Invasive Transitional Cell Carcinoma Research Articles

Robot-assisted Intracorporeal Ileal Conduit: Marionette Technique and Initial Experience at Roswell Park Cancer Institute

To present our technique and initial experience with patients who underwent robot-assisted intracorporeal creation of ileal conduit and to compare them with patients who underwent extracorporeal ileal diversion after robot-assisted radical cystectomy. Twenty-six patients diagnosed with invasive transitional cell carcinoma of the bladder underwent a robot-assisted radical cystectomy with bilateral extended pelvic lymphadenectomy with ileal conduit diversion. Total intracorporeal ileal conduit creation was performed in the last 13 patients. Operative data and short-term outcomes between the 2 groups were assessed. The novel surgical technique for intracorporeal ileal conduit will be presented. The intracorporeal group (IC) included 2 female and 11 male patients (mean age 71 years). The extracorporeal group (EC) included 4 female and 9 male patients (mean age 66 years). No significant differences were noted between the groups in terms of patient age, BMI, sex, prior surgery, or pathologic stage. Overall operative time and intraoperative complications were similar. No significant differences were noted between the 2 groups in terms of diversion time or estimated blood loss. There were 4 complications recorded in IC patients, including nonspecific colitis, small bowel obstruction requiring exploratory laparotomy with lysis of adhesions, a urine leak that eventually resolved but required a temporary nephrostomy tube, and a fever of unknown origin that resolved without intervention. Robot-assisted intracorporeal ileal conduit can be accomplished safely with acceptable operative times even during early experience. Larger series with favorable results will be required to add this new paradigm to minimally invasive surgery for bladder cancer.

Effects of Short-term Celecoxib Treatment in Patients with Invasive Transitional Cell Carcinoma of the Urinary Bladder

High-grade invasive transitional cell carcinoma (InvTCC) kills >14,000 people yearly in the United States, and better therapy is needed. Cyclooxygenase-2 (Cox-2) is overexpressed in bladder cancer. Cox inhibitors have caused remission of InvTCC in animal studies, and cancer regression was associated with doubling of the apoptotic index in the tumor. The purpose of this study was to determine the apoptosis-inducing effects of celecoxib (a Cox-2 inhibitor) in InvTCC in humans. Patients (minimum of 10 with paired tumor samples) with InvTCC who had elected to undergo cystectomy were enrolled. The main study end point was induction of apoptosis in tumor tissues. Patients received celecoxib (400 mg twice daily p.o. for a minimum of 14 days) between the time of diagnosis [transurethral resection of bladder tumor (TURBT)] and the time of cystectomy (standard frontline treatment for InvTCC). Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay and immunohistochemistry were done on TURBT and cystectomy samples. Of 13 cases treated with celecoxib, no residual invasive cancer was identified in 3 patients at the time of cystectomy (post celecoxib). Of the 10 patients with residual cancer, 7 had induction of apoptosis in their tumor. Induction of apoptosis was less frequent (3 of 13 cases; P < 0.04) in control patients not receiving a Cox inhibitor. Expression of vascular endothelial growth factor in the tumor cells decreased more frequently (P < 0.026) in the treated patients as compared with nontreated control cases. The biological effects of celecoxib treatment (increased apoptosis) justify further study of the antitumor effects of Cox-2 inhibitors in InvTCC.

Potential of molecular targeted therapy of HER-2 and Cox-2 for invasive transitional cell carcinoma of the urinary bladder

