Recidiva de los cánceres superficiales de vejiga posterior a quimioterapia intravesical con doxorrubicina / Recurrence of superficial bladder cancers after in-travesical chemotherapy with doxorubicin

Introducción: El cáncer de vejiga es una enfermedad de gran prevalencia, siendo su mayor problema la tendencia a la recidiva y a la progresión. Para disminuir en lo posible esta recidiva y progresión se han utilizado muchos quimioterapéuticos intravesicales aplicados a lo largo de meses tras la resección transuretral de vejiga con resultados desiguales. La doxorrubicina es un antibiótico antraciclino con actividad antitumoral producido por Streptococcus peucetius var. caesius. Tiene la capacidad de intercalarse con el DNA, afecta muchas de sus funciones e inhibe la síntesis de DNA y RNA, que por vía intravesical actúa evitando la implantación de células tumorales circulantes. Metodología: El estudio será de tipo observacional descriptivo, retrospectivo de corte transversal, comprendido entre el 1 de enero de 2018 y el 31 de enero de 2021 y desarrollado en el Servicio de Urología del Hospital Teodoro Maldonado Carbo. Resultados: Fueron 148 casos analizados. La especificidad del índice fue de 81 %, con un valor predictivo (VP) positivo del 77 % y VP negativo de 68 %. La sensibilidad de la ascitis 85 % y la masa abdominal palpable del 79 %. En las pacientes que presentaron valores de antígeno CA-125 menor a 1000 U/ml, el riesgo de obtener una citorreducción óptima fue OR: 0.15 (IC95% 0.069 ­ 0.307; P: 0.0001); las pacientes que presentaron valores del índice de irresecabilidad entre 1 y 2 puntos versus 3 y 4 fue de OR: 7.04 (IC95% 3.33 -14.87, P: 0.0001). Conclusiones: el cáncer de vejiga es una enfermedad prevalente que presenta desafíos significativos debido a su propensión a la recidiva y progresión. Para abordar este problema, se han utilizado diversos quimioterapéuticos intravesicales después de la resección transuretral de vejiga, aunque con resultados variables. La doxorrubicina, un antibiótico antraciclino con propiedades antitumorales, ha demostrado la capacidad de interferir con el ADN y el ARN, lo que la convierte en una opción valiosa para prevenir la implantación de células tumorales circulantes cuando se administra por vía intravesical.

Introduction: Bladder cancer is a highly prevalent disease; its most significant problem is its tendency to recur and progress. To reduce this recurrence and progression as much as possible, many intravesical chemotherapeutics applied over months after transurethral resection of the bladder have been used with mixed results. Doxorubicin is an anthracycline antibiotic with antitumor activity produced by Streptococcus peucetius var. cesius. It can intercalate with DNA, affects many of its functions, and inhibits the synthesis of DNA and RNA, which acts intravesically to prevent the implantation of circulating tumor cells. Methodology: The study will be of an observational, descriptive, retrospective, cross-sectional type between January 1, 2018, and January 31, 2021, and developed in the Urology Service of the Teodoro Maldonado Carbo Hospital. Results: A total of 148 cases were analyzed. The specificity of the index was 81%, with a positive predictive value (PV) of 77% and a negative PV of 68%. The sensitivity of ascites was 85%, and that of the palpable abdominal mass was 79%. In patients who presented CA-125 antigen values less than 1000 U/ml, the risk of obtaining optimal cytoreduction was OR: 0.15 (95% CI 0.069 - 0.307; P: 0.0001). The patients who presented unresectability index values between 1 and 2 points versus 3 and 4 points were OR: 7.04 (95% CI 3.33 -14.87, P: 0.0001). Conclusions: Bladder cancer is a prevalent disease that presents significant challenges due to its propensity for recurrence and progression. To address this problem, various intravesical chemotherapeutics have been used after transurethral resection of the bladder, although with variable results. Doxorubicin, an anthracycline antibiotic with antitumor properties, has demonstrated the ability to interfere with DNA and RNA, making it a valuable option to prevent the implantation of circulating tumor cells when administered intravesically.

