[A CASE OF FUMARATE HYDRATASE (FH)-DEFICIENT RENAL CELL CARCINOMA SUSPECTED OF HEREDITARY LEIOMYOMATOSIS RENAL CELL CARCINOMA].

We experienced a case of fumarate hydratase (FH) -deficient renal cell carcinoma (RCC) suspected of hereditary leiomyomatosis renal cell carcinoma (HLRCC) and herein report our findings. A 42-year-old man with an unremarkable medical history was referred to our hospital with an initial impression of renal cancer, cT3aN2M0. He underwent a right radical nephrectomy with lymph node dissection and showed a pathological diagnosis of FH-deficient RCC, pT3aN2. Clinicopathologic features indicated the possibility of HLRCC; however,-associated RCC. genetic testing showed negative for pathogenic FH mutation.HLRCC is an autosomal dominant condition caused by an FH gene mutation on chromosome 1q43. It is also a syndrome that develops in the smooth muscles of the skin and uterus, and has a renal cancer risk of 10-16%. HLRCC-associated RCC tends to metastasize early and shows poor prognosis. In FH-deficient RCC, the possibility of HLRCC-related RCC should be considered; thus, if patients fulfill the clinical diagnostic criteria, genetic counseling and screening of HLRCC are needed. Even if genetic testing does not confirm HLRCC, FH-deficient RCC still has a poor prognosis and careful follow-up is required.

[A CASE REPORT OF VESICAL CALCULUS FORMATION WITH CHROMIC CATGUT AT THE URETEROVESICAL ANASTOMOTIC SITE 28 YEARS AFTER RENAL TRANSPLANTATION].

A 69-year-old man underwent renal transplantation due to chronic renal failure of unknown cause in 1991. Furthermore, in 2012 he again underwent renal transplantation due to renal graft dysfunction with focal segmental glomerulosclerosis. After the second renal transplantation, his renal function has been stable. In 2019, he presented to the urology department with gross hematuria. Cystoscopy revealed a 2 cm vesical calculus at the dome of the bladder near the right lateral wall. Therefore, we performed transurethral lithotripsy using the holumium laser method. The vesical calculus was crushed, revealing a suture at the center, suggesting the suture as the cause. We tried to remove the suture during operation, however, it was impossible. Although the remaining suture posed a risk for calculus development, there has been no recurrence of a calculus for 6 months after the operation. This case reports a vesical calculus at the ureterovesical anastomotic site, wherein the core was an absorbable suture used during the initial renal transplantation. It should be taken into consideration that there is a possibility of anastomotic calculus occurrence with absorbable sutures, even long after renal transplantation.

Successful completion of transurethral lithotripsy in a patient with factor XIII deficiency: A case report.

Factor XIII (FXIII) deficiency is a rare inherited coagulopathy. Standard perioperative management in those with FXIII deficiency requiring surgical procedures has not been elucidated. Herein, we report the case of a patient with FXIII deficiency who successfully underwent transurethral lithotripsy. Recombinant FXIII was used effectively in perioperative management and safely without any bleeding complications. This is the first report of a patient with FXIII deficiency in the field of urology.

Methylation pattern of urinary DNA as a marker of kidney function decline in diabetes.

INTRODUCTION: Renal tubular injury contributes to the decline in kidney function in patients with diabetes. Cell type-specific DNA methylation patterns have been used to calculate proportions of particular cell types. In this study, we developed a method to detect renal tubular injury in patients with diabetes by detecting exfoliated tubular cells shed into the urine based on tubular cell-specific DNA methylation patterns. RESEARCH DESIGN AND METHODS: We identified DNA methylation patterns specific for human renal proximal tubular cells through compartment-specific methylome analysis. We next determined the methylation levels of proximal tubule-specific loci in urine sediment of patients with diabetes and analyzed correlation with clinical variables. RESULTS: We identified genomic loci in SMTNL2 and G6PC to be selectively unmethylated in human proximal tubular cells. The methylation levels of SMTNL2 and G6PC in urine sediment, deemed to reflect the proportion of exfoliated proximal tubular cells due to injury, correlated well with each other. Methylation levels of SMTNL2 in urine sediment significantly correlated with the annual decline in estimated glomerular filtration rate. Moreover, addition of urinary SMTNL2 methylation to a model containing known risk factors significantly improved discrimination of patients with diabetes with faster estimated glomerular filtration rate decline. CONCLUSIONS: This study demonstrates that patients with diabetes with continual loss in kidney function may be stratified by a specific DNA methylation signature through epigenetic urinalysis and provides further evidence at the level of exfoliated cells in the urine that injury of proximal tubular cells may contribute to pathogenesis of diabetic kidney disease.

