Subclassification of pT3 upper tract urothelial carcinoma: a multicenter retrospective study.

PURPOSE: The prognosis of patients with pT3 upper tract urothelial carcinoma (UTUC) varies. The current study aimed to further classify patients with pT3 UTUC into different survival outcome groups based on tumor location and site of invasion. METHODS: This retrospective study included 323 patients with pT3 UTUC who underwent nephroureterectomy at 11 hospitals in Japan. Histological and clinical data were obtained via a chart review. Univariate and multivariate Cox proportional hazards analyses showed the effect of different variables on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median age of the patients was 72 years. Patients with pT3 UTUCs were divided into two groups: those with renal parenchymal invasion only (pT3a, n = 95) and those with peripelvic or periureteral fat invasion (pT3b, n = 228). pT3b UTUC was significantly associated with hydronephrosis, low preoperative estimated glomerular filtration rate (eGFR), histological nodal metastasis, nuclear grade 3, lymphovascular invasion (LVI), carcinoma in situ, and positive surgical margin. Based on the univariate analyses, patients with pT3b UTUC had a significantly lower 5-year RFS (42.4% vs. 70.1%, p < 0.0001), 5-year CSS (54.3% vs. 80.0%, p = 0.0002), and 5-year OS (47.8% vs. 76.8%, p < 0.0001) than those with pT3a UTUC. According to the multivariate analyses, nodal metastasis, LVI, adjuvant chemotherapy, preoperative eGFR, nuclear grade (RFS only), surgical margin (RFS only), and Charlson comorbidity index (OS only), but not pT3b stage, were associated with survival. CONCLUSION: Compared with pT3a UTUC, pT3b UTUC was significantly associated with worse histological features, consequently resulting in unsatisfactory survival outcomes.

Immunological risk and complement genetic evaluations in early onset de novo thrombotic microangiopathy after living donor kidney transplantation: A Japanese multicenter registry.

BACKGROUND: Thrombotic microangiopathy (TMA) after kidney transplantation (KTx), particularly early onset de novo (dn) TMA, requires immediate interventions to prevent irreversible organ damage. This multicenter study was performed to investigate the allogeneic clinical factors and complement genetic background of dnTMA after KTx. METHODS: Perioperative dnTMA after KTx within 1 week after KTx were diagnosed based on pathological or/and hematological criteria at each center, and their immunological backgrounds were researched. Twelve aHUS-related gene variants were examined in dnTMA cases. RESULTS: Seventeen recipients (15 donors) were enrolled, and all dnTMA cases were onset within 72-h of KTx, and 16 of 17 cases were ABO incompatible. The implementation rate of pre-transplant plasmaphereses therapies were low, including cases with high titers of anti-A/anti-B antibodies. Examination of aHUS-related gene variants revealed some deletions and variants with minor allele frequency (MAF) in Japan or East Asian genome databases in genes encoding alternative pathways and complement regulatory factors. These variants was positive in 8 cases, 6 of which were positive in both recipient and donor, but only in one graft loss case. CONCLUSIONS: Although some immunological risks were found for dnTMA after KTx, only a few cases developed into TMA. The characteristic variations revealed in the present study may be novel candidates related to dnTMA in Japanese or Asian patients, but not pathogenic variants of aHUS. Future studies on genetic and antigenic factors are needed to identify factors contributing to dnTMA after KTx.

Improved survival in real-world patients with advanced urothelial carcinoma: A multicenter propensity score-matched cohort study comparing a period before the introduction of pembrolizumab (2003-2011) and a more recent period (2016-2020).

OBJECTIVES: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.

Smaller decline of renal function after nephroureterectomy predicts poorer prognosis of upper tract urothelial carcinoma: a multicentre retrospective study.

