Non-transitional Cell Carcinoma Research Articles

Uncovering the Uncommon: Institutional Insights Into the Clinical and Epidemiological Characteristics of Rarer Forms of Bladder Cancer Beyond Transitional Cell Carcinoma.

Introduction Non-transitional cell carcinomas of the bladder (NTCCB) represent a significant clinical challenge due to their rarity, heterogeneity, and poor prognosis. Despite their poor prognosis, the treatment of NTCCB has historically been based on the same principles used for transitional cell carcinomas (TCCs). Our study focuses on the management of non-transitional cell carcinomas and aims to identify areas where treatment outcomes can be improved based on our institutional experience. Materials and methods A retrospective analysis of patients with NTCCB who presented at Kasturba Hospital Manipalwas conducted between 2012 to 2021. Patient data were collected, and demographic characteristics, presenting symptoms, history of other primary malignancies, comorbidities, location of the tumour, stage at presentation, histopathological subtype, site of systemic metastasis, and primary treatment given were analyzed descriptively. Median overall survival was determined by calculating the time from the initial diagnosis to the date of death. Results Among 31 patients with NTCCB, 15 (48%) presented with metastatic disease, five (16%) with locally advanced disease, and 11 (36%) with localized disease. The most common histopathological subtypes were squamous cell carcinoma and adenocarcinoma, as noted in 14 (45.2%) and 13 (41.9%) patients, respectively, followed by neuroendocrine tumours in two (6.5%), extra-adrenal phaeochromocytoma in one (3.3%), and sarcomatoid carcinoma in one (3.3%) patient, respectively. The lung was the most frequent site of systemic metastasis as noted in six (40%) patients, followed by the liver and skeletal system in three (20%) patients each, peritoneum in two (13.3%), cerebral cortex in one (6.7%), and non-regional lymph nodes in one (6.7%) patient. The primary treatment given included palliative chemotherapy in 14 (45.2%) patients, radical cystectomy with ileal conduit in 10 (32.3%), neoadjuvant chemotherapy only in four (12.9%), partial cystectomy in one (3.2%), pelvic exenteration with ileal conduit in one (3.2%), and peritoneal debulking with palliative chemotherapy in one (3.2%) patient. The overall median survival was 15 months, with a one-year survival rate of 67.4%. Conclusion NTCCB exhibits aggressive clinical behaviour and presents with nonspecific clinical features in the early stages, often leading to late diagnosis and an advanced tumour stage at presentation. Multi-institutional studies with larger patient cohorts are needed to recommend best clinical practices for early detection and optimal treatment strategies to improve patient survival.

Cox Regression Analysis of Prognostic Factors of Intensity-Modulated Radiotherapy in Patients with Bladder Cancer.

This paper aims to explore the prognostic factors of intensity-modulated radiotherapy (IMRT) in patients with bladder cancer by Cox regression analysis and to provide evidence for prolonging the survival of patients and improving the treatment status. A total of 153 cases of patients with bladder cancer who received IMRT were selected as research objects, and their clinical data were retrospectively analyzed and followed up. Kaplan-Meier survival analysis was conducted to calculate the median survival period, univariate and multivariate Cox regression were used to analyze the prognostic factors of IMRT in patients with bladder cancer, and receiver operating characteristic curve was adopted to evaluate the prediction efficiency of influencing factors. Patients were followed up for 9-40 months, and 55 patients died by the end of the follow-up. The median survival time was 30 months, and the 3-year survival rate was 64.05% (98/153). Univariate analysis showed that T stage, total cystectomy, lymph node, pathological type and hydronephrosis influenced the prognosis of IMRT for patients with bladder cancer (p < 0.05). Multivariate Cox regression analysis showed T3 stage (odds ratio (OR) = 0.149, 0.068-0.327), T4 stage (OR = 27.639, 3.677-207.758), lymph node presence (OR = 0.152, 0.050-0.467), pathological type (OR = 0.086, 0.025-0.296) and hydronephrosis (OR = 7.402, 1.161-47.192) were independent factors affecting the prognosis of IMRT in patients with bladder cancer (p < 0.05), while total cystectomy (OR = 1.037, 0.171-6.301) was not an independent factor affecting the prognosis of IMRT in patients with bladder cancer (p > 0.05). T stage, lymph nodes, nontransitional cell carcinoma with pathological type and hydronephrosis can influence the prognostic effect of IMRT in patients with bladder cancer.