Safe duration of silicon catheter replacement in urological patients

Objectives: This study compared the infection rates, degree of encrustation, symptoms, and complications in patients regarding the duration of urethral catheterisation (three weeks, six weeks, and eight weeks). Design: A cross-sectional study with stratified simple random sampling Setting: Urology Unit, Korle Bu Teaching Hospital Participants: One hundred and thirty-seven male patients with long-term urinary catheters Interventions: Participants were grouped into 3 weeks, 6 weeks, and 8 weeks duration of catheter replacementsPrimary outcomes measures: Symptoms due to the urinary catheters, urinalysis, urine and catheter tip cultures, sensitivity, and catheter encrustations were assessed. Results: Eighty-six patients had a primary diagnosis of benign prostatic hyperplasia (BPH), 35 had urethral strictures,13 had prostate cancer, two had BPH and urethral strictures, and one participant had bladder cancer. There was no difference in the symptoms the participants in the different groups experienced due to the urinary catheters (p > 0.05). The frequency of occurrence of complications (pyuria, p = 0.784; blocked catheter, p=0.097; urethral bleeding, p=0.148; epididymo-orchitis, p=0.769 and bladder spasms, p=1.000) showed no differences in the three groups. There was no statistical difference in the urinalysis for the three groups (p>0.05) and the degree of encrustations (3 weeks: 0.03 ± 0.06, 6 weeks: 0.11±0.27 and eight weeks: 0.12 ±0.27) with p=0.065. Conclusions: In this study, the duration of urinary catheterisation using silicone Foley's catheters did not influence the complication and symptom rates; hence silicon catheters can be placed in situ for up to 8 weeks before replacement instead of the traditional three-weekly change.

Tabaquismo y tumores mayores de 2 centímetros son predictores de mortalidad en pacientes sometidos a nefro-ureterectomías por carcinoma de urotelio alto / Prognostic factors in patients with upper urinary tract urothelial carcinoma undergoing nephro-ureterectomy

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) represents 5-10% of urothelial carcinomas. It is managed with nephroureterectomy (NUR); however, kidney-sparing techniques are growingly used. AIM: To report the results of a 20-year series of NUR conducted in an academic center. Patients and Methods: Review of clinical and pathological characteristics of patients undergoing NUR between 1999 and 2020. Patients were followed for 63 months. Global survival curves (OS) and mortality predictors were established through Cox regression. RESULTS: We included 90 patients with a median age of 68 years undergoing NUR, of whom 68 (75%) had a pelvic tumor and 22 (25%) had a proximal ureteral tumor. A laparoscopic NUR was performed in 60 patients (66%). Thirty-three patients (37%) had tumors confined to the urothelium (pTa), penetrating the lamina propria (pT1) or carcinoma in situ (CIS), 10 patients (11%) had a tumor spreading to the muscle layer (pT2) and 47 (52%) had a tumor spreading to nearby organs (pT3 / T4). Average tumor size was 3.69 cm, nodal disease (pN) was present 12 patients (13%). Twelve patients (13%) received adjuvant chemotherapy. A higher mortality was observed among smokers (Hazard ratio (HR) 8.79, 95% confidence intervals (CI) 1.5-49.0, p = 0.01), patients with tumors classfied as pT≥ 2 (HR 1.09, 95% CI 0.01-1.0, p = 0.04) and those with tumors larger than 2 cm (HR 14.79, CI 95% 1.5-272, p = 0.01). CONCLUSIONS: Smoking patients, those with invasive tumors (T2-T4) and greater than 2 cm have higher mortality. Therefore, they should not be candidates for conservative management.

Bricker ileal conduit vs. Cutaneous ureterostomy after radical cystectomy for bladder cancer: a systematic review

ABSTRACT Purpose: A systematic review of the literature with available published literature to compare ileal conduit (IC) and cutaneous ureterostomy (CU) urinary diversions (UD) in terms of perioperative, functional, and oncological outcomes of high-risk elderly patients treated with radical cystectomy (RC). Protocol Registration: PROSPERO ID CRD42020168851. Materials and Methods: A systematic review, according to the PRISMA Statement, was performed. Search through the Medline, Embase, Scopus, Scielo, Lilacs, and Cochrane Database until July 2020. Results: The literature search yielded 2,883 citations and were selected eight studies, including 1096 patients. A total of 707 patients underwent IC and 389 CU. Surgical procedures and outcomes, complications, mortality, and quality of life were analyzed. Conclusions: CU seems to be a safe alternative for the elderly and more frail patients. It is associated with faster surgery, less blood loss, lower transfusion rates, a lower necessity of intensive care, and shorter hospital stay. According to most studies, complications are less frequent after CU, even though mortality rates are similar. Studies with long-term follow up are awaited.

