Higher serum alkaline phosphatase value indicates the need for bone mineral density testing in non-metastatic prostate cancer patients undergoing androgen deprivation therapy.

PURPOSE: Osteoporosis is a well-known adverse effect of androgen deprivation therapy for prostate cancer. This study aimed to reveal the factors associated with the diagnosis of osteoporosis in prostate cancer patients undergoing androgen deprivation therapy. METHODS: This retrospective cross-sectional study included 106 prostate cancer patients treated with androgen deprivation therapy. Patients with bone metastasis at the initiation of androgen deprivation therapy and those with castration-resistant prostate cancer were excluded. Bone mineral density was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Osteoporosis was defined as bone mineral density equal to or below either -2.5 SD or 70% of the mean in young adults. The association between clinicopathological variables and bone mineral density or diagnosis of osteoporosis was investigated. RESULTS: Thirty-six (34%) patients were found to have osteoporosis. The incidence of osteoporosis increased in a stepwise manner depending on the duration of androgen deprivation therapy. Multivariate logistic regression analysis identified a longer duration of androgen deprivation therapy (months, odd's ratio = 1.017, P = 0.006), lower body mass index (kg/m2, odd's ratio = 0.801, P = 0.005) and higher serum alkaline phosphatase value (U/l, odd's ratio 1.007, P = 0.014) as the factors independently associated with the diagnosis of osteoporosis. Eleven out of 50 (22%), 14 out of 35 (40%) and 11 out of 20 patients (55%) were osteoporotic in the patients with serum alkaline phosphatase values <238 U/l, 238-322 U/l and >322 U/l, respectively (P = 0.022). CONCLUSIONS: Osteoporosis is common in prostate cancer patients undergoing androgen deprivation therapy; furthermore, its incidence increases depending on the duration of androgen deprivation therapy. Bone mineral density testing should be considered for all patients on androgen deprivation therapy, especially for those with a lower body mass index and higher serum alkaline phosphatase value.

Preoperative chronic kidney disease is predictive of oncological outcome of radical cystectomy for bladder cancer.

PURPOSE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes after radical cystectomy (RC) for bladder cancer. METHODS: We reviewed the medical records of patients with urothelial bladder carcinoma who underwent RC with curative intent at seven hospitals between 1990 and 2013. After excluding patients with a history of upper urinary tract urothelial cancer or neoadjuvant chemotherapy, we analyzed 594 cases for the study. Preoperative estimated glomerular filtration rate (eGFR) was calculated using the three-variable Japanese equation for GFR estimation from serum creatinine level and age. Patients were divided into four groups of different CKD stages based on eGFR values (mL/min/1.73 m2), i.e., ≥ 60 (CKD stages G1-2), 45-60 (G3a), 30-45 (G3b), and < 30 (G4-5). Survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression analyses addressed survivals after RC. RESULTS: Median age of patients was 67 years. Patients were classified into CKD stages: G1-2 (n = 388; 65.3%), G3a (n = 122; 20.5%), G3b (n = 51; 8.6%), and G4-5 (n = 33; 5.6%). During a median follow-up of 4.0 years, 200 and 164 patients showed cancer progression and died of bladder cancer, with the 5-year progression-free survival (PFS) and cancer-specific survival (CSS) of 64.9 and 70.2%, respectively. On multivariate analyses, CKD stages of G3b or greater, advanced pT stage, lymph node metastasis, and positive lymphovascular invasion were independent poor prognostic factors for PFS and CSS. CONCLUSIONS: We demonstrated that the advanced preoperative CKD stage was significantly associated with poor oncological outcomes of the bladder cancer after RC.

Oncologic Outcome of Metastasectomy for Urothelial Carcinoma: Who Is the Best Candidate?