Risk for Arterial Thromboembolic Events (ATEs) in Patients with Advanced Urinary Tract Cancer (aUTC) Treated with First-Line Chemotherapy: Single-Center, Observational Study.

Arterial thromboembolism has been associated with cancer or its treatment. Unlike venous thromboembolism, the incidence and risk factors have not been extensively studied. Here, we investigated the incidence of arterial thromboembolic events (ATEs) in an institutional series of advanced urinary tract cancer (aUTC) treated with cytotoxic chemotherapy. The ATE definition included peripheral arterial embolism/thrombosis, ischemic stroke and coronary events. A total of 354 aUTC patients were analyzed. Most patients (95.2%) received platinum-based chemotherapy. A total of 12 patients (3.4%) suffered an ATE within a median time of 3.6 months from the start of chemotherapy. The most frequent ATE was ischemic stroke (n = 7). Two ATEs were fatal. The 6-month and 24-month incidence were 2.1% (95% confidence interval [CI]: 0.9–4.1) and 3.6% (95% CI: 1.9–6.2), respectively. Perioperative chemotherapy increased the risk for ATE by 5.55-fold. Tumors other than UTC and pure non-transitional cell carcinoma histology were also independent risk factors. No association with the type of chemotherapy was found. Overall, ATEs occur in 4.6% of aUTC patients treated with chemotherapy and represent a clinically relevant manifestation. Perioperative chemotherapy significantly increases the risk for ATE. The role of prophylaxis in high-risk groups should be prospectively studied.

A phase II trial of durvalumab (MEDI4736) and tremelimumab in metastatic, nontransitional cell carcinoma of the urothelial tract.

514 Background: Non-transitional cell carcinoma of the urothelial tract (non-TCC) includes several distinct histologies and is associated with a poor prognosis. Prospective data regarding management of patients with metastatic non-TCC is scarce. In this single-arm, phase II study, we assessed the activity and safety of durvalumab and tremelimumab in patients with metastatic non-TCC (NCT03430895). Methods: Eligible patients had unresectable/metastatic non-TCC with ECOG PS 0-1 regardless of prior therapy (except for patients with small cell carcinoma who must have progressed after chemotherapy). Patients received treatment with durvalumab 1500 mg and tremelimumab 75 mg IV Q4W for up to 4 cycles, then durvalumab 1500 mg IV Q4W for a total treatment duration of 12 months. The primary endpoint was overall response rate by RECIST 1.1. The study was planned as a Simon’s minimax two-stage design, with 13 patients planned for stage 1. If 1 or more responses were seen in stage 1, an additional 14 patients were planned to be accrued for a total of 27. Results: Thirteen patients were treated (median age 57 years; range, 33-76), including 7 (54%) with small cell carcinoma, 3 (23%) with squamous cell carcinoma, and 3 (23%) with adenocarcinoma. 11 patients (85%) had visceral metastases, and 6 patients (46%) had liver metastases. The study was terminated after stage 1 as no responses were seen; 11 patients (85%) had PD and 2 patients (15%) had SD as their best response. Median PFS was 1.8 months (95% CI 1.25, not reached [NR]) with a median follow-up of 6.8 months (range 4.3 – 18.1 months). Median OS was 6.43 months (95% CI 4.36, NR). Grade 3-4 treatment-related adverse events occurred in 31% of patients. Conclusions: In this poor prognosis cohort of patients with non-TCC, no responses were seen with durvalumab and tremelimumab. Immune correlative studies to help determine mechanisms of resistance will be presented. Novel therapeutic strategies are urgently needed for patients with metastatic non-TCC. Clinical trial information: NCT03430895.

