bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell adhesion molecules in the progression of bladder cancer: The important role of cadherins and catenins.
Authors: Torres-Galea Patricia , Stoemmer Peter E. 
Published: March 2020

e15013 Background: Cell-adhesion- molecules (CAMs) are important factors in the maintenance of normal tissue structure, morphology, aggressivity and invasivity of tumors. Few CAMs, such as E-cadherin and its substitution by N-cadherin in the progression of urothelial neoplasia are wellknown. CAMs, such as cadherin P, catenins alpha and beta are much less known..We analysed their distribution in tumors of different patients and in respect to its architecture. Methods: 100 FFPE blocks of superficial ( pTa/ pTis and pT1) and myoinvasive (>pT1) carcinomas G1-3 were analysed by semiquantitative IHC- . Antibodies: E-Cadherin, P-Cadherin and Catenin Beta: Thermo Scientific, Freemont CA,USA . N-Cadherin Lab Vision, UK, Ltd, Catenin Alpha and H-CAM (CD44) Novocastra Laboratories Ltd. Results: E-Cadherin: Normal and reactive, inflammatory urothelium and dysplasia express high membranous E-cadherin-concentrations. High grade (HG) in-situ-carcinomas:discontinously ,intensively reacting cellmembranes; myoinvasive HG carcinomas lose their E-cadherin membranous component but show low diffuse intracytoplasmic reaction. N-Cadherin: in basal cells but not in normal transitional cells and LG dysplasia. High expression in HG dysplasia and deep invasive carcinomas, HG. P-cadherin:normal urothelium, as well as papillary LG and HG and CIS show an extensive membranous expression. Catenin alpha: high expression in pTa/pT1 LG tumors; low expression in myoinvasive carcinomas. Catenin beta: high membranous expression in normal and dysplastic urothelium as well as in in pTa LG tumors; low membranous cytoplasmic and intranuclear expression in myoinvasive carcinomas and HG tumors. Transition of beta-catenin from cellmembrane to nucleus in neoplasms was not visible Conclusions: E-Cadherin to N-Cadherin shift in the EMT destabilize tumorcells for CAMs, enabling by this the connection to fibrous tissues and augmenting the invasive potential. Catenins alpha and beta: strong prognosticators of progression and recidives; as they are integral parts of E-cadherin, they disappear together with E-cadherin in invasive tumor cell complexes.
Prognostic implications of perineural invasion following radical cystectomy for urothelial carcinoma.
Authors: Rao Manoj , Vellos Ted , Barkan Guliz , Gupta Gopal Nand , Flanigan Robert Charles , Quek Marcus Lee 
Published: March 2020

e15014 Background: Perineural invasion(PNI) with urothelial carcinoma may be identified in radical cystectomy specimens, and its prognostic significance is controversial. We sought to determine the incidence and prognostic implications of PNI in a cohort of patients undergoing radical cystectomy for primary bladder cancer. Methods: From January 1996 to June 2011, 440 patients underwent radical cystectomy for urothelial bladder cancer with curative intent. Presence of PNI was determined in the cystectomy specimens, in addition to other histopathologic variables (grade, stage, surgical margins, lymphovascular invasion, concomitant variant secondary histologic subtypes, and presence of carcinoma-in-situ). Recurrence and survival data were analyzed to determine the prognostic significance of PNI in this cohort. Results: PNI was identified in 101 patients (23%) in our series. Those with extravesical primary tumors (61/128, 48%) and node-positive disease (34/86, 40%) were more likely to have PNI than organ-confined tumors (<pT2; 10/183, 5%) (p<0.001). Median follow-up was 2 years (range: 0.1 to 12.5 years). Compared to those with no evidence of PNI, recurrence-free survival was worse in the PNI-positive extravesical (p=0.01) and node-positive (p=0.02) tumors. Overall survival was also worse for PNI-positive patients (p<0.001). On multivariate analysis, PNI was an independent risk factor for recurrence after radical cystectomy (p=0.01, RR=2.8: 95% CI 2.0-10.0). In the setting of PNI, adjuvant chemotherapy significantly improved overall survival(p=0.01). When analyzing PNI and lymphovascular invasion(LVI), there appears to be a worse recurrence-free survival for those who have both PNI and LVI than those with either alone(p<0.001). Conclusions: PNI with urothelial carcinoma may be associated with a worse prognosis, especially for extravesical and node-positive disease following radical cystectomy. Adjuvant chemotherapy may benefit those patients who have PNI. Patients who have both PNI and LVI may be at higher risk for disease recurrence.
Neoadjuvant cisplatin/gemcitabine chemotherapy for muscle invasive bladder carcinoma: A single institution experience.
Authors: Kalachand Roshni Deepa , McDonnell Felicity , McHugh Deaglan , McDermott Raymond 
Published: March 2020

