Invasive High Grade Research Articles

314 - Invasive high grade B cell lymphoma manifesting as painful hepatosplenomegaly and elevated liver transaminases

314 - Invasive high grade B cell lymphoma manifesting as painful hepatosplenomegaly and elevated liver transaminases

IGF-2 mediated hypoglycemia and the paradox of an apparently benign lesion: a case report & review of the literature

BackgroundNon-islet cell tumour hypoglycemia (NICTH) is rarely encountered in clinical practice. Insulin-like growth factor 2 (IGF2) is the most common cause of NICTH observed in the setting of mesenchymal and epithelial neoplasia. This is a paraneoplastic syndrome caused by IGF2 activation of the insulin receptor.Case presentationAn 80 year old female presented with a short history of recurrent episodes of confusion with laboratory confirmed hypoglycemia with a plasma glucose of 2.7 mmol/L on fasting which fulfilled Whipple’s triad. Diagnostic clues to the aetiology at presentation include the fasting pattern of hypoglycemia, hypokalaemia and the absence of weight gain. A 72 hour fast with results showed early hypoglycemia and suppression of serum insulin, c-peptide, and proinsulin. Serum insulin antibody was not detected. Subsequent measurement of the serum IGF2:IGF1 ratio was elevated at 22.3 and consistent with IGF-2 mediated hypoglycemia and imaging studies demonstrated a pelvic mass. Dietary intervention and oral prednisolone abated hypoglycemia prior to surgery. Ultimately, hypoglycemia resolved following operative intervention and steroid therapy was successfully withdrawn. Histopathology was remarkable for dual neoplastic processes with uterine solitary fibrous tumour (SFT) confirmed as the source of IGF2 hypersecretion on IGF-2 immunohistochemistry and a coincidental invasive high grade serous carcinoma involving the fimbria of the right fallopian tube.ConclusionThe paradox in this case is that the benign solitary fibrous tumour accounted for patient morbidity through secretion of IGF2 and without treatment, posed a mortality risk. This is despite the synchronous presence of a highly malignant fallopian tube neoplasm. This case reinforces the need for thorough clinical evaluation of hypoglycemia to allow prompt and definitive management.

Outcome of Post-resection Intravesical BCG and Mitomycin C Therapy on Non-muscle Invasive High- Grade Transitional Cell Carcinoma of Urinary Bladder

Objective: This study aimed to compare the outcome of postoperative intravesical BCG and Mitomycin C therapy on non-muscle invasive high grade superficial bladder tumor. Methods: This prospective quasi experimental study was carried out among the patients with non-muscle invasive high grade transitional cell carcinoma (TCC) of urinary bladder, who underwent complete transurethral resection of bladder tumor of primary tumor attended at the urology department of DMCH, during March 2017 to August 2019. After pre-operative evaluation and counselling, 70 patients with histologically documented high grade superficial bladder tumor were included and divided in two groups. We instilled intravesical BCG in one group and Mitomycin C (MMC) therapy in other group. The patients were followed up at 3rd ,6th , 9th , 12th and 18th month. Results: The mean age of BCG group was 55.8 years while 60.2years in MMC group with majority between 45 to 65 years (>80%). Sex distribution in both groups were almost equal (p=0.062). There were equal number of TaG3 and T1G3 disease in each group (p=0.809). Local adverse reactions were significant in BCG group (p= 0.016), among them UTI, between two groups, was statistically significant (p=0.039). Incidence of hematuria (p=0.324), voiding frequency (p=0.163) and local rash (P=0.642) had no statistically significant difference. The incidence of post-instillation systemic adverse reactions between two groups were statistically significant (p=0.034). Fever (p=0.028) was significant among them. Intavesical BCG was significantly more effective than MMC in terms of disease recurrence (p=0.047) and progression (p=0.008). Conclusions: We analysed the efficacy and safety of intravesical BCG and MMC in two groups, showing that BCG was more effective in terms of disease recurrence and progression but local and systemic side effects were higher in BCG group. Bangladesh J. Urol. 2021; 24(1): 62-71

Immune Checkpoint and Telomerase Crosstalk Is Mediated by miRNA-138 in Bladder Cancer.

