Robotic surgery in public hospitals of Latin-America: a castle of sand?

INTRODUCTION: There is no information about the evolution of robotic programs in public hospitals of Latin-America. OBJECTIVE: To describe the current status and functioning of robotic programs in Latin-American public hospitals since their beginning to date. METHODS: We conducted a survey among leading urologists working at public hospitals of Latin-America who had acquired the Da Vinci laparoscopic-assisted robotic system. Questions included: date the program started, its utilization by other services, number and kind of surgeries, surgery paying system, surgery related deaths, occurrence and reasons of robotic program interruptions and its use for training purposes. Medians and 25-75 centiles (IQR) were estimated. RESULTS: Since 2009, there are ten public hospitals of four Latin-American countries that acquired the Da Vinci robotic system. The median number of months robotic programs has been functioning without considering transitory interruption: 43 (IQR 35, 55). Median number of urologic and total surgeries performed: 140 (IQR 94, 168) and 336 (IQR 292, 621), respectively. The corresponding median number of urologic and total surgeries performed per month: 3 (IQR 2, 5) and 8 (IQR 5, 11). Median number of total surgeries performed per year per institution was 94 (IQR 68,123). The median proportion of urologic cases was 40% (IQR 31, 48), ranging from 24 to 66%. Five of ten institutions had their urology programs transitory or definitively closed due to the high burden costs. CONCLUSION: Adoption and development of robotic surgery in some public hospitals of Latin-America have been hindered by high costs.

First Brazilian Consensus of Advanced Prostate Cancer: Recommendations for Clinical Practice.

INTRODUCTION: Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. OBJECTIVES: This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. MATERIALS AND METHODS: Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. RESULTS AND CONCLUSIONS: The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions.

Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience.

PURPOSE: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. MATERIAL AND METHODS: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. RESULTS: Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. CONCLUSION: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations.

BACKGROUND: Intronic and intergenic long noncoding RNAs (lncRNAs) are emerging gene expression regulators. The molecular pathogenesis of renal cell carcinoma (RCC) is still poorly understood, and in particular, limited studies are available for intronic lncRNAs expressed in RCC. METHODS: Microarray experiments were performed with custom-designed arrays enriched with probes for lncRNAs mapping to intronic genomic regions. Samples from 18 primary RCC tumors and 11 nontumor adjacent matched tissues were analyzed. Meta-analyses were performed with microarray expression data from three additional human tissues (normal liver, prostate tumor and kidney nontumor samples), and with large-scale public data for epigenetic regulatory marks and for evolutionarily conserved sequences. RESULTS: A signature of 29 intronic lncRNAs differentially expressed between RCC and nontumor samples was obtained (false discovery rate (FDR) < 5%). A signature of 26 intronic lncRNAs significantly correlated with the RCC five-year patient survival outcome was identified (FDR < 5%, p-value ≤ 0.01). We identified 4303 intronic antisense lncRNAs expressed in RCC, of which 22% were significantly (p < 0.05) cis correlated with the expression of the mRNA in the same locus across RCC and three other human tissues. Gene Ontology (GO) analysis of those loci pointed to 'regulation of biological processes' as the main enriched category. A module map analysis of the protein-coding genes significantly (p < 0.05) trans correlated with the 20% most abundant lncRNAs, identified 51 enriched GO terms (p < 0.05). We determined that 60% of the expressed lncRNAs are evolutionarily conserved. At the genomic loci containing the intronic RCC-expressed lncRNAs, a strong association (p < 0.001) was found between their transcription start sites and genomic marks such as CpG islands, RNA Pol II binding and histones methylation and acetylation. CONCLUSION: Intronic antisense lncRNAs are widely expressed in RCC tumors. Some of them are significantly altered in RCC in comparison with nontumor samples. The majority of these lncRNAs is evolutionarily conserved and possibly modulated by epigenetic modifications. Our data suggest that these RCC lncRNAs may contribute to the complex network of regulatory RNAs playing a role in renal cell malignant transformation.

Penile primary melanoma: analysis of 6 patients treated at Brazilian National Cancer Institute in the last eight years.

