment associated with urolithiasis during the period from January 2005 to December 2012. We reviewed the electronic medical records of these patients to analyze risk factors contributing to the development of uroseptic shock from APN in patients with urolithiasis. RESULTS: Urinary drainage with ureteral stent or nephrostomy was carried out in 62 cases. Septic shock requiring vasopressor infusion against circulatory collapse was observed in 25 patients, these patients showed significantly lower serum albumin levels and higher C-reactive protein (CRP) compared to patients who did not exhibit septic shock. Multivariate analysis revealed that serum albumin level and CRP were the significant risk factors for the development of uroseptic shock from calculous APN. CONCLUSIONS: Serum albumin level was the significant risk factor for the development of uroseptic shock from calculous APN. Emergency drainage to decompress the obstructed urinary tract is mandatory as an initial urological intervention for the patients with lower serum albumin level.

Urological surgery in elderly and the perioperative management.

Perioperative delirium and depression are characteristic of in elderly patients undergoing urological operation. The treatment for urological disease is stagnant, exchanged or inter- rupted by these complications. Furthermore, these complications may course to other more complications. Age, preoperative cognitive status, activities of daily living function, renal function and other factors were known for the risk factor of perioperative delirium. However, these complications should be managed immediately, prevention of these complications is most important. To prevent these complications, preoperative physical, mental and cognitive evaluation are done, measures for the complications will be contemplated. The control for sleep disturbance, pain and anxiety are important to prevent and manage for the periopera- tive delirium and depression.

Age-related changes in bladder function with altered angiotensin II receptor mechanisms in rats.

AIMS: To examine alterations in expression of angiotensin II type 1 receptors (AT1R) which induce organ tissue remodeling, angiotensin II type 2 receptors (AT2R) which protect against it, and related molecules in the bladder of matured rats with bladder dysfunction. METHODS: Female SD rats of three different ages were used: 8 weeks old (8W; n = 5), 9 months old (9M; n = 5), and 15 months old (15M; n = 5). After cystometry, the expression levels of AT1R, connexin43 (Cx43), MAP kinase (MAPK), collagen1, AT2R, PPAR-γ, adiponectin (Adipo), and adiponectin receptor (Adipo-R) were investigated in the bladder. RESULTS: Pressure threshold, post-void residual volume and the number of non-voiding contractions were significantly increased in 15M versus 8W rats (P < 0.01). Maximum voiding pressure was significantly decreased in 15M versus 8W rats (P < 0.05). There was no significant difference in CMG parameters between 8W and 9M rats. In the bladder, the mRNA expression of AT1R, Cx43, MAPK, collagen 1, AT2R, PPAR-γ, Adipo, and Adipo-R were significantly higher in 15M than in 8W rats. The relative expression ratio of AT1R protein against AT2R protein in the mucosa and detrusor was significantly increased in 15M versus 8W rats. CONCLUSIONS: These results indicate that matured rats exhibit not only bladder overactivity but also impaired voiding, which are associated with upregulation of AT1R. The upregulation of AT2R also may play a significant role in the suppressing of AT1R induced remodelling. However, because AT1R upregulation is more dominant than AT2R increases, AT2R activation may not be sufficient to suppress AT1R stimulation in matured rats. Neurourol. Urodynam. 35:908-913, 2016. © 2015 Wiley Periodicals, Inc.

Is the eGFR formula adequate for evaluating renal function before chemotherapy in patients with urogenital cancer? A suggestion for clinical application of eGFR formula.

BACKGROUND: Accurate evaluation of renal function is required before cancer chemotherapy. Various kinds of formula have been developed for estimating creatinine clearance (Ccr) or glomerular filtration rate (GFR) conveniently. We retrospectively examined the reliability of the GFR estimating formula using the renal function data in cancer chemotherapy. METHODS: Clinical data of 12 patients with urogenital cancer from 1998 to 2013 in Saga University Hospital were reviewed. Patients were treated with 6-21 (median 10.5) courses of chemotherapy and those patients underwent 9-29 (median 14.5) times of 24hrCcr tests before and during chemotherapy. We compared estimated GFR (eGFR) with 24hrCcr. In addition, we developed a novel method to estimate the Ccr using the patient-inherent 24hrCcr/eGFR ratio, which is calculated from initial 3 or 4 determinations of 24hrCcr and the corresponding eGFR. Those estimated Ccrs were also compared with 24hrCcr. RESULTS: The dissociation between 24hrCcr and eGFR was not constant, and a large dissociation was observed in some cases. The newly devised estimated Ccr demonstrated less dissociation from 24hrCcr compared with eGFR. CONCLUSIONS: The eGFR formula is not adequate for the clinical use in cancer chemotherapy. The absolute value of eGFR is not reliable, but clinical use of eGFR as relative value seems to be acceptable. To avoid troublesome 24hrCcr measurement in long-term cancer chemotherapy, eGFR formula can be used for estimating Ccr in combination with the specific inherent 24hrCcr/eGFR ratio, which is obtained from 3 or 4 times of actual 24hrCcr measurements.