BackgroundTumor recurrence and progression in non-muscle invasive bladder cancer (NMIBC), therapy failure, and severe side effects in muscle invasive bladder cancer (MIBC) are the major challenges in the clinical management of bladder cancer (BC). Here, we identify new molecular targetable signatures to improve BC patients’ stratification and the outcome of current immunotherapies.Material and MethodsIn a prospective cohort of 70 BC patients, we assessed the genetic and molecular regulation of TERT in maintaining telomere length in parallel to immune checkpoint and microRNA expression.ResultsTERT was undetectable in healthy bladder tissues but upregulated in invasive BC stages and high tumor grade. Its expression was linked with the combined effect of the C250T mutation and THOR hypermethylation, associated with progressing tumors and maintaining of telomere length. In the same cohort, PD-L1 scored highest in NMIBC, while PD-L2 was upregulated in MIBC. We also show that miR-100-5p and 138-5p were highly expressed in healthy bladder specimens and cell line, while expression decreased in the BC tissues and BC cell lines. In line with the binding prediction for these miRNAs on target genes, miRs 100-5p and 138-5p expression strongly inverse correlated with TERT, PD-L1, and PD-L2 expression, but not PD1.ConclusionWe identify a loop involving TERT, PD1-ligands, and miR-138-5p in BC, that might represent not only a useful biomarker for improved diagnosis and patients’ stratification but also as a promising axis that might be therapeutically targeted in situ.

Association of pathological complete response rates and TILs in triple-negative breast cancer patients.

e12596 Background: Triple negative breast cancers (TNBC), characterized by the lack of expression of estrogen receptors and progesterone receptors as well as human epidermal growth factor receptor 2, are associated with high distant recurrence rate and death. As a result, the majority of patients with TNBC are treated with perioperative chemotherapy with the goal of eradicating micrometastases and preventing distrant relapse. The preoperative systemic therapy offers the advantages of permitting an assessment of chemo-sensitivity, increased rates of breast conserving surgery and the ability to adapt postoperative therapies depending on the response. Recently, neoadjuvant chemotherapy has been used at an increasing frequency. The response to neoadjuvant chemotherapy, as measured by the residual cancer burden index, for example, is correlated with the long-term prognosis of TNBC and HER2 expressing breast cancers. Previous studies suggest that tumor-infiltrating lymphocytes (TILs) may correlate with pathological complete response (pCR) rates in TNBC patients treated with neoadjuvant chemotherapy. The pathologic evaluation of TILs in TNBC has been recommended by the International TILs working group since 2014. In this study we sought to analyze the association of TILs with pCR in a cohort of TNBC patients treated with neoadjuvant chemotherapy. Methods: An IRB-approved single-institution retrospective analysis was performed on 127 patients diagnosed with TNBC who received neoadjuvant anthracycline and taxane based chemotherapy at the Ohio State University Comprehensive Cancer Center between January 1st, 2012 and November 31st, 2018. We analyzed TILs as a continuous variable as a part of a secondary analysis of this data. Whole tissue sections from archived H&E stained glass slides were scanned using Philips UltraFast Scanner at ×40 magnification with a single-focus layer. TIL scoring was performed according to guideline recommendations from the International TILs Working Group (2014). Results: A total of 127 female patients with TNBC were identified. The median age at diagnosis was 52.0 years (range 32.0, 74.0) and patients were predominately white (103, 81%), post-menopausal (68, 53.5%) and presented with invasive ductal cancer (113, 89%), stage II (88, 69%), and high grade (108, 85%). Of those patients, 56 had TILs measurement available. pCR was associated with statistically higher level of TILs in core biopsies taken prior to chemotherapy had (Wilcoxon rank-sum test, p = 0.04). Conclusions: The long-term prognosis of patients with TNBC is predicted by the response to neoadjuvant chemotherapy. Consistent with other studies, our study revealed that TILs are associated with a higher probability of pCR. Our future goals are to identify which TIL subsets correlate best with pCR and to identify the mechanism for the increased chemotherapy responsiveness of lymphocyte-infiltrated tumors.

275P Clinical outcomes of second transurethral resection in nonmuscle invasive high grade bladder cancer: a retrospective, multi-institutional, collaborative study

275P Clinical outcomes of second transurethral resection in nonmuscle invasive high grade bladder cancer: a retrospective, multi-institutional, collaborative study

Reassessment of p53 immunohistochemistry thresholds in invasive high grade bladder cancer shows a better correlation with TP53 and FGFR3 mutations