Expression of HER-2 and COX-2 was determined to assess the potential of molecular-targeted therapy against human epidermal growth factor receptor-2 (HER-2) and cyclooxygenase-2 (COX-2) for the treatment of invasive bladder cancer. The subjects were 46 patients who attended Aichi Medical University Hospital between January 2001 and August 2008, underwent total cystectomy with a diagnosis of M0 bladder cancer, and received a pathological diagnosis of invasive transitional cell carcinoma of the urinary bladder (pT2-pT4). Expression of HER-2 and COX-2 was determined by immunohistochemical staining, and the results were interpreted by two pathologists by classifying HER-2 expression into four grades, and considering COX-2 positive when 10% or more of the tumor cells were stained. In HER-2 immunostaining, 10 subjects (21.7%) were positive, all of whom had a Grade 3 tumor. Staging classification identified 2 subjects (2/22, 9.1%) with pT2 stage, 3 (3/16, 18.8%) pT3 stage, and 5 (5/8, 62.5%) pT4 stage. There was a correlation between HER-2 positivity and tumor stage (P=0.007). Lymph node metastasis was detected in 13 subjects, 3 of them (3/8, 37.5%) with pN2 metastasis were HER-2 positive. The 5-year cause-specific survival rate was 51.4% for HER-2-positive subjects and 83.4% for HER-2-negative subjects. The outcome was poorer in HER-2-positive subjects, but the difference in survival rate was not statistically significant (P=0.218). In COX-2 immunostaining, 27 subjects (58.7%) were found to be positive. Three (3/4, 75.0%) showed a Grade 2 tumor and 24 (24/42, 57.1%) a Grade 3 tumor. Staging classification identified 13 subjects (13/22, 59.1%) with pT2 stage, 9 (9/16, 56.3%) pT3 stage, and 5 (5/8, 62.5%) pT4 stage. There was no correlation between COX-2 positivity and tumor grade or stage (P=0.488 and 0.089, respectively). Classification by the extent of lymph node metastasis revealed that 6 subjects (6/8, 75.0%) with pN2 were COX-2 positive. There was a correlation between COX-2 positivity and the extent (pN1 or pN2) of lymph node metastasis (P=0.008). The 5-year cause-specific survival rate was 84.0% for COX-2-positive subjects and 71.7% for COX-2-negative subjects. However, the difference in survival rate was not significant (P=0.407). Seven subjects (7/46, 15.2%) were positive for both HER-2 and COX-2, and there was no statistically significant correlation between the status of HER-2 expression and that of COX-2 expression (P=0.2195). The present study failed to show any association between HER-2 or COX-2 positivity and outcome in subjects with invasive bladder cancer. However, HER-2-positive subjects tended to have a poorer outcome. This finding suggests that molecular-targeted therapy against HER-2 could be an effective therapy. Further studies involving a larger number of subjects are required.

Loss of Heterozygosis on IFN-α Locus is a Prognostic Indicator of Bacillus Calmette-Guerin Response for Nonmuscle Invasive Bladder Cancer

We evaluated the role of loss of heterozygosity on the interferon-alpha locus to predict the response to bacillus Calmette-Guerin therapy in patients with nonmuscle invasive bladder cancer. A total of 117 consecutive patients were selected, including 77 with nonmuscle invasive bladder cancer and 40 controls. Loss of heterozygosity on the interferon-alpha locus (chromosome 9p21) was assessed in blood and urine samples before transurethral resection. All patients underwent transurethral resection and then 6 weekly bacillus Calmette-Guerin instillations. Those with nonmuscle invasive bladder cancer were assigned to groups 1 and 2 with and without loss of heterozygosity on the interferon-alpha locus, respectively. Of the 77 patients with nonmuscle invasive bladder cancer 39 (50.6%) had loss of heterozygosity on the interferon-alpha locus (group 1) and 38 (49.4%) had no alteration (group 2). Only 1 of 40 controls showed loss of heterozygosity on the interferon-alpha locus. At the end of followup 13 patients in group 1 and 27 in group 2 were alive without recurrence. We noted a significant difference between loss of heterozygosity on interferon-alpha and followup status (dF 01, LR 11.252, p = 0.003). Kaplan-Meier analysis revealed a significant difference in recurrence probability (response to bacillus Calmette-Guerin) and loss of heterozygosity on interferon-alpha (p <0.0001). On multivariate analysis loss of heterozygosity (HR 4.09, 95% CI 2.59-6.28, p = 0.002), grade (grade 3 HR 3.31, 95% CI 1.38-3.35, p = 0.03) and the number of lesions (3 or greater HR 2.31, 95% CI 1.38-3.25, p = 0.03) were independent predictors of the bacillus Calmette-Guerin response. This study highlights the predictive value of loss of heterozygosity analysis on interferon-alpha in patients with nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin.

