Ocurrence enzootic hematuria in buffaloes in Brazil: epidemiological, clinical, and pathological aspects

ABSTRACT: 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 Brazils 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.

RESUMO: 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.

The safety and efficacy of trimodality treatment for invasive bladder cancer / 中华泌尿外科杂志

Objective:To evaluate the safety and efficacy of trimodality treatment (TMT) which is complete transurethral resection of bladder tumor with concurrent radiotherapy and chemotherapy for invasive bladder cancer.Methods:From Mar. 2016 to Oct.2021, patients who were indicated of radical cystectomy (RC) but refused were enrolled to TMT treatment prospectively. Inclusive criteria were: ① the patients refused radical surgery; ② male or female, no older than 80 years; ③ no matter the tumor size, the bladder tumor be completely resected by transurethral surgery, and the hydronephrosis be improved after resecting the tumor; ④ the postoperative pathology of urothelial carcinoma; ⑤ recurrent T 1 and high-grade non-muscle invasive bladder cancer (NMIBC) or T 2-4a muscle invasive bladder cancer (MIBC); ⑥ no definitive metastasis in preoperative chest, abdominal CT or MRI; ⑦ hemoglobin ≥100 g/L, white blood cell count ≥4×10 9/L, platelet count ≥100×10 9/L, and normal liver and renal function. The exclusion criteria were: ① tumor invading bladder neck or anterior or posterior urethra; ② bladder contracture or severe urethral stricture; ③ regional lymph node metastasis or distant metastasis by imaging examination; ④ no improvement of hydronephrosis after resection; ⑤ definitive contraindications of radiotherapy or chemotherapy; ⑥ uncontrolled hypertension, diabetes, coronary heart disease or other severe diseases. After cTURBT, paclitaxel (50 mg/m 2 on Day 1 of each week) combined with cisplatin(20 mg/m 2 on day 1-2 of each week)was administered with concurrent radiotherapy (2 Gy/fraction/day) for 4 weeks. If cystoscopy and/or radiographic detected no recurrence or metastasis, the patients were treated with concurrent chemoradiotherapy for 2 and a half weeks (total dose of 64 Gy). The side effects of radiotherapy and chemotherapy during TMT were observed, the quality of life(QOL)was evaluated by FACT-P scale, and the bladder recurrence, distant metastasis and survival were assessed with imaging and cystoscopy. From March 2016 to October 2021, 79 patients with RC were enrolled, including 67 males and 12 females, aged 44-86 years. The pathology of RC was urothelial carcinoma of the bladder. There was no definitive lymph node or distant metastasis in preoperative imaging. The progress and survival after TMT and RC treatment were followed up and the survival rates were calculated by Kaplan-Meier method. Results:Of the 30 patients who underwent TMT, including 25 males and 5 females, aged 32-76 years, there were 7 cases of cT 1 (23.3%), 19 cases (63.3%) of cT 2, 2 cases of cT 3 (6.7%)and 2 cases of cT 4(6.7%), respectively. A total of 132 adverse events of all grades of chemoradiotherapy occurred, of which only 4 were grade Ⅳ, with no bowel leakage or death due to complications. The mean scores of negative questions in FACT-P were 3.22±0.67, 1.30±0.63 and 0.87±0.69 before TMT treatment, 6 and 12 months after TMT treatment, respectively. The quality of life was significantly improved( F=129.081, P<0.001), and the rate of bladder preservation was 86.7%(26/30). Two cases underwent salvage RC(6.7%)and 2 cases died of bladder recurrence(6.7%). There were 8, 4 and 2 patients survived 4, 5 and 6 years, respectively. Seven cases (23.3%) had bladder recurrence, 3 cases (10.0%) underwent distant metastasis and 6 patients (20.0%)died after TMT because of the progression. The 1, 2 and 5 year overall survival rates by TMT treatment were 88.89%, 82.96% and 62.77%, respectively. Median follow-up was 19.5(6.8-44.5) months in the TMT group and 35.5(18.8-53.3) months in the RC group ( z=-1.998, P=0.046). Progression-free survival in the TMT and RC group were 66.7% and 80.0%( χ2=1.047, P=0.306), and the overall survival rates were 80.0% and 80.0% ( χ2=0.482, P=0.488) respectively. The difference was not statistically significant. Conclusions:The TMT is a safe and effective alternative for RC, which can improve the quality of life and control the tumor sufficiently.