Pattern of Distant Metastases and Promising Prognostic Factors in Bladder Cancer: A Population-Based Study

The aims of this study were to evaluate the incidence and survival rates of distant metastases in newly diagnosed bladder cancer patients, and to investigate the risk and prognostic factors as well. The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for the incidence and survival rates of patients diagnosed with bladder cancer between 2010–2015. Multivariate logistic regression analyses identified risk factors for distant metastases. The survival rates were calculated by Kaplan Meier analysis. Cox regression and Fine and Grey’s model analyses were used to estimate prognostic factors associated with metastatic bladder cancers. Totally, there were 65541 patients with bladder cancer obtained from the SEER database, and 2812 were diagnosed with distant metastases on initial diagnosis (4.3%). Metastatic distribution information was concluded liver, lung, bone, brain and others. Of these, 1029 patients were bone metastases, 988 patients were lung metastases, 687 patients were liver metastases and 97 patients were brain metastases. As a result, younger age, unmarried social status, Black race, non-transitional cell carcinoma subtypes, poor differentiated grade, increased tumor stage and lymph node stage, absence of surgery to primary sites or unknown were all significantly associated with early distant metastases by logistic regression. Multivariate Cox regression analysis showed that older age, female, unmarried social status, non-TCC subtypes, increased number of metastatic sites and absence of surgery to primary sites were significantly associated with reduced overall survival. These findings in metastatic bladder cancer may help to arrange thorough evaluation and then make individualized treatment plan.

Investigating the Levels of Shed Extracellular Domain of HER2 Protein in the Sera of Bladder Cancer Patients

Background: Receptor tyrosine-protein kinase ERBB2, also known as human epidermal growth factor receptor-2 (HER2), is heterogeneously expressed in a variety of human cancers, including bladder cancer. Based on previous studies that show its association with bladder cancer progression, HER2 has been included in novel multiplatform biomarkers for prediction of bladder cancer prognosis. However, the clinical significance of HER2 status remains underinvestigated and poorly linked to the patients’ clinicopathological features. Here, we aim to scrutinize the levels of the extracellular domain of HER2 in the sera of bladder cancer patients and correlate these levels with clinicopathological features of the tumor.Methods: In the present analytical cross-sectional study, we enrolled 60 pathologically confirmed bladder cancer patients along with 20 age-sex matched healthy controls, and compared their serum HER2 levels as measured by enzyme-linked immunosorbent assay.Results:We observed no statistically significant difference when comparing the levels of HER2 in the sera of cases and controls (P>0.05). Interestingly, serum HER2 levels of controls were higher than bladder cancer patients who had lymph node metastasis (P=0.036). Serum levels of HER2 were also higher in controls than bladder cancer patients with perineural invasion (P=0.028). We observed significantly higher HER2 serum levels in transitional cell carcinoma patients in comparison to non-transitional cell carcinoma patients (P=0.016).Conclusion: Our observations are suggestive of the absence of any association between bladder cancer prognostic factors and serum HER2 levels. To draw any definitive conclusion, further studies with larger sample sizes that examine the presence of neutralizing auto-antibodies against serum HER2, immunohistochemistry examination of HER2 in bladder tumor and lymph node samples, and urinary HER2 levels, along with measurement of its serum levels would be helpful.

The pathologist's role in the detection of rare variants of bladder cancer and analysis of the impact on incidence and type detection.

Histology is one of the most important factors determining the prognosis of bladder cancers and rare variants are generally associated with decreased disease specific survival compared to pure transitional cell carcinomas. We believe that rare bladder cancer variants are likely underdiagnosed in the absence of a dedicated uro-pathologist in many centers. The objective of this study is to evaluate the contribution of a dedicated uro-pathologist on the identification of rare bladder cancer variants. We retrospectively analyzed the clinical and histological records of all patients which underwent a radical cystectomy and lymph node dissection between January 2000 and September 2015. The sample was divided in two groups: Group A, consists of patients who underwent radical cystectomy in the absence of a dedicated uro-pathologist at our institution, whereas the Group B consists of patients who underwent surgery when a dedicated uro-pathology service was available. We then evaluated the impact of a dedicated uro-pathologist on rare variants detection. One hundred thirty-seven out of 551 (24.9%) of patients who underwent RC had at least one rare variant. In Group A 38/238 (16%) of patients showed a rare variant, while 99/313 (31.6%; P<0.001) in group B. Furthermore, the diagnosis of sarcomatoid variant was statistically significantly less common in group A (P=0.0026). The concordance between final radical cystectomy histology and previous transurethral resection of bladder tumor (TURBT) histology was poor in both groups (overall 50.4%). The presence of a dedicated urological anatomical pathologist is of paramount importance and significantly increases the detection rate of non-transitional cell carcinoma bladder cancer types, but it does not increase the concordance rate between histological diagnoses in TURBT and radical cystectomy specimens.