FGFR3 mutations are frequently mutually exclusive of TP53 mutations in invasive high grade urothelial carcinoma (HGUC) and p53 immunohistochemistry is often used as a surrogate for TP53 mutations. A 10 % staining cut off has been used in HGUC for designation as p53 positive or negative however, a novel contemporary method we have previously proposed (0% or >50 % - abnormal vs. 1–49 % - wild type) has shown significant correlation with oncologic outcome as well. We aimed to compare how a ≥10 % vs. 0 % and ≥ 50 % cut off p53 assessment method correlates with TP53 and FGFR3 mutation status. Tissue microarrays created from three retrospective cohorts (two cystectomy cohorts (cohort A, n = 206 and cohort B, n = 91; one T1 transurethral resection cohort (cohort C, n = 47)) were stained with p53 and scored by two blinded reviewers using both p53 scoring schemes. 50 cases from cohort A were assessed for TP53 and FGFR3 mutation status using next generation sequencing and FGFR3 mutation status was separately assessed in cohorts B and C using SNaPshot methodology. 202 (58.7 %) and 142 (41.3 %) cases showed abnormal and wild type p53 staining, respectively. Using the 10 % cut off, 254 cases were positive (73.8 %) and 90 cases were negative (26.2 %). 27 (14.4 %) and 15 (30 %) assessed cases demonstrated FGFR3 and TP53 mutations, respectively; 19/27 FGFR3 mutated showed a wild type pattern of p53 expression while 15/15 TP53 mutated tumours showed an abnormal pattern of p53 expression. There was a significant correlation between the contemporary p53 scoring scheme and TP53 and FGFR3 mutations (p < 0.0001 and p = 0.002, respectively). Improved sensitivity, specificity, positive predictive value, and negative predictive value for TP53 mutation was also seen compared to the 10 % cut off; specifically, the sensitivity and negative predictive value were 100 %. These findings might be of clinical relevance in the era of precision medicine.

MP55-08 FEASIBILITY OF FINDING CIRCULATING TUMORS CELLS AND ASSIGNING PD-L1 RECEPTOR STATUS USING SINGLE-CELL TECHNOLOGY COMBINED WITH CELSEE GENESIS SYSTEM

INTRODUCTION AND OBJECTIVE: enumerating circulating tumor cells (CTC) may improve our ability to differentiate between localized and metastatic bladder cancer (BC) and predict response to systemic therapies. However, previously used CTC identification platforms had limited utility in managing patients diagnosed with this disease because they lacked the appropriate sensitivity level. Also, they did not report on the PD-L1 receptor status, which is becoming an essential component of modern immunotherapy of BC METHODS: We used a novel device to enrich and retrieve CTCs from blood samples of patients with high grade and low-grade BC, as well as benign conditions, treated with cystectomy by using a microfluidic chip. The Celsee Genesis (Celsee Inc) captures CTCs with high sensitivity and allows the captured CTCs to be retrieved for molecular analysis. It uses the microfluidic chip, which has approximately 56,320 capture chambers. Based on differences in cell size and deformability, each chamber ensures that small blood cells escape while larger CTCs of varying sizes are trapped and isolated in the chambers. PD-L1 expression on the isolated tumor cells was then evaluated using 4-color single-cell technology (IncellDX Inc.) directly on the chip. RESULTS: Ten bladder cancer (5 extensive low grade (LG) and 5 invasive high grade (HG) disease) and two benign bladder pathology patients provided blood samples before their cystectomy. We found CTCs in 3 patients (two LG and one HG disease). CTCs were four times higher in the HG sample than in the LG samples. PD-L1 expression was high on CTCs isolated from the HG patient’s blood sample and lower in the two LG blood samples. No CTCs were detected in patients with benign bladder pathology. CONCLUSIONS: Our results show the feasibility of using novel, high sensitivity CTC detection, and PD-L1 single cell measuring technology in patients with BC. We also show that this technology has a potentially high sensitivity level for detecting CTC in patients with bladder malignancies by detecting low levels of CTCs in low-grade disease. More extensive studies are planned to validate our findings.Source of Funding: IncellDX and CelSee Inc.

The Histological Variants of Urothelial Carcinoma of the Bladder: It Is Affecting the Prognosis?

Urothelial carcinomas (UC) are likely to have particular morphological features that distinguish them from the typical form. These original aspects are called “histological variants of urothelial carcinoma”. They can constitute all or part of the tumor and concern mainly muscle invasive UC and high grade. Their frequency varies according to the type, but the knowledge of these variants is essential because of the diagnostic difficulties, and the implication of their presence on the prognosis.

