Abstract presentati all’AUA 2017
The activity of intravesical hyaluronic acid and chondroitin sulfate administration on urothelial gene expression of Epidermal Growth Factor Receptor and Fibronectin: Assessment in bladder washing of patients affected by non muscle-invasive bladder cancer.
Scalici Gesolfo C.1, , Di Maida F.1, Dispensa N1, Billone S1, Cangemi A.2, Russo A.2, Simonato A.1, Serretta V.1, GSTU Foundation, Palermo, Italy
1University of Palermo, Dept. of Urology, Palermo, Italy, 2University of Palermo, Dept. of Medical Oncology, Palermo, Italy
Introduction & Objectives: Hyaluronic acid (HA) and chondroitin sulfate (CS) are two major constituents of the bladder glycosaminoglycan layer. Recent data show that Fibronectin (FN) and Epidermal Growth Factor Receptor (EGFR) gene expression can be measured in bladder washings and could represent potential biomarkers of urothelial damage and tumor aggressiveness, respectively (1,2). The aim of our study was to investigate the interference of a single intravesical instillation of HA-CS solution on the expression of FN and EGFR genes in patients affected by non-muscle-invasive bladder cancer (NMIBC).
Material & Methods: A prospective double-blinded study included patients undergoing adjuvant intravesical therapy for NMIBC and age matched healthy controls. For EGFR evaluation, a single HA-CS solution was administered intravesically 14 days after transurethral resection of high risk NMIBC, before the start of the adjuvant therapy. For FN evaluation, a single HA-CS instillation was administered to patients showing local toxicity secondary to intravesical adjuvant therapy. Samples of bladder washings were collected before and one week after the HA-CS instillation, obtaining a cellular pellet stored at -80 °C. Cellular RNA was isolated by a miRNeasy Mini Kit (Qiagen®) and cDNA, obtained using a “High Capacity cDNA Reverse Transcription Kit” (Life Technologies®) was used to perform a gene expression analysis by a Real Time PCR. EGFR and FN gene expression values were expressed in FOLDs of change compared to healthy controls (FN and EGFR=1).
Results: Thirty-eight patients and 5 controls entered the study. Seventeen and 21 patients were evaluated for FN and EGFR respectively. In 21 patients with high risk NMIBC, the median EGFR expression decreased from 2.4 folds (range: 0.1-39.0) to 1.0 fold (range: 0.05-36.8) showing a statistically significant decrease of 58.3% (p<0.02). In patients showing clinically relevant toxicity secondary to intravesical adjuvant therapy (BCG in 9 and Epirubicin in 8 patients) the median FN expression value dropped from 1.8 folds (range: 0.07-8.1) to 0.9 fold (range: 0.1-7.5) after HA-CS administration with a statistically significant decrease of 50% (p<0.05).
Conclusions: FN gene expression in bladder washings appears related to the intensity of the urothelial damage, reaching higher expression levels in case of severe toxicity induced by intravesical adjuvant therapy (2). In our experience the FN gene expression
significantly decreases a week after the administration of HA-CS solution with contemporary symptomatic relief. Moreover the urothelial EGFR gene expression resulted significantly lowered one week after the HA-CS intravesical administration. The reduced availability of its receptor could limit the proliferative activity of EGF on the urothelium promoting recurrence and progression.
Acknowledgements: GSTU Foundation
References: 1. Serretta V, et al. Feasibility of EGFR evaluation in bladder washings of patients affected by non muscle-invasive bladder cancer. J Urol, 2016. 195 (4S): e327. 2. Alonge V, et al. Correlation between Fibronectin gene expression and local toxicity induced by adjuvant intravesical therapy. J Urol, 2015. 193 (4S): e539.
EGFR CELL EXPRESSION IN BLADDER WASHINGS AS A RISK MARKER TOOL IN NON MUSCLE-INVASIVE BLADDER CANCER. PRELIMINARY EXPERIENCE
Fabrizio Di Maida*, Vincenzo Serretta, Cristina Scalici Gesolfo, Marco Vella, Antonella Cangemi, Antonio Russo, Alchiede Simonato, GSTU Foundation, Palermo, Italy
INTRODUCTION AND OBJECTIVES: Up to day, EGFR expression has been determined mainly in tissue specimens of muscleinvasive bladder cancer and its overexpression has been associated with worse prognosis and shorter survival. Urothelial EGFR status after NMIBC transurethral resection (TUR) could indicate the risk of recurrence and progression. We investigated the feasibility of EGFR measurement in bladder washings of patients undergoing intravesical adjuvant therapy for NMIBC and its usefulness in identifying risk subgroups.