Non-transitional cell carcinoma only partly explains adverse survival outcomes in females with T1–T4 bladder cancer: A summary of UK epidemiological data

Objective: The objective of this article is to investigate why bladder cancer (BC) survival is worse in females using national cancer datasets. Patients and methods: All BC diagnoses since the year 2000 were identified from the National Cancer Data Repository (NCDR) using ICD-10 Code C67 (Bladder cancer T1–T4). Age-standardised relative survival rates for males and females diagnosed with BC between 2000 and 2010 were obtained from Public Health England. Results: Five-year relative survival of men with transitional cell carcinoma (TCC) BC (Code C67) was 61%, but in females was significantly less at 52%. One in four female BC (27%) patients are non-TCC, proportionately far more compared to 1:6 (16%) non-TCC BC in males. Five-year relative survival in non-TCC BC subtypes was notably reduced to 23% in females compared to 35% in men. Only 47% of patients with non-TCC BC receive surgical treatment compared to 82% for all BC. Conclusion: Relative survival from non-TCC BC is significantly less than the overall survival from TCC BC. Female patients with invasive BC have a worse survival than men. This is partly explained by the proportionately higher incidence of non-TCC BC in females, but women with TCC BC also have worse outcomes so other factors must contribute. Female gender should be recognised as an adverse risk factor in BC survival and influence management decisions.

Non-transitional Cell Carcinoma of The Bladder: Single Center Experience

Non-transitional Cell Carcinoma of The Bladder: Single Center Experience

Reassessment of the predictive role of perivesical fat invasion in invasive bladder cancer prognosis in 151 Chinese patients.

Perivesical fat invasion is considered as an important prognostic factor for bladder cancer. However, the predictive role of perivesical fat invasion in invasive bladder cancer prognosis has never been reported in Chinese patients. The aim of the study was to assess the predictive value of perivesical fat invasion for prognoses of T2 and T3 bladder cancer in Chinese patients. One hundred and fifty-one patients who underwent radical cystectomy for pT2-3N0M0 invasive bladder cancer from 2001 to 2007 were studied. Cancer-specific survival rate (CSS) and recurrence-free survival rate (RFS) were compared between the pT2 and pT3 patient groups. Other clinicopathological parameters were also retrospectively analyzed by univariate and multivariate analyses to identify the independent predictor for the prognoses of this cohort. Average patient age at surgery was 58 years. Ninety (60.3%) patients had grade I and II disease. During follow-up (median 66 months), 27 patients (17.9%) had tumor recurrence and 18 (11.9%) died of bladder cancer. In the univariate analysis, the CSS and RFS curves between T2 and T3 patients showed no significant difference (P = 0.756 and 0.354, respectively). Multivariate Cox regression showed that histological classification and grade were independent predictors for CSS, while grade was the sole independent predictor for RFS. For this group of Chinese patients, perivesical fat invasion did not demonstrate a statistically significant difference in prognosis between T2 and T3 patients. Nontransitional cell carcinoma (non-TCC) and high-grade patients had short CSS, and patients with high-grade tumor had higher recurrent risk.

Clinical features and outcomes of nontransitional cell carcinomas of the urinary bladder: Analysis of 125 cases.

Objectives:The aim was to evaluate pathologic diagnosis, treatment and prognosis of 125 patients with nontransitional cell carcinoma of the urinary bladder.Materials and Methods:A total of 3590 patients with bladder tumors operated in our clinic between September 1998 and May 2013 were retrospectively evaluated. A total of 125 patients (107 men and 18 women) with nontransitional cell bladder cancer, confirmed by histopathology, were included in this study. The patients’ characteristics, including age, gender, smoking history, tumor size, and localization, histological types, pathological tumor stages, treatment modalities, and survival rates were all recorded.Results:Of these tumors, 47 (37.6%) were adenocarcinoma (AC), 42 (33.6%) were squamous cell carcinoma (SCC), 23 (18.4%) were undifferentiated carcinoma (UC), 13 (10.4%) were other types of bladder carcinoma. Sixty-three (50.4%) patients had undergone radical cystectomy and pelvic lymphadenectomy ± adjuvant treatment (chemotherapy [CT]/radiotherapy) and 52 (41.6%) patients received radiotherapy ± CT. The median survival time of patients with AC and SCC were significantly higher than patients with UC (AC vs UC, P = 0.001; SCC vs UC, P = 0.000; AC vs. SCC, P = 0.219). Median survival time was significantly higher in radical cystectomy ± adjuvant treatment group (P < 0.05) in all histological types.Conclusion:Prognosis of urinary bladder tumors was directly related to histological type and stage of the tumor. CT or radiotherapy has limited response rates. Early radical cystectomy should be performed to improve prognosis.