Relevance of concurrent hypercalcemia in ureteric sarcoidosis complicated with bladder urothelial carcinoma: a case report.

BACKGROUND: Sarcoidosis is a multisystem inflammatory disorder and can affect any organ; however, ureteric involvement is extremely rare with only four cases reported in the literature to date, all of which were diagnosed with surgical ureteral resection including a nephroureterectomy. This study reports the first case of ureteric sarcoidosis controlled with medical therapy where a differential diagnosis was performed based on the diagnostic clue of hypercalcemia. A definitive diagnosis was established without surgical resection of the ureter. CASE PRESENTATION: A 60-year-old man presented with anorexia and weight loss. Blood tests showed renal dysfunction and hypercalcemia. Computed tomography revealed left hydronephrosis associated with left lower ureteral wall thickening, which showed high signal intensity on diffusion-weighted magnetic resonance imaging. Similarly, we detected a bladder tumor on cystoscopy, and a 2-cm-long stenosis was revealed by retrograde ureterography; therefore, ureteral cancer was suspected. Meanwhile, considering the clinical implication of hypercalcemia, a differential diagnosis of sarcoidosis was established based on elevated levels of sarcoidosis markers. Fluorodeoxyglucose positron emission tomography showed fluorodeoxyglucose accumulation in the left lower ureter, skin, and muscles, suggestive of ureteric sarcoidosis with systemic sarcoid nodules. For a definitive diagnosis, transurethral resection of the bladder tumor and ureteroscopic biopsy were performed. Histopathological examination revealed ureteric sarcoidosis with bladder urothelial carcinoma. Following an oral administration of prednisolone, hypercalcemia instantly resolved, the renal function immediately improved, and the left ureteral lesion showed complete resolution with no recurrence. CONCLUSIONS: In this case, the co-occurrence of ureteral lesion with bladder tumor evoked a diagnosis of ureteral cancer. However, considering a case of ureteral lesion complicated with hypercalcemia, assessment for differential diagnosis was performed based on the calcium metabolism and sarcoidosis markers. In cases of suspected ureteric sarcoidosis from the assessment, pathological evaluation with ureteroscopic biopsy should be performed to avoid nephroureterectomy.

Outcome of renal cell carcinoma in patients on dialysis compared to non-dialysis patients.

PURPOSE: To investigate the impact of hemodialysis on survival in renal cell carcinoma (RCC) patients. METHODS: We studied 388 patients who underwent radical or partial nephrectomy for RCC at Toranomon Hospital from 2005 to 2013. Survival curves were drawn according to the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model to assess the prognostic influence of hemodialysis on cancer-specific survival. RESULT: Of the 388 patients, 66 were on hemodialysis and 322 were not on dialysis. In the hemodialysis patients, incidental diagnosis of RCC was less frequent than in the non-dialysis patients. In addition, RCC was more likely to be multicentric (41% vs 1.2%), bilateral (14% vs 0.6%), and papillary (18% vs 7%) in hemodialysis patients. Moreover, tumors were smaller, the stage was lower, and the Fuhrman nuclear grade was higher in the patients on hemodialysis. The 5-year cancer-specific survival rate was 82.8% for hemodialysis patients and 93.5% for nondialysis patients. Multivariate analysis indicated that hemodialysis, stage, and Fuhrman nuclear grade were independent prognostic factors for RCC. CONCLUSIONS: This study suggested that hemodialysis was an independent prognostic factor for cancer-specific survival in RCC patients, along with the tumor stage and Fuhrman nuclear grade.

Intrascrotal hibernoma mimicking liposarcoma: A case study.

Hibernoma is a rare benign lipomatous tumor derived from brown fat, which is typically found in infants. Specifically, intrascrotal hibernoma is extremely rare with only one case reported to date. We encountered the second case, which was successfully treated with surgical resection without any recurrence at 3 years. The patient was first misdiagnosed with an intrascrotal liposarcoma preoperatively. Preoperative usefulness of imaging modalities to discriminate hibernomas and liposarcomas is limited due to lack of specific features of hibernomas with its rarity. Here, we report a case of intrascrotal hibernoma in addition to a current literature review.