METHODS: Our prospective study included patients after TUR of NMIBC and healthy controls. A cellular pellet was obtained from bladder washing, and RNA extraction performed by miRNeasy Mini Kit (Qiagen). Good quality of RNA was checked. The cDNA obtained from RNA was used to perform a gene expression analysis by a Real Time PCR, according to the method of the comparative quantification (DDCt) with an endogenous control (Cyclophilin). Every reaction was set in triplicate as a guarantee of quality. Patients were grouped for EAU risk class and maintained in follow-up. The EGFR expressions were statistically analyzed according to EAU risk groups and to patients’outcome. EGFR gene expression values were expressed in FOLDs of change compared to healthy controls (EGFR=1).
RESULTS: Fifty-eight patients and 21 healthy age-matched controls were entered. An adequate cellular pellet was obtained in 50 patients (86.2%) showing a median EGFR expression of 2.0 folds (IQR 0.6-4.3, p=0.0004). After TUR and adjuvant intravesical therapy, 22 (55%) out of 40 high-risk patients, showed EGFR decrease to 1.3 folds (IQR 0.9-1.5), while 18 (45%) showed elevated EGFR, median 4.7 (IQR 4.1-11.6). At 25 months median follow-up (IQR 19.0-34.8), 20 (40%) patients recurred and 6 (12%) progressed. Among patients with or without EGFR gene increase, 9 (22.5%) and 5 (12.5%) recurred and 5 (12.5%) and 1 (2.5%) progressed, respectively.
CONCLUSIONS: In our experience EGFR expression measurement was feasible in more than 85% of patients and resulted related to EAU risk classes for recurrence and progression, showing different behavior during intravesical therapy. It was possible to identify a subgroup of high risk patients overexpressing EGFR in spite of intravesical adjuvant therapy. EGFR evaluation in bladder washing could represent a repeatable and useful tool to identify a subgroup of patients at risk for progression unresponsive to intravesical adjuvant therapy and candidate to early radical cystectomy.
Source of Funding: none
LIMITS OF TRANSURETHRAL RESECTION IN DETECTING UNCOMMON HISTOLOGICAL VARIANTS WITHIN BULKY BLADDER TUMORS IN REAL-LIFE CLINICAL PRACTICE
Cristina Scalici Gesolfo*, Alessio Guarneri, Sandro Billone, Palermo, Italy; Marco Moschini, Renzo Colombo, Matteo Ferro, Ottavio De Cobelli, Milan, Italy; Alchiede Simonato, Vincenzo Serretta, Palermo, Italy
INTRODUCTION AND OBJECTIVES: Rare histotypes represent almost 10% of bladder tumors, more often represented within large and muscle invasive transitional cell carcinomas of the bladder (MIBC). Neoadjuvant chemotherapy is recommended (Grade A) by international guidelines. Rare histological variants, more aggressive and less responsive to systemic chemotherapy might remain unrecognized at initial transurethral resection (TURBT) in everyday clinical practice. We investigated the accuracy of TURBT in detecting rare histological variants in patients with large bladder tumors candidate to cystectomy.
METHODS: The clinical and pathologic data of 540 patients submitted to TURBT and/or cystectomy for bladder cancer between Jan. 2010 and Oct. 2016, were reviewed. The presence of uncommon histotypes within urothelial bladder carcinoma has been assessed. Rare variants were diagnose according WHO criteria. Standard hematoxilyn-eosin stain was adopted and further immunohistochemistry was performed. Inferential statistical analysis was performed.
RESULTS: Out of 540 patients, 43 (7,9%) showed rare histotypes of bladder cancer. In 5 (11,6%) cases the uncommon histotypes was revealed by palliative TURBT . The remaining 38 patients were submitted to cystectomy for bladder tumors of considerable size (mean diameter 7,8 cm; range of 5-11 cm); 14 (36,8%) harbored a pT4 tumor. The rare histotypes were: squamous carcinoma 6 (13,9%), sarcomatoid 2 (4,8%), undifferentiated 5 (11,6%), neuroendocrine 3 (6,9%), mixed 27 (62,8%). TUR revealed an uncommon histotypes in 26 (68,4%) cases only. Moreover, in 5 (23.8%) patients an additional uncommon histology not detected by previous TUR, was demonstrated in cystectomy specimens.