A retrospective analysis of incidence and its associated risk factors of upper urinary tract recurrence following radical cystectomy for bladder cancer with transitional cell carcinoma: the significance of local pelvic recurrence and positive lymph node.

ObjectiveThe aim of this study is to examine the incidence and risk factors of upper urinary tract recurrence (UUTR) following radical cystectomy (RC) in bladder cancer and to evaluate its relationship with neobladder (Neo) or ileal conduit (IC).Materials and MethodsAll clinicopathologic parameters and perioperative parameters of 311 patients who underwent RC with either Neo or IC by a single surgeon from 1999 to 2012 were retrospectively included in this study. Patients with a history of renal surgery, concomitant UUTR, or a histopathology of non-transitional cell carcinoma were excluded. For statistical analyses of predictive risk factors of UUTR, a multivariate analysis was performed with known risk factors of UUTR, including type of urinary diversion with significance defined as P < 0.05.ResultsDuring the median follow-up period of 53 months, 143 (46.0%) IC and 168 (54.0%) Neo were performed, resulting in 11 (3.5%) cases of UUTR (Neo 7 and IC 4) after RC and all patients then underwent nephroureterectomy. No significant differences in incidence and overall survival in UUTR were observed according different types of urinary diversion (p = 483), and the prognosis for survival of Neo was insignificantly better than that of IC (5-year overall survival 78% vs 74%, respectively, p>0.05). Higher number of positive lymph nodes (HR 9.03) and the presence of pelvic local recurrence (HR 7286.08) were significant predictive factors of UUTR (p<0.05).ConclusionThis study reports a UUTR rate of 3.5%, and positive lymph nodes and presence of local recurrence at the pelvis as important risk factors. No significant differences in incidence and survival were observed between Neo and IC.

Long-term outcomes in patients with muscle-invasive bladder cancer after bladder-preserving combined-modality therapy: A pooled analysis of RTOG 8802, 8903, 9506, 9706, 9906, and 0233.

264 Background: Multiple prospective RTOG studies have evaluated bladder preserving combined-modality therapy (CMT) including local resection with chemo-radiation for the treatment of muscle invasive bladder cancer (MIBC) reserving cystectomy for salvage. Here we report a pooled analysis of long-term outcomes. Methods: We performed a pooled analysis of 468 patients (pts) with MIBC enrolled on six RTOG bladder preservation studies, including five Phase II studies: RTOG 8802, 9506, 9706, 9906, and 0233, and one phase III study: 8903. Overall survival (OS) was estimated with the Kaplan-Meier method, and disease specific survival (DSS), local failure (LF) and distant metastasis (DM) were estimated by the cumulative incidence method. Results: The median age of the pts was 66 (range, 34-93), and the majority had a Zubrod performance status (PS) of 0 (89.1%). The most common tumor histology was transitional cell carcinoma (94.2%). Clinical tumor stage distribution included 60.6% T2, 29.1% T3a, 6.2% T3b, and 3.9% T4a. A complete response to CMT was observed in 72.0% of pts. With a median follow-up of 4.29 years among all pts, and 7.80 years among survivors (n=205), the 5-year and 10-year results were as follows (Table). Examining outcomes by subgroups, higher clinical T-stage (T2 vs. T3/T4) was associated with decreased DSS (5-year DSS: 74% vs. 66%; 10-year DSS: 69% vs. 60%; p=0.05), and OS (5-year OS: 62% vs. 49%; 10-year OS: 41% vs. 30%; p=0.002). On multivariate analysis, after adjusting for age and PS, higher T-stage was associated with decreased DSS (Hazard ratio: 1.65; 95% confidence interval: 1.19-2.27; p=0.002). Among pts with non-transitional cell carcinoma histology (n=29), the 5-year and 10-year DSS was 66% and 60%, respectively, and 5-year and 10-year OS was 41% and 21%. Conclusions: This pooled analysis of RTOG trials of bladder preserving CMT for MIBC demonstrates long-term OS and DSS comparable to modern immediate cystectomy-based strategies with and without neoadjuvant chemotherapy. CMT can be considered as an alternative to radical cystectomy in selected pts. [Table: see text]