[THE EFFECT OF LOW-DOSE INTRAVESICAL BACILLUS CALMETTE-GUÉRIN (BCG) INFUSION THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER].

(Objective) Bacillus Calmette-Guérin (BCG) intravesical infusion therapy plays an important role in the treatment of patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Our institute performs low-dose (40 mg) BCG intravesical infusion therapy (completed 8 times) to reduce side effects. We retrospectively investigated its efficacy and side effects. (Patients and methods) We analyzed the response, non-recurrence, and side effect rates by risk stratification in 179 patients who received low-dose BCG intravesical infusion therapy from September 2003 to November 2018 in Nagano Municipal Hospital. Complications were classified using the Common Terminology Criteria for Adverse Events version 4.0. (Results) The median age was 73 years, and the male/female ratio was 137:42. The median observation period was 32 months, and infusion was completed 8 times in 149 cases (83.2%). The overall response rate was 88.8%. The response rate was significantly higher in the low-grade pathology group than in the high-grade group. However, no significant differences in G1/G2/G3 side effects, sex, age, presence of carcinoma in situ (CIS), depth of invasion, purpose of administration, and grade of side effects were observed. The overall non-recurrence rates were 91.8%, 76.7%, and 71.3% at 1, 3, and 5 years, respectively. Nevertheless, there were no significant differences in the non-recurrence rates with respect to depth of penetration, the degree of dysmorphism, purpose of administration, presence of CIS, and completed of infusion. A total of 71 G2 side effects (39.7%) were identified, and 3 cases of G3 side effects required hospitalization. (Conclusion) In our institution, the completion rate of low-dose BCG intravesical infusion therapy was high, with few side effects. Furthermore, it demonstrated similar therapeutic effect to that reported with standard-dose administration. Low-dose BCG intravesical infusion therapy may be an effective treatment, particularly for pathologically low-grade NMIBC.

[CLINICAL RESULTS OF TWO PATIENTS WITH LATE RECURRENCE OF RENAL CELL CARCINOMA AFTER LONG TERM OBSERVATION WITHOUT TREATMENT].

Two patients with late recurrence of renal cell carcinoma were observed long term without treatment. Case 1 is an 83-year-old woman who underwent right nephrectomy at 57 years of age following a renal tumor diagnosis. Histopathological results revealed clear cell renal cell carcinoma, G2, pT1aN0M0. Pancreatic metastasis developed at age 71, and pancreatic tail excision was performed. A metastatic lesion appeared again at the head of the pancreas at age 74. The patient has been followed by observation only for 9 years without any new lesions. Tumor doubling time calculated from abdominal ultrasonography was 13.3 months.Case 2 is a 91-year-old male. At 78 years of age, right nephrectomy and inferior vena cava tumor embolectomy were performed for renal tumor. Histopathological results revealed clear cell renal cell carcinoma, G2, pT3bN0M0. Left adrenal metastasis appeared at age 84, and the patient has been followed for 7 years without new lesions. Tumor doubling time calculated from abdominal computed tomography (CT) images was 14.1 months.In both patients, no symptoms due to tumor recurrence ever appeared, and their activities of daily living (ADL) were maintained fairly well. In the case of solitary late recurrence in elderly renal cancer patients, observation may be a treatment option that avoids adverse effects and complications caused by treatment. In addition, it appears possible to predict the need for subsequent treatment by calculating the doubling time using several sequential CT images obtained after recurrence. If a new recurrent metastatic lesion appears or if the doubling time during a 2-to 3-year follow-up period is relatively short, however, new treatment should be considered without delay.