1013P - Incidental early occult ovarian cancer after risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers followed in a community public hospital

BackgroundCarriers of germline BRCA1/2 mutations are at high risk of developing ovarian, tubal or peritoneal cancer. Actually, risk-reducing bilateral salpingo-oophorectomy (RRSO) is the only definite preventive strategy. The aim of this study is to characterize the clinical and pathological features of early occult malignancies incidentally diagnosed after a RRSO in carriers of BRCA1/2 mutations followed at a high risk familial cancer clinic in a community public hospital in NW Spain. MethodsData were prospectively collected from 95 consecutive BRCA-positive women diagnosed at our high risk familial cancer clinic from March 2014 to March 2017. ResultsAmong 95 BRCA1/2 carriers (median age 45 years) 38 women were healthy and 57 have had a previous breast cancer diagnosis. Half of the carriers hold the founder mutation R71G in BRCA1 (69 in BRCA1, 25 in BRCA2, and 1 was a carrier of a mutation in both genes). RRSO was performed in 29 cases (21 in BRCA1 and 8 in BRCA2; median age 50 years). Three BRCA1/2 carriers older than 45 years-old refused to undergo a RRSO. After RRSO two patients (6.4%), both BRCA1-positive, were found to have an early occult adnexal malignancy upon pathology study. One 64-year-old carrier had an invasive serous fallopian tube carcinoma stage I with no involvement of the ovaries plus a stage I endometrial endometrioid carcinoma on the staging hysterectomy. The second 44-year-old women were found at the time of the RRSO a stage Ia invasive high grade serous ovarian carcinoma with no fallopian tubes involvement. ConclusionsA 6.4% incidence of early occult adnexal malignancy after RRSO was found in our cohort of BRCA1/2 carriers. This incidence is similar to that previously published in studies done at international reference centers. The coordinated management of BRCA1/2 mutation carriers between different departments of our institution allows results comparable to international standards. Greater efforts must be made to improve the acceptance of RRSO by BRCA carriers, especially after the age of 40. Legal entity responsible for the studyAuthor: Begoña Graña Suárez. FundingHas not received any funding. DisclosureB. Grana Suarez: Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Servier. All other authors have declared no conflicts of interest.

Abstract IA15: Early detection of ovarian cancer: An update

Abstract IA15: Early detection of ovarian cancer: An update

V08-11 ROBOT-ASSISTED PLACEMENT OF PELVIC TISSUE EXPANDER FOR RADIATION AFTER PROSTATECTOMY AND CYSTECTOMY FOR TREATMENT OF PROSTATE CANCER BIOCHEMICAL RECURRENCE

You have accessJournal of UrologyProstate & Renal Oncology II1 Apr 2018V08-11 ROBOT-ASSISTED PLACEMENT OF PELVIC TISSUE EXPANDER FOR RADIATION AFTER PROSTATECTOMY AND CYSTECTOMY FOR TREATMENT OF PROSTATE CANCER BIOCHEMICAL RECURRENCE Scott Quarrier and Guan Wu Scott QuarrierScott Quarrier More articles by this author and Guan WuGuan Wu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1977AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Local treatment of biochemical recurrence of prostate cancer after surgical resection of the prostate and bladder is complicated by the interposition of small bowel in the empty prostatic bed. Salvage radiotherapy to the prostatic fossa has the increased morbidity associated with treatment levels of radiation applied to the small bowel. Commonly utilized radiation spacers focus on reduction of the doses applied to the rectum, however the morbidity of small bowel radiation is significantly higher than that of the rectum. Surgical spacers and mesh retention placement have been utilized previously in reports with other pelvic cancers. We present a robot-assisted surgical technique for overcoming the challenges of a patient with two prior pelvic surgeries and small bowel in the radiation target. METHODS A 72-year-old male required treatment of his biochemical recurrent prostate cancer. In 2006 this patient presented with a PSA of 5.74, Gleason 3+3 prostate cancer. He underwent a robot-assisted laparoscopic radical prostatectomy for pT2a disease. In 2008, the patient was found to have muscle invasive high grade papillary urothelial carcinoma and underwent robot-assisted cystectomy and ileal conduit with final pathology pT2bN0 disease. In 2017 he had biochemical recurrence of his prostate cancer with a PSA of 0.30. Pelvic CT showed small bowel deep into his prostatic bed behind the pubic bone. A robot-assisted lysis of adhesions and placement of a PMT corporation tissue expander in the prostatic fossa was performed. Three robotic ports and one assistant port were utilized. The sigmoid and small bowel were displaced during lysis of adhesions. The tissue expander was passed through the midline trocar site deflated and inflated after entry into the abdomen. This was filled with 330 cc of saline. The tissue expander was secured with proline sutures in a dependent position. The patient subsequently underwent IRMT of 66 Gray to the prostatic fossa. Eleven days after IMRT the patient underwent successful laparoscopic removal of the tissue expander. RESULTS The patient tolerated IMRT without any complications. There were no gastrointestinal complaints following radiation therapy. CONCLUSIONS Robotic placement of a tissue expander in patients who have undergone multiple pelvic surgeries is a feasible procedure that can reduce the morbidity associated with pelvic radiation. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e822-e823 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Scott Quarrier More articles by this author Guan Wu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP44-15 ANXA10 AND ATP7A ARE THE MTOR PATHWAY DOWNSTREAM TO PREDICT THE RECURRENCE AND PROGRESSION IN NON-MUSCLE INVASIVE HIGH GRADE UROTHELIAL CARCINOMA OF THE BLADDER