e15016 Background: Neoadjuvant chemotherapy (NAC) with MVAC has been shown to improve overall survival in patients with muscle invasive transitional cell carcinoma of the bladder (MIBC), with pathological complete response (pCR) correlating with a survival benefit. Despite the lack of randomized data for cisplatin/gemcitabine (GC) in the neoadjuvant setting, it is commonly used in clinical practice, given its favorable toxicity profile and comparable efficacy to MVAC in the context of metastatic disease. Methods: Data was retrospectively obtained on 93 patients with T2-T4, N0-2 M0 MIBC treated with curative intent in our institution between 2005-2011. Characteristics of patients treated with GC NAC, along with treatment tolerance and outcomes, were collected. Results: Of 93 patients, 27% (n=25) were treated with GC NAC. Median age was 66 (range 49-81). 88% (n=22) of patients were clinical stage T3/4 and/or N1/2. 68% of patients received 28-day cycles of GC, with 32% receiving 21-day cycles of GC. One patient had split cisplatin dosing. 91% and 82% of planned cisplatin and gemcitabine were delivered, respectively. There were no treatment-related deaths. On completion of NAC, 52% (n=13) of patients underwent radical cystectomy, of whom 38% (n=5) achieved a pCR, and 62% (n=8) were downstaged to non-muscle invasive bladder cancer (nMIBC). Definitive chemoradiotherapy was used in 20% (n=5) of patients, whilst 12% (n=3) had no radical treatment due to progressive disease (n=2), or to a decline in ECOG performance status (n=1). Amongst patients without radical cystectomy, 12% (n=3) of patients achieved a biopsy-proven clinical complete response (cCR). In the intent-to-treat population, median disease-free survival was 32 months, and median overall survival 38.8 months. All patients with a pCR, cCR, or downstaging to nMIBC (n=12), were alive at a median follow-up of 16 months (3.9 – 49.1 months), although 1 patient had relapsed. Conclusions: GC is a well-tolerated regimen in the neoadjuvant treatment of MIBC, with a pCR rate comparable to that reported with MVAC. Our findings support the use of GC in the neoadjuvant treatment of MIBC.
The effect of neoadjuvant chemotherapy on pathologic downstaging and survival for patients with muscle-invasive bladder cancer with mixed histological features.
Authors: Lin James , Holder Dara Denise , Whalen Michael , Hruby Gregory , DeCastro Guarionex , McKiernan James M. 
Published: March 2020

e15019 Background: Urothelial carcinoma of the bladder (UCB) with mixed histological features (MH) is thought to portend a worse prognosis when compared to pure UC, based on reports of decreased survival for pure non-UC tumors. While patients with muscle-invasive UCB have been shown to derive a survival benefit from treatment with neoadjuvant chemotherapy (NC), the response of patients with MH is unclear. We sought to examine the pathologic and clinical outcomes of treatment with NC of patients with MH versus those with pure UC. Methods: Between 1990-2011, 318 patients were identified with clinical stage T2-T4a, N0-Nx, M0-Mx UCB who had either NC (+/- radical cystectomy) (n=67) or radical cystectomy (RC) alone (n=251). Among those given NC, 58% received methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and 24% received gemcitabine/cisplatin. 265 patients had pure UC and 53 patients had MH, defined as UC with concomitant squamous or glandular differentiation on final pathology (biopsy histology used if pT0 or RC not performed). Endpoints included downstaging to pT0 and overall survival. Multivariable Cox regression was used to estimate the effect of histological type (MH vs. pure UC) on all-cause mortality within each treatment arm (NC vs. RC only) and to test for treatment-by-histological type interaction. Results: The rate of downstaging to pT0 was significantly higher in NC treated patients (34.3%) compared to those with RC alone (4.4%, p<0.01). When stratified by histology, downstaging to pT0 was not significantly different for those treated with NC (37.0% for pure UC vs. 23.1% for MH, p=0.34). After adjusting for age, pathologic stage, and positive surgical margins on multivariate Cox regression, there was no difference in survival outcome for those with MH vs. pure UC (HR=1.5, p=0.5), nor for those treated with NC vs. RC only (HR=2.8, p=0.1). Conclusions: Prior evidence on the benefits of NC for patients with MH is mixed, but our data suggest that there is improvement in rate of pT0 on final pathology in those treated with NC, regardless of histology. As NC is not detrimental to the overall survival of MH patients, its administration should be continued.
Bilateral testicular germ cell tumors (TGCT) prevalence: The 24-year-long single-center experience.
Authors: Gamulin Marija , Grgic Mislav , Jajac Brucic Lana 
Published: March 2020

