First-line pembrolizumab for patients with early relapsing urothelial carcinoma after perioperative chemotherapy: a retrospective analysis of bladder cancer and upper urinary tract cancer.

BACKGROUND: First-line pembrolizumab is available for recurrent disease within 12 months after the receipt of platinum-based perioperative chemotherapy. However, the benefit of first-line pembrolizumab is unclear. This study evaluated the oncological outcome of patients treated with pembrolizumab compared with chemotherapy as first-line therapy for early relapsing disease after the receipt of platinum-based perioperative chemotherapy. METHODS: Data from a multicenter study included 454 patients diagnosed with unresectable or metastatic UC from November 2006 to July 2021. We identified patients with early and non-early relapsing disease. Oncological outcomes were evaluated using progression-free survival, overall survival, and survival with disease control. RESULTS: Fifty-three patients with early relapsing disease and 15 patients with non-early relapsing disease were identified. Of 53 patients with early relapsing disease, 26 (49.1%) were treated with pembrolizumab and 27 (50.9%) were treated with chemotherapy as first-line therapy. Fifteen patients with non-early relapsing disease were treated with chemotherapy. Early relapsing disease was associated with shorter progression-free survival and overall survival than non-early relapsing disease. Pembrolizumab was associated with longer progression-free survival and survival with disease control than chemotherapy in patients with early relapsing disease. There was no significant difference in overall survival between pembrolizumab and chemotherapy, but overall survival plateau with a long tail was observed in pembrolizumab. CONCLUSIONS: First-line pembrolizumab in earlier clinical settings for highly malignant tumors might improve the prognosis of patients with early relapsing disease after the receipt of platinum-based perioperative chemotherapy.

Comparison of the Safety and Efficacy of Photoselective Vaporization of the Prostate (PVP) and Transurethral Enucleation with a Bipolar System (TUEB): A Single-Center Retrospective Study.

PURPOSE: The aim of this study was to compare the safety and efficacy of photoselective vaporization of the prostate (PVP) and transurethral enucleation with a bipolar system (TUEB). PATIENTS AND METHODS: Patients who underwent PVP or TUEB surgery for lower urinary tract symptoms due to bladder outlet obstruction at our institution from September 2015 to May 2019 were retrospectively reviewed. A total of 83 patients (PVP: n=45, TUEB: n=38) who were available for follow-up at least 12 months after surgery were included. Preoperative characteristics, perioperative parameters, and postoperative outcomes-such as International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), and complications-at 3, 6, and 12 months after surgery were compared between the two groups. RESULTS: Although differences in age, IPSS, and QoL were not significant, a significantly greater prostate volume, lower Qmax, and greater PVR were noted in the TUEB group. In perioperative parameters, a significantly shorter operation time, less change in serum hemoglobin, fewer days of catheterization, and shorter length of stay were observed in the PVP group. As for postoperative outcomes, the IPSS storage subscore and PVR were significantly improved in the TUEB group. As complications, stress urinary incontinence was more frequently observed in the TUEB group, and urethral stricture was more common in the PVP group. CONCLUSION: The present data suggest that PVP and TUEB are efficient and safe surgical treatment options. Management of patients undergoing PVP in the perioperative period appears easy. Improvements of subjective and objective parameters were superior after TUEB than after PVP.

Daily salt intake is associated with leg edema and nocturnal urinary volume in elderly men.

AIMS: There is accumulating evidence that excessive salt intake contributes to nocturnal polyuria. We aimed to investigate the relationship between salt intake, leg edema, and nocturnal urine volume (NUV) to assess the etiology of nocturnal polyuria. METHODS: A total of 56 men aged ≥60 years who were hospitalized for benign prostatic hyperplasia or with suspected prostatic cancer were enrolled. Urine frequency-volume charts of the patients were maintained, and they underwent bioelectrical impedance analysis twice daily (at 5:00 pm and 6:00 am) and examination of blood (brain natriuretic peptide levels) and urine (sodium and creatinine levels and osmotic pressure) samples once daily (at 6:00 am). Free-water clearance, solute clearance, and sodium clearance at night were measured, and daily salt intake was estimated. RESULTS: The data of 52 patients were analyzed. Daily salt intake positively correlated with leg edema at 5:00 pm, differences in leg extracellular fluid levels between 5:00 pm and 6:00 am, and NUV, but not with diurnal urine volume. Partial correlation coefficients showed that salt intake was a factor of the correlation between NUV and change in extracellular volume in the legs between 5:00 pm and 6:00 am. A multivariate logistic model showed that sleep duration and sodium clearance were independent predictive factors for nocturnal polyuria. CONCLUSIONS: Sodium intake correlates with diurnal leg edema and NUV in elderly men. These results provide evidence supporting sodium restriction as an effective treatment for nocturnal polyuria.