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2017MP44-15 ANXA10 AND ATP7A ARE THE MTOR PATHWAY DOWNSTREAM TO PREDICT THE RECURRENCE AND PROGRESSION IN NON-MUSCLE INVASIVE HIGH GRADE UROTHELIAL CARCINOMA OF THE BLADDER Byung Hoon Chi, Subin Jin, Young Mi Whang, Seung Hyun Ahn, Jae Duck Choi, Shin Young Lee, In Ho Chang, and Bongsuk Shim Byung Hoon ChiByung Hoon Chi More articles by this author , Subin JinSubin Jin More articles by this author , Young Mi WhangYoung Mi Whang More articles by this author , Seung Hyun AhnSeung Hyun Ahn More articles by this author , Jae Duck ChoiJae Duck Choi More articles by this author , Shin Young LeeShin Young Lee More articles by this author , In Ho ChangIn Ho Chang More articles by this author , and Bongsuk ShimBongsuk Shim More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1346AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The cross-talk of mammalian target of rapamycin (mTOR) pathway is clinical limitation of mTOR inhibitor for the treatment of urothelial carcinoma (URCa) of the bladder. This study is to search mTOR pathway downstream genes to overcome cross-talk at non muscle invasive high grade (HG)-URCa of the bladder. METHODS Gene expression patterns, gene ontology, and gene clustering by triple (p70S6K, S6K and eIF4E) siRNAs or rapamycin in 5637 and T24 cell lines were investigated by microarray analysis and we selected mTOR pathway downstream genes which were suppressed to siRNAs more than two fold, and rapamycin up-regulated or rapamycin down-regulated. And then we validated mTOR downstream genes with immunohistochemistry using tissue microarray of 125 non-muscle invasive HG-URCa patients whether genes can predict clinical aggressiveness and long-term outcomes, and knockout study to evaluate the synergistic effect with rapamycin. RESULTS In the microarray analysis, we selected mTOR pathway downstream genes which consisted of 4 rapamycin up-regulated (FABP4, H19, ANXA10, and UPK3A), and 4 rapamycin down-regulated (FOXD3, ATP7A, plexin D1 and ADAMTS5). In tissue microarray, FABP4 and ATP7A were more expressed at T1, and FOXD3 was at Ta. ANXA10 and ADAMTS5 were more expressed at 3 cm or less than 3cm. In Kaplan-Meier curve, ANXA10 was a significant predictor of recurrence, and FABP4 and ATP7A were significant predictors of progression of HG-URCa of the bladder. In multivariate Cox regression model, ANXA10 was a significant predictor of recurrence and ATP7A was a significant predictors of progression in non-muscle invasive HG-URCa of the bladder. In ATP7A knock out model, rapamycin treatment showed synergistic effect to inhibit cell viability, wound healing, and invasion ability compared to rapamycin only. CONCLUSIONS ANXA10 and ATP7A might be mTOR pathway downstream genes to predict recurrence and progression in non-muscle invasive high-grade urothelial carcinoma of the bladder and ATP7A knockout overcome the rapamycin coss-talk. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e569 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Byung Hoon Chi More articles by this author Subin Jin More articles by this author Young Mi Whang More articles by this author Seung Hyun Ahn More articles by this author Jae Duck Choi More articles by this author Shin Young Lee More articles by this author In Ho Chang More articles by this author Bongsuk Shim More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP15-11 BLADDER PRESERVATION IN ELDERLY PATIENTS HAVING NON-MUSCLE INVASIVE HIGH GRADE RECURRENT TA, T1 UROTHELIAL CARCINOMA WITH GEMCITABINE, PACLITAXEL, DOXORUBICIN AND RADIOTHERAPY: SURVIVAL AND QUALITY OF LIFE.

