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.

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.

Preoperative hydronephrosis predicts adverse pathological features and postoperative survival in patients with high-grade upper tract urothelial carcinoma

ABSTRACT Purpose: Epidemiological studies reported conflicting results about preoperative hydronephrosis in upper tract urothelial carcinoma (UTUC). This study aimed to investigate the association between preoperative hydronephrosis and pathologic features and oncologic outcomes in patients with UTUC treated by radical nephroureterectomy (RNU). Materials and Methods: This was a retrospective, single-center cohort study of 377 patients treated by RNU without perioperative chemotherapy between January 2001 and December 2014. Logistic regression, Cox regression, and survival analyses were performed. Results: Among the 226 patients with high-grade UTUC, 132 (58%) had preoperative hydronephrosis. Multivariable logistic regression revealed that hydronephrosis was independently associated with advanced pT stage (P=0.017) and lymph node or lymphovascular invasion (P=0.002). Median follow-up was 36 months (interquartile range: 20-48 months). The 3- and 5-year overall survival (OS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P <0.001). The 3- and 5-year cancer-specific survival (CSS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P=0.001). Hydronephrosis was independently associated with OS and CSS (P=0.001 and P=0.004, respectively). Among the 151 patients with low-grade UTUC, hydronephrosis was not associated with pathologic features and postoperative survival. Conclusions: Preoperative hydronephrosis was significantly associated with adverse pathologic features and postoperative survival in patients with high-grade UTUC.

Retrograde pyelography before radical nephroureterectomy for upper tract urothelial carcinoma is associated with intravesical tumor recurrence

ABSTRACT Purpose: To investigate the association between preoperative retrograde pyelography (RGP), conducted to evaluate upper tract urothelial carcinoma (UTUC), and intravesical recurrence (IVR) after radical nephroureterectomy (RNU). Materials and Methods: Of 114 patients that underwent RNU, 72 patients without preoperative ureteroscopy and a history of bladder tumor were selectively enrolled. Variables associated with IVR were identified. Results: RGP was performed at a mean duration of 24.9 days prior to RNU in 41 (56.1%) of study subjects. During the mean follow-up period of 64.5 months, IVRs were identified in 32 (44.4%) patients at 22.3±18.8 (mean±SD) months after RNU. Despite similar tumor characteristics in the RGP and non-RGP groups, the incidence of IVR was considerably higher in the RGP group (63.4%) than in the non-RGP group (19.4%, p <0.001). The following variables differed significantly between the IVR and non-IVR groups: age (64.6±8.51 vs. 59.6±9.65 years), tumor location (lower or upper; 53.1% vs. 20%), tumor invasiveness (> pT2; 53.1% vs. 17.5%), preoperative hemoglobin (12.8±1.36 vs. 13.9±1.65), preoperative creatinine (1.29±0.32 vs. 1.11±0.22), and preoperative RGP (81.3% vs. 37.5%), respectively. Multivariate Cox regression model showed that tumor location (p=0.020, HR=2.742), preoperative creatinine level (p=0.004, HR=6.351), and preoperative RGP (p=0.045, HR=3.134) independently predicted IVR. Conclusion: Given the limitations of retrospective single-center series, performance of RGP before RNU was shown to have a negative effect on IVR after surgery.

Can Neutrophil-to-Lymphocyte ratio predict the response to BCG in high-risk non muscle invasive bladder cancer?

ABSTRACT Objectives: To evaluate the neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor for response of high risk non muscle invasive bladder cancer (HRNMIBC) treated with BCG therapy. Materials and Methods: Between March 2010 and February 2014 in a tertiary center 100 consecutive patients with newly diagnosed HRNMIBC were retrospectively analyzed. Patients were divided according to NLR value: 46 patients with NLR value less than 3 (NLR < 3 group), and 54 patients with NLR value more than 3 (NLR ≥ 3 group). At the end of follow-up 52 patients were high grade disease free (BCG-responder group) and 48 patients underwent radical cystectomy for high grade recurrence or progression to muscle invasive disease (BCG non-responder group). The average follow-up was 60 months. Intervention: analysis and correlation of preoperative NLR value with response to BCG in terms of recurrence and progression. Results: The optimal cut-off for NLR was ≥ 3 according to the receiver operating characteristics analysis (AUC 0.760, 95% CI, 0.669-0.850). Mean NLR value was 3.65 ± 1.16 in BCG non-responder group and 2.61 ± 0.77 in BCG responder group (p = 0.01). NLR correlated with recurrence (r = 0.55, p = 0.01) and progression risk scores (r = 0.49, p = 0.01). In multivariate analysis, NLR (p = 0.02) and EORTC recurrence risk groups (p = 0.01) were associated to the primary endpoint. The log-rank test showed statistically significant difference between NLR < 3 and NLR ≥ 3 curves (p < 0.05). Conclusions: NLR value preoperatively evaluated could be a useful tool to predict BCG response of HRNMIBC. These results could lead to the development of prospective studies to assess the real prognostic value of NLR in HRNMIBC.

