Browsing by Subject "urothelial carcinoma"

Now showing 1 - 6 of 6
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    Clinicopathological characteristics of ypT0N0 urothelial carcinoma following neoadjuvant chemotherapy and cystectomy
    (BMJ, 2019-08) Magers, Martin J.; Kaimakliotis, Hristos Z.; Barboza, Marcelo P.; Bandali, Elhaam; Adra, Nabil; Koch, Michael O.; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
    Aims To describe a large tertiary care academic centre’s experience with patients who achieve a complete pathological response (ie, ypT0N0) following neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with emphasis on morphological features present in the RC and clinical outcome. Methods 41 patients with ypT0N0 disease following transurethral resection of bladder tumour (TURBT), NAC and RC with available clinical follow-up information were analysed. Slides from all RCs were reviewed to confirm pathological stage and assess for morphological parameters (eg, foreign body giant cell reaction, dystrophic calcification, scar and fat necrosis). Results With median follow-up of 32.8 months, the recurrence-free survival at 1 and 5 years was 97.4% and 93.5%, while the overall survival at 3 and 5 years was 94.2% and 88.6%, respectively. No patients died of urothelial carcinoma. Stage assigned at TURBT was 1 pTa (2%), 1 pT1 (2%), 38 pT2 (93%) and 1 pT3a (2%). 17 TURBTs demonstrated variant histology, with the majority of these being squamous (65%). The most common morphological features present at RC were scar (100%), foreign body giant cell reaction (80%), chronic inflammation within lamina propria (68%) and dystrophic calcifications (39%). Other morphological features were less common or absent. Conclusion ypT0N0 disease at RC portends an excellent prognosis, regardless of stage or variant histology in the TURBT; scar, foreign body giant cell reaction, chronic inflammation and dystrophic calcifications are often present.
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    Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma
    (MDPI, 2020-06-02) Mollica, Veronica; Rizzo, Alessandro; Montironi, Rodolfo; Cheng, Liang; Giunchi, Francesca; Schiavina, Riccardo; Santoni, Matteo; Fiorentino, Michelangelo; Lopez-Beltran, Antonio; Brunocilla, Eugenio; Brandi, Giovanni; Massari, Francesco; Pathology and Laboratory Medicine, School of Medicine
    Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials.
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    Evolving concepts of micropapillary variant urothelial carcinoma
    (AME, 2016-12) Monn, M. Francesca; Cheng, Liang; Department of Urology, School of Medicine
    Micropapillary variant (MPV) urothelial carcinoma remains an uncommon, challenging to treat entity. Recent research has emerged that examines the genetic expression profile of MPV urothelial carcinoma and provides a new perspective on this challenging to treat form of bladder cancer. Ongoing research is necessary to determine the most appropriate treatment algorithms for managing patients with MPV urothelial carcinoma.
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    Immune checkpoint inhibitors for metastatic bladder cancer
    (Elsevier, 2018-03) Massari, Francesco; Di Nunno, Vincenzo; Cubelli, Marta; Santoni, Matteo; Fiorentino, Michelangelo; Montironi, Rodolfo; Cheng, Liang; Lopez-Beltran, Antonio; Battelli, Nicola; Ardizzoni, Andrea; Pathology and Laboratory Medicine, School of Medicine
    Chemotherapy has represented the standard therapy for unresectable or metastatic urothelial carcinoma for more than 20 years. The growing knowledge of the interaction between tumour and immune system has led to the advent of new classes of drugs, the immune-checkpoints inhibitors, which are intended to change the current scenario. To date, immunotherapy is able to improve the overall responses and survival. Moreover, thanks to its safety profile immune-checkpoint inhibitors could be proposed also to patients unfit for standard chemotherapy. No doubts that these agents have started a revolution expected for years, but despite this encouraging results it appears clear that not all subjects respond to these agents and requiring the development of reliable predictive response factors able to isolate patients who can more benefit from these treatments as well as new strategies aimed to improve immunotherapy clinical outcome. In this review we describe the active or ongoing clinical trials involving Programmed Death Ligand 1 (PD-L1), Programmed Death receptor 1 (PD-1) and Cytotoxic-T Lymphocyte Antigen 4 (CTLA 4) inhibitors in urothelial carcinoma focusing our attention on the developing new immune-agents and combination strategies with immune-checkpoint inhibitors.