Loss of 15-Hydroxyprostaglandin Dehydrogenase Expression Contributes to Bladder Cancer Progression

Prostaglandin E2, which is known to contribute to cancer progression, is inactivated by the catabolic enzyme, 15-hydroxyprostaglandin dehydrogenase (PGDH), which has tumor-suppressor activity in lung, colon, breast, and gastric cancers. Therefore, we evaluated the expression of PGDH in human bladder cancer tissue specimens and cell lines. Immunoperoxidase staining of bladder cancer tissues demonstrated that (1) PGDH is highly expressed by normal urothelial cells but (2) reduced in many low stage (Ta/Tis) bladder cancers, and (3) PGDH is completely lost in most invasive bladder cancers. Of eight cancer cell lines tested, only two relatively well-differentiated bladder cancer cell lines, RT4 and UM-UC9, expressed PGDH. Moreover, inhibition of PGDH expression in well-differentiated RT4 cells using small inhibitory RNA or short hairpin RNA resulted in a more aggressive phenotype with increased motility and anchorage-independent growth. Additionally, PGDH knockdown affected prostaglandin E2 signaling as measured by cAMP generation. These data indicate that loss of PGDH expression contributes to a more malignant bladder cancer phenotype and may be necessary for bladder cancer development and/or progression.

Primary transitional cell carcinoma of the prostate: a male disease with dismal prognosis despite cisplatin-based systemic chemotherapy

Background Primary urothelial carcinoma of the prostate is an infrequent male malignancy with a dismal prognosis, that originates in the periurethral prostatic gland. This neoplasia is considered, in general terms, to be chemosensitive but prospective trials regarding therapy and prognosis are lacking, due to the infrequent nature of this entity. This paper is a case series regarding the accumulated experience in our institution with the use of cisplatin-based chemotherapeutic regimens in these patients. Methods The clinico-pathological findings of a series of 12 patients with primary urothelial carcinoma of the prostate diagnosed and treated over a 10 year period are reviewed, with an emphasis on therapy and evolution. Results No patient in the series reached long-term survival. Mean time to death was 24.1 months (range 5–48 months). The combination of local treatment plus cisplatin-based systemic chemotherapy did not achieve satisfactory results. However, patients treated with radical surgery (cystectomy or prostatectomy) and at least 3 cycles of multiple chemotherapy behaved better than the rest. Radical surgery achieved better local control than radiotherapy, but repeated transurethral resection of the prostate plus systemic chemotherapy may also provide local control in selected patients. Conclusion Despite combined therapeutic efforts that pursued both local control and the prevention of a systemic relapse, the prognosis of advanced primary prostatic urothelial carcinoma remains dismal. Early diagnosis appears difficult because clinical presentation differs to that of males with adenocarcinoma of the prostate or invasive transitional cell carcinoma (TCC) of the bladder. Cisplatin-based systemic chemotherapy does not allow prolonged survival.

Abstract A48: In vivo evaluation of Cox-2 inhibition to prevent the progression of invasive urinary bladder cancer