Bladder-sparing treatment following noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy for muscle-invasive bladder cancer / 中华泌尿外科杂志

Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.

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.

Factors associated with utilization of neoadjuvant chemotherapy in charlson comorbidity zero non-metastatic muscle-invasive bladder cancer patients

ABSTRACT Background: Guideline-based best practice treatment for muscle invasive bladder cancer (MIBC) involves neoadjuvant chemotherapy followed by radical cystectomy (NACRC). Prior studies have shown that a minority of patients receive NACRC and older age and renal function are drivers of non-receipt of NACRC. This study investigates treatment rates and factors associated with not receiving NACRC in MIBC patients with lower comorbidity status most likely to be candidates for NACRC. Materials and Methods: Retrospective United States National Cancer Database analysis from 2006 to 2015 of MIBC patients with Charlson comorbidity index (CCI) of zero. Analysis of NACRC treatment trends in higher CCI patients was also performed. Results: 15.561 MIBC patients met inclusion criteria. 1.507 (9.7%) received NACRC within 9 months of diagnosis. NACRC increased over time (15.0% in 2015 compared to 3.6% in 2006). Higher NACRC was noted in females, cT3 or cT4 cancer, later year of diagnosis, and academic facility treatment. Lower utilization was noted for blacks and NACRC decreased with increasing age and CCI. Only 16.9% of patients aged 23-62 in the lowest age quartile with muscle invasive bladder cancer and CCI of 0 received NACRC. Conclusions: Although utilization is increasing, receipt of NACRC remains low even in populations most likely to be candidates. Further study should continue to elucidate barriers to utilization of NACRC.

Proteomic research and diagnosis in bladder cancer: state of the art review

ABSTRACT Purpose: Proteomic biomarkers have been emerging as alternative methods to the gold standard procedures of cystoscopy and urine cytology in the diagnosis and surveillance of bladder cancer (BC). This review aims to update the state of the art of proteomics research and diagnosis in BC. Materials and Methods: We reviewed the current literature related to BC research on urinary, tissue, blood and cell line proteomics, using the Pubmed database. Findings: Two urinary protein biomarkers are FDA-approved (NMP22® and BTA® tests), only if performed along with cystoscopy for surveillance after initial diagnosis, but not in the primary diagnostic setting due to high false-positive rates in case of infections, stones and hematuria. There are a great number of non-FDA approved proteins being studied, with good preliminary results; panels of proteins seem valuable tools to be refined in ongoing trials. Blood proteins are a bigger challenge, because of the complexity of the serum protein profile and the scarcity of blood proteomic studies in BC. Previous studies with the BC tissue proteome do not correlate well with the urinary proteome, likely due to the tumor heterogeneity. Cell line proteomic research helps in the understanding of basic mechanisms that drive BC development and progression; the main difficulty is culturing low-grade tumors in vitro, which represents the majority of BC tumors in clinical practice. Conclusion: Protein biomarkers have promising value in the diagnosis, surveillance and prognostic of BC. Urine is the most appropriate body fluid for biomarker research in BC due to its easiness of sampling, stability and enrichment of shed and secreted tumor-specific proteins. Panels of biomarkers may exhibit higher sensitivity than single proteins in the diagnosis of BC at larger populations due to clinical and tumor heterogeneity. Prospective clinical trials are warranted to validate the relevance of proteomic data in the clinical management of BC.

