Tumor cell-based glycolytic metabolism and single-cell sequencing of urinary exfoliated cells for the diagnosis and molecular profiling of urothelial carcinoma / 中华病理学杂志

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.

A novel upper tract ureteroscopic biopsy technique: the "form tackle"

ABSTRACT Introduction and Objective: Upper tract urothelial carcinoma (UTUC) represents 5% of all urothelial malignancies (1-3). Accurate pathologic diagnosis is key and may direct treatment decisions. Current ureteroscopic biopsy techniques include cold-cup, backloaded cold-cup and stone basket (4-6). The study objective was to compare a standard cold-cup biopsy technique to a novel cold-cup biopsy technique and evaluate histopathologic results. Materials and Methods: We developed a novel UTUC biopsy technique termed the "form tackle" biopsy. Ureteroscope is passed into ureter/renal collecting system. Cold-cup forceps are opened and pressed into the lesion base (to engage the urothelial wall/submucosal tissue) then closed. Ureteroscope/forceps are advanced forward 3-10mm and then extracted from the patient. We compared standard versus novel upper tract biopsy techniques in a series of patients with lesions ≥1cm. In each procedure, two standard and two novel biopsies were obtained from the same lesion. The primary study aim was diagnosis of malignancy. IRB approved: 21-006907. Results: Fourteen procedures performed on 12 patients between June 2020 and March 2021. Twenty-eight specimens sent (14 standard, 14 novel) (Two biopsies per specimen). Ten procedures with concordant pathology. In 4 procedures the novel biopsy technique resulted in a diagnosis of UTUC (2 high-grade, 2 low-grade) in the setting of a benign standard biopsy. Significant difference in pathologic diagnoses was detected between standard and novel upper tract biopsy techniques (p=0.008). Conclusions: The "form tackle" upper tract ureteroscopic biopsy technique provides higher tissue yield which may increase diagnostic accuracy. Further study on additional patients required. Early results are encouraging.

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.

How we do it: robotic-assisted distal ureterectomy with ureteral reimplantation

ABSTRACT Background: High risk upper tract urothelial carcinoma (UTUC) is typically managed with radical nephroureterectomy, however, renal preservation can be attempted when UTUC is localized to the distal ureter in the presence of chronic kidney disease (1-3). Distal ureterectomy is typically managed with a ureteral reimplantation and psoas hitch in order to maintain urothelial continuity, to avoid comprising the contralateral ureter, and reducing risk of chronic urinary tract infections and electrolyte abnormalities (4). We present our case of distal ureteral UTUC managed robotically with a distal ureterectomy with ureteral reimplantation. Technique and Follow-Up: Initially, an Orandi needle on a resectoscope circumscribed the left ureteral orifice. Next, robotically, the retroperitoneum was exposed and a left sided pelvic lymphadenectomy was completed. The left ureter was mobilized and the diseased ureteral segment was transected. The mobilized bladder was sutured to psoas fascia. After a cystotomy, the ureter was re-anastomosed to the bladder. The patient was discharged on postoperative day three and re-evaluated one week later with a cystogram. Final pathology was downgraded to non-invasive low-grade papillary urothelial carcinoma with negative lymph nodes and margins. Conclusion: High risk UTUC localized to the distal ureter in the setting of chronic kidney disease can be managed with a distal ureterectomy (3). Robotic distal ureterectomy with ureteral reimplantation can be assisted by an Orandi needle to achieve negative margins. Utilizing a robotic technique can offer challenges with the ureteral spatulation and reanastomosis (5-7). By fixating the ureter to the bladder prior to reanastomosis, our technique offers a solution for these difficulties.