Computed-tomography based scoring system predicts outcome for clinical lymph node-positive patients undergoing radical cystectomy

ABSTRACT Purpose: Contrast-enhanced CT scan is the standard staging modality for patients with bladder cancer undergoing radical cystectomy (RC). Involvement of lymph nodes (LN) determines prognosis of patients with bladder cancer. The detection of LN metastasis by CT scan is still insufficient. Therefore, we investigated various CT scan characteristics to predict lymph node ratio (LNR) and its impact on survival. Also, pre-operative CT scan characteristics might hold potential to risk stratify cN+ patients. Materials and Methods: We analyzed preoperative CT scans of patients undergoing RC in a tertiary high volume center. Retrospectively, local tumor stage and LN characteristics such as size, morphology (MLN) and number of loco-regional LN (NLN) were investigated and correlation to LNR and survival was analyzed. CT scan characteristics were used to develop a risk stratification using Kaplan-Maier and multivariate analysis. Results: 764 cN0 and 166 cN+ patients with complete follow-up and imaging data were included in the study. Accuracy to detect LN metastasis and locally advanced tumor stage in CT scan was 72% and 62%. LN larger than 15mm in diameter were significantly associated with higher LNR (p=0.002). Increased NLN correlated with decreased CSS and OS (p=0.001: p=0.002). Furthermore, CT scan based scoring system precisely differentiates low-risk and high-risk profiles to predict oncological outcome (p <0.001). Conclusion: In our study, solely LN size >15mm significantly correlated with higher LNR. Identification of increased loco-regional LN was associated with worse survival. For the first time, precise risk stratification based on computed-tomography findings was developed to predict oncological outcome for clinical lymph node-positive patients undergoing RC.

Casticin inhibits the proliferation, migration and invasion of bladder cancer cells by inhibition of TM7SF4 expression / 中华肿瘤杂志

Objective: To explore the effect and mechanism of Casticin (CAS) on the proliferation, migration and invasion of bladder cancer T24 cells. Methods: T24 cells were cultured in vitro and divided into control group, 5, 10, 20 μmol/L CAS groups, si-NC group, si-TM7SF4 group, CAS+ pcDNA group and CAS+ pcDNA-TM7SF4 group. Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell was used to detect cell migration and invasion; western blot was used to detect the protein expressions of cyclin D1, p21, MMP-2, MMP-9 and TM7SF4, and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of TM7SF4 mRNA. Results: The inhibition rates of T24 cells in the 5, 10, 20 μmol/L CAS groups were (17.68±1.41)%, (33.54±3.16)% and (61.44±5.50)%, respectively, higher than (0.00±0.00)% of the control group (P<0.001), but the numbers of migration and invasion were 72.83±5.66, 59.13±4.27, 41.25±3.22 and 55.83±5.15, 42.19±3.06, 31.13±3.22, respectively, lower than 86.11±5.16 and 68.82±5.29 of the control group (P<0.001). The protein expression levels of cyclin D1, MMP-2, MMP-9, TM7SF4 and the expression levels of TM7SF4 mRNA in the 5, 10, and 20 μmol/L CAS groups were lower than the control group (P<0.001). However, the protein expression levels of p21 were 0.37±0.03, 0.51±0.04, and 0.66±0.06, respectively, higher than 0.25±0.03 in the control group (P<0.001). The inhibition rate of T24 cells in the si-TM7SF4 group was (50.35±4.67)%, higher than (6.31±0.58)% in the si-NC group (P<0.001), but the numbers of migration and invasion were 53.51±4.18 and 42.92±3.81, lower than 85.26±4.99 and 67.93±4.64 of the si-NC group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2, MMP-9 in the si-TM7SF4 group were lower than the si-NC group (P<0.001). However, the protein expression level of p21 in the si-TM7SF4 group was higher than the si-NC group (P<0.001). The inhibitory rate of T24 cells in the CAS+ pcDNA-TM7SF4 group was (21.45±2.46)%, lower than (64.06±4.49)% of the CAS+ pcDNA group (P<0.001), but the number of migration and invasion in the CAS+ pcDNA-TM7SF4 group were 75.66±6.57 and 59.35±5.40, higher than 40.43±3.85 and 30.25±3.32 in the CAS+ pcDNA group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2 and MMP-9 in the CAS+ pcDNA-TM7SF4 group were higher than the CAS+ pcDNA group (P<0.001), but the protein expression level of p21 was lower than the CAS+ pcDNA group (P<0.001). Conclusion: CAS may suppress the proliferation, migration and invasion of bladder cancer T24 cells by inhibiting the expression of TM7SF4.

Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation / 中国天然药物

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

MiR-133b regulates the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4 / 中南大学学报(医学版)

OBJECTIVES@#Bladder cancer is one of the most common urothelial tumors with high incidence and mortality rates. Although it has been reported that microRNA (miR)-133b can regulate tumorigenesis of bladder cancer, the mechanism remains unclear. Sex-determining region Y-box transcription factor 4 (SOX4) exhibits an important role in tumorigenesis, but it is unclear whether SOX4 and miR-133b are associated with regulation of pathogenesis of bladder cancer. This study aims to determine the expressions of SOX4 and miR-133b in bladder cancer tissues and cells, investigate their effects on the proliferation, colony formation, and invasion of bladder cancer cells, and to explore the association between miR-133b and SOX4 in regulating biological featurss of bladder cancer cells.@*METHODS@#The bladder cancer and adjacent tissue samples of 10 patients who underwent surgical resection in the Second Xiangya Hospital of Central South Universty from Januray to June 2015 were obtained. The levels of miR-133b were tested by real-time PCR, and the protein levels of SOX4 were evaluated using Western blotting in bladder cancer tissues, matched adjacent tissues, and cell lines. The correlation between miR-133b expression and SOX4 expression in bladder cancer tissues was analyzed. Using the online database TargetScan, the relationship between SOX4 and miR-133b was predicted. MiR-133b mimics, miR-133b inhibitor, and short hairpin RNA (shRNA)-SOX4 were transfected into T24 cells by Lipofectamine 2000. The relationship between miR-133b and SOX4 was also verified by a dual-luciferase reporter assay. The proliferation of T24 cells cultured for 0, 12, 48, 72, and 96 h was evaluated by cell counting kit-8 (CCK-8) assay. The colony formation capacity of bladder cancer cells was tested after 14-day culture, and cell invasion capacity was evaluated with Transwell invasion assay.@*RESULTS@#Bladder cancer tissue and bladder cancer cells had low level of miR-133b but high level of SOX4, compared with matched adjacent tissues and normal bladder epithelial cells. A negative correlation between miR-133b mRNA and SOX4 protein levels in bladder cancer tissues was also found (r=-0.84). The results of online database TargetScan showed that miR-133b targets at SOX4, and overexpression of miR-133b significantly attenuated the expression of SOX4 in T24 cells. Both overexpression of miR-133b and knockdown of SOX4 significantly inhibited the proliferation, colony formation, and invasion capacity of bladder cancer cells in vitro. SOX4 down-regulation restored the effects of miR-133b inhibitor on the proliferation, colony formation, and invasion capacity of T24 cells.@*CONCLUSIONS@#The up-regulation of SOX4 contributes to the progression of bladder cancer, and miR-133b can regulate the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4.

Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF- κ B and PI3K/AKT Signaling In Vitro and In Vivo / 中国结合医学杂志

OBJECTIVE@#To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.@*METHODS@#For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.@*RESULTS@#Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01).@*CONCLUSIONS@#Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.