Abstract Background: Invasive transitional cell carcinoma (InvTCC) of the urinary bladder has a propensity to metastasize, is only partially responsive to chemotherapy, and causes &amp;gt; 14,000 deaths yearly in the United States. The development of effective means to prevent the development and progression of InvTCC is crucial. Cyclooxygenase-2 (Cox-2) is over-expressed in InvTCC in humans and animals. In a pilot study, a Cox-2 inhibitor induced apoptosis of InvTCC in humans. Cox-2 inhibitors may offer an avenue for prevention of InvTCC progression. The purpose of this study was to determine the effects of Cox-2 inhibitor treatment in preventing the progression of InvTCC in a highly relevant animal model, canine InvTCC. Naturally-occurring InvTCC in dogs closely mimics human InvTCC in cellular and molecular features (including Cox-2 expression), sites and frequency of metastasis, and response to therapy. Methods: Dogs with histologically confirmed InvTCC who failed or whose owner declined standard chemotherapy protocols, and with expected survival of &amp;gt; 6 weeks were prospectively enrolled. The Cox-2 inhibitor deracoxib (Novartis, Greensboro, NC) was given as a single agent with a planned dose of 3mg/kg/day orally. Dogs were evaluated prior to and during therapy with abdominal ultrasound including mapping of the urinary bladder masses, thoracic radiographs, complete blood count, serum biochemistry profiles and urinalyses. Toxicity was assessed by clinical signs and serial blood work. Tumor response was defined as: complete remission (CR), no evidence of disease detected; partial remission (PR) ≥ 50% reduction in tumor volume; stable disease (SD) &amp;lt;50% change in tumor volume; or progressive disease (PD) ≥ 50% increase in tumor volume or new lesions. A whole blood assay was used to confirm selective Cox-2 inhibition. Results: Thirty-nine dogs with InvTCC received deracoxib at a mean dose of 2.79 mg/kg/day (range 1.18 mg/kg/day to 4.08mg/kg/day). Of 39 dogs, 1 had nodal metastasis, and 3 had distant metastasis at diagnosis. Initial responses in 30 dogs with measurable disease included PR in 4 dogs (13%), SD in 17 dogs (57%), and PD in 3 dogs (10%); and in 6 dogs, response to therapy has not been determined. Mean time to subsequent PD (n=20) was 167 days (range 36 – 482 days). After PD was noted, 10 dogs went on to receive other therapy (leukeran, mitoxantrone, mitomycin-C, 5 azacitidine, carboplatin). Of the 39 dogs treated, 9 had microscopic residual disease after surgical intervention. Of these 9 dogs, 4 had relapse (median time to relapse, 221 days), and 3 had not relapsed at the time of death from other causes (median time to death 772 days). The median survival times for dogs with measurable disease and microscopic disease were 349 and 772 days, respectively. Conclusion: The results of this work help justify further study of the use of Cox-2 inhibitors in preventing the progression of InvTCC. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A48.

Superficially invasive transitional cell carcinoma of the bladder associated with distant cutaneous metastases

Cutaneous metastases from transitional cell carcinoma of the bladder are rare and most often associated with a deeply invasive primary tumor. This case report describes a 69-year-old male with previously resected superficially invasive primary transitional cell carcinoma of the bladder who presented with distant cutaneous and central nervous system metastases associated with recurrent bladder cancer. In addition, this case highlights the differential diagnosis of metastatic carcinomas that display a CK7/CK20 positive immunophenotype including transitional cell carcinoma, pancreatic carcinoma, cholangiocarcinoma and rare gastric carcinomas.

Lymphoepithelioma-like carcinoma of the urinary bladder: report of a rare case

Lymphoepithelioma-like carcinoma (LELC) is a rare malignant neoplasm in the urinary bladder, which can histologically mimic lymphoma, poorly differentiated invasive transitional cell carcinoma or poorly differentiated squamous cell carcinoma with a lymphoplasmacytic background. A urinary bladder tumor was identified in a 65-year-old man suffering from hematuria for several weeks. Transurethral biopsy revealed an undifferentiated tumor with prominent lymphocytes and plasma cell infiltration. Immunohistochemical evaluation showed positive staining for cytokeratin and epithelial membrane antigen. Subsequent radical cystectomy showed pure LELC. We present the case to highlight the significance of recognizing this unusual bladder tumor and discuss the important differential diagnosis, treatment options and prognosis.