Evaluating the impact of preoperative anemia on the prognosis of upper tract urothelial carcinoma following radical nephroureterectomy: A single-center retrospective study of 686 patients / 北京大学学报(医学版)

OBJECTIVE@#To identify the effect of preoperative anemia on the prognosis of patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy.@*METHODS@#Clinicopathological and prognosis data on 686 patients with UTUC who underwent RNU at Peking University First Hospital between January 2000 and December 2013 were retrospectively analyzed. Preoperative anemia was defined as hemoglobin <130 g/L in men and <120 g/L in women based on the World Health Organization classification. The Kaplan-Meier method with log-rank test was applied to estimate the effect of anemia on survival. The associations of clinicopathologic features with overall survival and cancer-specific survival were evaluated using univariate and multivariate Cox regression models.@*RESULTS@#There were 303(44.2%, 303/686) male and 383(55.8%, 383/686) female patients, and the median age was 68 years (interquartile range: 60-74 years). In all, 320 (46.6%, 320/686) patients were anemic before surgery. The median follow-up duration was 47 months. In all, 160 (23.3%) patients died, 141 (20.6%) died of cancer and 19 (2.7%) died of other disease or accidents. Preoperative anemia was associated with gender (P=0.002), age (P<0.001), lymph node positive (P=0.026), increased tumor grade (P=0.018), concomitant carcinoma in situ (P=0.038), tumor necrosis (P=0.007) and poor renal function (P<0.001). In univariate analysis, overall mortality was correlated with pre-operative anemia (P<0.001), gender (P=0.009), hydronephrosis (P=0.024), tumor stage (P<0.001), lymph node positive (P<0.001), tumor grade (P<0.001), tumor architecture(P<0.001), sarcomatoid differentiation (P=0.013), history of ureteroscope (P=0.033) and tumor hemorrhage (P<0.001); cancer-specific mortality was correlated with preoperative anemia (P=0.001), gender (P=0.001), hydronephrosis (P=0.043), tumor stage (P<0.001), lymph node positive (P<0.001), tumor grade (P<0.001), tumor architecture (P<0.001), sarcomatoid differentiation (P=0.016), history of ureteroscope (P=0.028) and tumor hemorrhage (P=0.003). A multivariate Cox proportional hazards model indicated that preoperative anemia was an independent prognositic predictor for overall mortality (P<0.001, HR=1.861) and cancer-specific mortality (P=0.003, HR=1.688).@*CONCLUSION@#The preoperative anemia is an independent risk factor for cancer-specific survival and overall survival. Hemoglobin levels should be considered during patient counseling and in decision-making for further therapy.

The demographic features, clinical outcomes, prognosis and treatment options for patients with sarcomatoid carcinoma of the urinary bladder: a single centre experience

ABSTRACT Introduction Carcinosarcoma of the bladder is a very rare neoplasm. The pathogenesis of carcinosarcomas is not clearly understood and remains a subject of debate. Whilst there is some research conceptualizing the histopathological findings of bladder carcinosarcomas, the demographic features, clinical outcomes, prognosis and treatment options remain unclear. Materials and Methods We analyzed 12 consecutive cases of patients with sarcoma-toid bladder cancer who were treated surgically at a single Urology Department be-tween 1999 and 2015. Radiology, pathology and surgical reports were reviewed to determine the pathological staging at the time of cystectomy. These were directly compared with 230 patients having cystectomies for urothelial cell carcinoma. The sarcomatoid patients, were compared to patients with urothelial cell cancers. The other histological sub types, squamous cell (17), neuroendocrine (9), metastatic (7), mixed (4), adenocarcinoma (3), were not included. Results and conclusion Carcinosarcoma of the urinary bladder is often described in the literature as a highly malignant neoplasm that is rapidly lethal. We found that the sarcoma does not offer a worse prognosis than conventional high-grade urothelial car-cinoma. There is no significant difference in grade, stage, positive surgical margin rate, nodal involvement, associated prostate cancer or incidence rates of progression, all cause or disease specific mortality. There was a barely significant difference in carcinoma in-situ. However, carcinosarcomas are three times the volume of urothelial cell tumors which may contribute to its reputation as an aggressive tumour (44cc v 14cc). Sarcomatous elements do not appear, from our small study, to bestow a worse prognosis.