Expert consensus of multi-disciplinary collaboration on bladder-preserving treatment for bladder cancer in China / 中华肿瘤杂志

Objective: Bladder cancer is one of the most common malignant tumors in urology. Urothelial carcinoma accounts for about 90% of all bladder malignancies. According to whether the tumor invades the bladder muscle, it can be divided into non-muscle invasive bladder cancer and muscle invasive bladder cancer. Radical cystectomy is the standard treatment for muscle invasive bladder cancer patients and high-risk non-muscle invasive bladder cancer patients who have failed Bacillus Calmette-Guerin treatment. Due to the comorbidity of bladder cancer and the potential deterioration of the quality of life after surgery, many patients were not suitable or refused for radical cystectomy. Therefore, it is vital to find a bladder-preserving treatment that can achieve cure other than radical cystectomy. Bladder-preserving therapy that balances tumor control and quality of life serves as an alternative and supplement to radical cystectomy. This consensus is based on contemporary evidence-based medicine, combined with the native clinical practice of bladder preservation in a multidisciplinary treatment manner. To some extent, this consensus serves as a guidance for bladder-preservation therapy of bladder cancer in China. Several issues are extensively discussed here, including organizational structure and workflow of multidisciplinary treatment, the selection of patients for bladder-preserving therapy, treatment options and regimens, follow-up, as well as regimen choices of recurrence after bladder-preserving therapy.

Beyond diabetes mellitus: role of metformin in non-muscle-invasive bladder cancer

INTRODUCTION@#Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes.@*METHODS@#Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed. Kaplan-Meier curves were used to assess overall survival (OS) and disease-specific survival (DSS).@*RESULTS@#At a median follow-up duration of 102 (range 3-357) months, 53 (43.4%) patients experienced disease recurrence and 21 (17.2%) experienced disease progression. There was no significant difference in mortality between patients with and without diabetes mellitus. There was significant difference in OS between patients without diabetes mellitus, patients with diabetes mellitus on metformin and patients with diabetes mellitus but not on metformin (p = 0.033); patients with diabetes mellitus on metformin had the best prognosis. Metformin use was associated with significantly lower DSS (p = 0.042). Other oral hypoglycaemic agents, insulin or statins were not associated with disease recurrence or progression.@*CONCLUSION@#Metformin use was associated with improved oncological outcomes in patients with non-muscle-invasive bladder cancer treated with intravesical BCG. Prospective studies with larger patient populations are needed to validate the role of metformin as potential therapy for bladder cancer.

Ocurrence enzootic hematuria in buffaloes in Brazil: epidemiological, clinical, and pathological aspects / Ocorrência de hematúria enzoótica em búfalos no Brasil: aspectos epidemiológicos, clínicos e patológicos

It is reported the occurrence of enzootic hematuria (EH) in buffaloes in Brazil after performing an epidemiological survey and clinicopathological analises. To date, EH caused by ingestion of Pteridium esculentum subsp. arachnoideum, a radiomimetic plant popularly known as "bracken fern", has not been described in this species in Brazil. Bovine EH is responsible for high economic losses in Brazil's Southeast Region not only because of the deaths it causes, but also owing to its negative effect on productivity. In São José do Barreiro County, São Paulo, some farmers in areas with a high incidence of bovine EH have been replacing cattle with buffaloes, based on the premise that the latter would be more resistant to poisoning by ingestion of Pteridium spp. However, even though initial observations indicated that buffaloes are indeed less sensitive than cattle to the toxic principle of Pteridium spp., cases of hematuria in this species have been reported. According to preliminary date, EH only occurs in buffaloes over six years of age. Macroscopic examination revealed a thickened urinary vesicle mucosa, along with multiple foci of ulcerated, exophytic, verrucous, and pedunculated lesions. In one of the buffaloes studied, the bladder wall was ruptured and exhibited marked secondary inflammation. Histologically, neoplastic and non-neoplastic changes similar to those described in cattle poisoned by Pteridium spp. were observed. The neoplasms found included papilloma, carcinoma in situ, urothelial carcinoma (low and high grade), inverted, microcystic, and trabecular variants, urothelial carcinoma with divergent differentiation (squamous and glandular), squamous cell carcinoma, lymphangioma, hemangioma, and hemangiosarcoma. There was also coexistence of epithelial and mesenchymal neoplasms. Bovine papillomavirus particles were not detected by polymerase chain reaction in the bladder samples analyzed.