PURPOSE: To describe our experience in treating penile melanoma in 06 patients followed at our institution. MATERIALS AND METHODS: Between 2004 and 2012 six consecutive patients with penile melanoma were treated at our Institution. Stage of the disease was classified according to the 2002 AJCC pathologic system. Melanoma in situ (TIS) was diagnosed in one patient. One patient was staged as T1b, two patients as T2b and two patients as T4b. The clinical and pathological findings were evaluated. Immunohistochemical tests were performed for Melan-A, HNB-45, S-100 and C-KIT. All histological specimens were examined by the same pathologist (ABSS). The patients with Cis, stages T1b and one patient T2b underwent only local excision. One patient T2b underwent local excision and sentinel lymph node dissection. Two patients with melanoma stage T4b underwent partial penile amputation. One of these last patients had palpable inguinal lymph nodes at diagnosis and underwent bilateral inguinal lymphadenectomy and received systemic chemotherapy (dacarbazine, 30 cycles). RESULTS: Mean follow-up was 36.3 months. One patient, with stage T2b, died after 12 months due to disease recurrence with bilateral inguinal involvement. The patient who underwent chemotherapy progressed with lung metastases and died after 14 months of follow up. The disease-free survival at five years was 33.3%. CONCLUSION: Penile melanoma is a disease with poor prognosis in most cases. Local excision or partial penile amputation may have effective control for stages T1 and T2 lesions. Patients who have clinically proven metastases died despite surgical and adjuvant chemotherapy.

Recommendations on robotic-assisted radical prostatectomy: a Brazilian experts' consensus.

Radical prostatectomy is a commonly adopted treatment for localized/locally advanced prostate cancer in men with a life expectancy of ten years or more. Robotic-assisted radical prostatectomy (RARP) is comparable to open radical prostatectomy on cancer control and complication rates; however, new evidence suggests that RARP may have better functional outcomes, especially with respect to urinary incontinence and erectile dysfunction. Some of the surgical steps of RARP are not adequately described in published literature and, as such, may have an impact on the final outcomes of the procedure. We organized a Brazilian experts' panel to evaluate best practices in RARP. The confection of the recommendations broadly involved: selection of the experts; establishment of working groups; systematic review of the literature and elaboration of a questionnaire; and construction of the final text with the approval of all participants. The participants reviewed the publications in English from December 2019 to February 2020. A one-round Delphi technique was employed in 188 questions. Five reviewers worked on the final recommendations using consensual and non-consensual questions. We found 59.9% of questions with greater than 70% agreement that were considered consensual. Non-consensual questions were reported according to the responses. The recommendations were based on evidence-based literature and individual perceptions adapted to the Brazilian reality, although some issues remain controversial. We believe that these recommendations may help urologists involved in RARP and hope that future discussions on this surgical procedure may evolve over the ensuing years.

Identification of protein-coding and intronic noncoding RNAs down-regulated in clear cell renal carcinoma.

The clear cell subtype of renal cell carcinoma (RCC) is the most lethal and prevalent cancer of the urinary system. To investigate the molecular changes associated with malignant transformation in clear cell RCC, the gene expression profiles of matched samples of tumor and adjacent non-neoplastic tissue were obtained from six patients. A custom-built cDNA microarray platform was used, comprising 2292 probes that map to exons of genes and 822 probes for noncoding RNAs mapping to intronic regions. Intronic transcription was detected in all normal and neoplastic renal tissues. A subset of 55 transcripts was significantly down-regulated in clear cell RCC relative to the matched nontumor tissue as determined by a combination of two statistical tests and leave-one-out patient cross-validation. Among the down-regulated transcripts, 49 mapped to untranslated or coding exons and 6 were intronic relative to known exons of protein-coding genes. Lower levels of expression of SIN3B, TRIP3, SYNJ2BP and NDE1 (P < 0.02), and of intronic transcripts derived from SND1 and ACTN4 loci (P < 0.05), were confirmed in clear cell RCC by Real-time RT-PCR. A subset of 25 transcripts was deregulated in additional six nonclear cell RCC samples, pointing to common transcriptional alterations in RCC irrespective of the histological subtype or differentiation state of the tumor. Our results indicate a novel set of tumor suppressor gene candidates, including noncoding intronic RNAs, which may play a significant role in malignant transformations of normal renal cells.

Analysis of the Learning Curve of Surgeons without Previous Experience in Laparoscopy to Perform Robot-Assisted Radical Prostatectomy.