Clinical significance of serum miR-187 and miR-143 in the diagnosis of gallbladder cancer / 中华肝胆外科杂志

Objective To investigate the clinical significance of serum miR-187 and miR-143 in the development and diagnosis of gallbladder cancer.Methods 75 serum samples in patients with gallbladder cancer were selected as gallbladder cancer group.75 serum samples in patients with gallbladder benign disease and 45 serum samples in healthy physical examinations at same period were selected as the benign gallbladder disease group and healthy control group.Quantitative RT-PCR was used to detect the serum miR-187 and miR-143 expression in each group,and the expression of those related with the clinicopathological factors,the proliferation and migration of gallbladder cancer cells,and the efficacy in diagnosis of gallbladder cancer was observed.Results The serum miR-187 expression in gallbladder cancer group was significantly higher than that in benign gallbladder disease and healthy control;the serum expression of that in benign gallbladder disease was significantly higher than that in healthy control;after surgery,the expression of that was significantly lower than that before treatment (all P ＜ 0.05).The serum expression of miR-143 in gallbladder cancer group was significantly lower than that in benign gallbladder disease and healthy control;the serum expression of that in benign gallbladder disease was significantly lower than that in healthy control;after surgery the serum expression of that was significantly higher than that before surgery (all P ＜0.05).The serum expression levels of miR-187 and miR-143 in gallbladder cancer were not correlated with gender and age (both P ＞ 0.05),and were significantly correlated with Nevin stage,TNM stage,differentiation and lymphatic metastasis (all P ＜ 0.05).Furthermore,it was confirmed that miR-187 promoted the proliferation and migration of gallbladder cancer cells in vitro,while miR-143 inhibited the proliferation and migration.In the diagnosis of gallbladder,the diagnostic efficacy of miR-187 and miR-143 was significantly better than that of CA199 and CA242 (both P ＜ 0.05).Combined detection could further improve the efficacy in diagnosis of gallbladder cancer.Conclusions miR-187 and miR-143 are involved in the development of gallbladder cancer.Combined detection of serum miR-187 and miR-143 in gallbladder cancer has a high diagnostic efficiency in the diagnosis of gallbladder cancer.

Incidencia y mortalidad del cáncer de vejiga en Costa Rica y Panamá, 2007-2013 / Incidence and mortality of bladder cancer in Costa Rica and Panama, 2007-2013

Resumen Objetivo: Se desconoce el comportamiento epidemiológico del cáncer de vejiga en Panamá y Costa Rica; globalmente, se reporta un aumento de la incidencia de dicha patología. Este estudio tiene como propósito reportar la incidencia, mortalidad y severidad del cáncer de vejiga, durante el período comprendido entre 2007 y 2013, en ambos países. Métodos: Se realiza un análisis epidemiológico transversal en el periodo comprendido entre 2007 y 2013, contemplando los casos incidentes y fallecidos por cáncer de vejiga en Costa Rica y Panamá. La tasa de incidencia y mortalidad anual para cada uno de los países y según sexo fue estimada de acuerdo con las proyecciones anuales de población. La severidad del comportamiento de la esta neoplasia se evaluó mediante la razón de incidencia / mortalidad. Resultados: Se identifica un total de 2048 casos de cáncer de vejiga. Se evidencia un aumento de las tasas de incidencia y mortalidad en los últimos 3 años del periodo de estudio, con un compromiso mayor en el sexo masculino. La tasa de incidencia aumentó de 2007 a 2013 en un 42,3 % en Costa Rica y un 71,4 % en Panamá. En dicho periodo, la mortalidad aumentó un 25,9 % para Costa Rica y un 44,7 % para Panamá. La razón de incidencia / mortalidad se mantuvo estable para ambos países durante el periodo de estudio. Conclusión: Existe una tendencia creciente en las tasas de incidencia y mortalidad por cáncer de vejiga, en Costa Rica y Panamá.

Abstract Aim: The incidence and mortality of bladder cancer has increased in some regions of the world. However, the epidemiological profile of this neoplasia is largely unknown in Panama and Costa Rica. Therefore, the aim of this study was to report the incidence, mortality, and severity of this disease during years 2007 to 2013. Methods: An epidemiological cross-sectional study was conducted between 2007 and 2013 with all incident and mortality cases of bladder cancer in Costa Rica and Panama. The annual incidence and mortality rates for each country, and according by sex were estimated based on the annual population estimates. The incidence/mortality ratio was estimated as a measure to evaluate the severity of the pathology. Results: A total of 2048 cases of bladder cancer were included. During the last 3 years of the study period we detected an increased in incidence and mortality rates, predominately in males. The incidence rate increased from year 2007 to year 2013 in 42.3% and 71.4% in Costa Rica and Panama, respectively. During the same period the mortality rate also increased 25.9% in Costa Rica and 44.7% in Panama. The incidence/ mortality rate had a steady behavior during the study period. Conclusion: These findings confirm a growing trend in the incidence and mortality rates of bladder cancer in Costa Rica and Panama.