Resultados oncológicos en pacientes con cáncer de vejiga pT0 posterior a cistectomía radical / Oncological outcomes of Patients with pT0 Bladder Cancer after Radical Cystectomy

Introducción: El estadío pT0 del cáncer de vejiga implica la ausencia de enfermedad en la pieza de cistectomía radical (CR). El objetivo de este estudio es describir los resultados oncológicos de los pacientes con estadío pT0 posterior a CR por carcinoma urotelial de vejiga. Materiales y métodos: Estudio retrospectivo de pacientes sometidos a CR por cáncer de vejiga, en una sola institución, sin neoadyuvancia, entre junio de 2005 y julio de 2013. Se incluyeron aquellos pacientes con diagnóstico histológico de estadío pT0 pN0. Se estimó la sobrevida global, sobrevida cáncer-específica y sobrevida libre de recidiva con el método de Kaplan-Meier. Resultados: De 254 pacientes cistectomizados, 17 presentaron estadío pT0 pN0 (6,7%). La mediana de edad fue 67 años (rango 49-85), 15 pacientes fueron hombres (88%). Los resultados patológicos posterior a resección transuretral de vejiga (RTUv) fueron 17% pT1 (n=3) y 83% pT2 (n=14). La mediana de tiempo entre RTUv y CR fue 60 días (rango 30- 95). Al 41% se le realizó derivación urinaria tipo Bricker y al 59%, una neovejiga. La mediana de estadía hospitalaria fue 8 días (rango 6-44). Se evidenció adenocarcinoma de próstata en 4 pacientes. La mediana de ganglios resecados fue 6 (rango 2-17). Ningún paciente recibió adyuvancia. La mediana de seguimiento fue 69 meses (rango 5-120). Un paciente presentó recidiva uretral a los 72 meses de la CR. La sobrevida cáncer-específica fue 100%, la sobrevida libre de recaída a 5 años fue 83,3% (intervalo de confianza [IC] de 95%: 53,5-100) y la sobrevida global a 5 años fue 82,4% (IC 95%: 64,7-100). Conclusión: El estadío pT0 del cáncer de vejiga presenta resultados oncológicos más favorables que los estadíos más avanzados. Sin embargo, la posibilidad de recurrencia existe, por lo que no se debe discontinuar el seguimiento de estos pacientes (AU)

Introduction: There are cases in which there is no evidence of disease in the radical cystectomy (RC) specimen (pT0 stage). The purpose of this study is to evaluate oncological outcomes of patients with pT0 bladder cancer after RC, in a single institution, without neo-adjuvant therapy. Materials and methods: Patients who underwent radical cystectomy from June 2005 to July 2013 were reviewed retrospectively. All patients had history of bladder urothelial carcinoma, treated with transurethral resection of the bladder (TURB) and confirmed with pathological analysis. Study variables included TURB pathology, time to RC, and pathologic features. Overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) were estimated. Results: RC was performed on 254 patients; 17 patients (6.7%) had pT0N0 stage. Median age was 67 years (range 49-85 years); 15 patients were male (88%). TURB pathology specimens were 17% pT1 (n=3), and 83% pT2 (n=14). Median time between TURB and RC was 60 days (range 30-95). Seven patients (41%) received an ileal conduit, and ten patients (59%) received a neobladder. Median hospital stay was eight days (range 6-44). Prostate adenocarcinoma was found in four (23%) patients. Median resected lymph nodes were six (range 2-17). No patients received adjuvant chemotherapy. Median follow-up was 69 months (range 5-120 months). One patient had a urethral relapse 72 months after RC. There was no cancer-specific mortality. RFS at 5 years was 83.3% (confidence interval [CI] 95%: 53.5-100); OS at 5 years was 82.4% (CI 95%: 64.7-100). Conclusion: pT0 stage after radical cystectomy shows more favorable oncologic outcomes than higher stages. However, cancer recurrence was found in a low number of patients, thus, patient follow-up should be maintained (AU)