Effect of tadalafil add-on therapy in patients with persistant storage symptoms refractory to α1 -adrenoceptor antagonist monotherapy for benign prostatic hyperplasia: A randomized pilot trial comparing tadalafil and solifenacin.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of tadalafil add-on therapy with α1 -adrenoceptor antagonists. METHODS: Patients with persistent storage symptoms refractory to α1 -adrenoceptor antagonists for benign prostatic hyperplasia were enrolled in the study. Patients were randomly assigned to either a 5 mg tadalafil or 5 mg solifenacin treatment group for 12 weeks. International Prostate Symptom Score, Overactive Bladder Symptom Score, urinary flow rates, residual urine volume, and blood pressure were measured prospectively before treatment and after 4 and 12 weeks of treatment. Changes from baseline were compared between groups. The rate of treatment discontinuation due to adverse effects was evaluated. RESULTS: Of the 75 patients recruited to the study, 38 and 37 were assigned to the tadalafil and solifenacin groups, respectively. There were no significant difference in baseline characteristics between the two groups. The change in the amount of residual urine volume was significantly larger in the solifenacin- than tadalafil-treated group; other parameters, including lower urinary tract symptoms and uroflowmetry measures, did not differ significantly between the two groups. Seven (18%) and 12 (32%) patients in the tadalafil and solifenacin groups, respectively, discontinued treatment because of adverse events. The main reasons for discontinuation in the tadalafil group were stomach discomfort or nausea and dizziness or vertigo; voiding difficulty and constipation were the main reasons for discontinuation in the solifenacin group. There was no significant difference in blood pressure fluctuations from baseline between the two groups. CONCLUSIONS: Tadalafil add-on therapy was not inferior to solifenacin add-on therapy in terms of effect and safety. Therefore, tadalafil could be an alternative add-on drug for patients with persistent lower urinary tract symptoms refractory to α1 -adrenoceptor antagonists.

Macroscopic hematuria caused by running-induced traumatic bladder mucosal contusions.

INTRODUCTION: To clarify the mechanisms responsible for running-induced asymptomatic gross hematuria. CASE PRESENTATION: We identified 12 patients who visited our outpatient clinic with hematuria after running as a chief complaint. In 9 of 12 patients (75%), cystoscopic findings revealed mucosal contusions at the center of the posterior wall. Our examination including cystoscopy and magnetic resonance imaging revealed that this bladder contusion development was caused by the repeated contact of the bladder posterior wall against the fixed bladder neck by vertical motion in the empty bladder lumen during running. All patients with bladder contusion were male because the bladder neck is more firmly fixed to the pelvic floor by the protruding prostate in men than women. Gross hematuria in all patients quickly resolved without treatment after running cessation. CONCLUSION: This is the first report in which cystoscopic findings showed that running-induced macroscopic hematuria can be frequently caused by traumatic bladder contusion.

[A CASE REPORT: EOSINOPHILIC CYSTITIS PRESENTED WITH DEEP VEIN THROMBOSIS].

A 76-year-old man presented with gross hematuria and reported the use of anticoagulant for deep vein thrombosis (DVT). Blood tests revealed eosinophilia and thrombocytopenia. Urine cytology revealed a class I specimen with a few eosinophils in the urine. We performed cystoscopy, which revealed bladder masses with friable mucosa diffusely throughout the bladder. Magnetic resonance imaging revealed possible invasion of the bladder muscle by the masses. We performed transurethral resection of the bladder masses, and histopathological examination revealed eosinophilic infiltration of the bladder wall stroma without cancerous tissue. Therefore, the patient was diagnosed with eosinophilic cystitis.Eosinophilia and thrombocytopenia promptly resolved, and the bladder masses disappeared following the administration of prednisolone for eosinophilic cystitis. DVT also improved without recurrence of eosinophilic cystitis.

[DRUG-INDUCED BILATERAL NEPHROLITHIASIS IN AN ULCERATIVE COLITIS PATIENT: A CASE REPORT].

A 59-year-old female experienced gross hematuria and right back pain, and she visited our hospital in March 2015. Abdominal computed tomography (CT) showed bilateral renal pelvic calculi; the right stone was 15 mm and the left stone was 18 mm in diameter. She had ulcerative colitis and had been taking salazosulfapyridine (SASP) for about 30 years. Urinalysis showed aciduria and deposition of urate crystals. An abdominal X-ray picture did not show a calculus shadow. We suspected uric acid calculus and started treatment with urinary alkalizer and uric acid production inhibitor.Three months later, abdominal CT showed enlargement of the bilateral renal pelvic calculi; the right stone was 25 mm and the left stone was 24 mm in diameter. She also complained of worse right back pain and underwent transurethral ureterolithotripsy for the right renal pelvic stone. The stone was orange, comparatively soft, and chipped down until it was approximately half of its original size. The stone analysis suggested suspected drug-induced urolithiasis, but not uric acid calculus. Thus, we investigated the stone and SASP using infrared spectroscopy, and the infrared absorption pattern was similar in both. The stone analysis demonstrated drug-induced urolithiasis induced by SASP.The patient's ulcerative colitis therapy was switched to mesalazine, and the amount of urinary alkalizer was increased. Abdominal CT 3 months thereafter showed dissipation of bilateral renal pelvic calculi. The patient did not take any preventative medication, and there was no recurrence of urolithiasis.