Prognostic value of serum paraoxonase-1 in patients with non-muscle-invasive bladder cancer / 中国医师进修杂志

Objective@#To explore the prognostic value of serum paraoxonase-1(PON-1) in patients with non-muscle-invasive bladder cancer.@*Methods@#Serum levels of paraoxonase-1 (PON-1) in one hundred and twenty non-muscle-invasive bladder cancer patients (bladder cancer group) and fifty healthy controls (healthy control group) in Hankou Hospital of Wuhan were detected using spectrophotometric rate assay with p-nitrophenol as the substrate. The overall survival and disease-free survival curve was drawn by Kaplan-Meier method in different serum PON-1 levels, and independent prognostic factors were analyzed by Cox proportional hazards model.@*Results@#The serum levels of PON-1 in bladder cancer group was (116.52 ± 21.91) U/L, in healthy control group was (237.96 ± 46.97) U/L, and there was significant difference (t=23.004, P < 0.01). The patients in bladder cancer group were divided into high PON-1 group (≥ 116.52 U/L, 64 patients) and low PON-1 group (< 116.52 U/L, 56 patients) by the median of PON-1(116.52 U/L). Serum PON-1 levels were closely correlated with age of bladder cancer patients (P < 0.05), but not correlated with gender, Karnofsky score, anesthesia risk grading(ASA grade), tumor multiplicity, T stage, pathological grade and tumor size (P > 0.05). The median over-all survival time of the high PON-1 group was 62 months, and 52 months in the low PON-1 group, and there was significant difference (Log-rank=7.004, P=0.008). The median disease-free survival time of the high PON-1 group was 57 months, and 49 months in the low PON-1 group, and there was significant difference (Log-rank=4.068, P=0.044). Cox multivariate regression analysis showed that T stage, serum PON-1 levels was independently associated with overall survival and disease-free survival of patients with non-muscle invasive bladder cancer (P < 0.05).@*Conclusions@#Serum PON-1 levels is increased in non-muscle invasive bladder cancer patients, and PON-1 is an independent prognostic indicator of overall survival and disease-free survival in patients with bladder cancer.

Prognostic value of serum paraoxonase-1 in patients with non-muscle-invasive bladder cancer / 中国医师进修杂志

Objective To explore the prognostic value of serum paraoxonase-1(PON-1) in patients with non-muscle-invasive bladder cancer. Methods Serum levels of paraoxonase-1 (PON-1) in one hundred and twenty non-muscle-invasive bladder cancer patients (bladder cancer group) and fifty healthy controls (healthy control group) in Hankou Hospital of Wuhan were detected using spectrophotometric rate assay with p-nitrophenol as the substrate. The overall survival and disease-free survival curve was drawn by Kaplan-Meier method in different serum PON-1 levels, and independent prognostic factors were analyzed by Cox proportional hazards model. Results The serum levels of PON-1 in bladder cancer group was (116.52 ± 21.91) U/L, in healthy control group was (237.96 ± 46.97) U/L, and there was significant difference (ti23.004, P < 0.01). The patients in bladder cancer group were divided into high PON-1 group ( ≥116.52 U/L, 64 patients) and low PON-1 group (< 116.52 U/L, 56 patients) by the median of PON-1(116.52 U/L). Serum PON-1 levels were closely correlated with age of bladder cancer patients (P < 0.05), but not correlated with gender, Karnofsky score, anesthesia risk grading( ASA grade), tumor multiplicity, T stage, pathological grade and tumor size (P > 0.05). The median over-all survival time of the high PON-1 group was 62 months, and 52 months in the low PON-1 group, and there was significant difference (Log-ranki7.004, Pi0.008). The median disease-free survival time of the high PON-1 group was 57 months, and 49 months in the low PON-1 group, and there was significant difference (Log-ranki4.068, Pi0.044). Cox multivariate regression analysis showed that T stage, serum PON-1 levels was independently associated with overall survival and disease-free survival of patients with non-muscle invasive bladder cancer (P < 0.05). Conclusions Serum PON-1 levels is increased in non-muscle invasive bladder cancer patients, and PON-1 is an independent prognostic indicator of overall survival and disease-free survival in patients with bladder cancer.