Serious Hypokalemia Associated with Abiraterone Acetate in Patients with Castration-Resistant Prostate Cancer.

INTRODUCTION: The treatment strategy for castration-resistant prostate cancer (CRPC) has changed with the approval of several new agents. In 2011, abiraterone acetate was approved for the treatment of metastatic CRPC; however abiraterone is known to cause mineralocorticoid excess syndrome characterized by hypokalemia, fluid retention, and hypertension. We experienced two cases of grade 4 hypokalemia associated with abiraterone treatment. CASE PRESENTATION: Case 1: a 71-year-old male with metastatic CRPC presented with convulsive seizures two weeks after receiving abiraterone plus prednisone. The serum potassium level was 2.1mEq/l. We determined that convulsive seizure was caused by hypokalemia associated with abiraterone. Case 2: a 68-year-old male with metastatic CRPC presented with severe lethargy one month after receiving abiraterone plus prednisone. The serum potassium level was 1.7mEq/l and we concluded that severe lethargy was caused by hypokalemia associated with abiraterone. They were treated with potassium supplementation and increased prednisone following withdrawal of abiraterone. DISCUSSION: The two patients had been on glucocorticoid therapy before abiraterone therapy. Prolonged administration of exogenous glucocorticoid can lead adrenocortical insufficiency and consequently reduce endogenous glucocorticoid production. This situation may increase the risk of abiraterone-induced mineralocorticoid excess. To reduce the risk of abiraterone-induced hypokalemia, evaluation of adrenocortical insufficiency is required.

Increased Urine Production Due to Leg Fluid Displacement Reduces Hours of Undisturbed Sleep.

OBJECTIVE: To investigate whether or not the leg fluid displacement observed when moving from the standing to recumbent position at bedtime reduces the hours of undisturbed sleep (HUS). METHODS: Men aged 50 years or older who were hospitalized for urological diseases were investigated. Body water evaluation was performed three times with a bioelectric impedance method: (i) 17:00, (ii) 30 min after (short-term), and (iii) waking up (long-term). A frequency volume chart was used to evaluate the status of nocturnal urine production, and the factors affecting HUS were investigated. RESULTS: A total of 50 patients (mean age: 68 years) were enrolled. Short-term changes in extracellular fluid (ECF in the legs showed a significant positive correlation with urine production per unit of time at the first nocturnal voiding (UFN/HUS) (r = 0.45, P = 0.01). In the comparison between patients who had <3 HUS vs. those who had ≥3 HUS, the <3 HUS group showed significantly greater short-term changes in leg fluid volume, night-time water intake (17:00-06:00), and UFN/HUS. Multivariate analysis to assess the risk factors for <3 HUS indicated UFN/HUS as a risk factor in the overall model, and short-term changes in leg ECF and night-time water intake as risk factors in the model that only considered factors before sleep. CONCLUSIONS: Nocturnal leg fluid displacement may increase urine production leading up to first voiding after going to bed, and consequently, induce early awakening after falling asleep.

Evaluation of biochemical recurrence in patients with high-risk prostate cancer treated with radical prostatectomy and radiotherapy plus androgen deprivation therapy.

OBJECTIVE: The aim of this study was to evaluate the biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa) treated with radical prostatectomy (RP) or radiotherapy (RT) plus androgen deprivation therapy (ADT). METHODS: Subjects were patients with National Comprehensive Cancer Network-defined high-risk PCa treated with either RP or RT plus ADT. We calculated BCR-free survival in patients with those treatments and evaluated risk factor against BCR. RESULTS: A total of 114 patients, 71 RP and 43 RT plus ADT, were evaluated. A total of 59 and 20.9% of patients experienced BCR in the RP and RT treatment groups, respectively. The 5-year BCR-free survival probabilities improved significantly for patients who received RT compared to those who received RP (81.3 vs 37.3%, P<0.001). According to the number of risk factors, 59.2% of patients in the RP and 51.2% of patients in the RT treatment groups were classified with one risk factor (P<0.014). The 5-year BCR-free survival probabilities for patients treated with RP were 46.6 and 21.7% for one and multiple risk factors, respectively (P=0.008). On univariate analysis, only the number of risk factors had a significant impact on the risk of BCR. Meanwhile, there were no significant differences in the 5-year BCR-free survival probabilities between one and multiple risk factors in patients treated with RT. CONCLUSION: Among patients treated with RP, a marked heterogeneity existed in the oncological outcomes. Based on these findings, the number of risk factors should be emphasized to decide the optimal treatments for patients with high-risk PCa.