The loss of BAP1 protein expression predicts poor prognosis in patients with nonmetastatic clear cell renal cell carcinoma with inferior vena cava tumor thrombosis.

OBJECTIVES: Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC) and is associated with poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts poor prognosis. The aim of this study was to elucidate the association between BAP1 protein expression and clinicopathological outcomes in patients with nonmetastatic ccRCC with an IVC tumor thrombus (IVCTT). MATERIAL AND METHODS: Thirty-five patients with nonmetastatic ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy at our institution from 1999 to 2010 were retrospectively evaluated. Immunohistochemical (IHC) analyses were performed for the expression of BAP1 protein, and the associations between the expression of BAP1 and clinical outcomes were assessed. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate analyses of the associations between disease-free survival (DFS) and clinical variables including BAP1 protein expression, tumor size, Karnofsky performance status (KPS) score, and the extension level of the tumor thrombus were performed using a Cox proportional hazard model. RESULTS: The median follow-up time was 58.8 months (range: 2-130 months). The median age was 68 years (range: 37-80 years). The median size of the primary tumor was 9.6cm (range: 3.0-15.0cm). The IVCTT extended above and below the diaphragm in 10 (28.6%) and 25 (71.4%) patients, respectively. The KPS score was>80 in 23 patients (65.7%). BAP1 protein expression on IHC was positive in 24 cases (68.8%) and negative in 11 cases (31.2%). The median overall survival in cases with BAP1-negative and -positive tumor on IHC staining were 44.7 and 81.5 months, respectively (P = 0.052). BAP1-negative tumor on IHC staining was associated with a significantly shorter DFS than BAP1-positive tumor (median DFS = 10.0 vs. 26.0 months, respectively; P = 0.011). Multivariate analysis showed that only BAP1-negative tumor on IHC staining was significantly associated with shorter DFS (P = 0.004). CONCLUSIONS: Patients whose tumors had loss of BAP1 protein expression were significantly associated with poor prognosis in patients with ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy.

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.

Clinicopathological characteristics of patients with upper urinary tract urothelial cancer with loss of immunohistochemical expression of the DNA mismatch repair proteins in universal screening.

OBJECTIVES: To assess the detection rate of putative Lynch syndrome-associated upper urinary tract urothelial cancer among all upper urinary tract urothelial cancers and to examine its clinicopathological characteristics. METHODS: A total of 143 patients with upper urinary tract urothelial cancer who had received total nephroureterectomy were immunohistochemically stained for the expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. For all suspected mismatch repair-deficient cases, MMR genetic testing was recommended and clinicopathological features were examined. RESULTS: Loss of mismatch repair proteins was found in seven patients (5%) who were thus categorized as putative Lynch syndrome-associated upper urinary tract urothelial cancer. Five of these patients showed dual loss of MSH2/MSH6. Two patients were confirmed to be MSH2 germline mutation carriers. Histologically, all seven tumors were low-grade atypical urothelial carcinoma and showed its unique histological features, such as an inverted papilloma-like growth pattern and a villous to papillary structure with mild stratification of tumor cells. Six tumors had no invasion of the muscularis propria. No recurrence or cancer-related deaths were reported in these seven patients. Just three patients met the revised Amsterdam criteria. CONCLUSIONS: This is the first report that universally examined mismatch repair immunohistochemical screening for upper urinary tract urothelial cancers. The prevalence (5%) of putative Lynch syndrome-associated upper urinary tract urothelial cancers is much higher than we had expected. We ascertained that putative Lynch syndrome-associated upper urinary tract urothelial cancers were clinically in the early stage and histologically classified into low-grade malignancy with its characteristic pathological features. The clinicopathological characteristics that we found in the present study could become additional possible markers in the diagnosis of Lynch syndrome-associated upper urinary tract urothelial cancers.

Phenotypical change of tumor-associated macrophages in metastatic lesions of clear cell renal cell carcinoma.