Adenocarcinoma de uraco: presentación de dos casos / Urachal adenocarcinoma: report of two cases

OBJETIVOS: Revisión de la literatura del Adenocarcinoma de uraco y presentación de dos casos MÉTODOS/RESULTADOS: Analizamos las características epidemiológicas, clínicas y terapéuticas del Adenocarcinoma de uraco y presentamos dos casos diagnosticados y tratados en nuestro centro CONCLUSIONES: El Adenocarcinoma de uraco es una neoplasia rara, con mal pronóstico y cuyo tratamiento generalmente es la cistectomía parcial o radical con resección en bloque del uraco y el ombligo. Debido a su gravedad, debería tenerse en cuenta a la hora del diagnóstico.AU

OBJECTIVE: Literature review of Urachus adenocarcinoma and report of two cases. METHODS/RESULTS: We analyze epidemiological, clinical and therapeutic features of the Urachus adenocarcinoma and we report two cases diagnosed and treated in our institution. CONCLUSIONS: The Urachus adenocarcinoma is a rare cancer, with poor prognosis and treatment of which usually is radical or partial cystectomy with umbilicotomy and removal of the urachus in bloc. Due to its gravity, you should keep it in mind when you make a diagnosis.AU

Ureteral orifice involvement by urothelial carcinoma: long term oncologic and functional outcomes

ABSTRACT Purpose: Bladder cancer (BC) may involve the ureteral orifice, and the resection of the orifice has oncological and functional consequences such as development of upper tract urothelial carcinoma (UTUC), vesicoureteral reflux or ureteral stenosis. The aim of this study was to investigate the oncological and functional outcomes of the ureteral orifice resection in BC patients and determine the predictive factors for UTUC development. Materials and Methods: A total of 1359 patients diagnosed with BC, between 1992 and 2012, were reviewed retrospectively. Patients were grouped with respect to orifice resection and compared for development of UTUC, survival and functional outcomes. Kaplan-Meier method was used to compare survival outcomes. Logistic regression analysis was performed to determine predictors of UTUC development. Results: Ureteral orifice involvement was detected in 138 (10.2%) patients. The rate of synchronous (10.1% vs. 0.7%, p=0.0001) and metachronous (5.3% vs. 0.9%, p=0.0001) UTUC development was found to be higher in patients with ureteral orifice involvement. Orifice involvement and tumor stage were found to be associated with development of UTUC in the regression analysis. Overall (p=0.963) and cancer specific survival rates (p=0.629) were found to be similar. Hydronephrosis was also significantly higher in patients with orifice involved BC, due to the orifice obstruction caused by the tumor (33.3% vs. 13.9%, p<0.05). Conclusions: BC with ureteral orifice involvement has significantly increased the risk of having synchronous or metachronous UTUC. However, orifice involvement was not found to be associated with survival outcomes. Development of stricture due to resection is a very rare complication.

Efficiency of prophylactic intravesical chemotherapy after nephroureterectomy for primary upper tract urothelial carcinoma / 中华泌尿外科杂志