Genoproteomic Mining of Urothelial Cancer Suggests γ-Glutamyl Hydrolase and Diazepam-Binding Inhibitor as Putative Urinary Markers of Outcome after Chemotherapy

Urinary biomarkers for the detection of bladder cancer have been developed, but no similar markers exist for prediction of clinical outcomes after receiving chemotherapy. Here we evaluate an approach that combines genomic, proteomic, and therapeutic outcome datasets to identify novel putative urinary biomarkers of clinical outcome after neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). Using this method, we identified gamma-glutamyl hydrolase (GGH), emmprin, survivin, and diazepam-binding inhibitor (DBI). Interestingly, GGH is a protein associated with methotrexate resistance, whereas emmprin, survivin, and DBI had been previously identified as predictors of outcome after platinum-containing chemotherapeutic regimens when assessed on tumor tissue. Using disease-free survival as a marker for clinical outcome, we evaluated the ability of GGH, emmprin, survivin, and DBI expression in tumor tissue to stratify 27 patients treated with neoadjuvant MVAC. DBI (P = 0.046) but not GGH (P = 0.190), emmprin (P = 0.066), or survivin (P = 0.393) successfully stratified patients. When GGH was used with DBI the significance of stratification improved (P = 0.024), whereas the addition of survivin or emmprin to this latter two-gene model reduced its significance (P = 0.036 and P = 0.040, respectively). Although these predictive results were obtained on tumor tissues, the presence of GGH and DBI in urine serves as a rationale for developing them as urinary markers of clinical outcomes for patients treated with neoadjuvant MVAC.

Lipid profiles of canine invasive transitional cell carcinoma of the urinary bladder and adjacent normal tissue by desorption electrospray ionization imaging mass spectrometry.

Desorption electrospray ionization mass spectrometry (DESI-MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of canine spontaneous invasive transitional cell carcinoma of the urinary bladder (a model of human invasive bladder cancer) as well as adjacent normal tissue from four different dogs. The glycerophospholipids and sphingolipids that appear as intense signals in both the negative ion and positive ion modes were identified by tandem mass spectrometry product ion scans using collision-induced dissociation. Differences in the relative distributions of the lipid species were present between the tumor and adjacent normal tissue in both the negative and positive ion modes. DESI-MS images showing the spatial distributions of particular glycerophospholipids, sphinoglipids, and free fatty acids in both the negative and positive ion modes were compared to serial tissue sections that were stained with hematoxylin and eosin (H&E). Increased absolute and relative intensities for at least five different glycerophospholipids and three free fatty acids in the negative ion mode and at least four different lipid species in the positive ion mode were seen in the tumor region of the samples in all four dogs. In addition, one sphingolipid species exhibited increased signal intensity in the positive ion mode in normal tissue relative to the diseased tissue. Principal component analysis was also used to generate unsupervised statistical images from the negative ion mode data, and these images are in excellent agreement with the DESI images obtained from the selected ions and also the H&E-stained tissue.

Clusterin as a Diagnostic and Prognostic Marker for Transitional Cell Carcinoma of the Bladder

We investigated the feasibility of profiling and measuring the concentration of clusterin in urine and serum for individuals with transitional cell carcinoma (TCC) of the bladder and comparing it with nontumor controls. In addition, we analyzed the correlation of expression of clusterin in specimens of TCC to various clinicopathologic parameters and prognosis of bladder cancer. Blood and urine samples were used from 68 patients with TCC of the bladder and from 61 patients with benign urological diseases. Enzyme-linked immunosorbent assays (ELISA) were performed for clusterin from serum and urine. Quantitation of clusterin mRNA was carried out in 68 bladder tumor specimens from radical cystectomy or transurethral resection and 26 normal bladder specimens from BPH patients by using RT-PCR method. Correlation for the expression of clusterin mRNA with clinicopathologic parameters was analyzed. Serum and urine clusterin was significantly higher in individuals with bladder cancer than control (p = 0.001). Sensitivity and specificity of serum and urine clusterin as a tumor marker for TCC of the bladder was found to be 80%, 91%, 87.1% and 96.7% respectively. Clusterin expression was significantly higher in TCC specimens than normal tissue specimens (P < 0.001). Expression of clusterin was significantly higher in patients with invasive TCC of the bladder than that in patients with superficial TCC and control (P < 0.001). Overexpression of clusterin mRNA was significantly associated with tumor recurrence and overall survival (p < 0.001). The recurrence-free survival time of patients with overexpression of clusterin was significantly shorter than that of patients with weak expression of clusterin (9.8 months vs. 35.2 months). Clusterin may be considered as a potential diagnostic and prognostic biomarker for bladder cancer using urine, serum and/or molecular biology techniques.