Descreve-se, através de levantamento epidemiológico e avaliação clínico-patológica, a ocorrência de hematúria enzoótica (HE) em búfalos no Brasil. Essa condição, causada pela ingestão da planta radiomimética Pteridium esculentum subsp. arachnoideum, conhecida popularmente como "samambaia" ou "samambaia do campo", até então não havia sido descrita nessa espécie no Brasil. Na Região Sudeste, a HE bovina é responsável por elevadas perdas econômicas, devidas não apenas aos óbitos, mas também em função da queda de produtividade. No município de São José do Barreiro/SP, alguns produtores de áreas com alta incidência de HE bovina, vêm substituindo os bovinos por búfalos, com base na premissa de que estes seriam mais resistentes à intoxicação. Embora, de acordo com observações iniciais, os búfalos realmente sejam menos sensíveis que os bovinos ao princípio tóxico de Pteridium spp., ainda assim, tem-se verificado a ocorrência de casos de hematúria nessa espécie. De acordo com o levantamento inicial, a HE só ocorre em búfalos com idade a partir de seis anos. Ao exame macroscópico, verificou-se a mucosa da bexiga espessa, com múltiplos focos de lesões ulceradas, exofíticas, papiliformes, verrucosas, pedunculadas. Histologicamente, foram observadas alterações neoplásicas e não neoplásicas semelhantes às descritas nos bovinos com HE. Entre as neoplasias foram encontrados papiloma, carcinoma in situ, carcinoma urotelial (baixo e alto grau), variantes invertida, microcística e trabecular, carcinoma urotelial com diferenciação divergente (escamosa e glandular), carcinoma de células escamosas, linfangioma, hemangioma e hemangiossarcoma. Ocorreu também coexistência entre neoplasias epiteliais e mesenquimais. Não foram detectadas partículas de papilomavírus bovino pelo teste PCR nas amostras de bexiga analisadas.

Fibroblast growth factor receptor 3 gene (FGFR3) mutations in high-grade muscle-invasive urothelial bladder cancer in a Brazilian population: evaluation and prevalence

ABSTRACT Objective To understand the feasibility of FGFR3 tests in the Brazilian public health context, and to sample the mutational burden of this receptor in high-grade muscle invasive bladder cancer. Methods A total of 31 patients with high-grade muscle-invasive bladder cancer were included in the present study. Either transurethral resection of bladder tumor or radical cystectomy specimens were analyzed. Formalin-fixed paraffin-embedded tissue blocks were sectioned, hematoxylin and eosin stained, and histologic sections were reviewed. Total RNA was extracted using the RNeasy DSP formalin-fixed paraffin-embedded kit. Qualitative results were displayed in Rotor-Gene AssayManager software. Results Six patients were excluded. From the samples analyzed, four (16.7%) were considered inadequate and could not have their RNA extracted. Two patients presented FGFR3 mutations, accounting for 9.5% of material available for adequate analysis. The two mutations detected included a Y373C mutation in a male patient and a S249C mutation in a female patient. Conclusion FGFR3 mutations could be analyzed in 84% of our cohort and occurred in 9.5% of patients with high-grade muscle invasive bladder cancer in this Brazilian population. FGFR3 gene mutations are targets for therapeutic drugs in muscle-invasive bladder cancer. For this reason, know the frequency of these mutations can have a significant impact on public health policies and costs provisioning.

Melanoma metastásico a vejiga / Metastatic melanoma to the bladder / Melanoma metastático na bexiga