[PROCEDURE AND FEASIBILITY OF LAPAROSCOPIC RENAL BIOPSY].

OBJECTIVES: Recently, laparoscopic surgery is the standard procedure in urological field. We report the experience of laparoscopic renal biopsy for 4 patients who have contraindication of ultrasound-guided percutaneous renal biopsy. PATIENTS AND METHODS: We retrospectively reviewed the patients who underwent laparoscopic renal biopsy (LRB) from March 2010 to June 2013 in our hospital. Four female with mean age of 54.5 years old underwent LRB. Two patients had solitary kidney and the other 2 patients had bleeding tendency. All the biopsy was performed retroperitoneal approach. We used 18-gauge biopsy needle to take renal cortical tissue in all cases. In addition, one patient underwent small wedge biopsy with a cold knife. RESULTS: Mean operative time, pneumoperitoneal time, and estimated blood loss was 63.0 min (range 48-92 min), 37.5 min (range 22-75), and 11.25 ml (range 0-30 ml), respectively. No perioperative complication was observed. In all cases, we can diagnose pathologically by LRB. CONCLUSIONS: LRB is safe, effective, and feasible procedure for the patients in whom ultrasound-guided percutaneous renal biopsy is contraindication.

Chronic urinary retention could decrease the number of suburothelial myofibroblasts in the rat bladder.

AIMS: To demonstrate changes in the number of suburothelial myofibroblasts in the rat bladder due to chronic urinary retention (CUR). METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups: a CUR group and a sham-operated group. In the CUR rats, the urethra was intubated with a polyethylene catheter, and a double 4-0 silk ligature was placed around the proximal urethra, after which the catheter was removed. After 8 weeks, the cystometric findings and immunohistochemical staining of the suburothelial myofibroblasts were compared between the groups. RESULTS: The bladder weight of the control rats was 0.20 ± 0.01 g and that of CUR rats 1.6 ± 0.4 g. The bladder capacity of the control rats was 0.5 ± 0.3 ml and that of the CUR rats 12.9 ± 3.1 ml. The number of suburothelial myofibroblasts of the control rats was 417 ± 123 and that of the CUR rats 44 ± 42. The number of suburothelial myofibroblasts in the CUR rats was significantly less than that observed in the sham-operated rats (p < 0.01). CONCLUSIONS: In this study, we demonstrated that mechanical stress over a long period on the bladder wall can decrease the number of suburothelial myofibroblasts. The reduced expression of suburothelial myofibroblasts may be related to prolongation of the micturition interval by CUR.

A case of bleeding shock induced by injury of the intercostal artery following percutaneous nephrolithotripsy.

Introduction: The risk of postoperative bleeding complications should be concerned to perform percutaneous nephrolithotripsy. Most of the vascular injuries occurred at the peripheral renal artery in the previous reports. We experienced a case of bleeding shock induced by the injury of the intercostal artery in the abdominal wall following percutaneous nephrolithotripsy. Case presentation: A 56-year-old woman had been in the bleeding shock status on the 2nd day after percutaneous nephrolithotoripsy. Emergently, contrast-enhanced computed tomography was performed and extravasation of contrast agents was seen in the abdominal wall. Injuries of the intercostal artery were identified in the angiography and controlled by transcatheter arterial embolization. Conclusion: The intercostal arteries could be injured in the anterolateral zone of the abdominal wall over the end of the ribs. Contrast-enhanced computed tomography was useful to detect the bleeding point. Transcatheter arterial embolization was an effective and safe method to control bleedings from them.

Pediatric cystine stone successfully treated by mini-percutaneous nephrolithotripsy and antegrade ureteroscopy.

Introduction: Cystinuria is often diagnosed by large renal stone for pediatric patients. The patients suffer from recurrence of stone disease, develop the chronic kidney disease and fall into end-stage renal failure. Total removal of stone at the first intervention and prevention of recurrence are essential. Although, it is difficult to treat the pediatric stone patients for their anatomical feature. Case presentation: We report three cases of pediatric cystine stone patients (two 4-year-old boys and a 9-year-old girl) successfully treated by mini-percutaneous nephrolithotripsy and antegrade ureteroscopy. We could remove stones completely in all three cases, and the patients did not suffer from major complications. Conclusion: It is essential to select the surgical approach, the endourological device, and the patient's position which is suitable for the age, the body size, and the condition of stones at the initial intervention of pediatric cystine stone.