Clinical value of inflammatory biomarkers in predicting prognosis of patients with ureteral urothelial carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinical value of inflammation-related markers in predicting the prognosis of patients with ureteral urothelial carcinoma.@*METHODS@#200 patients with ureteral urothelial carcinoma were randomly divided into two groups by split sample validation: modeling group and validation group. Paraffin embedded pathological specimens of the patients were reviewed. Immunohistochemical method was used to detect tumor-infiltrating neutrophil (TIN) (CD66b+), tumor-associated macrophage (TAM) (CD163+), lymphocyte (CD+, CD4+, CD8+) counts, peripheral blood neutrophil / lymphocyte ratio (NLR) and tumor tissue neutrophil/monocyte ratio (NMR). According to the results of pathological staging, the patients were divided into non-muscle-invasive and muscle-invasive ureteral urothelial carcinoma group. The resolution of the models was evaluated, and the prognostic nomogram models including only peripheral blood parameters and all parameters were established to compare the accuracy of the two models in predicting the prognosis of patients with urothelial carcinoma of the ureter.@*RESULTS@#The median follow-up time was 36 months, the progression-free survival was 40 months, and 42 cases (21.0%) showed tumor progression within 3 years. Tumor size, pathological stage and pathological grade were all single-factor variables predicting the first recurrence of ureteral urothelial carcinoma three years after operation. Tumor size, pathological stage, pathological grade, TIN, TAM, NLR and NMR were multi-factor variables predicting the first recurrence three years after operation. Among 104 cases of non-muscle-invasive ureteral urothelial carcinoma, 10 cases (9.6%) recurred for the first time 3 years after operation, 96 cases (33.3%) of muscle invasive ureteral urothelial carcinoma, and the diffe-rence between the two groups was statistically significant (χ2=15.53, P < 0.05). The predictive nomogram model of progression free survival was established. The concordance index of progression free survi-val was 0.722 (95%CI: 0.70-0.78) in non-muscle-invasion group, and 0.725 (95%CI: 0.71-0.79) in muscle-invasion group, which was in good agreement with the observed 3-year survival rate. The results of discrimination test showed that the concordance index of the whole parameter prediction model of ureteral urothelial carcinoma was 0.726, which was higher than that of peripheral blood parameters (consistency index 0.672). The immune microenvironment of ureteral urothelial carcinoma improved the prediction accuracy of the model.@*CONCLUSION@#The prognosis prediction model based on immune inflammation-related markers was established as a perfection and supplement for the existing pathological grading and staging system, providing a basis for accurate individualized treatment of patients with urete-ral urothelial carcinoma. The prognosis prediction model based on the relevant indicators of peripheral blood samples is established, which is easy to obtain specimens, and the detection method is simple and economical, which is more conducive to clinical application.

Ureteropelvic junction obstruction caused by metastatic cholangiocarcinoma

ABSTRACT We describe the rare case of a 61-year-old female with right ureteropelvic junction (UPJ) obstruction caused by metastatic cholangiocarcinoma. Her past medical history was notable for cholangiocarcinoma treated with neoadjuvant chemoradiation and two orthotopic liver transplants six years earlier. Urology was consulted when she presented with flank pain and urinary tract infection. Diagnostic workup demonstrated right UPJ obstruction. She was managed acutely with percutaneous nephrostomy. She subsequently underwent robotic pyeloplasty and intrinsic obstruction of the UPJ was discovered. Histological examination revealed adenocarcinoma, consistent with systemic recurrence of the patient's known cholangiocarcinoma.