You have accessJournal of UrologyBladder Cancer: Non-invasive I1 Apr 2017MP15-11 BLADDER PRESERVATION IN ELDERLY PATIENTS HAVING NON-MUSCLE INVASIVE HIGH GRADE RECURRENT TA, T1 UROTHELIAL CARCINOMA WITH GEMCITABINE, PACLITAXEL, DOXORUBICIN AND RADIOTHERAPY: SURVIVAL AND QUALITY OF LIFE. Mohamed Wishahi, Hossam Elganzoury, and Amr Elkhouly Mohamed WishahiMohamed Wishahi More articles by this author , Hossam ElganzouryHossam Elganzoury More articles by this author , and Amr ElkhoulyAmr Elkhouly More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.496AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES INTRODUCTION: Non-muscle invasive carcinoma of the bladder (NMICB) of high grade Ta, T1 tumor that recurred after Intavesical BCG, had a high incidence of tumor progression. Elderly patient are often refuse radical cystectomy (RC) and urinary diversion, to keep their body image and quality of life. OBJECTIVES: To estimate the response rate of gemcitabine, paclitaxel, doxorubicin combined with radiotherapy aiming at bladder preservation in elderly patients =75 years old with recurrent high grade T1 urothelial carcinoma (UC). We conducted a prospective study to evaluate the multimodality treatment for bladder preservation in elderly patients. Overall survival, disease free survival, and quality of life were estimated and correlated with a matched arm of (RC). METHODS In a prospective study, we included 105 elderly patients with NMICB, 57 patients had high grade T1 tumor, 48 patients with high grade Ta, both TA and T1 were NMICB, patients were recurrent after complete course of intavesical BCG, patients asked for bladder preservation. The multimodality treatment arm was compared with matched arm of 60 patients treatment with RC. Follow up was up to 3 - 4years. Overall survival (OS) and disease free survival (DFS) was calculated using Kaplan-Mayer and Cox proportional hazards model and compared to a second arm of 30 patients with similar criteria that had RC. Inclusion criteria in both arms were non-metastatic NMICB, no prior chemotherapy, glomerular filtration rate <60?mL/min. Gemcitabine (900?mg/m(2)), paclitaxel (135?mg/m(2)), and doxorubicin (40?mg/m(2)) were administered on day 1 of each 14-day cycle. Pegfilgrastim was given with every cycle on either day 1 or day. low dose radiotherapy were given following chemotherapy. RESULTS Median age was 77 years (range 75-84). All patients had complete responses. Grade 3 and 4 nonhematologic toxicities were fatigue and mucositis (14% each). There were 12 episodes of neutropenic fever, no treatment-related deaths. Median overall survival was 28.5 months CONCLUSIONS Results of combination of gemcitabine, paclitaxel, and doxorubicin as first-line chemotherapy combination with radiotherapy for elderly patients with recurrent high grade Ta, T1 NMICB of UC in elderly patients =75 years old. Were compatible with RC. Bladder preservation with first line chemoradiothery would be considered as an alternative to RC in elderly patients as it offers better quality of life © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e174-e175 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Mohamed Wishahi More articles by this author Hossam Elganzoury More articles by this author Amr Elkhouly More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

275P Clinical outcomes of second transurethral resection in non-muscle invasive high grade bladder cancer: a retrospective, multi-institutional, collaborative study

275P Clinical outcomes of second transurethral resection in non-muscle invasive high grade bladder cancer: a retrospective, multi-institutional, collaborative study

MMTV-cre;Ccn6 knockout mice develop tumors recapitulating human metaplastic breast carcinomas.

Metaplastic breast carcinoma is an aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition (EMT). However, the defining molecular events are unknown. Here we show that CCN6 (WISP3), a secreted matricellular protein of the CCN (CYR61/CTGF/NOV) family, is significantly down regulated in clinical samples of human spindle cell metaplastic breast carcinoma. We generated a mouse model of mammary epithelial-specific Ccn6 deletion by developing a floxed Ccn6 mouse which was bred with an MMTV-Cre mouse. Ccn6fl/fl; MMTV-Cre mice displayed severe defects in ductal branching and abnormal age-related involution compared to littermate controls. Ccn6fl/fl ;MMTV-Cre mice developed invasive high grade mammary carcinomas with bona fide EMT, histologically similar to human metaplastic breast carcinomas. Global gene expression profiling of Ccn6fl/fl mammary carcinomas and comparison of orthologous genes with a human metaplastic carcinoma signature revealed a significant overlap of 87 genes (p=5×10−11). Among the shared deregulated genes between mouse and human are important regulators of epithelial morphogenesis including Cdh1, Ck19, Cldn3 and 4, Ddr1, and Wnt10a. These results document a causal role for Ccn6 deletion in the pathogenesis of metaplastic carcinomas with histological and molecular similarities with human disease. We provide a platform to study new targets in the diagnosis and treatment of human metaplastic carcinomas, and a new disease relevant model in which to test new treatment strategies.

