Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Advanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism‒related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism‒related proteins on patient prognoses in advanced stage ccRCCs. @*Materials and Methods@#All of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation. @*Results@#FPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cutoff value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low expression of FBXL5 (hazard ratio, 2.001; p=0.034) was significantly associated with shorter overall survival. @*Conclusion@#FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.

Synergistic Antitumor Effects of Combined Treatment with HSP90 Inhibitor and PI3K/mTOR Dual Inhibitor in Cisplatin-Resistant Human Bladder Cancer Cells

Purpose@#The current study aimed to investigate the synergistic antitumor effect of combined treatment with 17-DMAG (HSP90 inhibitor) and NVP-BEZ235 (PI3K/mTOR dual inhibitor) on cisplatin-resistant human bladder cancer cells. @*Materials and Methods@#Human bladder cancer cells exhibiting cisplatin resistance (T24R2) were exposed to escalating doses of 17-DMAG (2.5–20 nM) with or without NVP-BEZ236 (0.5–4 μM) in combination with cisplatin. Antitumor effects were assessed by CCK-8 analysis. Based on the dose-response study, synergistic interactions between the two regimens were evaluated using clonogenic assay and combination index values. Flow cytometry and Western blot were conducted to analyze mechanisms of synergism. @*Results@#Dose- and time-dependent antitumor effects for 17-DMAG were observed in both cisplatin-sensitive (T24) and cisplatin- resistant cells (T24R2). The antitumor effect of NVP-BEZ235, however, was found to be self-limiting. The combination of 17- DMAG and NVP-BEZ235 in a 1:200 fixed ratio showed a significant antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range, and clonogenic assay showed compatible results with synergy tests. Three-dimensional analysis revealed strong synergy between the two drugs with a synergy volume of 201.84 μM/mL2%. The combination therapy resulted in G1-phase cell cycle arrest and caspase-dependent apoptosis confirmed by the Western blot. @*Conclusion@#HSP90 inhibitor monotherapy and in combination with the PI3K/mTOR survival pathway inhibitor NVP-BEZ235 shows a synergistic antitumor effect in cisplatin-resistant bladder cancers, eliciting cell cycle arrest at the G1 phase and induction of caspase-dependent apoptotic pathway.

Temsirolimus in Asian Metastatic/Recurrent Non-clear Cell Renal Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC. MATERIALS AND METHODS: From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus. RESULTS: Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]). CONCLUSION: Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.

An Intrarenal Adrenocortical Carcinoma Arising in an Adrenal Rest

We describe a case of a 61-year-old Korean man who was diagnosed with renal cell carcinoma that was discovered on abdominopelvic computed tomography obtained after the patient complained of back pain. A radical nephrectomy was performed, and the surgical specimen showed a relatively well-circumscribed and yellowish lobulated hard mass. Microscopically, the tumor showed sheets and nests of hypercellular pleomorphic cells with thick fibrous septation, frequent mitoses, and areas of adrenal cortical-like tissue. Immunohistochemical staining revealed that the tumor cells were positive for inhibin-α, vimentin, synaptophysin, and melan A. It also revealed that the tumor cells were negative for pan-cytokeratin, epithelial membrane antigen, paired box 8, α-methylacyl-coenzyme A racemase, CD10, cytokeratin 7, carbonic anhydrase 9, c-Kit, renal cell carcinoma, transcription factor E3, human melanoma black 45, desmin, smooth muscle actin, S-100, chromogranin A, CD34, anaplastic lymphoma kinase, and integrase interactor 1. Based on these histopathological and immunohistochemical findings, we diagnosed the tumor as intrarenal adrenocortical carcinoma arising in an adrenal rest. Several cases of intrarenal adrenocortical carcinoma have been reported, although they are very rare. Due to its poor prognosis and common recurrence or metastasis, clinicians and pathologists must be aware of this entity.

Prostate Imaging-Reporting and Data System Version 2: Beyond Prostate Cancer Detection

The main purpose of Prostate Imaging-Reporting and Data System Version 2 (PI-RADSv2) is to effectively detect clinically significant prostate cancers (csPCa) using multiparametric magnetic resonance imaging. Since the first introduction of PI-RADSv2, researchers have validated its diagnostic performance in identifying csPCa, and these promising data have influenced biopsy and treatment schemes. However, in this article, we focused on the potential of PI-RADSv2 in relation to various aspects of PCa such as Gleason score, tumor volume, extraprostatic extension, lymph node metastasis, and postoperative biochemical recurrence, beyond prostate cancer detection.

Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression

PURPOSE: Loss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative ovarian cancer that is intermediary between serous and endometrioid subtypes, in regards to molecular and clinical behaviors. However, about half of O-CCCs still express BAF250a, the protein encoded by ARID1A. Herein, we aimed to identify signatures of ARID1A-positive O-CCC in comparison with its ARID1A-negative counterpart. MATERIALS AND METHODS: Seventy cases of O-CCC were included in this study. Histologic grades and patterns of primary tumor, molecular marker immunohistochemistry profiles, and clinical outcomes were analyzed. RESULTS: Forty-eight (69%) O-CCCs did not express BAF250a, which were designated as "ARID1A-negative." The other 22 (31%) O-CCCs were designated as "ARID1A-positive." ARID1A-positive tumors were more likely to be histologically of high grades (41% vs. 10%, p=0.003), ERβ-positive (45% vs. 17%, p=0.011), and less likely to be HNF1β-positive (77% vs. 96%, p=0.016) and E-cadherin-positive (59% vs. 83%, p=0.028) than ARID1A-negative tumors. Patient age, parity, tumor stage were not significantly different in between the two groups. Cancer-specific survival was not significantly different either. CONCLUSION: We classified O-CCCs according to ARID1A expression status. ARID1A-positive O-CCCs exhibited distinct immunohistochemical features from ARID1A-negative tumors, suggesting a different underlying molecular event during carcinogenesis.

Fibroblast Growth Factor Receptor 1 Overexpression Is Associated with Poor Survival in Patients with Resected Muscle Invasive Urothelial Carcinoma

PURPOSE: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3). RESULTS: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over-expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis. CONCLUSION: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC.

Lymphangiogenesis in Breast Cancer Correlates with Matrix Stiffness on Shear-Wave Elastography

PURPOSE: To correlate tumor stiffness and lymphangiogenesis in breast cancer and to find its clinical implications. MATERIALS AND METHODS: A total of 140 breast cancer patients were evaluated. Tumor stiffness was quantitatively measured by shear-wave elastography in preoperative ultrasound examination, calculated as mean elasticity value (kPa). Slides of resected breast cancer specimens were reviewed for most fibrotic area associated with tumor. D2-40 immunohistochemical staining was applied for fibrotic areas to detect the lymphatic spaces. Microlymphatic density, tumor stiffness, and clinicopathologic data were analyzed. RESULTS: Higher elasticity value was associated with invasive size of tumor, microlymphatic density, histologic grade 3, absence of extensive intraductal component, presence of axillary lymph node metastasis, and Ki-67 labeling index (LI) in univariate regression analysis, and associated with Ki-67 LI and axillary lymph node metastasis in multivariate regression analysis. Microlymphatic density was associated histologic grade 3, mean elasticity value, and Ki-67 LI in univariate regression analysis. In multivariate regression analysis, microlymphatic density was correlated with mean elasticity value. CONCLUSION: In breast cancer, tumor stiffness correlates with lymphangiogenesis and poor prognostic factors.

Genetic analysis of ovarian microcystic stromal tumor

Microcystic stromal tumor (MCST) of the ovary is a rare subtype of ovarian tumor first described in 2009. Although high nuclear expression of β-catenin and β-catenin gene (CTNNB1) mutation are related with ovarian MCST, the origin and genetic background of ovarian MCST remain unclear. In this study, two cases of ovarian MCST are presented. Microscopically, the tumors showed a microcystic pattern and regions with lobulated cellular masses with intervening hyalinized, fibrous stroma. Tumor cells of both cases were stained with CD10, vimentin, and Wilms tumor 1. Genetic analysis was performed and β-catenin gene (CTNNB1) mutation in exon 3 was detected in both cases. This is the first report in regards of detecting CTNNB1 mutation in ovarian MCST through the use of pyrosequencing (a novel sequencing technique).