OBJECTIVE: To assess the learning curve in robot-assisted radical prostatectomy (RARP) performed by surgeons without previous experience in laparoscopic prostatectomy. MATERIALS AND METHODS: We analyzed 119 patients submitted to RARP performed by two surgeons without previous experience in laparoscopic prostatectomy, with emphasis on the relevant outcomes such as continence, erectile function, and oncologic control with a minimum follow-up of 24 months. We used Fisher's exact test and the chi-square test to investigate the existence of a relationship between the variables and analysis of variance (ANOVA) to verify possible statistically significant differences between groups, at the 5% level. RESULTS: The patients' age varied from 41 to 72 years (mean = 61.09), with 68 (57.14%) cases having intermediate or high risk. There was a consistent decline in operative time. Of the 119 patients, 80.67% were continent 6 months after surgery and 89.07% 12 months afterward, while 35.29% were potent 6 months after surgery and 60.50% 12 months following surgery. Twelve months after surgery, the trifecta outcome rate was 51.26% and the pentafecta rate was 31.09%. There was progressive postoperative improvement and maintenance of continence and sexual potency until the last patient was operated in our sample. CONCLUSIONS: Robot-assisted radical prostatectomy does not require previous experience in laparoscopic radical prostatectomy, but the learning curve is not short to achieve the plateau.

Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer.

A large fraction of transcripts are expressed antisense to introns of known genes in the human genome. Here we show the construction and use of a cDNA microarray platform enriched in intronic transcripts to assess their biological relevance in pathological conditions. To validate the approach, prostate cancer was used as a model, and 27 patient tumor samples with Gleason scores ranging from 5 to 10 were analyzed. We find that a considerably higher fraction (6.6%, [23/346]) of intronic transcripts are significantly correlated (P< or =0.001) to the degree of prostate tumor differentiation (Gleason score) when compared to transcripts from unannotated genomic regions (1%, [6/539]) or from exons of known genes (2%, [27/1369]). Among the top twelve transcripts most correlated to tumor differentiation, six are antisense intronic messages as shown by orientation-specific RT-PCR or Northern blot analysis with strand-specific riboprobe. Orientation-specific real-time RT-PCR with six tumor samples, confirmed the correlation (P=0.024) between the low/high degrees of tumor differentiation and antisense intronic RASSF1 transcript levels. The need to use intron arrays to reveal the transcriptome profile of antisense intronic RNA in cancer has clearly emerged.

First brazilian consensus of advanced prostate cancer: recommendations for clinical practice

ABSTRACT Introduction Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. Objectives This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. Materials and Methods Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. Results and Conclusions The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions.

Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience

ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

Penile primary melanoma: analysis of 6 patients treated at Brazilian national cancer institute in the last eight years

Purpose To describe our experience in treating penile melanoma in 06 patients followed at our institution. Materials and Methods Between 2004 and 2012 six consecutive patients with penile melanoma were treated at our Institution. Stage of the disease was classified according to the 2002 AJCC pathologic system. Melanoma in situ (TIS) was diagnosed in one patient. One patient was staged as T1b, two patients as T2b and two patients as T4b. The clinical and pathological findings were evaluated. Immunohistochemical tests were performed for Melan-A, HNB-45, S-100 and C-KIT. All histological specimens were examined by the same pathologist (ABSS). The patients with Cis, stages T1b and one patient T2b underwent only local excision. One patient T2b underwent local excision and sentinel lymph node dissection. Two patients with melanoma stage T4b underwent partial penile amputation. One of these last patients had palpable inguinal lymph nodes at diagnosis and underwent bilateral inguinal lymphadenectomy and received systemic chemotherapy (dacarbazine, 30 cycles). Results Mean follow-up was 36.3 months. One patient, with stage T2b, died after 12 months due to disease recurrence with bilateral inguinal involvement. The patient who underwent chemotherapy progressed with lung metastases and died after 14 months of follow up. The disease-free survival at five years was 33.3%. Conclusion: Penile melanoma is a disease with poor prognosis in most cases. Local excision or partial penile amputation may have effective control for stages T1 and T2 lesions. Patients who have clinically proven metastases died despite surgical and adjuvant chemotherapy. .

Phase II trial of neoadjuvant gemcitabine and cisplatin in patients with resectable bladder carcinoma.