Macrophages are the main immune cells of the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). A high density of CD163+ or CD204+ tumor-associated macrophages (TAMs), rather than the density of total TAMs, is known to be linked to poor clinical outcome. In the present study, we investigated the phenotypical differences between the paired primary and metastatic lesions in ccRCC cases. Using immunostaining, the densities of CD163+ and CD204+ TAMs in metastatic lesions were found to be significantly lower compared to primary lesions, although the total number of TAMs was increased in metastatic lesions. Since CD163 and CD204 are considered to be the markers of an M2/protumor phenotype in macrophages, TAMs in metastatic lesions are suggested to have a greater M1/inflammatory function compared with those from primary lesions. These findings give new insights in regard to the immunological status of metastatic lesions of ccRCC.

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.

Effect of Lymphadenectomy During Radical Nephroureterectomy in Locally Advanced Upper Tract Urothelial Carcinoma.

BACKGROUND: The role of lymph node dissection (LND) for upper tract urothelial carcinoma (UTUC) patients remains controversial. The aim of this study was to evaluate the effect of LND on clinical outcomes during radical nephroureterectomy (RNU) and to determine prognostic factors of survival. PATIENTS AND METHODS: From 1985 to 2013, 404 patients with UTUC underwent RNU; 5 patients who received neoadjuvant chemotherapy were excluded. Among them, 182 (46%) were pathologically negative for lymph node metastasis (pN0), 177 (44%) were non-LND (pNx), and 40 (10%) were positive for lymph nodes metastasis (pN1/2). RESULTS: The 5-year disease-free survival (DFS) and cancer-specific survival (CSS) rate were higher in pN0 patients than in pNx patients and in pN1/2 patients. According to multivariate analysis, non-LND was an independent predictive factor of DFS (hazard ratio [HR], 1.91; P = .004) and CSS (HR, 2.28; P = .003). In the subgroup with muscle-invasive UTUC, the 5-year DFS and CSS rates were higher in pN0 patients than in pNx patients. However, there was no statistical difference between pN0 and pNx groups in terms of DFS and CSS in the pT2 cases. DFS and CSS times were significantly prolonged in the pN0 group in the locally advanced UTUC patients (≥pT3). CONCLUSION: In the ≥pT3 subgroup, the 5-year DFS and CSS were significantly prolonged in the pN0 group, but there were no statistical differences between pN0 and pNx groups in terms of DFS and CSS in the pT2 subgroup. LND for patients with locally advanced UTUC might improve disease prognosis.

Loss of BAP1 protein expression in the first metastatic site predicts prognosis in patients with clear cell renal cell carcinoma.

OBJECTIVES: To investigate the intratumoral heterogeneity of BAP1 and PBRM1 expression at the primary site and metastatic sites and to evaluate whether BAP1 and PBRM1 expression in metastatic sites of clear cell renal cell carcinoma (ccRCC) has prognostic value. METHODS AND MATERIALS: We collected paired samples from the primary site and the first metastatic site in 41 patients with ccRCC. Immunohistochemistry analyses were performed for the expression of BAP1 and PBRM1 proteins. We retrospectively analyzed the associations between the expression of BAP1 and PBRM1 and overall survival (OS). RESULTS: The most common first metastatic sites were lung (68.3%) and lymph node (12.2%). BAP1 protein expression was negative in 8 (19.5%) primary sites and in 11 (26.8%) metastatic sites. PBRM1 protein expression was negative in 9 (22.0%) primary sites and in 11 (26.8%) metastatic sites. The incidences of intratumoral heterogeneity for BAP1 and PBRM1 protein expression in primary/metastatic sites were 9.8%/2.4% and 24.4%/7.3%, respectively. The concordance rates between primary and metastatic sites for BAP1 and PBRM1 protein expression were 82.9% and 63.4%, respectively. Median OS from the first occurrence of metastasis in patients with BAP1-positive and BAP1-negative metastatic sites were 97 months (95% CI: 58-136) and 51 months (95% CI: 13-82), respectively (P = 0.0077). Median OS in patients with PBRM1-positive and PBRM1-negative metastatic sites were 82 (95% CI: 42-97) and 120 (95% CI: 52-120) months, respectively (P = 0.25). CONCLUSION: Intratumoral heterogeneity of BAP1 protein expression is more frequent in primary tumor than in metastatic sites. The loss of BAP1 protein expression in metastatic sites predicts poor prognosis in patients with ccRCC.