Pathological Evaluation of Radiation-Induced Vascular Lesions of the Brain: Distinct from De Novo Cavernous Hemangioma

PURPOSE: We aimed to evaluate the histologic and radiologic findings of vascular lesions after stereotactic radiosurgery (SRS) categorized as radiation-induced cavernous hemangioma (RICH). MATERIALS AND METHODS: Among 89 patients who underwent neurosurgery for cavernous hemangioma, eight RICHs from 7 patients and 10 de novo CHs from 10 patients were selected for histopathological and radiological comparison. RESULTS: Histologically, RICHs showed hematoma-like gross appearance. Microscopically, RICH exhibited a hematoma-like area accompanied by proliferation of thin-walled vasculature with fibrin deposits and infiltrating foamy macrophages. In contrast, CHs demonstrated localized malformed vasculature containing fresh and old clotted blood on gross examination. Typically, CHs consisted of thick, ectatic hyalinized vessels lined by endothelium under a light microscope. Magnetic resonance imaging of RICHs revealed some overlapping but distinct features with CHs, including enhancing cystic and solid components with absence or incomplete popcorn-like appearance and partial hemosiderin rims. CONCLUSION: Together with histologic and radiologic findings, RICH may result from blood-filled space after tissue destruction by SRS, accompanied with radiation-induced reactive changes rather than vascular malformation. Thus, the term "RICH" would be inappropriate, because it is more likely to be an inactive organizing hematoma rather than proliferation of malformed vasculature.

Expression of Sarcosine Metabolism-Related Proteins in Invasive Lobular Carcinoma: Comparison to Invasive Ductal Carcinoma

PURPOSE: The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results. MATERIALS AND METHODS: Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)]. RESULTS: The sarcosine metabolic phenotype differed between ILC and IDC (plow sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC. CONCLUSION: Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.

Renal Pelvic Urothelial Carcinoma With Vena Caval Thrombus Mimicking Renal Cell Carcinoma

A 61-year-old man presented with a right renal mass with a vena caval thrombus on computed tomography that was consistent with renal cell carcinoma. The results of routine laboratory examinations and urinalysis were within normal limits. Preoperative planning was critical owing to the presence of the vena caval thrombus. A radical nephrectomy, vena caval thrombectomy, and regional lymphadenectomy were done. The pathologic report was consistent with a high-grade, invasive urothelial carcinoma, with sarcomatoid differentiation involving the renal vein and inferior vena cava (Stage IV, T4N0M0). Thus, this was a rare case of upper tract urothelial carcinoma. Adjuvant chemotherapy with the methotrexate, vinblastine, doxorubicin, cisplatinum regimen is scheduled. To our knowledge, this is the first report in Korea of upper tract urothelial carcinoma of the sarcomatoid type with a vena caval thrombus.

Renal Pelvic Urothelial Carcinoma With Vena Caval Thrombus Mimicking Renal Cell Carcinoma

A 61-year-old man presented with a right renal mass with a vena caval thrombus on computed tomography that was consistent with renal cell carcinoma. The results of routine laboratory examinations and urinalysis were within normal limits. Preoperative planning was critical owing to the presence of the vena caval thrombus. A radical nephrectomy, vena caval thrombectomy, and regional lymphadenectomy were done. The pathologic report was consistent with a high-grade, invasive urothelial carcinoma, with sarcomatoid differentiation involving the renal vein and inferior vena cava (Stage IV, T4N0M0). Thus, this was a rare case of upper tract urothelial carcinoma. Adjuvant chemotherapy with the methotrexate, vinblastine, doxorubicin, cisplatinum regimen is scheduled. To our knowledge, this is the first report in Korea of upper tract urothelial carcinoma of the sarcomatoid type with a vena caval thrombus.

Charlson Comorbidity Index Is an Important Prognostic Factor for Long-Term Survival Outcomes in Korean Men with Prostate Cancer after Radical Prostatectomy