OBJECTIVES: Gemcitabine and cisplatin (GC) is an active combination in the treatment of metastatic bladder cancer. We have prospectively analyzed the efficacy and tolerability of GC as neoadjuvant treatment of invasive bladder cancer. MATERIALS AND METHODS: In this single-institution phase II trial, patients with muscle-invasive transitional cell carcinoma received three cycles of gemcitabine 1200 mg/m2 on days 1 and 8 with cisplatin 75 mg/m2 on day 1 prior to surgery. Radiologic response was evaluated by computed tomography and magnetic resonance imaging. All patients were referred to surgery after chemotherapy completion. RESULTS: Between June 2002 and March 2005, 22 patients (19 males) were enrolled. Median age was 63 years. Initial stage was II (T2) in 11 and III (T3-4) in 11 patients. Median follow-up is 26 months (4-43). Partial or complete radiologic response rate was documented in 13 out of 20 assessable patients (70%). One patient was excluded due to sarcomatoid carcinoma at definitive pathologic examination. Cystectomy was performed in 15 patients and pelvic radiotherapy in four patients. Nine out of 21 patients (43%) relapsed and four (19%) died due to disease progression. Complete pathologic response was observed in four patients (26.7% of 15). Median progression-free survival was 27 months (CI 95% not reached) with median overall survival of 36 months (CI 95%: 28.7 - 43.3). Grade III/IV toxicity was infrequent, with no deaths due to chemotherapy. CONCLUSIONS: The combination of GC is effective and well-tolerated when used as neoadjuvant therapy in muscle-invasive bladder cancer. Longer follow-up is necessary to evaluate its impact on the overall survival of these patients.

Phase II trial of neoadjuvant gemcitabine and cisplatin in patients with resectable bladder carcinoma

OBJECTIVES: Gemcitabine and cisplatin (GC) is an active combination in the treatment of metastatic bladder cancer. We have prospectively analyzed the efficacy and tolerability of GC as neoadjuvant treatment of invasive bladder cancer MATERIALS AND METHODS: In this single-institution phase II trial, patients with muscle-invasive transitional cell carcinoma received three cycles of gemcitabine 1200 mg/m² on days 1 and 8 with cisplatin 75 mg/m² on day 1 prior to surgery. Radiologic response was evaluated by computed tomography and magnetic resonance imaging. All patients were referred to surgery after chemotherapy completion RESULTS: Between June 2002 and March 2005, 22 patients (19 males) were enrolled. Median age was 63 years. Initial stage was II (T2) in 11 and III (T3-4) in 11 patients. Median follow-up is 26 months (4-43). Partial or complete radiologic response rate was documented in 13 out of 20 assessable patients (70 percent). One patient was excluded due to sarcomatoid carcinoma at definitive pathologic examination. Cystectomy was performed in 15 patients and pelvic radiotherapy in four patients. Nine out of 21 patients (43 percent) relapsed and four (19 percent) died due to disease progression. Complete pathologic response was observed in four patients (26.7 percent of 15). Median progression-free survival was 27 months (CI 95 percent not reached) with median overall survival of 36 months (CI 95 percent: 28.7 - 43.3). Grade III/IV toxicity was infrequent, with no deaths due to chemotherapy CONCLUSIONS: The combination of GC is effective and well-tolerated when used as neoadjuvant therapy in muscle-invasive bladder cancer. Longer follow-up is necessary to evaluate its impact on the overall survival of these patients.

Reservatório urinário continente: uma alternativa para a substituiçäo vesical / Contigent urinary reservoir: an alternative for vesical substitution

Um segmento de íleo e de cólon é utilizado para criar uma neobexiga, após cistectomia com uma anastomose ceco-uretal. Esta técnica cirúrgica denominada Mainz Pouch utiliza 15 cm de ceco e cólon ascendente e duas alças ileais do mesmo comprimento para a construçäo de um reservatório urinário. Esta neobexiga permite a continência urinária, um grande reservatório de baixa pressäo, o esvaziamento vesical voluntário e o reimplante uretral com técnica anti-refluxo. Quatro pacientes foram submetidos a este procedimento após a cistoprostatectomia, poupando-se, porém, a inervaçäo responsável pela ereçäo. O seguimento destes pacientes variou entre oito e 14 meses. Os quatro pacientes estäo continentes, durante os períodos diurno e noturno. Três esvaziam suas neobexigas espontaneamente, em intervalos normais. Um paciente tem ereçöes e relaçöes sexuais.