[The Influence of Change in Body Water Distribution Caused by Changing Position Upon Nocturia in Older Men].

A total of 29 men 60 years and older (mean age 74 years) who complained at least once about nocturnal voiding and were diagnosed with nocturnal polyuria in the frequency volume chart (FVC) were enrolled in this study. Body water was measured by bioelectric impedance analysis just after lying down at 4 pm and after raising legs 30 minutes later. Nocturnal urine production was measured by FVC, and urine production per unit of time at first nocturnal voiding (urine volume at first nocturnal voiding/hours of undisturbed sleep (HUS) : UFN/HUS), urine production per unit of time during sleep (total nocturnal urine volume/hours of sleep : TNV/HS), etc was evaluated. Extra cellular water (ECW) of 0.19 l (4.0%) in legs was reduced caused by body position changing. There was a significant positive correlation between the amount of ECW in legs and UFN/HUS, TNV/HS (r＝0. 57, p＝0.001 ; r＝0. 38, p＝0.042, respectively). Moreover, UFN/HUS had a significant correlation with soft lean mass in legs, ECW in legs and daytime water intake. This study suggested that a change in leg fluids caused by a change in position results in increased urine production and decreased HUS.

Risk factors of PSA progression and overall survival in patients with localized and locally advanced prostate cancer treated with primary androgen deprivation therapy.

BACKGROUND: Primary androgen deprivation therapy (PADT) has played an important role in the treatment of prostate cancer. We sought to identify factors of PSA progression in our series of patients with localized and locally advanced prostate cancer treated with PADT. METHODS: Six-hundred forty-nine patients with localized and locally advanced prostate cancer who received PADT from 1998 to 2005 by Nara Uro-Oncology Research Group were enrolled. Age, T classification, stage, PSA level at diagnosis, Gleason score, laterality of cancer detected by biopsy and seminal vesicle involvement (SVI) were adopted as parameters of PSA progression. Cox's proportional hazards model was used to determine the predictive factors for PSA progression. RESULTS: The median follow-up period and the median PSA level at diagnosis were 49 months and 15 ng/mL. The 5-year disease specific survival rate, overall survival rate and PSA progression-free survival (PFS) rate were 97.9 %, 91.9 % and 71.2 %, respectively. The univariate analysis showed that the PSA level at diagnosis, Gleason score, laterality of cancer detected by biopsy and SVI were independent predictive parameters of PSA-PFS. However, by multivariate analysis, only laterality of cancer detected by biopsy (unilateral vs. bilateral) was an independent predictive parameter of PSA-PFS (p = 0.034). The patients were classified into new risk groups base on three factors: PSA level at diagnosis, Gleason score, and laterality of cancer detected by biopsy. The PSA-PFS rates at 5-years in the low- (none or one factor), intermediate- (two factors) and high-risk (three factors) groups were 78.2 %, 62.5 % and 46.9 % (p < 0.001), respectively. CONCLUSION: In localized or locally advanced prostate cancer patients who received PADT, laterality of cancer detected by biopsy was a significant predictor associated with a longer PSA-PFS. Our new risk grouping indicates the usefulness of PSA-PFS.

Nadir PSA level and time to nadir PSA are prognostic factors in patients with metastatic prostate cancer.

BACKGROUND: Primary androgen deprivation therapy (PADT) is the most effective systemic therapy for patients with metastatic prostate cancer. Nevertheless, once PSA progression develops, the prognosis is serious and mortal. We sought to identify factors that predicted the prognosis in a series of patients with metastatic prostate cancer. METHODS: Two-hundred eighty-six metastatic prostate cancer patients who received PADT from 1998 to 2005 in Nara Uro-Oncology Research Group were enrolled. The log-rank test and Cox's proportional hazards model were used to determine the predictive factors for prognosis; rate of castration-resistant prostate cancer (CRPC) and overall survival. RESULTS: The median age, follow-up period and PSA level at diagnosis were 73 years, 47 months and 174 ng/mL, respectively. The 5-year overall survival rate was 63.0%. The multivariable analysis showed that Gleason score (Hazard ratio [HR]:1.362; 95% confidence interval [C.I.], 1.023-1.813), nadir PSA (HR:6.332; 95% C.I., 4.006-9.861) and time from PADT to nadir (HR:4.408; 95% C.I., 3.099-6.271) were independent prognostic factors of the incidence of CRPC. The independent parameters in the multivariate analysis that predicted overall survival were nadir PSA (HR:5.221; 95% C.I., 2.757-9.889) and time from PADT to nadir (HR:4.008; 95% C.I., 2.137-7.517). CONCLUSIONS: Nadir PSA and time from PADT to nadir were factors that affect both CRPC and overall survival in a cohort of patients with metastatic prostate cancer. Lower nadir PSA level and longer time from PADT to nadir were good for survival and progression.