PURPOSE: Renal function is frequently impaired in the patients with upper tract urothelial carcinoma. We aimed to evaluate the impact of renal function and its change after surgery on survival rates in patients with upper tract urothelial carcinoma after nephroureterectomy. METHODS: The study cohort comprised 755 patients with upper tract urothelial carcinoma who underwent nephroureterectomy between 1995 and 2016 at nine hospitals in Japan. Estimated glomerular filtration rate was calculated using the three-variable Japanese equation for glomerular filtration rate estimation from serum creatinine level and age. Outcomes were recurrence-free, cancer-specific and overall survivals. Univariate and multivariate Cox proportional hazards regression analyses were used. RESULTS: Median patients' age was 72 years old. Pre- and post-surgical median estimated glomerular filtration rate were 55.5 and 42.9 ml/min/1.73 m2, respectively. Median estimated glomerular filtration rate decline after surgery, which represents function of the affected side kidney, was 13.1 ml/min/1.73 m2. The 5-year recurrence-free, cancer-specific and overall survivals were 68.3, 79.4 and 74.0%, respectively. Multivariate analysis indicated that lower preoperative estimated glomerular filtration rate and estimated glomerular filtration rate decline were associated with poorer recurrence-free, cancer-specific and overall survivals, but post-operative estimated glomerular filtration rate was not. Estimated glomerular filtration rate decline was more significant poor-prognosticator than preoperative estimated glomerular filtration rate. Proportions of the patients with estimated glomerular filtration rate <60 ml/min/1.73 m2 before surgery were 50.6 and 73.2% in organ-confined disease and locally advanced disease, respectively (P < 0.0001). After surgery, they were 91.6 and 89.8%, respectively (P = 0.3896). CONCLUSIONS: Lower preoperative renal function, especially of the affected side kidney, was significantly associated with poor prognosis after nephroureterectomy for upper tract urothelial carcinoma. Many patients with locally advanced disease have reduced renal function at diagnosis and even more after surgery.

Dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.

BACKGROUND: Although it is known that malignancies can be associated with dermatomyositis, there are few reports on dermatomyositis associated with prostate cancer with neuroendocrine differentiation. CASE PRESENTATION: A 63-year-old man visited our hospital due to pollakiuria. High levels of PSA and NSE were observed, and prostate biopsy revealed an adenocarcinoma with neuroendocrine differentiation. Multiple metastases to the lymph nodes, bones, and liver were identified, and androgen deprivation therapy (ADT) was started immediately. Following 2 weeks of treatment, erythema on the skin, and muscle weakness with severe dysphagia appeared. The patient was diagnosed with dermatomyositis, and high-dose glucocorticoid therapy was initiated. ADT and subsequent chemotherapy with etoposide and cisplatin (EP) were performed for prostate cancer, which resulted in decreased PSA and NSE and reduction of all metastases. After the initiation of EP therapy, dermatomyositis improved, and the patient regained oral intake function. Although EP therapy was replaced by docetaxel, abiraterone, and enzalutamide because of adverse events, no cancer progression was consistently observed. Dermatomyositis worsened temporarily during the administration of abiraterone, but it improved upon switching from abiraterone to enzalutamide and dose escalation of glucocorticoid. CONCLUSIONS: We successfully treated a rare case of dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.

Prognostic significance of concentric left ventricular hypertrophy at peritoneal dialysis initiation.

BACKGROUND: Concentric left ventricular hypertrophy (cLVH) is a common left ventricular geometric pattern in patients undergoing maintenance dialysis, including peritoneal dialysis (PD). The relationship between cLVH at PD initiation and the prognosis of patients remains unclear, however. This study aimed to investigate the impact of cLVH at PD initiation on patient survival and major adverse cardiovascular events (MACE). METHODS: The retrospective cohort study included 131 patients who underwent echocardiography during the PD initiation period. Based on echocardiographic measurements, cLVH was defined as a condition with increased LV mass index and increased relative wall thickness. The relationship between cLVH and the prognosis was assessed. RESULTS: Concentric LVH was identified in 29 patients (22%) at PD initiation, and patient survival, MACE-free survival and PD continuation were significantly reduced in the cLVH group compared with the non-cLVH group. In the Cox regression analysis, cLVH was demonstrated as an independent risk factor of mortality (HR [95%CI]: 3.32 [1.13-9.70]) for all patients. For patients over 65 years old, cLVH was significantly associated with mortality and MACE (HR [95%CI]: 3.51 [1.06-11.58] and 2.97 [1.26-7.01], respectively). Serum albumin at PD initiation was independently correlated with cLVH. CONCLUSIONS: In our study, cLVH at PD initiation was independently associated with survival in all patients and with both survival and MACE in elderly patients. Evaluation of LV geometry at PD initiation might therefore help identify high-risk patients. Further studies involving larger numbers of patients are needed to confirm the findings from this study and clarify whether treatment interventions for factors such as nutrition status could ameliorate cLVH and improve patient outcomes.