e15031 Background: Theetiology andreliable biomarkers for the risk of bilateral TGCT are still under investigation. Long-term relapse risks of up to 20 years after the therapy in contralateral testes demand a specific model of surveillance. Due to the rarity of the tumor type, reports of national experiences of bilateral TGCT are of a crucial significance for a future global database. Methods: The study was conducted during the treatment of 1 823 patients with TGCT in a single center from 1987-2011. Their mean age was 24 years at the time of diagnosis. Results: Out of 1 823 patients diagnosed with TGCT, 33 developed the bilateral disease (1.81%), 11 of them had synchronous tumors (33%). In the rest of patients the second testicular tumor was diagnosed 1 to 17 years after the initial diagnosis. The mean age of patients with bilateral TGCT was 28. According to the histological type: 11 were seminoma, 14 non-seminoma and 8 mixed seminoma and non-seminoma. Seven patients with bilateral tumor had a seminoma component at initial diagnosis. Compared to 5 patients out of 11 with synchronous tumor, the yolk sac component was detected only in 2 out of 22 metachronous patients. Conclusions: The presented findings of bilateral TGCT prevalence (1.8%) are in concordance with similar previous studies. As this type of tumor may be effectively treated, the risk assessment of metachronous tumor development should in future be facilitated by new biomarkers based on omics techniques. Thus, the investigation of karyotyping, c-KIT and transcriptome specificities will contribute to elucidation which pathways contribute to germ cell neoplasms. The stem cell markers for pluripotency maintenance may in future become potential diagnostic markers used as predictors for metastatic germ cell tumors. The development of a global database on these rare tumors will be of a crucial importance.
Over 100 cases of zero-ischemia robotic/laparoscopic partial nephrectomy: Is global renal ischemia necessary?
Authors: Leslie Scott , Abreu Andre Luis de Castro , Lee Dennis J , Berger Andre K , Goh Alvin , Ahmadi Hamed , Bruins Harman Maxim , Ukimura Osamu , Aron Monish , Desai Mihir , Gill Inderbir S 
Published: March 2020

e15060 Background: We report peri-operative and short-term outcomes of a novel technique of zero-ischemia robotic and laparoscopic partial nephrectomy (PN) for renal masses. Methods: From March 2010 to July 2011, 100 zero-ischemia robotic (n=40) and laparoscopic (n=60) PN were performed at our institution. The technique consists of performing micro-dissection of tertiary or higher-order renal arterial branches to super-selectively devascularize the tumor and surrounding parenchyma. Blood flow continues uninterrupted to the remainder of the kidney. As such, PN is performed without hilar cross-clamping. The procedure was offered to all-comers regardless of the tumor complexity or renovascular anatomy. Results: Median patient age was 59 years, tumor size was 3cm (0.9-13.6), baseline serum creatinine (SCr) was 1 mg/dl (0.5-2.6), and estimated glomerular filtration rate (eGFR) was 73 ml/min per 1.73m2 (24-149). 9 patients had a solitary kidney and 8 patients had multiple ipsilateral tumors. Overall, 70% of tumors were complex: central (43%), completely intra-renal (23%), cT1b >4cm (21%), and hilar (19%). Median (range) RENAL, PADUA and C-Index scores were 8 (4-11), 9 (6-13), 2.2 (0.5 c 13.2), respectively. Warm ischemia time was zero, median operative time was 275 min (126-534), estimated blood loss was 200cc, percent of kidney excised was 20 (5-70) and hospital stay was 4 days (2-20). There were 13 complications in 12 patients, with major complications, Clavien grade ≥3, in 4 patients. Histology confirmed malignancy in 80% of tumors. All surgical margins were negative for cancer. There were no significant difference for median percent change in SCr, 0 mg/dl (-31 to 215), and eGFR, -1 (-74 to 53), at discharge. In 65 patients with more than 2 months (median 219 days) follow up data available, median percent change in SCr and eGFR were 18 (-31 to 154), p<.001 and -18 (-66 t0 53), p<.001, respectively. 1 patient developed pulmonary metastases at 1 year follow up. Conclusions: Zero-ischemia robotic/laparoscopic PN without hilar clamping is feasible and safe. It could be performed even in the setting of complex tumors and various vascular anatomy scenarios. Eliminating global renal ischemia now appears achievable.
The effect of continuing therapy for more than one course and CRP level on PFS and OS in the general practice of sunitinib therapy in Japanese patients with metastatic renal cancer.
Authors: Takayama Hitoshi , Kawashima Atsunari , Arai Yasuyuki , Nin Mikio , Tanigawa Go , Yasunaga Yutaka , Nomura Hironori , Mukai Masatoshi , Yoshioka Toshiaki , Uemura Motohide , Nakai Yasutomo , Nishimura Kazuo , Tsujimura Akira , Nonomura Norio ,   Osaka Renal Cell Carcinoma Clinical Study
Published: March 2020