Comparative Outcomes of Pure Squamous Cell Carcinoma and Urothelial Carcinoma With Squamous Differentiation in Patients Treated With Radical Cystectomy

We compared clinical outcomes, and identified predictors of cancer specific and overall survival after radical cystectomy in patients with urothelial carcinoma with squamous differentiation and those with pure squamous cell carcinoma. We reviewed data on 2,031 patients treated with radical cystectomy and pelvic lymph node dissection at a single high volume referral center. Of these patients 78 had squamous cell carcinoma and 67 had squamous differentiation. Survival estimates by histological subtype were described using Kaplan-Meier methods. Within histological subtypes pathological stage, nodal invasion, soft tissue margins, age and gender were evaluated as predictors of cancer specific survival and overall survival using univariate Cox regression. Median followup was 44 months. Of 104 patient deaths 60 died of their disease. We did not find a statistically significant difference between survival curves of patients with squamous cell carcinoma and squamous differentiation (log rank overall survival p = 0.6, cancer specific survival p = 0.17). Positive soft tissue margins were associated with worse cancer specific survival (HR 6.92, 95% CI 2.98-16.10, p ≤0.0005) and overall survival (HR 3.68, 95% CI 1.84-7.35, p ≤0.0005) in patients with pure squamous cell carcinoma. Among patients with squamous differentiation, pelvic lymphadenopathy was associated with decreased overall survival (HR 2.52, 95% CI 1.33-4.77, p = 0.004) and cancer specific survival (HR 3.23, 95% CI 1.57-6.67, p = 0.002). There appears to be no evidence of a difference in cancer specific survival or overall survival between patients with squamous cell carcinoma and those with squamous differentiation treated with radical cystectomy and pelvic lymph node dissection. Patients with squamous differentiation and tumor metastases to pelvic lymph nodes should be followed more closely, and adjuvant treatment should be considered to improve survival. Wide surgical resection is critical to achieve local tumor control and improve survival in patients with squamous cell carcinoma.

Prognostic Value of Cyclooxygenase-2 Expression in Squamous Cell Carcinoma of the Bladder

Inflammation is associated with the pathogenesis of carcinoma, including squamous cell carcinoma of the bladder. Cyclooxygenase-2 is an enzyme that is induced at inflammation sites. We assessed the expression pattern of cyclooxygenase-2 in patients with squamous cell carcinoma of the bladder and determined whether cyclooxygenase-2 expression is associated with clinical outcomes after radical cystectomy. Immunohistochemical staining for cyclooxygenase-2 was done on archival bladder specimens from 152 patients treated with radical cystectomy for squamous cell carcinoma on the Autostainer (DakoCytomation, Carpinteria, California). Bright field microscopy imaging coupled with advanced color detection software was used. Cyclooxygenase-2 was defined as over expressed when greater than 20% cells were positive. We assessed the relationship of cyclooxygenase-2 expression with pathological parameters and clinical outcome. The study included 99 male and 53 female patients with a mean age of 52 years who had squamous cell carcinoma, including 80.9% with bilharziasis. Presenting stage was T2 or greater and presenting grade was GII or less in 93.4% of patients. Median followup was 63.2 months. Cyclooxygenase-2 was over expressed in 74 cystectomy specimens (48.7%) and associated with higher pathological stage (p=0.003) and grade (p=0.049). On multivariate Cox proportional hazards regression analysis cyclooxygenase-2 over expression was associated with disease recurrence (p=0.031) and bladder cancer specific mortality (p=0.046). Cyclooxygenase-2 over expression is associated with pathological stage, grade and worse outcomes after radical cystectomy, suggesting a role in bladder squamous cell carcinoma progression. Our findings support the need for further evaluation of cyclooxygenase-2 and inflammatory signaling pathways, and cyclooxygenase-2 targeted prevention or therapy in patients with bladder squamous cell carcinoma.