Correction to: Treatment of stage II medication-related osteonecrosis of the jaw with necrosectomy and autologous bone marrow mesenchymal stem cells.

In the Original publication of the article, the co-author has been misspelled as Fabian Duttenhöfer in the article "Treatment of stage II medication-related osteonecrosis of the jaw with necrosectomy and autologous bone marrow mesenchymal stem cells" published in October 2017, Volume 105, Issue 4 of Odontology. The correct name is "Fabian Duttenhoefer".

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.

Prediction of immunoglobulin M reduction via therapeutic dose of simple plasma exchange and double filtration plasmapheresis using membrane separation in patients with hyperviscosity syndrome caused by Waldenstrom macroglobulinemia.

BACKGROUND: Plasma exchange (PE) and double filtration plasmapheresis (DFPP) are known as effective treatment options for hyperviscosity syndrome (HVS) caused by Waldenstrom macroglobulinemia. Nonetheless, few data are available for the relation between the prescribed dose of apheresis and the reduction rate of target molecule immunoglobulin M (IgM), especially in the modality using membrane separation. OBJECTIVES: This study was conducted to establish a model to predict the IgM reduction rate by the dose of simple PE and DFPP using membrane separation in patients with HVS and to compare the consumption of albumin between PE and DFPP. METHODS: We retrospectively analyzed data of total 17 sessions of PE and DFPP with various therapeutic doses performed for five patients at our institution. We used linear regression analysis to examine the relation between the ratio of processed plasma volume to estimated circulating plasma volume (X) and the reduction rate of IgM (Y). RESULTS: Regression analysis revealed that Y is expressed by X as the following equation: Y = 0.35X + 0.095. The total usage of albumin for replacement fluid was lower in DFPP than in PE (21.5 g vs 150 g per session), although the treatment efficacies of both modalities are similar. CONCLUSION: The dose of PE and DFPP using membrane separation can predict IgM reduction rate in the HVS patients. Predicted IgM reduction rates based on our model are lower than those calculated using a known theoretical model. In terms of the amount of use of albumin, DFPP is preferred to PE.

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.

Prognostic significance of serum neuron-specific enolase in small cell carcinoma of the urinary bladder.

PURPOSE: Small cell carcinoma of the urinary bladder (SCCB) is known for its aggressive clinical features and poor prognosis. No prognostic factor has been established so far. The aim of this study was to assess the significance of possible prognostic factors, including serum neuron-specific enolase (NSE), an established biomarker for small cell lung carcinoma. METHODS: We retrospectively reviewed 31 patients with primary SCCB treated at our eight affiliate institutions between 2001 and 2014. The association of various clinicopathological factors at diagnosis, including the serum NSE value, with cancer-specific survival (CSS) was assessed. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: Nineteen (61.3 %) died of SCCB during the follow-up, with a median survival time of 12.7 months. Prognostic factors were analyzed for the 25 patients after excluding six with missing data. Univariate analysis demonstrated that stage (extensive disease) and serum NSE ≥25 ng/ml were significantly associated with worse CSS. Multivariate analysis identified increased serum NSE value as a sole independent predictor of CSS (hazard ratio 18.52, p = 0.0022). CONCLUSIONS: Serum NSE value at diagnosis was an independent prognostic factor for primary SCCB and may serve as a useful biomarker in the management of SCCB.

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.

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.

Primary wound closure after tooth extraction for prevention of medication-related osteonecrosis of the jaw in patients under denosumab.

OBJECTIVES: Some recent reports have indicated that local infection causes osteonecrosis of the jaw and described that tooth extraction may not be a direct cause of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive medications. Tooth extraction and elimination of the source of infection are expected to reduce the risk of developing MRONJ. However, there is no data regarding prevention for developing osteonecrosis of the jaw in patients receiving denosumab. Therefore, the aim of this study was to investigate the outcome of tooth extractions with proper wound closure in patients receiving denosumab. PATIENTS AND METHODS: Forty teeth in 19 patients treated with denosumab therapy were extracted under preoperative intravenous antibiotics. Patients who had already developed MRONJ in the extraction sites or who had a history of radiation therapy were excluded. During surgery, bone edges were smoothed and all wounds were closed using the double-layered technique. RESULTS: Thirty-seven extraction sites (92.5 %) in 17 out of 19 patients (89.5 %) were healed. However, three extraction sites in two patients had complications; one patient had exposed bone and developed MRONJ (stage 1) and the other developed a mucosa fistula. Additional surgical procedures were performed and all wounds were completely healed. CONCLUSIONS: Tooth extractions in patients receiving denosumab can be performed in an appropriate manner and result in good outcomes. CLINICAL RELEVANCE: This study indicated that tooth extraction with proper wound closure to avoid secondary infection may be effective for the prevention of MRONJ even in high-risk patients.