BACKGROUND: Resection of metastatic lesions (metastasectomy) is performed for highly selected patients with metastatic urothelial carcinoma (mUC). This study aimed to identify the clinicopathologic factors associated with oncologic outcome for patients who underwent metastasectomy for mUC. METHODS: This analysis included 37 UC patients who underwent metastasectomy with curative intent at nine Japanese hospitals. The primary end point was cancer-specific survival. The Kaplan-Meier method with the log-rank test and the multivariable Cox proportional hazards model addressed the relationship between clinical characteristics and survival. RESULTS: Metastasectomy was performed for pulmonary (n = 23), nodal (n = 7), and other (n = 7) metastases. The median survival time was 35.4 months (interquartile range [IQR] 15.5, not reached) from the detection of metastasis and 34.3 months (IQR 13.1, not reached) from metastasectomy. The 5-year cancer-specific survival rate after detection of metastasis was 39.7%. In the multivariate analysis, the time from primary surgery to detection of metastasis (time-to-recurrence [TTR]) of 15 months or longer (hazard ratio [HR] 0.23; p = 0.0063), no symptoms of recurrence (HR 0.23; p = 0.0126), and serum C-reactive protein (CRP) levels lower than than 0.5 mg/dl (HR 0.24; p = 0.0052) were significantly associated with better survival. CONCLUSIONS: Long-term survival could be achieved for some patients with mUC who underwent metastasectomy. Lung and lymph nodes were predominant sites for metastasectomy. Symptoms, TTR, and CRP value were identified as associated with survival and should be taken into account when metastasectomy is considered.

Efficacy of post-nephroureterectomy cisplatin-based adjuvant chemotherapy for locally advanced upper tract urothelial carcinoma: a multi-institutional retrospective study.

PURPOSE: To evaluate the efficacy of adjuvant systemic chemotherapy for locally advanced (pT3-4pN0/xM0) upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 109 patients with pT3-4pN0/xM0 UTUC who had undergone radical nephroureterectomy between 1996 and 2013 at our four institutions. The patients were divided into two groups: those who received adjuvant chemotherapy (AC group) and those who did not (surgery-alone: SA group). All chemotherapy regimens were cisplatin-based. Cox proportional hazards regression models addressed the associations between clinicopathological factors and recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: Forty-three (39.5%) out of the 109 patients underwent one to four cycles of adjuvant chemotherapy after nephroureterectomy. Median follow-up was 46.5 months. There were no significant differences in the background characteristics of the two groups, except for age. Recurrence developed in 11 (25.6%) and 29 (43.9%) patients in the AC and SA groups, respectively. Ultimately, six (14.0%) and 18 (27.3%) patients in the AC and SA groups, respectively, died of disease progression. On univariate analysis, hydronephrosis, nuclear grade, lymphovascular invasion, and adjuvant chemotherapy were significantly associated with both RFS and CSS. Charlson comorbidity index was associated only with CSS. On multivariate analysis, adjuvant chemotherapy was the only independent factor associated with improved RFS (p = 0.0178, HR = 0.41). Moreover, adjuvant chemotherapy (p = 0.0375, HR = 0.33), lower nuclear grade (p = 0.0070), and the absence of hydronephrosis (p = 0.0493) were independently associated with better CSS. CONCLUSION: Locally advanced (pT3-4pN0/xM0) UTUC patients who underwent cisplatin-based adjuvant chemotherapy demonstrated better RFS and CSS than those without adjuvant chemotherapy.

Skeletal-related events and prognosis in urothelial cancer patients with bone metastasis.

BACKGROUND: The aim of the present study was to elucidate the details of bone metastasis (BM) and the resulting skeletal-related events (SREs), and survival and prognostic factors, in urothelial cancer (UC) patients with BM. METHODS: A total of 48 UC patients with BM who were treated at our institution between 1994 and 2013 were enrolled. Details of BM and SREs were investigated. The Kaplan-Meier method was used to estimate survival duration. Relationships between several clinical features and survival were analyzed using the log-rank test and the Cox hazard model. RESULTS: Of the 48 patients, 39 (81.3%) were male, with a median age at diagnosis of BM of 68 years [interquartile range (IQR), 61-75 years]. Frequent metastatic sites included the pelvis (31 patients, 64.6%) and spine (28, 58.3%). SREs occurred in 31 patients (64.6%) at a median duration of 0.9 months (IQR, 0.3-5.4 months) after diagnosis of BM, including radiation therapy (n = 23; 74.2%), spinal cord compression (n = 4; 12.9%), pathological fracture (n = 3; 9.7%) and hypercalcemia (n = 1; 3.2%). Median overall survival periods after diagnosis of BM and SREs were 6.2 and 5.6 months, respectively. On multivariate analysis, factors significantly associated with survival after BM were performance status [hazard ratio (HR) for ≥2 vs. 0-1, 4.94; P = 0.0003], liver metastasis (HR, 4.08; P = 0.0018), chemotherapy after BM (HR, 0.31; P = 0.0018), and use of bone-modifying agents (HR, 0.36; P = 0.0147). CONCLUSIONS: We revealed clinicopathological factors that are predictive of prognosis of UC patients with BM. Although the prognosis is poor, chemotherapy and bone-modifying agents may confer survival benefits.