Introducción. El compromiso tumoral metastásico del melanoma al tracto genitourinario es frecuente, pero, la metástasis a vejiga es rara, constituye menos del 2% de los casos. Sin embargo, en autopsias realizadas a pacientes con melanoma se ha encontrado metástasis en la vejiga en entre un 18% y un 37% de los casos, lo que la convierte en la segunda en incidencia posterior al adenocarcinoma gástrico. La media de supervivencia suele ser entre 6 - 7.5 meses. El objetivo de este trabajo es presentar el caso de un melanoma metastásico a vejiga, entidad poco frecuente y poco diagnosticada por ser la mayoría de las veces asintomática. Presentación del caso. Paciente femenina de 62 años, con antecedente de melanoma al nivel del primer artejo del pie, con manejo quirúrgico y farmacológico. Consultó por hematuria. La cistoscopia evidenció una lesión única sólida, eritematosa, con necrosis y fácil sangrado y se indicó realizar resección transuretral (RTU). La patología demostró compromiso por melanoma ulcerado metastásico. Se inició manejo de segunda línea (Pembrolizumab) y presentó progresión a miembros superiores y recaída a nivel vesical. La paciente falleció un año después. Discusión. Las metástasis de melanoma al tracto genitourinario son frecuentes, pero las metástasis vesicales aisladas son raras. El tratamiento suele ser RTU de la lesión, cistectomía, quimioterapia y radioterapia. La RTU es curativa para las lesiones restringidas al epitelio, aunque la cistectomía radical suele ser la terapia de elección ante un paciente con un tumor localizado. El Pembrolizumab ha demostrado aumentar la supervivencia. El pronóstico depende del tamaño y profundidad de la invasión. Conclusiones. El compromiso vesical metastásico es poco frecuente y diagnosticado, puede estar presente en pacientes con melanoma, síntomas irritativos urinarios no específicos y hematuria. Suele ser de mal pronóstico, y requiere de manejo quirúrgico asociado a manejo sistémico.

Introduction. Metastatic tumor compromise of melanoma to the genitourinary tract is frequent, but metastasis to the bladder is rare, representing less than 2% of cases. However, autopsies performed on patients with melanoma have found metastases in the bladder in 18-37% of cases, making it the second incidence after gastric adenocarcinoma. The median survival is usually 6 to 7.5 months. The objective of this work is to present the case of a metastatic melanoma to the bladder, a rare and underdiagnosed condition because most of the time it is asymptomatic. Case Presentation. 62-year-old female patient, with a history of melanoma at the level of the first toe, with surgical and pharmacological management. The reason for consultation was hematuria. Cystoscopy revealed a single solid, erythematous lesion with necrosis and easy bleeding, and a transurethral resection (TUR) was indicated. The pathology found compromise for metastatic ulcerated melanoma. Second-line treatment (Pembrolizumab) was started and presented progression to the upper limbs and relapse at the bladder level. The patient died a year later. Discussion. Melanoma metastases to the genitourinary tract are common, but isolated bladder metastases are rare. Treatment is usually TUR of the lesion, cystectomy, chemotherapy, and radiation therapy. TUR is curative for lesions restricted to the epithelium, although radical cystectomy is usually the therapy of choice in patients with a localized tumor. Pembrolizumab has been shown to increase survival. The prognosis depends on the size and depth of the invasion. Conclusions. Metastatic bladder compromise is rare and underdiagnosed, it may be present in patients with melanoma, non-specific urinary irritative symptoms, and hematuria. It tends to have a poor prognosis, and requires surgical management associated with systemic management.

Introdução. O comprometimento do tumor metastático do melanoma no trato geniturinário é comum, mas a metástase na bexiga é rara, constituindo menos de 2% dos casos. Entretanto, em autópsias realizadas em pacientes com melanoma, foi encontrada metástase na bexiga entre 18% e 37% dos casos, o que a torna a segunda em incidência após o adenocarcinoma gástrico. A média de sobrevivência é geralmente entre 6 - 7,5 meses. O objetivo deste trabalho é apresentar o caso de um melanoma metastático na bexiga, uma entidade pouco frequente e subdiagnosticada, pois na maioria das vezes é assintomática. Apresentação do caso. Paciente do sexo feminino, 62 anos, com antecedentes de melanoma no nível do hálux, com manejo cirúrgico e farmacológico. Ela consultou por hematúria. A cistoscopia revelou uma única lesão sólida, eritematosa com necrose e sangramento fácil, e foi indicada uma ressecção transuretral (RTU). A patologia mostrou comprometimento de melanoma ulceroso metastático. O tratamento de segunda linha (Pembrolizumab) foi iniciado e a patologia avançou para os membros superiores e uma recaída no nível da bexiga. A paciente morreu um ano depois. Discussão. As metástases de melanoma para o trato geniturinário são frequentes, mas as metástases vesicais isoladas são raras. O tratamento é geralmente RTU da lesão, cistectomia, quimioterapia e radioterapia. A RTU é curativa para lesões restritas ao epitélio, embora a cistectomia radical seja geralmente a terapia de escolha para um paciente com um tumor localizado. O Pembrolizumab demonstrou aumentar a sobrevivência. O prognóstico depende do tamanho e da profundidade da invasão. Conclusões. O comprometimento vesical metastático é raro e subdiagnosticado, pode estar presente em pacientes com melanoma, sintomas irritantes urinários não específicos e hematúria. Geralmente tem um prognóstico negativo e requer manejo cirúrgico em associação com manejo sistêmico.