Treatment of stage II medication-related osteonecrosis of the jaw with necrosectomy and autologous bone marrow mesenchymal stem cells.

Treatment strategies for medication-related osteonecrosis of the jaw (MRONJ) remain controversial. Although the AAOMS suggests a conservative approach, a surgical management with necrosectomy is often required when conservative management has failed. Moreover, recent studies have shown promising results using an early stage surgical treatment. Over the past decade, cell-based bone regeneration utilizing bone marrow mesenchymal stem cells (MSCs) received increased attention. MSCs are known to promote wound healing and induce new bone formation in compromised tissue. Accordingly, the aim of this study was to assess the role of MSCs in the management of MRONJ. This study included 6 patients referred to our department with the diagnosis of MRONJ. Upon informed consent, the patients underwent surgical resection of necrotic bone followed by MSCs grafting. The MSCs were separated from bone marrow cells aspirated from the iliac crest using a bone marrow aspirate concentrate system. The MSCs were grafted into the defect with autologous thrombin and the defect was covered with a collagen membrane. In all cases, bony edges were rounded and the wound was closed using a three-layered technique. In the follow-up from 12 to 54 months, all patients including those who had impaired conditions, sepsis, or pathological fracture, showed satisfactory healing with no signs of wound infection. This pilot study indicated that surgical management in combination with MSCs transplantation seems to be a promising treatment modality in the therapy of MRONJ.

Validation of major prognostic models for metastatic urothelial carcinoma using a multi-institutional cohort of the real world.

BACKGROUND: Several prognostic models predicting survival of patients with metastatic urothelial carcinoma (UC) have been developed; however, of them, the first model by Bajorin in 1999 is still the most representative and widely used, and validations of newer models are lacking. This study aimed to validate three major prognostic models for metastatic UC constructed based on clinical trials. METHODS: We reviewed 200 patients with metastatic UC who received first-line chemotherapy at our five affiliate institutions between 2003 and 2011. Using this multi-institutional cohort, we validated the following models: the "Bajorin model," a model consisting of visceral metastasis and performance status; the "Apolo model," a nomogram including visceral metastasis, performance status, albumin and hemoglobin; and the "Galsky model," a nomogram including leukocyte count, number of sites of visceral metastases, site of primary tumor, performance status and lymph node metastasis. Harrell's c-index was calculated for each model. Cox proportional hazards regression model was used for multivariate analysis. RESULTS: Among 200 patients, 171 (85.5%) died during the follow-up, with a median survival of 12.0 months. Multivariate analysis demonstrated ECOG performance status, visceral metastasis and leukocyte count to be independent predictors of overall survival. C-index results (95% confidence interval) were Bajorin: 0.86 (0.74-0.95); Apolo: 0.89 (0.78-0.98); and Galsky: 0.82 (0.69-0.93). CONCLUSIONS: All models were demonstrated to have high external validities in real-world patients, and of them, the "Apolo model" achieved the highest c-index in the present population. Further studies with larger populations are needed for establishment of the next standard model.

Cessation of long-term adjuvant androgen deprivation therapy after radical prostatectomy: is it feasible?