Adjuvant Chemotherapy for High Risk Upper Tract Urothelial Carcinoma: Results From the Upper Tract Urothelial Carcinoma Collaboration

There is relatively little literature on adjuvant chemotherapy after radical nephroureterectomy in patients with upper tract urothelial carcinoma. We determined the incidence of adjuvant chemotherapy in high risk patients and the ensuing effect on overall and cancer specific survival. Using an international collaborative database we identified 1,390 patients who underwent nephroureterectomy for nonmetastatic upper tract urothelial carcinoma between 1992 and 2006. Of these cases 542 (39%) were classified as high risk (pT3N0, pT4N0 and/or lymph node positive). These patients were divided into 2 groups, including those who did and did not receive adjuvant chemotherapy, and stratified by gender, age group, performance status, and tumor grade and stage. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall and cancer specific survival in the cohorts. Of high risk patients 121 (22%) received adjuvant chemotherapy. Adjuvant chemotherapy was more commonly administered in the context of increased tumor grade and stage (p <0.001). Median survival in the entire cohort was 24 months (range 0 to 231). There was no significant difference in overall or cancer specific survival between patients who did and did not receive adjuvant chemotherapy. However, age, performance status, and tumor grade and stage were significant predictors of overall and cancer specific survival. Adjuvant chemotherapy is infrequently used to treat high risk upper tract urothelial carcinoma after nephroureterectomy. Despite this finding it appears that adjuvant chemotherapy confers minimal impact on overall or cancer specific survival in this group.

Correlation of RRM1 expression in muscle invasive locally advanced urothelial cancer with age

e16021 Background: RRM1, the regulatory subunit of ribonucleotide reductase, plays a role in DNA repair after chemotherapy damage and in gemcitabine metabolism. Prior studies demonstrated a survival benefit to high expression in resected early stage lung cancer and a trend toward longer time to progression with low expression in advanced bladder cancers treated with gemcitabine and cisplatin. We hypothesized that patients with resected locally advanced (T2–4NxM0) urothelial transitional cell carcinoma (TCC) whose tumors had higher RRM1 expression would have longer overall survival (OS). Methods: 84 radical cystectomy specimens with muscle invasive TCC were identified from existing tissue microarrays (TMAs) containing 343 specimens. The medical records of these patients were retrospectively reviewed to confirm pathology and stage. Presence of muscle invasion was required. Specimens were analyzed for RRM1 expression using AQUA. The median value of RRM1 was established a priori as the cutoff for high and low expression. Results: Median age of the patients was 69.3 years. There was near equal distribution of stages: 30%, 38%, and 32% for stage II, III, and IV respectively. The majority were high grade (99%) with no nodal involvement (69%). Median OS was 2.0 years (0–13.1). Median RRM1 expression was 1493.3. Degree of RRM1 expression did not correlate with OS, but when adjusted for age, adding an interaction term, high RRM1 expression in younger patients correlated with increased OS (p = 0.0278). Median OS for high expressors age &lt;69.3 years was 6 years compared to 2.3 years for low expressors. 35% of patients less than 70 years were high expressors. Conclusions: Our results suggest that high RRM1 expression may be a prognostic factor for improved survival in locally advanced TCC patients less than 70 years old. These results deserve further study in a larger prospective analysis with disease-specific survival assessment and correlation with other possible prognostic genes such as ERCC1. [Table: see text]

Plasmacytoid urothelial carcinoma of the bladder: a case report.