Biphasic decline in renal function after radical cystectomy with urinary diversion.

BACKGROUND: We evaluated short- and long-term renal function in patients after radical cystectomy with urinary diversion and identified risk factors for the deterioration of renal function. METHODS: This retrospective study comprised 91 patients who underwent radical cystectomy and urinary diversion for bladder cancer and survived ≥3 years after surgery. The estimated glomerular filtration rate (eGFR) was calculated, and longitudinal changes of eGFR were assessed. Deterioration in renal function in early and late postoperative years was defined as a ≥25 % decrease in the eGFR from preoperative to postoperative year one, and a reduction in the eGFR of >1 mL/min/1.73 m2 annually in subsequent years, respectively. Univariate and multivariate logistic regression analyses were used to evaluate its association with clinicopathologic features. RESULTS: The median follow-up period after surgery was 7 years (range 3-26). The mean eGFR decreased from preoperative 65.1 to 58.9 mL/min/1.73 m2 1 year after the surgery, followed by a continuous decline of ~1.0 mL/min/1.73 m2 per year thereafter. Multivariate analyses identified ureteroenteric stricture as the sole risk factor associated with early renal function deterioration [odds ratio (OR) 4.22, p = 0.037]. Diabetes mellitus (OR 8.24, p = 0.015) and episodes of pyelonephritis (OR 4.89, p = 0.038) were independently associated with the gradual decline in the late postoperative period. CONCLUSION: In cystectomy patients with urinary diversion, the rapid deterioration of renal function observed during the first year after surgery and the gradual but continuous decline in function thereafter were found to be associated with different risk factors.

Geriatric 8 and Vulnerable Elders Survey-13 predict length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery.

INTRODUCTION: The Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) are established screening tools for assessing vulnerability in older patients. Here we investigated their usefulness as predictors of length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery. MATERIALS AND METHODS: This study included 643 patients who underwent urological surgery (74% were for malignancy) at our institute from 2017 to 2020. G8 and VES-13 scores were routinely recorded upon admission. These indices and other clinical data were obtained through chart review. The correlation between G8 group (high, >14; intermediate, 11-14; low, <11) or VES-13 group (normal, <3; high, ≥3) and length of total hospital stay (LOS), postoperative hospital stay (pLOS), and postoperative complications including delirium were analyzed. RESULTS: The median patient age was 69 years. A total of 44%, 45%, and 11% of patients were classified into high, intermediate, and low G8 groups, respectively, while 77% and 23% were classified into normal and high VES-13 groups, respectively. Univariate analyses revealed that low G8 scores were associated with prolonged LOS (vs. intermediate, odds ratio [OR] 2.87, P < 0.001; vs. high, OR 3.87, P < 0.001), prolonged pLOS (vs. intermediate, OR 2.37, P = 0.005; vs. high, OR 3.06, P < 0.001), and delirium (vs. intermediate, OR 3.23, P = 0.007; vs. high, OR 5.38, P < 0.001), and high VES-13 scores were associated with prolonged LOS (OR 2.85, P < 0.001), prolonged pLOS (OR 2.97, P < 0.001), and Clavien-Dindo grade ≥ 2 complications (OR 1.74, P = 0.044), and delirium (OR 3.18, P = 0.001). Furthermore, multivariate analyses revealed that low G8 and high VES-13 scores were independent factors which predicted prolonged LOS (low G8; vs. intermediate, OR 2.96, P < 0.001; vs. high, OR 3.94, P < 0.001; high VES-13; OR 2.98, P < 0.001) and prolonged pLOS (low G8; vs. intermediate, OR 2.41, P = 0.008; vs. high, OR 3.18, P = 0.002; high VES-13; OR 3.47, P < 0.001), respectively. DISCUSSION: The G8 and VES-13 may be effective tools for predicting prolonged LOS/pLOS and postoperative complications in Japanese patients who undergo urological surgery.

[FOURNIER GANGRENE: AN ANALYSIS OF 15 CASES].