The incidence of venous thromboembolism and its effect on survival among patients with primary bladder cancer

The incidence, risk factors, time course, and impact on survival of venous thromboembolism (VTE) in a large, population-based study of patients with bladder cancer have not been identified previously. The California Cancer Registry was merged with the California Patient Discharge Data Set to determine the incidence of VTE in patients with newly diagnosed bladder cancer within a 6-year period. Cox proportional hazards models were used to determine the risk factors for VTE and the effects of VTE on survival. Among 24,861 patients with bladder cancer, the 2-year incidence of VTE was 1.9%. The highest incidence of VTE occurred in the first 6 months regardless of age, sex, race, tumor stage, or histologic subtype. In a multivariate model, significant risk factors for the development of VTE included major surgery, advancing disease stage, and increasing number of comorbidities. Compared with the general population, the 1-year standardized incidence ratio for VTE in the bladder cancer cohort was 5.3 (95% confidence interval, 4.8-5.9). Among patients with bladder cancer, significant risk factors for death included advancing disease stage, increasing comorbidities, African-American race, nontransitional cell carcinoma histology, and the development of VTE. Patients with bladder cancer had a 1.9% 2-year incidence of VTE. Metastatic disease was the strongest predictor of both VTE and death. It was noteworthy that cancer-associated surgery was associated with a higher risk of VTE, which differed from the results reported from other studies in solid tumors. VTE was a significant predictor of death in the first 2 years.

23. Neoplastic myeloid cells in voided urinary cytology in a patient with acute myeloid leukaemia (aml): a case report

Background/Aims The typical role of cytology in urine analysis is in the detection of urothelial bladder malignancies. We report a case of acute myeloid leukaemia (AML) with involvement of the bladder. The aim was to review the cytomorphological features of lymphoma/leukaemia in voided urine cytology. We also highlight the importance of Giemsa staining in appreciating the cytomorphological features of neoplastic myeloid cells. Case report A 73-year-old man presented to the Royal Brisbane and Women’s Hospital with chest pain. He was diagnosed with acute myeloid leukaemia and a bladder mass. Methods The initial urine samples were received fresh. After centrifugation, smears were prepared from the urinary sediment. Discussion Acute leukaemia can result in leukaemic infiltration of many organs, but leukaemic infiltration of the bladder is rare. The morphology of the tumour cells was highly suggestive of a haematological malignancy. Giemsa stain is rarely used routinely, if at all, in most laboratories dealing with urine specimens. This patient demonstrates the value of urinary cytology in diagnosing non-transitional cell carcinoma.

Upper Urinary Tract Recurrence After Radical Cystectomy for Bladder Cancer—Who is at Risk?

Patients who underwent radical cystectomy for bladder cancer are at risk for upper urinary tract recurrence. We identified subgroups of patients at increased risk for upper urinary tract recurrence. All 1,420 patients who underwent radical cystectomy for bladder cancer at our center between January 1986 and October 2008 were included in the study. Negative frozen sections of the ureteral margins were obtained from all patients. Data analysis included preoperative tumor history, pathological findings of the cystectomy specimen and complete followup. Survival was calculated using the Kaplan-Meier method. Until October 2008, 25 cases of upper urinary tract recurrence were observed. The overall rate of upper urinary tract recurrence at 5, 10 and 15 years was 2.4%, 3.9% and 4.9%, respectively. Of the patients 3 had superficial tumors of the renal pelvis and 22 had invasive upper tract transitional cell carcinoma. Upper urinary tract recurrence did not develop in any patients with nontransitional cell carcinoma. Four risk factors for upper urinary tract recurrence were identified including history of carcinoma in situ (RR 2.3), history of recurrent bladder cancer (RR 2.6), cystectomy for nonmuscle invasive bladder cancer (RR 3.8) and tumor involvement of the distal ureter in the cystectomy specimen (RR 2.7). Patients with transitional cell carcinoma who had none of these risk factors had an upper urinary tract recurrence rate of only 0.8% at 15 years. This rate increased with the number of positive risk factors, ie 8.4% in patients with 1 to 2 risk factors and 13.5% in those with 3 to 4 risk factors. Patients who underwent cystectomy for transitional cell carcinoma and with at least 1 risk factor for upper urinary tract recurrence should have closer followup regimens than those with nontransitional cell carcinoma or without any of these risk factors.