Objective To explore the efficiency of prophylactic intravesical chemotherapy after nephroureterectomy for primary upper tract urothelial carcinoma.Methods Forty-seven patients with primary upper tract urothelial carcinoma who underwent nephroureterectomy were retrospectively analyzed.There were 25 male and 22 female patients with mean age of 68 years.Patients were divided into intravesical chemotherapy group (n =32) and non-intravesical chemotherapy group (n =15).In the intravesical chemotherapy group, there were 14 male and 18 female patients with mean age of 70.3 years;20 cases located at left side while 12 at the right side.In non-intravesical chemotherapy group, There were 11 male and 4 female patients with mean age of 65.0 years;10 cases located at left side while 5 at the right side.The age, gender, side of the two groups were not statistical different.The two groups were followed up, and the tumor stage, grade, recurrence rate, cancer-free survival time were compared.Results The pathology results of all cases were urothelial carcinoma.In the intravesical chemotherapy group, 23 cases were high grade tumors with 9 low grade tumors.There were 15 cases of Ta-T1 stage, 8 cases of T2 stage and 9 cases of T3 stage;the tumor of 19 cases located at pelvis, 12 located at ureter, 1 located at pelvis and ureter;the mean size of the tumors was (2.75 ± 1.49) cm;8 cases were multiple while 24 were single.In the non-intravesical chemotherapy group, 12 cases were high grade tumors with 3 low grade tumors, there were 6 cases of Ta-T1 stage, 4 cases of T2 stage and 5 cases of T3 stage;the tumor of 11 cases located at pelvis, 3 located at ureter, 1 located at pelvis and ureter;the mean size of the tumors was (3.11 ± 1.48) cm;6 cases were multiple while 9 were single.The items mentioned above did not reach statistical difference between the two groups(P ＞0.05).6 patients relapsed in intravesical chemotherapy group while 7 in non-intravesical chemotherapy group.The recurrence rate of bladder cancer of intravesical chemotherapy group was lower than that of non-intravesical chemotherapy group (18.75％ vs.46.67％, χ2 =3.978, P =0.046).Compared with non-intravesical chemotherapy group, intravesical chemotherapy group had longer cancer-free survival, but it did not reach statistical difference (36.5months vs.29.6months, t =1.079, P =0.286).The age and tumor grade were risk factors of bladder cancer recurrence, meanwhile the gender, tumor side, tumor stage, voided urine cytology, tumor size, and location were not.Conclusion Prophylactic intravesical chemotherapy after nephroureterectomy for primary upper tract urothelial carcinoma could reduce the recurrence rate of bladder cancer.

A case report of bladder urothelial carcinoma in combination with trophoblast and the literature review / 中华泌尿外科杂志

Objective To investigate the clinical features,therapeutic methods,therapeutic effect and prognosis of a case of bladder urothelial carcinoma patients in combination with trophoblast.Methods The pathological data of a patient with bladder high grade urinary epithelial carcinoma in combination with trophoblast was retrospectively analyzed and the related literatures were reviewed.It was a male patient,69 years old,presenting with total painless gross hematuria.The CT scan showed irregular nodules on the anterior wall of bladder.Results Cystoscopy showed 1.5 cm cauliflower mass on the anterior wall of bladder,and transurethral resection of bladder tumor was performed.The pathology and immunohistochemistry showed urothelial carcinoma.Lung metastases was found due to hemoptysis,and increased serum beta human chorionic gonadotropin (β-HCG) was detected simuhaneously.Pathology was double checked and bladder urothelial carcinoma with trophoblast cell differentiation was considered.Three cycles gemcitabine + cisplatin (GC regimen) and 2 cycles etoposide + methotrexate + vincristine + cyclophosphamide (modified EMA-CO regimen) therapies were given,and the disease was stable at that time.The patient died on June 10,2016,and the total survival period was 9 months.Conclusions The clinical and imaging of urothelial carcinoma with trophoblast differentiation is not special.Diagnosis must depend on the pathological and immunohistochemistry examinations.The efficacy can be evaluated by combining imaging with serumβ-HCG.Treatment should be systemic venous chemotherapy.