Plasmacytoid bladder cancer is a rare variant of transitional cell carcinoma. A 57-year-old man was referred to our institution for management of invasive transitional cell carcinoma diagnosed at a peripheral hospital. His complaints were of vague lower abdominal pain with associated urgency and frequency requiring oxybutynin. Metastatic workup was negative and was subsequently scheduled for a radical cystectomy. Routine colonoscopy 3 weeks prior to surgery was negative. Intraoperatively, he was found to have metastatic urothelial cancer involving the cecum and multiple metastatic deposits within the mesentery of the small intestines. He underwent a palliative cystectomy with ileal conduit formation. Final pathology revealed metastatic plasmacytoid variant of urothelial cancer. Histology and immunohistochemistry were compatible with plasmacytoid variant of urothelial cancer. Here we present our case of this rare variant of urothelial cancer with a review of its characteristics.

Plasmacytoid urothelial carcinoma of the bladder: a case report

Plasmacytoid bladder cancer is a rare variant of transitional cell carcinoma. A 57-year-old man was referred to our institution for management of invasive transitional cell carcinoma diagnosed at a peripheral hospital. His complaints were of vague lower abdominal pain with associated urgency and frequency requiring oxybutynin. Metastatic workup was negative and was subsequently scheduled for a radical cystectomy. Routine colonoscopy 3 weeks prior to surgery was negative. Intraoperatively, he was found to have metastatic urothelial cancer involving the cecum and multiple metastatic deposits within the mesentery of the small intestines. He underwent a palliative cystectomy with ileal conduit formation. Final pathology revealed metastatic plasmacytoid variant of urothelial cancer. Histology and immunohistochemistry were compatible with plasmacytoid variant of urothelial cancer. Here we present our case of this rare variant of urothelial cancer with a review of its characteristics.

Integrated Treatment with Hyperthermia and Chemotherapy for Non-Muscle Invasive Bladder Cancer

Oncology-applied hyperthermia is a very old form of therapy. In recent years hyperthermia has been investigated with the aim of improving the treatment for non-muscle invasive bladder cancer to prevent relapse and disease progression, in association with mitomycin-C, a well-known chemotherapeutic agent, to enhance its effect. Target patients are those with non-muscle invasive transitional cell carcinoma, showing medium (Ta-T1, G1–2, multifocal, diameter &gt;3 cm) or high (T1, G3, multifocal or rapidly relapsing, CIS) risk for recurrence or progression. The treatment may be prophylactic following tumor eradication, or ablative when tumor cannot be otherwise eradicated. Several studies have shown the benefits of thermochemotherapy with lower risk for relapse than other treatment options, and 66–80% complete responses following ablative treatment. This association of treatments has a synergic therapeutic effect, higher than administering hyperthermia and drug therapy as single treatment.

Tumor markers of bladder cancer: the schistosomal bladder tumors versus non-schistosomal bladder tumors