CONCLUSIONS: The prognostic role of uncommon histotypes in bladder cancer is well documented. Unrecognized rare histotypes might have important therapeutic implications since possibly less responsive to neoadjuvant chemotherapy. These patients could benefit from an immediate cystectomy avoiding neo-adjuvant chemotherapy. The inaccuracy of TUR in everyday clinical practice in detecting uncommon variants could be explained by an inadequate sampling of large tumors. The “pre-cystectomy” TUR is often performed only to confirm the infiltration. As a matter of fact, the pathologists might not receive an adequate amount of tissue. To standardize the TURBT strategy including sampling of different areas of bulky tumors could be of clinical value in patients undergoing neoadjuvant chemotherapy.
Source of Funding: none
Virtual multidisciplinary managemen of difficult urological cases adopting Whatsapp Messenger as a real-time tool
Serretta V.1, Scalici Gesolfo C.1, Fazio I.2, Mortellaro G.3, Blasi L.4, Borsellino N.5, Spada M.6, Ferrera G.4, Rinaldi G.7, La Paglia L.2, Adamo M.S.8, Cicero G.7, Curti Giardina M.9, Di Trapani D.10, Di Maida F.1, GSTU Foundation, Palermo, Italy 1University of Palermo, Dept. of Urology, Palermo, Italy, 2″Macchiarella” Clinic, Dept. of Radiation Oncology, Palermo, Italy, 3ARNAS Civico Hospital, Dept. of Radiation Oncology, Palermo, Italy, 4ARNAS Civico Hospital, Dept. of Medical Oncology, Palermo, Italy, 5″BuccheriLa Ferla” Hospital, Dept. of Medical Oncology, Palermo, Italy, 6Fondazione Istituto G. Giglio, Dept. of Medical Oncology, Cefalù, Italy, 7University of Palermo, Dept. of Medical Oncology, Palermo, Italy, 8University of Palermo, Clinical Epidemiology and Cancer Registry, Palermo, Italy, 9A.S.P. 209, Dept. of Urology, Trapani, Italy, 10″Buccheri-La Ferla” Hospital, Dept. of Urology, Palermo, Italy
Introduction & Objectives: Communication between doctors is traditionally conducted by written clinical charts. Mobile health is becoming an integral part of modern healthcare system, improving accessibility and quality of medical care. Recent papers suggest that an increasing number of doctors are using in their practice mobile tools to communicate clinical informations (1,2). The aim of our study was to verify the adoption of WhatsApp Messenger in everyday clinical practice to obtain a real-time multidisciplinary collaboration among medical centers located in different areas of the city.
Material & Methods: In January 2016 a WhatsApp Messenger group was created among 25 specialists: 9 urologists, 9 oncologists, 3 urology residents, 3 radiotherapists and 1 general practitioner. A general coordinator and a group coordinator for each speciality was monthly appointed. The participants were invited to condivide within the group clinical cases of genitourinary tumors of particular complexity requiring a multidisciplinary approach. All the chats were registered. A preliminary analysis of the activity of the group was planned after the first 10 entered patients. An evaluation questionnaire was sent after 6 months to evaluate the level of appreciation. The questionnaire was composed of a first section investigating the appreciation among the members of the group and a second section analyzing the impact in their everyday clinical practice of whatsapp multidisciplinary consultation.
Results: In 10 (91%) out of 11 patients the WhatsApp consultation was completed, one case was not of oncological interest. An average of 8 (range: 2-13) specialists joined the chat for each patient. An average of 17.6 (range: 4-43) interventions for each clinical case was recorded. On the average, 27% (range: 0-45), 54% (range: 33-67) and 19% (range: 0-33) of the interventions for each clinical case were provided by oncologists, urologists and radiotherapists respectively. In 9 (81.8%) cases a final agreement on patient’s management was reached. At the evaluation questionnaire in a scale 110, the average rating score of appreciation was 7.8 (range: 4-10). Relevant suggestions to improve the Whatsapp Messenger consultation were obtained and will be considered to ameliorate the tool.
Conclusions: WhatsApp is a useful alternative and a powerful complementary communication tool because of its capability to rapidly transfer large amounts of clinical and radiological data. In our
experience this approach improved multidisciplinary collaboration among different specialists in different areas of the city through an easier and more informal change of opinions. In complex cases a rapid multidisciplinary approach permitted a personalized management and a tailored therapy for the patient.
Acknowledgments: GSTU Foundation
References: 1. Sidhoum N. et al. WhatsApp: Improvement tool for surgical team communication. J Plast Reconstr Aesthet Surg, 2016. [Epub ahead of print]. 2. Gould G. et al. WhatsApp Doc? BMJ Innov. 2016 Jul; 2(3): 109–110.