e15069 Background: Sunitinib is a multikinase inhibitor used as first- and second-line treatment of metastatic renal cell carcinoma (mRCC). However, there are few reports on the efficacy and adverse events (AE) profile of sunitinib in general practice with Japanese patients. We examined clinical outcomes of sunitinib therapy in a multi-institutional study. Methods: A study population of 98 mRCC patients was eligible for this investigation. Clinical outcomes were evaluated according to clinical features and duration of therapy. Results: he most frequent grade 3/4 laboratory AE were decreased platelet (30.6%) and white blood cell (20.4%) counts. Treatment was discontinued in 20 patients (32.8%) initially receiving a 50-mg/day dose within only one course, and only 2 patients (3.3%) who were initially medicated with 50 mg/day could continue this oral dose. Median PFS time was 2.3 months in patients treated for only one course and 10.8 months in patients treated for more than one course (P < 0.0001). Multivariate analysis showed that duration of treatment, regardless of initial sunitinib dose (50 mg/day or <50 mg/day) was significantly associated with both PFS (HR: 0.120, 95% CI: 0.049-0.294, P < 0.001) and OS (HR: 0.196, 95% CI: 0.082-0.472, P < 0.001). Moreover, C-reactive protein level was significantly associated with PFS and OS times. Conclusions: Sunitinib therapy of 50 mg/day might be an overdose in Japanese patients. Continuing therapy for more than one course and CRP level were very important in the prolongation of PFS and OS times.
External validation of a sunitinib prognostic nomogram in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Yu Changhong , Kattan Michael W. , Hutson Thomas E. , Hudes Gary R. , Yuan Jinyu , Valota Olga , Motzer Robert John 
Published: March 2020

e15070 Background: A nomogram was previously developed from pretreatment clinical features to predict the probability of achieving 12-month progression-free survival (PFS) with sunitinib in treatment (Tx)-naïve mRCC pts from a randomized, phase 3 trial (Cancer 2008;113:1552). Here, validation and update of this nomogram using pts from a phase 2 sunitinib mRCC study (Renal EFFECT Trial) is reported, as is evaluation of its usefulness for clinical decision making. Methods: The Tx-naïve mRCC pts included in the current analysis were randomized 1:1 to sunitinib 50 mg/d on a 4-weeks-on-2-weeks-off schedule (Schedule 4/2; n=146) or 37.5 mg/d on a continuous daily dosing (CDD) schedule (n=146). The variables included in the prior nomogram and used here for validation purposes were corrected serum calcium, number of metastatic sites, hemoglobin, prior nephrectomy, presence of lung and liver metastases, ECOG performance status, thrombocytosis, time from diagnosis to treatment, alkaline phosphatase, and lactate dehydrogenase. The nomogram was updated by removing prior nephrectomy as a variable, including baseline neutrophils and presence of bone metastases, and replacing thrombocytosis with baseline platelets. Validation of the existing and updated nomograms consisted of quantification of the discrimination with the concordance index. A decision curve analysis was used to examine whether this prediction model is useful for medical decision making. Results: With comparable pt characteristics and no significant difference in PFS (8.5 vs. 7.0 months; P=0.070) between the Schedule 4/2 and CDD arms of the phase 2 trial, the combined pt population (N=292) was used to validate the existing nomogram. The overall concordance index was 0.615. Based on the decision curve analysis, the existing nomogram has clinical utility when the probability of 12-month PFS exceeds 60%. Using Schedule 4/2 pts only, the concordance index was 0.594 for the updated nomogram; however, its utility showed more variability. Conclusions: The sunitinib nomogram has been validated in a similar pt cohort; however, its clinical utility may be limited and more research is needed to refine the tool further.
Translocation renal cell carcinomas: An evolving entity.
Authors: Power Derek Gerard , Battley Jodie E , McCarthy Aoife , Brady Claire , Sweeney John P. , Fleming Stewart , Mayer Nicholas J. , Bambury Richard Martin 
Published: March 2020