Retrospective study of young bladder urothelial carcinoma from a single center within 16 years / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinical and pathological features, treatment and prognosis for bladder urothelial carcinoma in relative young patients under 40 years.@*METHODS@#A retrospective study involved a total of 43 consecutive patients of bladder urothelial carcinoma, which were under 40 years old from January 2001 to December 2016.@*RESULTS@#The incidence rate of bladder urothelial carcinoma in the patients under 40 years was 2.2%, and 35 males and 8 females were included. The average age was 33 years (ranging from 23 to 40 years). At initial visit, 62.8% of the patients presented with painless gross hematuria, 9 patients were discovered by routine examination, and 7 patients experienced lower urinary tract symptoms. Solitary tumor occurred in 34 cases whereas multiple carcinomas had been discovered in 9 cases，and all the 9 multiple cases were from 31-40-year-old subgroups. All the patients received proper surgical intervention according to their own clinical stages. Post-operative pathological results showed 29 low-grade urothelial carcinoma and 14 high-grade cases which included 31 Ta cases, with 7 cases of T1, 1 case of T3, and 3 cases of T4 and one case of T1 plus Tis. The total follow-up was from 5 to 165 months, 3 cases were lost. The overall recurrence rate was 12.5% (5 cases from 40). One patient developed distal metastasis, one died of metastasis after 13 months, and the other three received secondary trans-urethral resection of bladder tumors. The average recurrence time was 39 months (ranging from 3 to 105 months). The progression rate was 5% among all the followed-up patients (2 cases from 40). The recurrence rate in multiple lesions group (33%, 3/9) was significantly higher than that (5.9%, 2/34) in solitary lesion group (P=0.000 3).@*CONCLUSION@#The incidence rate of bladder urothelial carcinoma in young patients under 40 years becomes increasingly higher over years. The major initial presentation is painless gross hematuria among these young patients, but lower urinary tract symptoms should also be noticed for young patients to rule out tumor. Postoperative tumor recurrence might be associated with multiple lesions, which is not related to the tumor size or pathological features.

Laparoscopic radical cystectomy with novel orthotopic neobladder with bilateral isoperistaltic afferent limbs: initial experience

ABSTRACT Purpose To introduce a new method of constructing an orthotopic ileal neobladder with bilateral isoperistaltic afferent limbs, and to describe its clinical outcomes. Materials and Methods From January 2012 to December 2013, 16 patients underwent a new method of orthotopic ileal neobladder after laparoscopic radical cystectomy for bladder cancer. To construct the neobladder, an ileal segment 60cm long was isolated approximately 25cm proximally to the ileocecum. The proximal 20cm of the ileal segment was divided into two parts for bilateral isoperistaltic afferent limbs. The proximal 10cm of the ileal segment was moved to the distal end of the ileal segment for the right isoperistaltic afferent limb, and the remaining proximal 10cm ileal segment was reserved for the left isoperistaltic afferent limb. The remaining length of the 40cm ileal segment was detubularized along its antimesenteric border to form a reservoir. The neobladder was sutured to achieve a spherical configuration. Results All procedures were carried out successfully. The mean operative time was 330 min, mean blood loss was 328mL, and mean hospital stay was 12.5 days. The mean neobladder capacity 6 and 12 months after surgery was 300mL and 401mL, respectively. With a mean follow-up of 22.8 months, all patients achieved daytime continence and 15 achieved nighttime continence. The mean peak urinary flow rate was 11.9mL/s and 12.8mL/s at 6 and 12 months postoperatively, respectively. Conclusions This novel procedure is feasible, safe, simple to perform, and provides encouraging functional outcomes. However, comparative studies with long-term follow-up are required to prove its superiority.

Diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma is Independently Associated with Intravesical Recurrence after Radical Nephroureterectomy

ABSTRACT Purpose: To determine the effect of diagnostic ureteroscopy on intravesical recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). Materials and Methods: We conducted a retrospective analysis of 664 patients who were treated with RNU for UTUC from June 2000 to December 2011, excluding those who had concomitant/prior bladder tumors. Of the 664 patients, 81 underwent diagnostic ureteroscopy (URS). We analyzed the impact of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan-Meier method. Univariate and multivariate analyses were used to determine the independent risk factors. Results: The median follow-up time was 48 months (interquartile range (IQR): 31-77 months). Patients who underwent ureteroscopy were more likely to have a small (p<0.01), early-staged (p=0.019), multifocality (p=0.035) and ureteral tumor (p<0.001). IVR occurred in 223 patients during follow-up within a median of 17 months (IQR: 7-33). Patients without preoperative ureteroscopy have a statistically significant better 2-year (79.3%±0.02 versus 71.4%±0.02, p<0.001) and 5-year intravesical recurrence-free survival rates (64.9%±0.05 versus 44.3%±0.06, p<0.001) than patients who underwent ureteroscopy. In multivariate analysis, the diagnostic ureteroscopy (p=0.006), multiple tumors (p=0.001), tumor size <3cm (p=0.008), low-grade (p=0.022) and pN0 stage tumor (p=0.045) were independent predictors of IVR. Conclusions: Diagnostic ureteroscopy is independently associated with intravesical recurrence after radical nephroureterectomy.

Radical cystectomy with pelvic lymphadenectomy: pathologic, operative and morbidity outcomes in a Brazilian cohort

ABSTRACT Introduction and Objective Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for muscle invasive bladder cancer and the oncologic outcomes following it are directly related to disease pathology and surgical technique. Therefore, we sought to analyze these features in a cohort from a Brazilian tertiary oncologic center and try to identify those who could negatively impact on the disease control. Patients and Methods We identified 128 patients submitted to radical cystectomy, for bladder cancer treatment, from January 2009 to July 2012 in one oncology tertiary referral public center (Mario Penna Institute, Belo Horizonte, Brazil). We retrospectively analyzed the findings obtained from their pathologic report and assessed the complications within 30 days of surgery. Results We showed similar pathologic and surgical findings compared to other large series from the literature, however our patients presented with a slightly higher rate of pT4 disease. Positive surgical margins were found in 2/128 patients (1.5%). The medium number of lymph nodes dissected were 15. Major complications (Clavien 3 to 5) within 30 days of cystectomy occurred in 33/128 (25.7%) patients. Conclusions In the management of invasive bladder cancer, efforts should focus on proper disease diagnosis and staging, and, thereafter, correct treatment based on pathologic findings. Furthermore, extended LND should be performed in all patients with RC indication. A critical analysis of our complications in a future study will help us to identify and modify some of the factors associated with surgical morbidity.

Adjuvant chemotherapy for locally advanced upper tract urothelial carcinoma: updated results of the Seoul National university hospital experience

Objectives: The objective of this study was to update the long-term outcome in the treatment of locally advanced upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) regarding the role of adjuvant chemotherapy. Materials and methods: Clinical data from 138 patients who underwent RNU for locally advanced UTUC (pT3/4 or pN+) were analyzed. Results: The adjuvant chemotherapy group comprised 66 patients, and other 72 patients did not receive adjuvant chemotherapy. Cisplatin-based chemotherapy was the most common regimen, depending on the patient's eligibility and renal function. The median follow-up period was 48.7 months (interquartile range: 29.2-96.9 months). The 3-and 5-year disease-specific survival (DSS) rates were 76.0% and 69.9% for the non-adjuvant chemotherapy group versus 74.6% and 54.5% for the adjuvant chemotherapy group (p=0.301, log-rank test). Overall survival (OS) rates for the same time period were 70.1% and 62.9% for the non-adjuvant chemotherapy group versus 73.8% and 53.2% for the adjuvant chemotherapy group (p=0.931, log-rank test). On multivariate analysis, adjuvant chemotherapy could not predict DSS and OS after surgery. When patients who received cisplatin-based adjuvant chemotherapy (n=59) were compared to those who did not receive adjuvant chemotherapy, similar results were found. Conclusions: There does not appear to be a significant DSS or OS benefit associated with adjuvant chemotherapy. Prospective randomized clinical trials are necessary to verify the effect of adjuvant chemotherapy on locally advanced UTUC.