Expression and clinical significance of nuclear matrix protein 22 and cytokeratin 18 in transitional cell carcinoma of the bladder

To evaluate the expression and clinical significance of urinary nuclear matrix protein (NMP22) and cytokeratin 18 (CK18) for transitional cell carcinoma of the bladder. Urinary NMP22 and CK18 levels of 293 patients with transitional cell carcinoma of the bladder, 400 patients with non-transitional cell carcinoma of the bladder, and 105 bladder benign disease were analysed by enzyme-linked-immunosorbent assay (ELISA). The levels of urinary NMP22 and CK18 in the patients with transitional cell carcinoma of the bladder (M = 17.3 U/ml, M(CK18) = 484.2 U/L) were significantly higher than those in the non-transitional cell carcinoma of the bladder (M = 6.8 U/ml, M(CK18) = 156.0 U/L) and the benign disease group (M(NMP22) = 2.3 U/ml, M(CK18) = 66.6 U/L) (P < 0.001). The sensitivity and specificity of urinary NMP22 and CK18 were 79.2%, 88.6% and 78.2%, 82.9%, respectively, for transitional cell carcinoma of the bladder before any treatment. The joint sensitivity of the two markers was 91.7%. The NMP22 and CK18 levels were significantly lower in the recovered patients after surgical operation (P < 0.01), while in patients with recurrence or metastasis the levels of the markers were significantly higher (P < 0.01). There was a significant relationship between NMP22 and CK18, (r = 0.689, P < 0.01). The levels of urinary nmp22 and CK18 were significantly different among pathological grade G1, G2, G3, and stage Ta, T1, T2, T3 (P < 0.01). NMP22 and CK18 are useful tumor marker for diagnosis of transitional cell carcinoma of the bladder and for monitoring the state of illness. The joint use of the two markers can improve the sensitivity of cancer detection. NMP22 and CK18 may become a new class of tumor markers, and to be the basis for development of a new assay with an increased efficacy for the detection and treatment of bladder cancer.

Palliative chemotherapy for non-transitional cell carcinomas of the urothelial tract

Non-transitional cell carcinomas of the urothelial tract comprise 5-10% of urothelial cancers. Clinical information regarding the clinical behavior and chemotherapy outcome of non-transitional cell carcinomas of the urothelial tract are incomplete due to their rarity. The object of this study was to evaluate the clinical features and the efficacy of palliative chemotherapy in advanced non-transitional cell carcinomas of the urothelial tract. We analyzed the clinical records of 21 consecutive patients who received palliative chemotherapy for unresectable or metastatic non-transitional cell carcinomas of the urothelial tract between January 1995 and November 2007. All the 21 patients received first-line chemotherapy with platinum-based regimens which are known to be effective in transitional cell urothelial carcinomas. The median age of the patients was 57 years (range, 27-71 years). The primary sites of involvement were the bladder, urethra, urachus, and ureter in 43%, 29%, 19%, and 10% of the patients, respectively. Adenocarcinoma was the most common histological type (67%); squamous cell carcinoma and small cell carcinoma comprised 24 and 10% of the histologic types, respectively. With a median duration of follow-up of 32 months (range, 12-71 months), the median overall survival for all 21 patients from the day of first-line chemotherapy was 13 months (95% CI, 6.8-19.2). The expected 1-year survival rate was 50.6% (95% CI, 28.6-72.5). Univariate analysis showed a better median overall survival in patients with adenocarcinoma, compared to non-adenocarcinomas (47 vs. 10 months, P = 0.049). The median overall survival of patients who received platinum-based palliative chemotherapy for advanced non-transitional cell carcinomas was comparable to previous studies for patients with transitional cell carcinomas. Adenocarcinomas appear to have a favorable prognosis for the survival of the patients who received platinum-based chemotherapy for advanced non-transitional cell carcinomas.