Diagnosis and treatment of micro-paragangliomas in urinary bladdler / 基础医学与临床

Objective To develope the diagnostic criteria and surgical methods to treat micro-paraganagliomas (<1 cm) of urinary bladder ( PUB) , we now report a case series study including 5 individual cases .Methods Clinical data of 5 patients with micro-PUBs who underwent surgical treatment were obtained and analyzed retrospectively . Two male patients and three female patients were included in our study with the mean age of 51 ( range from 41 to 65 years) .4 patients were reported as symptomatic due to hypercatecholaminemia , while the other was free of symptoms.24-hour urine catecholamine ( CA) examination was utilized to qualitatively diagnose PUB , positive in 75%patients.Ultrasonography(USG), CT, MRI, 111In-DTPA-Octreotide scintigraphy (OctreoScan) and 131 I-MIBG scintigraphy were used to locate the tumor , positive in 80%, 20%, 75%, 25%and 33%patients respectively .What's more, all 5 patients underwent transurethral resection of tumor .Overfilling of bladder and puncture following ultra-sonography guidance were performed to locate the tumors , when tumors were absent in surgical vision .Results All tumors were located and resected completely with no open conversions .It took 0.5 to 26 minutes to locate the tumor and another 3 to 10 minutes to resect the tumors .All lesions were diagnosed by histopathological confirma-tion, especially by immunohistochemical staining.Blood pressure return to normal level after the procedures.No local recurrence or distal metastasis were observed by performing 24-hour urine CA test , USG, cystoscopy and MRI within adequate follow-up.The mean follow-up duration was 38.6 months, ranging from 6 to 120 months.Conclu-sions USG and MRI examination were considered better in detecting micro PUB than CT-scan.Overfilling of blad-der and puncture following USG guidance may support more accurate tumor location intraoperatively if the tumors were not found in transurethral resection procedures .

Analysis of diabetes mellitus increasing the risk of intravesical recurrence in patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy / 中国肿瘤临床

Objective:To investigate whether the risk of intravesical recurrence increases in patients with upper urinary tract urothelial carcinoma (UUT-UC) and diabetes mellitus (DM) after radical nephroureterectomy (RNU) with bladder cuff excision. Methods:We ret-rospectively analyzed the clinicopathological data of 282 UUT-UC patients with no history of bladder neoplasm and who underwent RNU with bladder cuff excision in the Second Hospital of Tianjin Medical University from January 2005 to December 2013. The recurrence-free survival (RFS) and cancer-specific survival (CSS) were compared between the non-diabetic (233 patients) and diabetic (49 patients) patients. The factors influencing intravesical recurrence in patients with UUT-UC after RNU were analyzed. These factors included age, DM, pathologic grade, and stage. Results:Among the 282 patients included in the study, 80 (28.4%) patients developed intravesical recurrence during the median fol ow up of 41 months, and the median time to recurrence was 11 months. Non-diabetic patients had a significantly longer duration of bladder neoplasm RFS than diabetic patients (P=0.013). Multivariate analysis using Cox's regression model indicated that DM (P=0.014), renal pelvis and ureter tumor (P=0.001), and postoperative chemotherapy (P=0.024) were independent influential factors for intravesical recurrence in patients with UUT-UC after RNU with bladder cuff excision. Conclusion:DM posed an increased risk for intravesical recurrence after RNU with bladder cuff excision in patients with UUT-UC. Therefore, these patients need to be closely monitored, and their blood glucose must be controlled.

Febrile Urinary Tract Infection after Radical Cystectomy and Ileal Neobladder in Patients with Bladder Cancer

Urinary tract infection (UTI) is one of the most common complications after radical cystectomy and orthotopic neobladder reconstruction. This study investigated the incidence and implicated pathogen of febrile UTI after ileal neobladder reconstruction and identify clinical and urodynamic parameters associated with febrile UTI. From January 2001 to May 2015, 236 patients who underwent radical cystectomy and ileal neobladder were included in this study. Fifty-five episodes of febrile UTI were identified in 46 patients (19.4%). The probability of febrile UTI was 17.6% and 19.8% at 6 months and 24 months after surgery, respectively. While, Escherichia coli was the most common implicated pathogen (22/55, 40.0%), Enterococcus spp. were the most common pathogen during the first month after surgery (18/33, 54.5%). In multivariate logistic regression analysis, ureteral stricture was an independent risk factor associated with febrile UTI (OR 5.93, P = 0.023). However, ureteral stricture accounted for only 6 episodes (10.9%, 6/55) of febrile UTI. Most episodes of febrile UTI occurred within 6 months after surgery. Thus, to identify risk factors associated with febrile UTI in the initial postoperative period, we assessed videourodynamics within 6 months after surgery in 38 patients. On videourodyamic examination, vesicoureteral reflux (VUR) was identified in 16 patients (42.1%). The rate of VUR presence in patients who had febrile UTI was not significantly different from those in patients without febrile UTI (50% vs. 39.3%, P = 0.556). Patients with febrile UTI had significantly larger residual urine volume (212.0 ± 193.7 vs. 90.5 ± 148.2, P = 0.048) than those without. E. coli and Enterococcus spp. are common pathogens and ureteral stricture and residual urine are risk factors for UTI after ileal neobladder reconstruction.

Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective, Multi-Institutional Study

PURPOSE: To identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data were collected and analyzed for 2412 NMIBC patients from 15 centers who were initially diagnosed after transurethral resection of bladder tumor (TURBT) from January 2006 to December 2010. Using univariable and multivariable Cox proportional hazards models, the prognostic value of each variable was evaluated for the time to first recurrence and progression. RESULTS: With a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy. CONCLUSION: A preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.

Prognostic significance of pelvic lymphadenectomy in patients with bladder cancer / 中国肿瘤临床

Objective:To evaluate the prognostic significance of standard pelvic lymphadenectomy on the disease-free survival (DFS) rate of bladder cancer patients undergoing radical cystectomy (RC) and to discuss the influencing factors of lymph node positivity and the relationship between positive lymph nodes and lymphadenectasis. Methods:This prospective analysis includes 120 cases of bladder cancer treated with pelvic lymphadenectomy and RC in Tianjin Medical University Cancer Institute and Hospital between 2008 and 2013. The cases were divided into two groups, namely, the standard pelvic lymphadenectomy group (Group A) and the nonstandard pelvic lymphadenectomy group (Group B). The relationships among positive lymph nodes, lymphadenectasis, tumor stage, and patho-logical grade were retrospectively analyzed. Results:The 1-, 3-, and 5-year overall survival rates of 120 patients were 84%, 69.9%, and 57.9%, respectively. Group A was significantly correlated with a better 3-year overall survival rate than Group B, i.e., 78.4%vs. 46.2%(P<0.05). Lymphadenectasis influenced the DFS rate of bladder cancer patients after RC with pelvic lymphadenectomy, i.e., 50.0%vs. 86.4%(χ2=9.303, P<0.05). Meanwhile, lymphadenectasis was positively correlated with lymph node positivity (P<0.001). Tumor stage, histological subtype (urothelial carcinoma and non-urothelial carcinoma), and age were the prognostic factors for bladder cancer (P<0.05). Conclusion:Intraoperative lymphadenectasis is the influencing factor of lymph node positivity. This study determined that standard pel-vic lymphadenectomy and lymphadenectasis may influence the DFS rate after RC and are the independent risk factors for the prognosis of bladder cancer. Creating evidence-based guidelines of standardized lymphadenectomy for further improvement of the surgical quali-ty and survival of bladder cancer patients is essential.

Is Intravesical Bacillus Calmette-Guerin Therapy Superior to Chemotherapy for Intermediate-risk Non-muscle-invasive Bladder Cancer?: An Ongoing Debate

The objective of this study was to evaluate the risk of recurrence in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) after intravesical instillation with chemotherapeutic agents or Bacillus Calmette-Guerin (BCG) therapy. A cohort of 746 patients with intermediate-risk NMIBC comprised the study group. The primary outcome was time to first recurrence. The recurrence rates of the transurethral resection (TUR) alone, chemotherapy, and BCG groups were determined using Kaplan-Meier analysis. Risk factors for recurrence were identified using Cox regression analysis. In total, 507 patients (68.1%), 78 patients (10.5%), and 160 (21.4%) underwent TUR, TUR+BCG, or TUR+chemotherapy, respectively. After a median follow-up period of 51.7 months (interquartile range=33.1-77.8 months), 286 patients (38.5%) developed tumor recurrence. The 5-yr recurrence rates for the TUR, chemotherapy, and BCG groups were 53.6%+/-2.7%, 30.8%+/-5.7%, and 33.6%+/-4.7%, respectively (P<0.001). Chemotherapy and BCG treatment were found to be predictors of reduced recurrence. Cox-regression analysis showed that TUR+BCG did not differ from TUR+chemotherapy in terms of recurrence risk. Adjuvant intravesical instillation is an effective prophylactic that prevents tumor recurrence in intermediate-risk NMIBC patients following TUR. In addition, both chemotherapeutic agents and BCG demonstrate comparable efficacies for preventing recurrence.