(Objectives) This study aimed to evaluate the clinical characteristics and the mortality risk factors of 15 patients with Fournier gangrene in the past decade at Teikyo University Hospital. (Materials and methods) We retrospectively assessed 15 patients with Fournier gangrene between May 2009 and April 2019. We compared the demographic characteristics along with several clinical variables including Fournier Gangrene Severity Index of the survivors and nonsurvivors. We also assessed the risk factors associated with mortality. (Results) All patients were men with a median age of 67 years. Among the 15 patients, 9 had diabetes mellitus (60%). Furthermore, 14 patients (93%) underwent surgical debridement, 5 (33%) required orchiectomy, 3 (20%) were treated with cystostomy for urinary diversion, and 3 (20%) needed temporary colostomy for fecal diversion. Three patients died of the disease with a mortality rate of 20%. The nonsurvivors were significantly older (p = 0.043) and had a smaller body mass index (p = 0.038) than the survivors. The scores of clinical risk models, such as the Fournier Gangrene Severity Index, were higher in nonsurvivors than in survivors, with no statistical significance presumably due to the small sample size. (Conclusions) The mortality rate for Fournier gangrene during the past decade at our institution was 20%. Fournier gangrene was a potentially fatal disease even in the 2010s.

[A CASE OF SPINDLE CELL LIPOMA ARISING IN THE INGUINAL SUBCUTIS: A CASE REPORT].

A 39-year-old man was referred to us for further examination of a right inguinal mass. He had noticed the mass several months prior and had undergone positron emission tomography/computed tomography, which revealed a mass with an SUVmax of 1.48 at the right inguinal subcutis. Magnetic resonance imaging (MRI) showed a well-circumscribed, heterogeneously enhanced adipose tumor 7cm in length, adjacent to the right spermatic cord and corpora cavernosa with clear boundaries. The tumor was a suspected atypical lipomatous tumor (well-differentiated liposarcoma), and he underwent tumor extirpation surgery. At surgery, the right inguinal canal was not opened, and the right spermatic cord and corpora cavernosa were safely spared. The excised specimen was composed of lipomatous tissue macroscopically. Histopathological diagnosis was of a spindle cell lipoma. Spindle cell lipomas are relatively rare, benign tumors, comprising only 1.5% of all lipomatous tumors. They arise most commonly in the shoulder and posterior region of the neck, and rarely develop in the groin. Differential diagnosis includes atypical lipomatous tumors, but radiological diagnosis is often difficult because of similar findings on MRI. Spindle cell lipomas typically present as a subcutaneous tumor, while atypical lipomatous tumors arise in the deep layers of connective tissue. This difference in the site of the tumor may contribute to their differential diagnosis before surgery.

Nomogram for predicting survival of postcystectomy recurrent urothelial carcinoma of the bladder.

PURPOSE: We aimed to identify prognostic clinicopathological factors and to create a nomogram able to predict overall survival (OS) in recurrent urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC). MATERIALS AND METHODS: Among 1,087 patients with UCB who had undergone RC at our 11 institutions between 1990 and 2010, 306 patients who subsequently developed distant metastasis or local recurrence or both were identified. Clinical data were collected with medical record review. Univariate and multivariate Cox regression models addressed OS after recurrence. A nomogram predicting postrecurrence OS was constructed based on Cox proportional hazards model, without using postrecurrence factors (systemic chemotherapy and resection of metastasis). The performance of the nomogram was internally validated by assessing concordance index and calibration plots. RESULTS: Of the 306 patients, 268 died during follow-up with a median survival of 7 months (95% CI: 5.8-8.5). Postrecurrence chemotherapy was administered in 119 patients (38.9%). Multivariable analysis identified 9 independent predictors for OS; period of time from RC to recurrence (time-to-recurrence), symptomatic recurrence, liver metastasis, hemoglobin level, serum alkaline phosphatase level, serum lactate dehydrogenase level, serum C-reactive protein level, postrecurrence chemotherapy, and resection of metastasis. A nomogram was formed with the following 5 variables to predict OS: time-to-recurrence, symptomatic recurrence, liver metastasis, albumin level, and alkaline phosphatase level. Concordance index rate was 0.75 (95% CI: 0.72-0.78) by internal validation using Bootstraps with 1,000 resamples. Calibration plots showed that the nomogram fitted well. CONCLUSIONS: We identified 9 clinicopathological factors as independent OS predictors in postcystectomy recurrence of UCB. We also created a validated nomogram with 5 variables that efficiently stratified those patients regardless of eligibility for chemotherapy. The nomogram would be useful for acquiring relevant prognostic information and for stratifying patients for clinical trials.

A single nucleotide polymorphism in kidney anion exchanger 1 gene is associated with incomplete type 1 renal tubular acidosis.