Improvement of the surgical curability of locally confined prostate cancer including non-organ-confined high-risk disease through retropubic radical prostatectomy with intentional wide resection.

BACKGROUND: Retropubic radical prostatectomy with intentional wide resection (RRP-WR), which enables clear location of the prostate apex and the performance of posterolateral wider resection to remove extraprostatic extension, was introduced to our institutions. The aim of this study is to assess the feasibility and the efficacy of RRP-WR as a surgical intervention for locally confined prostate cancer. METHODS: A total of 90 Japanese patients with pathologically proven and clinically locally confined hormone-naïve prostate cancer were treated through RRP-WR, and the surgical morbidity was assessed. The patients were observed without immediate treatment until biochemical recurrence (BCR). RESULTS: The surgical morbidities were comparable to conventional procedures. No positive surgical margin (pSM) was pathologically identified in pT2 cases from prostatectomy specimens. It was identified in only 14.3% of pT3a cases, 36.4% of pT3b cases and 100% of pT4 cases. No apical pSM was found except for one of the pT4 cases in the levator ani muscle. PSA was at an undetectable level in 80.0% of all cases, 90.0% of pT2 cases, and 67.5% of pT3 and pT4 cases after surgery. The BCR-free survival rate in all cases was 82.4% and that of high-risk cases without pSM was 76.9% at a median follow-up of 19.3 months (3.3 to 59.2). CONCLUSIONS: RRP-WR is feasible and effective in removing organ-confined prostate cancer as well as extraprostatic extension without pSM. Thus, it is worthwhile to evaluate if this procedure improves the clinical outcome of locally confined prostate cancer including high-risk conditions treated by surgical intervention.

[A case of neobladder-cutaneo fistula after cystectomy].

A 69-year-old man was admitted for the treatment of muscle-invasive bladder carcinoma. Total cystectomy was performed and an ileal neobladder was constructed by a modification of Studer's method. However, a week later, a subcutaneous abscess occurred withwound dehiscence. Open drainage and wound debridement was carried out. Three weeks later, a neoblader-cutaneous fistula was seen on cystography. We managed it conservatively by means of wound debridement and washing with physiological saline. The fistula was closed on the 95th day after operation. The patient can now pass urine by himself.

[A case of renal perivascular epithelioid cell tumor (PEComa)].

A 44-year-old woman was admitted with acute hepatic dysfunction. Screening computed tomography showed an enhancing mass of about 9 cm in the right renal upper pole. An open right nephrectomy was performed for the pre-operative diagnosis of renal cell carcinoma. Pathological examination revealed a perivascular epithelioid cell tumor (PEComa). PEComa is a rare tumor, which includes angiomyolipoma and lymphangiomyomatosis. It is sometimes associated with aggressive clinical behavior such as local recurrence and metastasis. She had no evidence of recurrence at 34 months follow up.

[Small cell carcinoma of the urinary bladder detected by urinary cytology : a case report].

A 70-year-old man complaining of fever and chills was admitted to our hospital. A computerized tomography scan revealed a bladder tumor (cT3bN0M0), and urinary cytology demonstrated neuroendocrine carcinoma. Prostate specific antigen (PSA) was 4.089 ng/ml and human cytokeratin 19 fragment (CYFRA 21-1) was 3.8 ng/ml. He underwent transurethral resection of bladder tumor and needle biopsy of the prostate. Pathological examination demonstrated small cell carcinoma in the bladder tumor specimen and well differentiated adenocarcinoma (cT1c) with a Gleason score of 34 in the prostatic specimen. He underwent cystoprostatectomy with bilateral cutaneous ureterostomy. He did not receive adjuvant chemotherapy because of the poor postoperative systemic condition and he died of acute myocardial infarction 5 months later.

[A case report of toxic shock syndrome after high orchiectomy].

We report our experience of toxic shock syndrome (TSS) in a 54-year-old male patient after high orchiectomy for testicular cancer. Four days after the surgery, he began to have diarrhea, high fever, and diffuse erythroderma followed by severe hypotension. There were no signs of postsurgical wound infection, so serious drug eruption was suspected. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the culture of the drain and result of skin biopsy, leading to the diagnosis of TSS. Following treatment with intravenous fluids, antibiotics, human immunoglobulin and corticosteroids, the symptoms went into remission. TSS progresses rapidly and becomes life-threatening if treatment is delayed. Therefore, when TSS is suspected in postsurgical patients who experience fever of 39 degrees C or higher, dermal erythema, shock, treatment should be started promptly.