Two cases of nivolumab plus ipilimumab therapy for dialysis patients with advanced bone metastasis from renal cell carcinoma.

Nivolumab and ipilimumab are immune checkpoint inhibitors. Combination therapy with these two drugs has been shown to improve the outcome of advanced renal cell carcinoma. However, data about the safety and the efficacy of combination therapy with these two drugs in hemodialysis patients are small. A 59-year-old male hemodialysis patient presented with bone metastasis from renal cell carcinoma, which was located at the right femur. He received nivolumab plus ipilimumab therapy. At 7 months after treatment, he was diagnosed with diabetes as an immune-related adverse event. He was managed with insulin therapy. At 11 months after treatment, CT revealed cytoreduction of metastasis. A 74-year-old male hemodialysis patient presented with bone metastasis of renal cell carcinoma located at the sacrum and left scapula. He received nivolumab plus ipilimumab therapy. At 6 months after treatment, CT showed no progression of metastasis. Nivolumab and ipilimumab therapy might be a viable treatment for hemodialysis patients with bone metastasis from renal cell carcinoma. However, close attention should be paid immune-related adverse events in such patients.

Changes in angiotensin II type 1 receptor expression in the rat bladder by bladder outlet obstruction.

PURPOSE: To demonstrate the change in the expression of angiotensin II type 1 receptor (AT1) in the rat bladder with partial bladder outlet obstruction (P-BOO). MATERIALS AND METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups, a P-BOO group and a control group. The rats of the P-BOO group were divided into six groups: a sham-operated control group, 1 day postoperatively, 2 days postoperatively, 4 days postoperatively, 7 days postoperatively and 14 days postoperatively. The cystometric findings and immunohistochemical staining of the detrusor muscle with the AT1 antibody were compared in each group. RESULTS: AT1 localized on the cell membrane of the detrusor smooth muscle and in cytoplasm of suburothelial myofibroblasts in the control rats. The expression of AT1 disappeared in the detrusor muscle and suburothelial myofibroblasts in P-BOO, but AT1 was highly expressed in urothelial cells 1 day after surgery. The expression of AT1 in urothelial cells gradually decreased with time after surgery. AT1 completely disappeared in urothelial cells 14 days after surgery. CONCLUSIONS: The present study demonstrated that the site of AT1 expression changes in response to the mechanical stress caused by P-BOO, and finally there was no expression of AT1 in rat bladder tissue following P-BOO. These data suggest the change in AT1 expression may play a role in bladder function.

ALK rearrangement-associated renal cell carcinoma morphologically mimicking mucinous tubular and spindle cell carcinoma: a case report.

BACKGROUND: Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC) is an extremely rare tumor and ALK-RCC that mimics mucinous tubular and spindle cell carcinoma (MTSCC) has been very reported only in one instance. CASE PRESENTATION: A 42-year-old Japanese woman was admitted to our hospital for the treatment of a left renal tumor measuring 5 cm in maximum dimension. She underwent a laparoscopic left nephrectomy. Histologically, the tumor formed tubular or focally papillary structures with a small amount of spindle-shaped tumor cells against the background of prominent extracellular mucin. Although the tumor cells were negative for immunohistochemistry (IHC) of alpha-methylacyl-CoA racemase (AMACR) and lymph node metastasis was presented (these are atypical findings for MTSCC), we initially diagnosed the tumor as MTSCC based on its morphological characteristics with mucin deposition. However, an additional IHC analysis revealed that the tumor cells were diffusely positive for ALK-IHC. In addition, TPM3 exon 8 - ALK exon 20 fusion gene was detected by RNA sequencing. The tumor was thus correctly diagnosed as ALK rearrangement-associated renal cell carcinoma (ALK-RCC). CONCLUSIONS: Since the use of molecular targeted therapy with an ALK inhibitor for ALK-RCC is promising, the correct pathological diagnosis of ALK-RCC is quite important. We strongly recommend that ALK-IHC be routinely performed for renal tumors with negative AMACR staining that mimic MTSCC.

Bystander effects induced by the interaction between urothelial cancer cells and irradiated adipose tissue-derived stromal cells in urothelial carcinoma.