e15078 Background: Translocation renal cell carcinomas (tRCCs) are a novel, rare and distinct clinicopathological entity. The term refers to RCCs with overexpression of transcription factor E3 (TFE3) due to translocation involving the Xp11 locus or less commonly with overexpression of transcription factor EB (TFEB) due to a t(6:11) translocation. In children it is estimated that these tumours account for 40% of RCCs but in adults this proportion is estimated to be 1-4%. These neoplasms are only recently recognised and outcome data are premature. We report 2 cases of tRCC in an Irish regional cancer centre and describe clinicopathological characteristics and early outcome. Methods: : Approximately 70 new cases of RCC are referred to our centre annually. Recently, 2 renal cell carcinomas were suspected to be tRCCs on morphology and immunohistochemical(IHC) features (RCC+/CK7-/EMA-). Using IHC we tested for expression of TFE3 and TFEB. Results: : Both tumours were tRCCs. The first case was a 74 year old lady who presented with right upper quadrant pain and had a 9cm right renal mass with no metastatic disease on CT imaging. Radical nephrectomy was performed and histology revealed a pT3aN2, Fuhrman grade 4 RCC with mixed clear cell and papillary architecture. IHC for TFE3 showed focal nuclear positivity consistent with an Xp11 translocation RCC. She relapsed 9 months later with local recurrence, retroperitoneal adenopathy and lung metastases. She commenced sunitinib and response assessment is pending. The 2nd case was a 46 year old man with an incidental finding of a right renal mass on ultrasound abdomen. Staging CT revealed no metastatic disease and he underwent laparoscopic nephrectomy. Histology revealed a pT1aNx, Fuhrman grade 3 renal cell carcinoma with predominantly alveolar architecture and focal papillary and microcystic areas. IHC for TFEB was positive consistent with a t6:11 translocation RCC. He remains disease free 9 months post surgery. Conclusions: We report 2 new cases of this rare subset of RCC. The therapeutic implications for patients with these mutations are as yet unclear. We plan to update with ongoing follow-up and will also report 3 further cases suspected to be tRCCs based on morphology and IHC. Confirmatory TFE3/TFEB IHC is awaited.
Clinical analysis of introduction chemotherapy for advanced germ cell tumors at Japanese high-volume center.
Authors: Nakamura Terukazu , Mikami Kazuya , Kimura Yasunori , Hongo Fumiya , Takaha Natsuki , Miki Tsuneharu 
Published: March 2020

e15099 Background: Recently, cure rate of advanced testicular cancer even with poor prognostic factors have much improved. Inadequate treatment, however, may lead the patients "difficult-to-treat" situation. The aim of this study is to assess the results of the induction therapy at the Japanese single high volume center. Methods: We assessed clinical outcomes about 82 cases of advanced germ cell tumors that had induction chemotherapy at our hospital from Jun, 1998 until Dec, 2010. Results: Median age was 58 year-old (range:17-34y.o.). Seminoma was found in 16 cases (19.5%) and non-seminoma in 66 cases (80.5%), regarding primary histology. Clinical stageII was 37 cases, stageIIIA, IIIB, IIIC was 8, 24, 13 cases, respectively. IGCCC showed good in 41 cases (50%), intermediate 25 (30.5%), poor 15 (19.5%). BEP therapy was done in 74 (90.3%), EP 5 (6.1%), VIP 2 (2.4%) and PVB 1 (1.2%). Median cycles of induction therapy was 4 (range 1~5). Complete response was observed in 14 cases (17.1%), partial response with marker normalization in 58.5%, partial response without marker normalization in 12.2%, progressive disease in 8.5% including 4 cases of growing teratoma. RPLND after induction therapy was performed in 55 patients. Necrosis was found in 56.4%, teratoma only in 27.3% and viable cancer in 16.3%. Patients with salvage chemotherapy were 22 (27.5%) cases. Five- and 10-year overall survival was 93.3% and 89.6%, respectively. Clinical outcomes at 63 months of median follow-up was as follows; no evidence of disease 73 cases (89.0%), alive with disease 1case (2.4%) and death 7 cases (8.6%). Stratified by IGCCC, 5-year overall survival was 97.6% in good prognosis, 96.0% in intermediate prognosis and 79.0% in poor prognosis. Causes of death were as follows; pancreatic juice leakage after RPLND in 1 case, cerebral infarction in 1 case, cerebral bleeding in 1 case, traffic accident in 1 case, and cancer death in 3 cases. Conclusions: Clinical outcomes at Japanese high volume center were good, especially in good and intermediate prognosis. It was very clear that improvement of poor prognosis, especially high tumor volume, was required.