C9orf72-related disorders: expanding the clinical and genetic spectrum of neurodegenerative diseases / Distúrbios relacionados ao C9orf72: expandindo o espectro clínico e genético das doenças neurodegenerativas

Neurodegenerative diseases represent a heterogeneous group of neurological conditions primarily involving dementia, motor neuron disease and movement disorders. They are mostly related to different pathophysiological processes, notably in family forms in which the clinical and genetic heterogeneity are lush. In the last decade, much knowledge has been acumulated about the genetics of neurodegenerative diseases, making it essential in cases of motor neuron disease and frontotemporal dementia the repeat expansions of C9orf72 gene. This review analyzes the main clinical, radiological and genetic aspects of the phenotypes related to the hexanucleotide repeat expansions (GGGGCC) of C9orf72 gene. Future studies will aim to further characterize the neuropsychological, imaging and pathological aspects of the extra-motor features of motor neuron disease, and will help to provide a new classification system that is both clinically and biologically relevant.

As doenças neurodegenerativas representam um grupo heterogêneo de condições neurológicas envolvendo fundamentalmente síndromes demenciais, doenças do neurônio motor e distúrbios de movimento. Relacionam-se, em sua maioria, a processos fisiopatológicos distintos, destacadamente nas formas familiares em que a heterogeneidade clínica e genética são exuberantes. Na última década, muito conhecimento se acumulou a respeito da genética das doenças neurodegenerativas, tornando-se bastante importante nos casos de doenças do neurônio motor e de demência frontotemporal as expansões de repetições do gene C9orf72. Esta revisão aborda os principais aspectos clínicos, radiológicos e genéticos relativos aos fenótipos relacionados à expansão de repetição do hexanucleotídeo (GGGGCC) no gene C9orf72. Estudos futuros vão objetivar a caracterização dos aspectos neuropsicológicos, de imagem e patológicos dos achados extra-motores da doença do neurônio motor e ajudarão a fornecer um novo sistema de classificação relevante em termos clínicos e biológicos.

The Characteristics of Recurrent Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy without Bladder Cuff Excision

PURPOSE: To investigate oncological outcomes based on bladder cuff excision (BCE) during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) and to provide clinical evidence of tumor recurrence in patients without BCE. MATERIALS AND METHODS: We retrospectively collected data of 372 consecutive patients who underwent RNU at our institution from May 1989 through October 2010. After excluding some data, we reviewed 336 patients for the analysis. RESULTS: Of the patients who underwent RNU with BCE (n=279, 83.0%) and without BCE (n=57, 17.0%), patients without BCE had poorer cancer-specific and overall survival rates. Among 57 patients without BCE, 35 (61.4%) experienced tumor recurrence. Recurrence at the remnant ureter resulted in poor oncological outcomes compared to those in patients with bladder recurrence, but better outcomes were observed compared to recurrence at other sites. No significant predictors for tumor recurrence at the remnant ureter were identified. In patients without BCE, pathological T stage [hazard ratio (HR), 5.73] and lymphovascular invasion (HR, 3.65) were independent predictors of cancer-specific survival, whereas age (HR, 1.04), pathological T stage (HR, 5.11), and positive tumor margin (HR, 6.50) were independent predictors of overall survival. CONCLUSION: Patients without BCE had poorer overall and cancer-specific survival after RNU than those with BCE. Most of these patients experienced tumor recurrence at the remnant ureter and other sites. Patients with non-organ confined UTUC after RNU without BCE may be considered for adjuvant chemotherapy with careful follow-up.

Current status of flexible ureteroscopy in urology

Retrograde intrarenal surgery (RIRS) is being performed for the surgical management of upper urinary tract pathology. With the development of surgical instruments with improved deflection mechanisms, visuality, and durability, the role of RIRS has expanded to the treatment of urinary calculi located in the upper urinary tract, which compensates for the shortcomings of shock wave lithotripsy and percutaneous nephrolithotomy. RIRS can be considered a conservative treatment of upper urinary tract urothelial cancer (UTUC) or for postoperative surveillance after radical treatment of UTUC under an intensive surveillance program. RIRS has a steep learning curve and various surgical techniques can be used. The choice of instruments during RIRS should be based on increased surgical efficiency, decreased complications, and improved cost-benefit ratio.