Cell-cell interactions between cancer cells and neighboring adipose tissue-derived stromal cells (ATSCs) are known to regulate the aggressiveness of cancer cells. In addition, the radiation-induced bystander effect is an important modulator of cancer cell kinetics. Radiation therapy is often given for urinary cancer, but the biological effects of the irradiated cancer stroma, including adipose tissue, on urothelial carcinoma (UC) remain unclear. We investigated the bystander effect of irradiated ATSCs on UC using a collagen gel culture method to replicate irradiated ATSC-cancer cell interactions after a single 12-Gy dose of irradiation. Proliferative activity, invasive capacity, protein expression and nuclear translocation of p53 binding protein-1 (53BP1) were analyzed. Irradiated ATSCs significantly inhibited the growth and promoted the apoptosis of UC cells in comparison to non-irradiated controls. The invasiveness of UC cells was increased by irradiated ATSCs, but not irradiated fibroblasts. Nuclear translocation of 53BP1 protein due to the bystander effect was confirmed in the irradiated group. Irradiated ATSCs regulated the expressions of the insulin receptor, insulin-like growth factor-1 and extracellular signal-regulated kinase-1/2 in UC. In conclusion, the bystander effect of irradiated ATSCs is a critical regulator of UC, and the actions differed depending on the type of mesenchymal cell involved. Our alternative culture model is a promising tool for further investigations into radiation therapy for many types of cancer.

Benzalkonium chloride induced corrosive balanoposthitis in a man requiring clean intermittent catheterization.

INTRODUCTION: Men who require intermittent catheterization may be susceptible to balanoposthitis. Benzalkonium chloride is commonly used to disinfect reusable catheters, but the concentration of this solution is critical. CASE PRESENTATION: A 40-year-old man presented with fever, pus around the glans and foreskin, and difficult catheterization. On physical examination, his urethral meatus was too narrow to insert a catheter. Suprapubic catheterization and 2 weeks of intravenous and topical treatment cured the ulcer of the glans. However, after restarting catheterization, the ulcer of the glans relapsed, and the patient's urethral meatus was completely closed. Circumcision and incision of the meatus were performed, and antibiotics were administered. Unexpectedly, restarting catheterization caused recurrent balanoposthitis. Close inquiry revealed that the patient was using a 10% benzalkonium chloride soaking solution for a reusable catheter, which was a toxic concentration. CONCLUSION: The disinfectant concentration should be confirmed when refractory balanoposthitis is encountered in patients who require catheterization.

Transvesical Laparoscopic Surgery for a Stone in the Ureterocele.

Background: Ureteroceles containing stones present as a unique challenge to the urologist. When a calculus has to be removed from within the ureterocele, a large opening leads to de novo vesicoureteral reflux (VUR), which may result in recurrent infections and renal parenchymal damage. Case Presentation: We present a case of a 13-mm stone in the ureterocele in an 11-year-old boy. He was asymptomatic but presented with abnormal urinalysis results and unilateral hydronephrosis. To avoid de novo VUR, we performed minimally invasive transvesical laparoscopic ureterolithotomy, which included partially suturing the incision at the roof of the ureterocele so that a small opening is maintained for drainage of urine. The surgery was performed with no complications and with normal postoperative urinalysis results. The patient's hydronephrosis resolved, and postoperative voiding cystourethrography showed no VUR. Conclusion: Transvesical laparoscopic ureterolithotomy with partial suturing of the incision at the roof of the ureterocele is a good treatment option, particularly for asymptomatic patients.

[THE ROLE OF CYSTOSCOPY IN THE STAGING OF CERVICAL CANCER].

(Objectives) For the staging of cervical cancer, we investigated the relationship between computed tomography/magnetic resonance imaging (CT/MRI) and cystoscopy and evaluated the need for cystoscopy to diagnose bladder invasion resulting from cervical cancer. (Patients and Methods) We retrospectively reviewed the patients who underwent cystoscopy because of a diagnosis of bladder invasion of cervical cancer from April 2012 to March 2017 in our hospital. A total of 217 women (median age 53 years old) underwent cystoscopy. We also reviewed whether or not there were findings showing bladder wall infiltration on CT/MRI and cystoscopy. (Results) CT was performed in all cases, and MRI was performed in 216 cases. Seventy cases were judged to have possible bladder infiltration by CT, and 35 were judged to have possible bladder infiltration by MRI. In cystoscopy, 24 cases were reported to have "suspicion of bladder invasion" by urologists, but only 12 cases had bladder mucosal findings with "ridges and furrows" (defined as bladder infiltration without a bladder biopsy in this study). The sensitivity and negative predictive values of CT/MRI were both 100%. Only one case underwent a bladder biopsy, and the histological diagnosis was cystitis. (Conclusions) The findings of our investigation suggested that cystoscopy is not required when there were no obvious findings of bladder invasion by CT/MRI at the clinical staging of cervical cancer.