BACKGROUND: Adjuvant androgen deprivation therapy is a common treatment option for prostate cancer after radical prostatectomy, especially in Asia. However, no study has investigated the oncological outcome after cessation of long-term adjuvant androgen deprivation therapy with favorable prostate-specific antigen  control. METHODS: Among 855 patients undergoing radical prostatectomy at our institution between 2000 and 2012, we identified 56 men with pT2-4N0-1M0 prostate cancer who had received long-term (>2 years) adjuvant androgen deprivation therapy after radical prostatectomy and subsequently stopped it under a condition of continued prostate-specific antigen values <0.1 ng/mL. The oncological outcome was evaluated using biochemical recurrence, defined as two consecutive prostate-specific antigen values ≥0.2 ng/mL, as the primary endpoint. Cox proportional hazards model was used for multivariate analysis. Age at androgen deprivation therapy cessation was dichotomized as <68 years and ≥68 years, based on the most discriminatory cutoff. RESULTS: Median duration of adjuvant androgen deprivation therapy was 70 months. Overall, 13 of 56 (23%) patients developed biochemical recurrence with a median follow-up period of 41 months after androgen deprivation therapy cessation. Multivariate analysis identified age at androgen deprivation therapy cessation <68 years and pN1 as independent predictors of biochemical recurrence. Predisposition of younger age to poorer survival may be related to more frequent testosterone recovery in younger men (73 vs 33%, P = 0.0299). One patient had evidence of clinical metastasis and no one died of prostate cancer. CONCLUSIONS: Androgen deprivation therapy cessation would be feasible in most men who received long-term adjuvant androgen deprivation therapy after radical prostatectomy with favorable prostate-specific antigen control. Risk factors of biochemical recurrence after androgen deprivation therapy cessation included younger age at androgen deprivation therapy cessation and pN1.

METASTATIC SMALL CELL CARCINOMA OF THE URINARY BLADDER TREATED WITH SYSTEMIC CHEMOTHERAPY INCLUDING AN AMRUBICIN; A CASE REPORT.

We report a 59-year-old male patient with metastatic small cell carcinoma of the bladder treated with systemic chemotherapy including an amrubicin. The patient was referred to our hospital complaining of macrohematuria. A cytoscopy revealed a non-papillary, broad-based tumor extending from the right to the posterior wall of the bladder. A computed tomography showed bilateral hydronephrosis caused by the bladder tumor and multiple metastases to the para-aortic and common iliac lymph nodes. The histopathological findings following a transurethral resection of the bladder tumor revealed a T2N3M1, LYM, stage IV small cell carcinoma. We administered two courses of systemic chemotherapy consisting of cisplatin (CDDP) plus an etoposide (VP-16), a first-line treatment usually administered to patients with small cell carcinoma of the lung. We then administered second-line chemotherapy consisting of CDDP plus an irinotecan. When the first and second-line therapies failed to halt progression of the disease, we decided to use amrubicin as the third-line therapy concomitant with radiotherapy for local control. Although the NSE (neuron-specific enolase) value decreased, the patient died 11 months after the initial examination. To our knowledge, this is the first case in which small cell carcinoma of the bladder was treated with amrubicin.

Pretreatment neutrophil-to-lymphocyte ratio as an independent predictor of survival in patients with metastatic urothelial carcinoma: A multi-institutional study.

OBJECTIVES: To evaluate the prognostic significance of the pretreatment neutrophil-to-lymphocyte ratio in patients with metastatic urothelial carcinoma who underwent salvage chemotherapy. METHODS: We reviewed 200 metastatic urothelial carcinoma patients who received salvage chemotherapy at our five affiliate institutions between 2003 and 2011. The associations of pretreatment clinicopathological factors, including neutrophil-to-lymphocyte ratio, with cancer-specific survival and overall survival from the start of chemotherapy were assessed. Cox proportional hazards model was used for multivariate analysis. RESULTS: A total of 15 cases with missing data were excluded. Among the remaining 185 patients, 157 died during follow up, with a median survival of 13.0 months. Multivariate analysis showed that the pretreatment neutrophil-to-lymphocyte ratio ≥3, Eastern Cooperative Oncology Group performance status ≥2 and liver metastasis were independent poor prognostic factors, both for cancer-specific survival and overall survival. A prognostic model predicting overall survival was constructed based on the number of these three variables (0, 1 and ≥ 2). The classified patients showed significantly different overall survival (each P < 0.0001, log-rank test), with Harrell's concordance index as high as 0.81. CONCLUSIONS: Pretreatment neutrophil-to-lymphocyte ratio elevation was an independent poor prognostic factor for metastatic urothelial carcinoma undergoing salvage chemotherapy. Our newly constructed prognostic model including the pretreatment neutrophil-to-lymphocyte ratio proved to be an excellent discriminator of overall survival.