BackgroundThe aim of this study is to comparatively elucidate the underlying molecular pathways and clinicopathological criteria in schistosomal bladder tumor (SBT) versus non-schistosomal bladder tumor (NSBT).MethodsThis study explored the role of p53, p16, bcl-2, ki-67, c-myc, Rb and EGFR, by using Immunohistochemistry assay, in 45 SBT and 39 NSBT patients in comparison with 16 schistosomal chronic cystitis (SC), 28 non-schistosomal chronic cystitis (NSC), and 20 normal control (CTL) subjects. The studied markers in SBT and NSBT were correlated with different clinicopathological criteria namely, tumor histopathology, grading, invasiveness, stage, and presentation of the disease.ResultsSBT was associated with high grade invasive squamous cell carcinoma (SCC) while NSBT was associated with lower grade less invasive transitional cell carcinoma (TCC). The expression of p53, bcl-2, c-myc, and EGFR was higher in SBT than in NSBT while Rb was higher in NSBT than in SBT. However, p16 and ki-67 were not different between SBT and NSBT. The profile of molecular markers in SC was similar to NSC except for EGFR which was higher in SC than in NSC. Both SC and NSC showed higher level of p53, bcl-2, ki-67, and EGFR than in CTL group while p16, Rb, and c-myc were not different. p53 was associated with high grade SCC in both SBT and NSBT. Bcl-2 was associated with high grade invasive tumors in SBT and NSBT. P16 was associated with low grade, late stage, and recurrent SBT and high grade, invasive, late stage, and recurrent NSBT. Rb was associated with SCC in SBT, invasive tumors in NSBT, and late stage and recurrent presentation in both SBT and NSBT. C-myc was associated with high grade, invasive, and late stage SBT and SCC, high grade, invasive, and late stage NSBT. EGFR was associated with invasive SCC in SBT and invasive, high grade, and late stage TCC in NSBT. ki-67 was associated with invasive SBT and high grade late stage NSBT.ConclusionSBT and NSBT showed distinct molecular profile of tumor development and progression which can be taken into consideration in fine adjusting the anti-cancer therapy for SBT and NSBT.

Robot-Assisted Laparoscopic Distal Ureterectomy and Ureteral Reimplantation

Sung Gu Kang, Hoon Choi, Young Hwii Ko, Bum Sik Tae, Seok Cho, Hong Jae Ahn, Ji Yun Chae, Seok Ho Kang, Jun Cheon From the Department of Urology, Korea University School of Medicine, Seoul, Korea We report here on our technique and outcomes of the first case of robot-assisted laparoscopic distal ureterectomy with a bladder cuff excision and ureteroneocystostomy. A 74-year-old male patient who had a distal ureter tumor underwent robot-assisted transperitoneal distal ureterectomy. After distal ureterectomy with bladder cuff excision was performed, direct ureteroneocystostomy was performed. The whole procedure was successfully performed by using the robot without conversion to open surgery. The total operative time was 207 minutes, and the estimated blood loss was 30 ml. The final pathological examination showed stage T2 invasive transitional cell carcinoma of the distal ureter. The patient's postoperative recovery was uneventful and the bladder cuff was free of tumor. Robot-assisted laparoscopic distal ureterectomy with ureteroneocystostomy is safe and feasible and offers patients the advantages of minimally invasive surgery. (Korean J Urol 2009;50:921-924) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Elective endoscopic management of transitional cell carcinoma first diagnosed in the upper urinary tract

To report our experience using ureteroscopic or percutaneous management of upper urinary tract (UUT) transitional cell carcinoma (TCC) in patients with no history of bladder TCC. Between 1983 and 2004 we identified 22 patients who underwent endoscopic management of TCC first diagnosed in the UUT and in the setting of a normal contralateral kidney. We performed a retrospective chart review and conducted outcome analyses. The median (range) age at diagnosis was 64 (37-86) years and the median tumour size was 0.8 (0.3-2.6) cm. The tumour grade was 1, 2, or diagnosed as visual low grade in two (9%), seven (32%), and 13 (59%) patients, respectively; no patient had grade 3 TCC at diagnosis. Tumour stage was Ta or visual Ta in all patients. The median follow-up was 4.9 (0.4-17) years during which 11 (50%) patients developed 21 UUT recurrences and 10 (45%) patients developed bladder TCC. At last follow-up, seven (32%) patients required a nephroureterectomy for recurrent TCC and two (9%) patients died from TCC. Among 13 patients with a diagnosis based on visual inspection only, three recurred with grade 3 invasive TCC during follow-up. No patient with pathological confirmation of low-grade/stage TCC recurred with high-grade or invasive TCC. Recurrence is common after endoscopic management of UUT-TCC, underscoring the need for strict surveillance. Patients diagnosed visually, without adequate tissue for pathological examination, can recur with high-grade invasive TCC. No patient with pathological confirmation of low-grade TCC developed progressive disease during follow-up.