PURPOSE: To analyze overall survival (OS), prostate cancer (PCa)-specific survival (PCaSS), and non-PCaSS according to the Charlson Comorbidity Index (CCI) after radical prostatectomy (RP) for PCa. MATERIALS AND METHODS: Data from 336 patients who had RP for PCa between 1992 and 2005 were analyzed. Data included age, preoperative prostate-specific antigen (PSA), prostate volume, clinical stage, and pathologic stage. Pre-existing comorbidities were evaluated by the CCI, and patients were classified into two CCI score categories (0, > or =1). RESULTS: The mean age of patients was 64.31+/-6.12 years. The median PSA value (interquartile range, IQR) was 11.30 (7.35 and 21.02) ng/mL with a median follow-up period (IQR) of 96.0 (85.0 and 121.0) months. The mean CCI was 0.28 (0-4). Five-year OS, PCaSS, and non-PCaSS were 91.7%, 96.3%, and 95.2%, respectively. Ten-year OS, PCaSS, and non-PCaSS were 81.9%, 92.1%, and 88.9%, respectively. The CCI had a significant influence on OS (p=0.022) and non-PCaSS (p=0.008), but not on PCaSS (p=0.681), by log-rank test. In multivariate Cox regression analysis, OS was independently associated with the CCI [hazard ratio (HR)=1.907, p=0.025] and Gleason score (HR=2.656, p<0.001). PCaSS was independently associated with pathologic N stage (HR=2.857, p=0.031), pathologic T stage (HR=3.775, p=0.041), and Gleason score (HR=4.308, p=0.001). Non-PCaSS had a significant association only with the CCI (HR=2.540, p=0.009). CONCLUSION: The CCI was independently associated with both OS and non-PCaSS after RP, but the CCI had no impact on PCaSS. The comorbidities of a patient should be considered before selecting RP as a curative modality for PCa.

Diagnostic Algorithm to Reflect Regressive Changes of Human Papilloma Virus in Tissue Biopsies

PURPOSE: Landmark indicators have not yet to be developed to detect the regression of cervical intraepithelial neoplasia (CIN). We propose that quantitative viral load and indicative histological criteria can be used to differentiate between atypical squamous cells of undetermined significance (ASCUS) and a CIN of grade 1. MATERIALS AND METHODS: We collected 115 tissue biopsies from women who tested positive for the human papilloma virus (HPV). Nine morphological parameters including nuclear size, perinuclear halo, hyperchromasia, typical koilocyte (TK), abortive koilocyte (AK), bi-/multi-nucleation, keratohyaline granules, inflammation, and dyskeratosis were examined for each case. Correlation analyses, cumulative logistic regression, and binary logistic regression were used to determine optimal cut-off values of HPV copy numbers. The parameters TK, perinuclear halo, multi-nucleation, and nuclear size were significantly correlated quantitatively to HPV copy number. RESULTS: An HPV loading number of 58.9 and AK number of 20 were optimal to discriminate between negative and subtle findings in biopsies. An HPV loading number of 271.49 and AK of 20 were optimal for discriminating between equivocal changes and obvious koilocytosis. CONCLUSION: We propose that a squamous epithelial lesion with AK of >20 and quantitative HPV copy number between 58.9-271.49 represents a new spectrum of subtle pathological findings, characterized by AK in ASCUS. This can be described as a distinct entity and called "regressing koilocytosis".

Meta-Analysis of the Relationship between CXCR4 Expression and Metastasis in Prostate Cancer

PURPOSE: Experimental studies have suggested that the stromal-derived factor-1 (SDF-1)/CXCR4 axis is associated with tumor aggressiveness and metastasis in several malignancies. We performed a meta-analysis to elucidate the relationship between CXCR4 expression and the clinicopathological features of prostate cancer. MATERIALS AND METHODS: Data were collected from studies comparing Gleason score, T stage, and the presence of metastasis with CXCR4 levels in human prostate cancer samples. The studies were pooled, and the odds ratio (OR) of CXCR4 expression for clinical and pathological variables was calculated. RESULTS: Five articles were eligible for the current meta-analysis. We found no relationship between CXCR4 expression and Gleason score ( or =7). The forest plot using the fixed-effects model indicated an OR of 1.585 (95% confidence interval [CI]: 0.793~3.171; p=0.193). Further, CXCR4 expression was not associated with the T stage ( or =T3), and the relevant meta-analysis showed OR=1.803 (95% CI: 0.756~4.297, p=0.183). However, increased CXCR4 expression was strongly associated with metastatic disease with a fixed-effects pooled OR of 7.459 (95% CI: 2.665~20.878, p<0.001). CONCLUSIONS: Our meta-analysis showed that the higher CXCR4 protein expression in prostate cancer specimens is significantly associated with the presence of metastatic disease. This supports previous experimental data supporting the role played by the SDF-1/CXCR4 axis in metastasis.