Non-muscle invasive high grade urothelial carcinoma of the bladder. Which factors can influence understaging at the time of radical cystectomy?

To evaluate the main factors which influence understaging in patients with T1G3 non-muscle invasive bladder cancer (NMIBC). 109 patients with T1/G3 underwent transurethral resection of bladder tumor (TURBT) and then radical cystectomy (RC) with pelvic lymph nodes dissection. A number of variables were considered when evaluating the detection of understaging. We considered the patients age and gender, as well as the size, number, location and morphology of their tumor. We also considered coexistence of bladder carcinoma in situ (CIS), microscopic vascular invasion and deep lamina propria invasion. The level of experience of the surgeon was also analyzed. in RC samples muscle invasion, that is understaging, was detected in 74 (67.9%) patients, while 35 (32.1%) patients were appropriately staged. In these cohort of patients with high grade tumors, understaging was associated with deep lamina propria and microscopic vascular invasion, multiple tumors, tumor size &gt; 6 cm, tumor location (trigone and dome), presence of residual tumor; age, gender, tumor morphology, CIS associated, and experience of urological surgeon were not associated with clinical understaging. in our study, evaluating patients with high grade NMIBC at first TURBT, we identified some risk factors that need to be considered and that are able to increase the risk of understaging: deep lamina propria and microscopic vascular invasion, multiple tumors, tumor size &gt; 6 cm, tumor location (trigone and dome), presence of residual tumor. When these risk factors are present, performing an early cystectomy, and not a re-TURBT, could lower the risk of worse pathological finding due to rapid disease progression of the high grade tumors, and can prolong survival.

MP83-15 EFFECT OF GEMCITABINE AND MITOMYCIN ON CANCER STEM CELLS IN UROTHELIAL CARCINOMA CELLS

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP83-15 EFFECT OF GEMCITABINE AND MITOMYCIN ON CANCER STEM CELLS IN UROTHELIAL CARCINOMA CELLS Rani Ojha, Shrawan Singh, Arup K Mandal, and Vivekanand Jha Rani OjhaRani Ojha More articles by this author , Shrawan SinghShrawan Singh More articles by this author , Arup K MandalArup K Mandal More articles by this author , and Vivekanand JhaVivekanand Jha More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2197AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To investigate the effect of chemotherapeutic agents on the behavior of cancer stem cell (CSC) subsets-side population in primary urothelial carcinoma cells (UCC). METHODS Low-grade urothelial carcinoma (LGUC), non muscle invasive high-grade (HGUC), muscle invasive high grade (MIUC) and bladder cancer cell lines (T24 and UM-UC-3) were used. Normal urothelial cells (NUC) were used as a control. Cytotoxicity of gemcitabine and mitomycin was measured by MTT assay in T24 and UM-UC-3 cells. Stemness properties were measured by isolation and characterization of side population (SP) using hoechst staining, by studying the expression of stemness genes using reverse transcriptase PCR analysis and tumor sphere forming ability. Effect of autophagy inhibition or induction on cell viability was measured by annexin-V/PI staining and caspase activity. RESULTS The number of SP was significantly higher in MIUCC (11.7%, p<0.05) and HGUCC (8.9%, p<0.05) as compared to LGUCC (4.2%) (Fig1A). SP cells showed more CD44 expression and tumor spheroid forming ability (Fig1B). Following treatment with gemcitabine or mitomycin, significantly increased number of SP cells was found in LGUCC (9.78%), HGUCC (13.56%), MIUCC (20.45%) and bladder cancer cell lines at 24 hours. In NUC only 1.7% SP cells were found and there was no increase in SP cells (Fig1C). Treatment with gemcitabine or mitomycin caused increased expression of stemness marker in SP (p<0.001) of HGUCC, LGUCC and MIUCC as compared to SP of NUC cells (Fig1D, E). SP of UCC cells treated with gemcitabine or mitomycin for 24 hours showed lower cell death as compared to NSP cells. Higher autophagic response was observed in SP of UCC in the presence of chemo-therapeutic agents as compared to NUC (Fig1F,G). Pharmacological inhibition or siRNA-mediated inhibition of autophagy led to decreased number of SP cells (Fig1H) and tumor sphere forming ability (Fig1I) with concomitant increase in caspase-mediated cell death (Fig1 J,K) in SP of UCC. CONCLUSIONS The present study is the first to show that urothelial cancer cells exposed to chemotherapeutic agents increases the stemness properties in UCC and could be the underlying cause of resistance and relapse of the tumor. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1086-e1087 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Rani Ojha More articles by this author Shrawan Singh More articles by this author Arup K Mandal More articles by this author Vivekanand Jha More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-term oncological and functional outcomes of prostate sparing cystectomy: Single tertiary care institution experience.