Various conditions including distal renal tubular acidosis (dRTA) can induce stone formation in the kidney. dRTA is characterized by an impairment of urine acidification in the distal nephron. dRTA is caused by variations in genes functioning in intercalated cells including SLC4A1/AE1/Band3 transcribing two kinds of mRNAs encoding the Cl-/HCO3- exchanger in erythrocytes and that expressed in α-intercalated cells (kAE1). With the acid-loading test, 25% of urolithiasis patients were diagnosed with incomplete dRTA. In erythroid intron 3 containing the promoter region of kAE1, rs999716 SNP showed a significantly higher minor allele A frequency in incomplete dRTA compared with non-dRTA patients. The promoter regions of the kAE1 gene with the minor allele A at rs999716 downstream of the TATA box showed reduced promoter activities compared that with the major allele G. Patients with the A allele at rs999716 may express less kAE1 mRNA and protein in the intercalated cells, developing incomplete dRTA.

Sarcopenia Evaluated Using the Skeletal Muscle Index Is a Significant Prognostic Factor for Metastatic Urothelial Carcinoma.

BACKGROUND: The purpose of the study was to evaluate the prognostic value of sarcopenia (muscle loss) in patients with metastatic urothelial carcinoma (UC), in a comparison of several methods of computed tomography (CT)-based evaluation of sarcopenia. PATIENTS AND METHODS: We retrospectively reviewed 100 patients with metastatic UC who underwent first-line systemic chemotherapy between 2003 and 2014. Sarcopenia was assessed by the following CT-based methods: skeletal muscle index (SMI), total psoas area (TPA), axial and/or transversal psoas thickness at the level of the third lumbar vertebrae, and axial and/or transversal psoas thickness at the umbilicus level (U-TPT). All parameters were standardized by either height or height squared. Cutoff points were SMI: < 55 cm(2)/m(2) (men), < 39 cm(2)/m(2) (women); others: lowest sex-specific quartiles. Predictive values for cancer-specific survival (CSS) were assessed using the Cox proportional hazards regression model. RESULTS: Sixty-four patients met the eligibility criterion for analysis: those who underwent CT scans within 30 days before chemotherapy. Of them, 52 (81%) died of UC during the follow-up, with a median survival time of 13 months. Univariate analysis associated decreased SMI, TPA, and U-TPT with poor CSS. Multivariate analysis together with other pretreatment clinicopathologic parameters showed decreased SMI to be an independent predictor of poor CSS. CONCLUSION: Evaluation using SMI showed sarcopenia was an independent predictor of poor prognosis for patients with metastatic UC who underwent first-line systemic chemotherapy. Our results might improve stratification of patients and help optimize evaluation of sarcopenia.

Adjuvant chemotherapy is possibly beneficial for locally advanced or node-positive bladder cancer.

BACKGROUND: This study aimed to evaluate the outcomes of cisplatin-based adjuvant chemotherapy (AC) after radical cystectomy (RC) in non-organ-confined bladder cancer. METHODS: Sixty-one patients who did not receive neoadjuvant chemotherapy (NAC) underwent RC for locally advanced (pT3-4) or node-positive (pN1-3) bladder cancer, or both, between 1990 and 2012. Of these patients, 39 (64%) received cisplatin-based AC after RC (AC group) and the remaining 22 patients (36%) did not (non-AC group). Cancer-specific survival (CSS) and recurrence-free survival (RFS) were compared between the groups. RESULTS: The AC group was significantly younger (P = .004), but no significant differences were noted between the groups for pT stage, pN stage, nuclear grade, renal function, and salvage chemotherapy rates after recurrence. During a follow-up of 29 months (median), 40 patients (67%) experienced recurrence/metastasis and 34 (56%) died of recurrent bladder cancer. The AC group showed better RFS than the non-AC group, but the difference was not statistically significant (median survival time [MST], 23.7 vs. 11.4 months, respectively; P = .154). CSS was significantly better for the AC group than for the non-AC group (MST, 57.4 vs. 17.9 months, respectively; P = .008). On multivariate analysis, AC was an independent predictive factor for both RFS (hazard ratio [HR], 0.325; P = .005) and CSS (HR, 0.186; P < .001), along with surgical margin status and lymphovascular invasion (LVI). In a subgroup analysis of 31 node-positive cases, the AC group had a significantly better CSS compared with the non-AC group (P = .029). Analysis of node-negative cases (n = 30) yielded no significant benefit for AC. CONCLUSION: Our observations suggest that postoperative cisplatin-based AC improves survival in locally advanced or node-positive bladder cancer, especially in node-positive cases.