Human papillomavirus: wearisome or awesome issue? / 부인종양

No abstract available.

High-Grade Hydronephrosis Predicts Poor Outcomes After Radical Cystectomy in Patients with Bladder Cancer

We examined whether the presence and severity of preoperative hydronephrosis have prognostic significance in patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. The medical records of 457 patients who underwent radical cystectomy for bladder cancer between 1986 and 2005 were retrospectively reviewed. Following the Society for Fetal Urology grading system, patients were divided into low-, and high-grade hydronephrosis groups. Clinicopathologic factors associated with preoperative hydronephrosis and survival were evaluated. Of a total of 406 patients, unilateral hydronephrosis was found in 74 (18.2%), bilateral hydronephrosis in 11 (2.7%), and no hydronephoris in 321 (79.1%). Low-grade hydronephrosis was found in 57 (12.2%) patients and high-grade hydronephrosis in 28 (6%). Preoperative hydronephrosis was related to higher pT stage and lymph node invasion. In univariate analysis, the presence of hydronephrosis, hydronephrosis grade, age, pT and pN stage, tumor grade, surgical margin, number of retrieved nodes, carcinoma in situ, and lymphovascular invasion were significant prognostic factors for cancer-specific survival. In multivariate analysis, bilateral hydronephrosis and high-grade hydronephrosis remained significant predictors for decreased survival. The presence of preoperative hydronephrosis, and high-grade hydronephrosis are significant prognostic factors in patients with bladder cancer after radical cystectomy.

Pattern of Failure in Bladder Cancer Patients Treated with Radical Cystectomy: Rationale for Adjuvant Radiotherapy

Thus far, the role of adjuvant radiotherapy (RT) after radical cystectomy (RC) in urinary bladder cancer patients has yet to be defined. The purpose of this study is to analyze patterns of failure, and suggest the rationale for RT. Between 1986 and 2005, a total of 259 patients treated with RC and pelvic lymph node dissection was enrolled. The age range was 27-82 yr (median, 62 yr). Node positivity increased according to tumor staging. Patients were divided into the following two groups based on pathologic analysis: organ-confined disease group (n=135) and extravesical/lymph node-positive disease group (n=80). Pelvic failures (PF) were observed in 8 (4.9%) in organ-confined disease group, and 21 (21.7%) in extravesical/lymph node-positive disease group. Five-year PF-free survival rates were 91.2% in organ-confined disease group and 68.0% in extravesical/lymph node-positive disease group. Five-year cancer-specific survival rates were 86.2% in organ-confined disease group and 53.9% in extravesical/lymph node-positive disease group. In conclusion, a relatively high PF rate was observed in extravesical lymph node-negative and lymph node-positive disease patients in this study. Adjuvant pelvic RT may be considered to reduce pelvic failures in extravesical lymph node-positive bladder cancer. Future prospective trials are required to test the clinical benefit of adjuvant RT.

Clinical Significance of Lymph Node Dissection in Patients with Muscle-Invasive Upper Urinary Tract Transitional Cell Carcinoma Treated with Nephroureterectomy

We investigated the value of lymph node dissection in patients with cN0 muscle-invasive transitional cell carcinoma of the upper urinary tract (UUT-TCC). Medical records of 152 patients with cN0 muscle-invasive UUT-TCC, who underwent nephroureterectomy between 1986 and 2005, were reviewed. Sixty-three patients (41.4%) underwent lymph node dissection. The median number of lymph nodes harvested was 6 (range, 1 to 35), and from these, lymph node involvement was confirmed in 9 patients (14.3%). Locoregional recurrence (LR) and disease-recurrence (DR) occurred in 29 patients and 63 patients, respectively. Fifty-five patients (36.2%) had died of cancer at the last follow-up. The number of lymph nodes harvested was associated with the reduction of LR (chi-square(trend)=6.755, P=0.009), but was not associated with DR (chi-square(trend)=1.558, P=0.212). In the survival analysis, N stage (P=0.0251) and lymph node dissection (P=0.0073) had significant influence on LR, but not on DR or disease-specific survival. However, the number of lymph nodes harvested did not affect LR-free, DR-free, or disease-specific survival. We conclude that lymph node dissection may improve the control of locoregional cancer, as well as staging accuracy, in cN0 muscle-invasive UUT-TCC, but that it does not clearly influence survival.