413 Background: To analyze the oncological and functional outcome of Prostate Sparing Cystectomy (PSC) in the treatment of Bladder Cancer (BC) in a single tertiary care referral institution. Methods: At our institution, we treated 147 patients (1992 – 2014) with PSC for muscle invasive BC and recurrent high grade non-muscle invasive BC. Out of these, 64 patients received a standardized PSC technique featuring a Millin adenomectomy between 2001 – 2014 and composed the population of the study. Inclusion criteria were: Normal prostate examination and prostate specific antigen (PSA) +/- negative transrectal ultrasound guided biopsies; Frozen section negative for cancer in prostatic urethra prostate base, distal ureters and trigone. Oncological outcome was evaluated with Overall survival (OS); Cancer-specific survival (CSS); Recurrence-free survival (RFS). Functional outcomes: Continence - being pad-free or leak-free requiring ≤ 1 pad per day/night. Sexual function was assessed by self- reported erectile function sufficient for intercourse with or without medical treatment. Results: Median age was 62 years (IQR 55-67,5) with a median follow-up of 70 months (IQR 46-103). Thirty one (48,4%) patients ≤ pT1, 19 (29,7%) pT2, 14 (21,9%) ≥ pT3 at pathological diagnosis. Lymphadenectomy was performed in 95,3% of the cases. Positive lymph nodes were found in 4.9% patients and 3.1% patients showed positive surgical margins. Ten patients (15,7%) had Clavien grade 3–5 complications.The 5 and 10-y survival rates were OS: 84,7% and 68,3%; CSS: 84,7% and 77,5%; RFS: 76% and 65,5% respectively. No case of recurrence at the remnant prostatic urothelium was observed. Pad-free and leak-free continence, were achieved in 85.9% and 93.8% for daytime continence respectively, with 50% and 85,9% for night continence, respectively. Erectile function was maintained in 56,3%. Prostate cancer was diagnosed in 3 (4,7%) patients, 2 at the pathology report of the adenomectomy followed with active surveillance, and 1 was diagnosed during the follow up being treated with brachytherapy. Conclusions: PSC appears to be an oncologically safe procedure with adequate functional outcomes in treating selected patients with BC.

Evaluation of prognostic factors in upper tract urothelial carcinoma (UTUC).

372 Background: UTUC is relatively rare (5-10% of UC). Limited data on prognostic factors is available. Methods: A retrospective study of UTUC patients (pts) who had surgery (1995-2014) at Cleveland Clinic (n = 454) was conducted. Univariable (UVA) and multivariable (MVA) analysis (proportional hazards) with a stepwise selection algorithm (p = .10 and .05, as criteria for entry and retention in the model) was used to identify independent predictors of recurrence-free survival (RFS) and overall survival (OS). Results: 192 pts with invasive high grade UTUC were identified; median age at resection was 72; 69% men. 72% of pts had laparoscopic and 17% open nephrouretectomy, 23% had +ve margins (including bladder/ureter cuff), 22% had multifocal tumor. Median tumor size 3.5 cm (0.2-12); 70% had tumors &lt; 5 cm; 65% pT3, 8% pT4 stage; among pts with lymph node (LN) dissection, 25% had +ve LN. All but 3 pts (2 sarcomatoid, 1 small cell) had primarily UC; 28% mixed UC histology; 40% CIS, 54% confirmed lymphovascular invasion (LVI); 10 neoadjuvant, 14 confirmed adjuvant therapy). Among 116 pts with RFS data available 59% had disease recurrence; 8% died with no known recurrence. Estimated median RFS was 13.1 months (m) (95%CI 8.6-18.6). In UVA, age, positive margins, tumor size, smoking history, pT stage, LVI, primary site impacted RFS. In MVA, margin status (p = .04), age (p = .04), pT stage (p = .05) were independently associated with RFS. Among 175 pts with OS data available, 38% died with estimated median OS 44.6 m (95%CI 24.1-107.4); median follow-up was 13.8 m (0.1-185.7) in pts alive at last follow up. In UVA, LVI, tumor size, age, pT stage, tumor location, ECOG PS impacted OS. In MVA, tumor size (p = .002), CIS (p = .004), tumor location (p = .04), LVI (p = .04) independently predicted OS. Using these factors, 3 prognostic groups were identified for each outcome (see table). Conclusions: Clinic-pathological parameters can be prognostic in UTUC; further validation is needed. [Table: see text]