[A case of acute pulmonary thromboembolism after retroperitoneoscopic nephrectomy : a case report].

A 65-year old woman underwent retroperitoneoscopic nephrectomy, for left renal mass which was suspected to be renal cell carcinoma. On the 2nd postoperation day, she suddenly complained of dyspnea and chest pain. Enhanced computed tomography revealed a defect of peripheral pulmonary artery, and ventilation-perfusion lung scanning showed large defect of the uptake in bilateral lung fields. Based on the arterial blood gas and imagings, she was diagnosed with a PTE (pulmonary thromboembolism). Thrombolytic therapy and anti-coagulant therapy were started. Thereafter, she recovered from hypoxia. However, these therapies gave rise to postoperative hemorrhage resulting in a massive retroperitoneal hematoma.

[Prostate cancer and left ectopic ureter opening to seminal vesicle with left renal agenesis: a case report].

We report a case of prostate cancer and left ectopic ureter opening to seminal vesicle with left renal agenesis. A 62-year-old man was admitted to our hospital for treatment of prostate cancer with cyst formation. On the rectal examination, a cystic tumor was palpable on the left side of prostate. The left kidney was not detected by intravenous pyelography and ultrasonography. Magnetic resonance imaging revealed a retrovesical cystic lesion in the left side. Total prostatectomy and left ureterectomy were performed under the diagnosis of clinical T1cN0M0 prostate cancer and left ectopic ureter opening to seminal vesicle with left renal agenesis. The pathological findings showed well differentiated adenocarcinoma, Gleason score 3 + 3, and left ectopic ureter entering into the seminal vesicle and left renal agenesis. The patient was well 39 months after the total prostatectomy and left ureterectomy without evidence of recurrence. There have been no cases of the association of this urogenital anomaly, such as ectopic ureter opening to seminal vesicle with renal agenesis and prostate cancer and the combined management of both. Our case seems to be first case in the Japanese literature.

[Bilateral adrenal metastases from renal cell carcinoma: a case report].

We report a case of renal cell carcinoma with bilateral adrenal metastases. A 57-year-old man was admitted to our hospital for a left renal mass. Computerized tomography and magnetic resonance imaging revealed a 4.5 cm left renal tumor and bilateral adrenal masses (3.0 cm on the right side and 2.0 cm on the left). A left nephrectomy and bilateral adrenalectomies were performed. The pathological findings showed clear cell carcinoma, G2 of left kidney metastasizing to both adrenal glands. The patient was administered supplementary hydrocortisone and was well 8 months after the nephrectomy and adrenalectomies without evidence of recurrence. Bilateral adrenal metastases from renal cell carcinoma are relatively rare. Our case seems to be the thirteenth case in the Japanese literature.

Prostatic volume and volume-adjusted prostate-specific antigen as predictive parameters for T1c prostate cancer.

We examined the usefulness of the volume-adjusted prostate-specific antigen (PSA) parameters for prediction of T1c prostate cancer on 210 patients who had abnormal PSA levels but no abnormal findings in digital transrectal examination (DRE) or transrectal ultrasonography (TRUS). PSA, prostate volume (PV), transition zone volume (TZV), PSAD (PSA/PV) and PSATZD (PSA/TZV) were assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Simple and stepwise logistic regression models were used to calculate the odds ratios of these parameters. Fifty-three (25.2%) of all 210 patients and 31 (19.9%) of 156 patients with intermediate PSA levels had biopsy-proved prostate cancer. The ROC curves of all patients revealed that PSA, PV, TZV, PSAD and PSATZD had significant predictive values, while AUCs of PV, PSAD and PSATZD had significant predictive values as compared to that of PSA. In the patients with intermediate PSA levels, the ROC curves revealed that PV, TZV, PSAD and PSATZD had significant predictive values, but there were no significant differences in AUCs among these parameters. The stepwise logistic regression analysis showed that PV and PSATZD were significant predictive parameters in all patients and that PSATZD was the only significant predictive parameter in the patients with intermediate PSA levels. In conclusion, not only PSAD and PSATZD but also PV and TZV had significant predictive values in discriminating prostate cancer. However, the multivariate analysis showed that PSATZD had the strongest predictive value in all patients and in those with intermediate PSA levels.