Dissecting the role of radical cystectomy and urinary diversion in post-operative complications: an analysis using the American College of Surgeons national surgical quality improvement program database

ABSTRACT Objective: To characterize the contribution of the extirpative and reconstructive portions of radical cystectomy (RC) to complications rates, and assess differences between urinary diversion (UD) types. Materials and Methods: We conducted a retrospective cohort study comparing patients undergoing UD alone or RC+UD for bladder cancer from 2006 to 2017 using ACS National Surgical Quality Improvement Program database. The primary outcome was major complications, while secondary outcomes included minor complications and prolonged length of stay. Propensity score matching (PSM) was utilized to assess the association between surgical procedure (UD alone or RC+UD) and outcomes, stratified by diversion type. Lastly, we examined differences in complication rates between ileal conduit (IC) vs. continent UD (CUD). Results: When comparing RC + IC and IC alone, PSM yielded 424 pairs. IC alone had a lower risk of any complication (HR 0.63, 95% CI 0.52-0.75), venous thromboembolism (HR 0.45, 95% CI 0.22-0.91) and bleeding needing transfusion (HR 0.41, 95% CI 0.32-0.52). This trend was also noted when comparing RC + CUD to CUD alone. CUD had higher risk of complications than IC, both with (56.6% vs 52.3%, p = 0.031) and without RC (47.8% vs 35.1%, p=0.062), and a higher risk of infectious complications, both with (30.5% vs 22.7%, p<0.001) and without RC (34.0% vs 22.0%, p=0.032). Conclusions: RC+UD, as compared to UD alone, is associated with an increased risk of major complications, including bleeding needing transfusion and venous thromboembolism. Additionally, CUD had a higher risk of post-operative complication than IC.

Simultaneous laparoscopic nephroureterectomy and robot-assisted anterior pelvic exenteration with intracorporeal ileal conduit urinary diversion: step-by-step video-illustrated technique

ABSTRACT Introduction: One of the most remarkable characteristics of urothelial carcinomas is multifocality. However, occurrence of synchronous bladder cancer and upper urinary tract urothelial cancer (UTUC) is exceptional. Minimally invasive approach for these synchronous tumors was just occasionally reported (1-4). The aim of this video article is to describe step-by-step the technique for simultaneous laparoscopic nephroureterectomy and robot-assisted anterior pelvic exenteration with intracorporeal ileal conduit urinary diversion (ICUD). Patients and methods: A 66-year-old female presented with synchronous BCG refractory non-muscle invasive bladder cancer and a right-side UTUC. She was a former smoker and had previously been submitted to multiple transurethral resections of bladder tumor, BCG and right distal ureterectomy with ureteral reimplant. We performed a simultaneous laparoscopic right nephroureterectomy and robot-assisted anterior pelvic exenteration with totally intracorporeal ICUD. Combination of robot-assisted and pure laparoscopic approaches was proposed focusing on optimization of total operative time (TOT). Results: Surgery was uneventful. TOT was of 330 minutes. Operative time for nephroureterectomy, anterior pelvic exenteration and ICUD were 48, 135, 87 minutes, respectively. Estimated blood loss was 150mL. Postoperative course was unremarkable and patient was discharged after 7 days. Histopathological evaluation showed a pT1 high grade urothelial carcinoma plus carcinoma in situ both in proximal right ureter and bladder, with negative margins. Twelve lymph nodes were excised, all of them negative. Conclusion: In our preliminary experience, totally minimally invasive simultaneous nephroureterectomy and cystectomy with intracorporeal ICUD is feasible. Pure laparoscopic approach to upper urinary tract may be a useful tactic to reduce total operative time.