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    Plasmacytoid/diffuse urothelial carcinoma: a single-institution immunohistochemical and molecular study of 69 patients
    (Elsevier, 2019-08) Perrino, Carmen M.; Eble, John; Kao, Chia-Sui; Whaley, Rumeal D.; Cheng, Liang; Idrees, Mohammad; Hashemi-Sadraei, Neda; Monn, M. Francesca; Kaimakliotis, Hristos Z.; Bandali, Elhaam; Grignon, David; Pathology and Laboratory Medicine, School of Medicine
    Accurate diagnosis of plasmacytoid urothelial carcinoma (PUC) is important given its poor prognosis and frequent presentation at high stage. We aim to assess the clinicopathological features, molecular aberrations, and follow-up data in a series of PUC cases from a single tertiary cancer center. Seventy-two urinary bladder, ureteral, and renal pelvic specimens with urothelial carcinoma with plasmacytoid differentiation were identified. Immunohistochemical stains were performed on 48 cases. Among urinary bladder origin markers, GATA3 was most sensitive (96%). Breast carcinoma markers (estrogen receptor, mammaglobin) were usually negative, but progesterone receptor stained 1 case (4%). Neuroendocrine markers CD56 and TTF-1 were each positive in 1 case (4% and 4%, respectively). Gastrointestinal adenocarcinoma marker CDX2 was positive in 4 cases (15%), but nuclear β-catenin was negative in all cases. CD138 was positive in 83% and E-cadherin expression was lost in 57% of cases. Fluorescence in situ hybridization using the UroVysion Bladder Cancer Kit and FGFR3 mutational analysis using polymerase chain reaction were performed on 15 cases; deletion of chromosome 9p21 was common (60%), and FGFR3 mutations were detected in 60% of cases (5 cases had both deletion 9p21 and FGFR3 mutations). Cases were divided into 3 morphologic groups: classic (29%), desmoplastic (35%), and pleomorphic (36%). The 3 morphologic subtypes had distinct survival outcomes (P = .083), with median survival for all patients 18 being months versus 10 months for the desmoplastic group.
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    Variant morphology in upper urinary tract urothelial carcinoma: a fourteen-year case series of biopsy and resection specimens
    (Elsevier, 2017) Hayashi, Hiroyuki; Mann, Steven; Kao, Chia-Sui; Grignon, David; Idrees, Muhammad T.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Upper urinary tract urothelial carcinoma exhibiting variant morphology, especially in higher-grade tumors, is a recognized phenomenon but has not been comparatively studied in biopsy versus resection material. We studied the morphologic patterns and clinicopathological features, and provide a comparison between biopsy and resection specimens. Consultation cases were evaluated separately to investigate for possible consultation bias. A total of 383 in-house cases from 352 patients including 314 resection specimens and 69 biopsies from 2001–2014 were reviewed from a single institution. Histologic type, tumor grade, invasion, pathologic stage, nodal status, metastasis, and the presence and type of variant morphology for each case were evaluated. Variant morphology was identified in 5 biopsy specimens (7.2%) and 42 resection specimens (13.4%). The most common variant morphologic pattern was squamous differentiation (16 cases, 4.5%) followed by an inverted growth pattern (8 cases, 2.2%). The presence of variant morphology in resection specimens had a significant association with higher tumor grade, higher pT stage, and non-papillary configuration. Out of 69 patients with biopsies, 31 had a subsequent resection. In comparison, 181 consultation cases from 168 patients showed variant morphology in six biopsies (7.1%) and twenty-seven resections (28.1%). In conclusion, the frequency of recognizing variant morphology in biopsies is about one-half of that in resections. The inclusion of consultation cases can inflate the incidence of variant morphology. As a result, the frequency of variant morphology in our in-house cases is lower than the percentage reported in the literature, most likely secondary to a consultation bias.