Application of totally extraperitoneal renal autotransplantation with Boari flap-pelvis anastomosis in upper urinary tract urothelial carcinomas treatment / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the feasibility and effectiveness of the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis in the treatment of upper urinary tract urothelial carcinoma (UTUC), and to review the experience of renal autotransplantation for UTUC treatment.@*METHODS@#One case of applying the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis to the UTUC treatment was reported, and related literature was reviewed. The patient was a sixty-four-year old man who received right radical nephroureterectomy for right ureteral carcinoma 1 year before and diagnosed as left ureteral carcinoma(G2, high grade) this time. In order to preserve his renal function and avoid the shortness of common kidney-sparing surgery, a totally extraperitoneal procedure, including retroperitoneoscopic nephrectomy, ureterectomy, renal autotransplantation and Boari flap-pelvis anastomosis, was performed to the patient.@*RESULTS@#The operation was completed successfully without perioperative complications. The renal function recovered to preoperative level within 1 week. No deterioration of renal function during the follow-up and no tumor recurrence was observed under cystoscopy at the 3-month postoperative consult.@*CONCLUSION@#The totally extraperitoneal renal autotransplantation with Boari flap-pelvis anastomosis is a feasible and effective treatment for UTUC. The innovative procedure has several advantages compared to the former ones. The extraperitoneal procedure results in significantly less pain, shorter hospital stay, decreased overall time to recovery and lower bowel complications risk without warm ischemia time extension. Meanwhile, the Boari flap-pelvis anastomosis simplifies the follow -up protocols and creates an easy route for cystoscopy and topical therapy. From the systematic clinical analysis, as well as the related literature review, it's been concluded that the renal autotransplantation can be a reasonable option for the patients who have UTUC in solitary kidney or have bilateral UTUC. This type of treatment possesses advantages of preservation of renal function and total resection of malignant lesions. But long-term data and large cohort study on renal function or tumor recurrence are still absent which will be necessary to confirm the advantages of this approach.

Impact of diagnostic ureteroscopy and biopsy on radical nephroureterectomy of upper tract urothelial carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the impact of preoperative diagnostic ureteroscopy and biopsy (UB) on radical nephroureterectomy (RNU) and the prognosis of upper tract urothelial carcinoma (UTUC).@*METHODS@#The clinical data of UTUC patients receiving RNU between Jan. 2007 and Dec. 2016 were retrospectively collected. The median follow up time was 40 months. The operation time and blood loss of RNU were compared between UB group and non-UB group. Subgroup analyses were conducted according to the time interval between UB and RNU, and surgery methods of lower ureter. The linear regression model was used to adjust for other common factors that impacted operation time.@*RESULTS@#A total of 163 UTUC patients were included in the final analysis. For the lower ureter, open ureterectomies were performed in 91 patients (55.9%), while retroperitoneal laparoscopic ureterectomies were performed in 72 patients (44.1%). A total of 110 (67.5%) patients received preoperative UB. Compared with non-UB group, the average operation time of UB group was significantly longer [(252.5±79.8) min vs. (221.3±79.8) min, P=0.019], but no difference of blood loss was found (median, 50 mL vs. 50 mL, P=0.143). In subgroup analysis, the average operation time of RNU was significantly prolonged when RNU was performed after 1 week of UB (P=0.023). Meanwhile, the median blood loss of RNU increased significantly when it was done after 2 weeks of UB compared with non-UB group (100 mL vs. 50 mL, P=0.012). UB was also significantly prolonged the operation time of RNU in retroperitoneal laparoscopic ureterectomy group (P=0.012). In multivariable analysis, UB (P=0.049), ≥pT3 (P=0.039), pN+ (P=0.018) and ureterectomy method (P=0.005) were independent risk factors of prolonged operation time. The 3-year cancer specific survival (CSS) rate was 87.2% in our cohort. UB had no significant impact on cancer specific survival (P=0.435).@*CONCLUSION@#UB was an independent risk factor of prolonged RNU time, but did not significantly influence cancer specific survival of upper tract urothelial carcinoma patients.

Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This descriptive study assessed the current trends in the incidence of urological cancers and patient survival in Korea. MATERIALS AND METHODS: In this nationwide retrospective observational study based on the data from the Korea National Cancer Incidence Database (KNCIDB), this study analyzed the age-standardized incidence rates (ASRs) and annual percentage changes (APCs) of kidney, bladder, prostate, testicular, and penile cancers as well as cancer of the renal pelvis and ureter between 1999 and 2012. The relative survival rates (RSRs) were calculated for urological cancer patients diagnosed between 1993 and 2012 from the KNCIDB data. RESULTS: Prostate cancer was diagnosed in 66,812 individuals followed by bladder (41,549) and kidney (36,836) cancers. The overall ASR (18.26 per 100,000) increased with age because of the higher ASRs of bladder and prostate cancers in the elderly. The ASR for kidney cancer was highest in the 40-59-year-old group, whereas testicular cancer occurred most frequently before the age of 40. The incidence of most urological cancers increased (overall APC, 6.39%; p < 0.001), except for penile (APC, –2.01%; p=0.05) and bladder (APC, –0.40%; p=0.25) cancers. The overall survival increased steadily (5-year RSR, 66.4% in 1993-1995 vs. 84.2% in 2008-2012; p < 0.001), particularly for prostate (by 34.10%) and kidney (by 16.30%) cancers, but not for renal pelvis and ureter cancers (–7.20%). CONCLUSION: The most common urological cancer in Korea was prostate cancer followed by bladder and kidney cancers. The incidence of most urological cancers, except for penile and bladder cancers, increased. Survival also increased, particularly for prostate and kidney cancers.

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.

Incidental Detection of Struma Ovarii on the Whole Body Scan in a Differentiated Thyroid Cancer Patient

Post-therapeutic whole body scan (RxWBS) after radioactive iodine (RAI) remnant ablation (RRA) is useful for detect recurrent or metastatic foci of differentiated thyroid carcinoma (DTC) after total thyroidectomy. However, there is rare possibility of false positive iodine uptake in WBS. Here, we report a case of a 72-year-old woman, who underwent RRA after total thyroidectomy due to follicular variant papillary thyroid carcinoma. There is an abnormal iodine uptake in RxWBS in pelvic cavity. Additional single photon emission computed tomography (SPECT)-computed tomography (CT) imaging showed an intensive I-131 avid mass in left ovary. There was a multiple calcified mass in left ovary and enhancing wall thickening in left ureter with hydronephrosis in contrast enhanced CT. She underwent hysterectomy, oophorectomy, left ureterectomy and nephrectomy and diagnosed as mature cystic teratoma with thyroid tissues and ureter cancer. Struma ovarii should be considered if there was abnormal RAI uptake in pelvic cavity. I-131 SPECT-CT is useful for differential diagnosis of abnormal iodine uptakes in WBS.

Incidental Detection of Struma Ovarii on the Whole Body Scan in a Differentiated Thyroid Cancer Patient

Post-therapeutic whole body scan (RxWBS) after radioactive iodine (RAI) remnant ablation (RRA) is useful for detect recurrent or metastatic foci of differentiated thyroid carcinoma (DTC) after total thyroidectomy. However, there is rare possibility of false positive iodine uptake in WBS. Here, we report a case of a 72-year-old woman, who underwent RRA after total thyroidectomy due to follicular variant papillary thyroid carcinoma. There is an abnormal iodine uptake in RxWBS in pelvic cavity. Additional single photon emission computed tomography (SPECT)-computed tomography (CT) imaging showed an intensive I-131 avid mass in left ovary. There was a multiple calcified mass in left ovary and enhancing wall thickening in left ureter with hydronephrosis in contrast enhanced CT. She underwent hysterectomy, oophorectomy, left ureterectomy and nephrectomy and diagnosed as mature cystic teratoma with thyroid tissues and ureter cancer. Struma ovarii should be considered if there was abnormal RAI uptake in pelvic cavity. I-131 SPECT-CT is useful for differential diagnosis of abnormal iodine uptakes in WBS.

Trends in Urogenital Cancer Incidence in Jeju (1999-2012)

PURPOSE: Incidence of cancer has been increasing each years. The incidence of genitourinary cancer are also being increased. We aim to describe the time trends in genitourinary cancer incidence in Jeju province. MATERIALS AND METHODS: Age-standardized rates for incidence of genitourinary tract cancer in Korea and world standard population were calculated using the databases from the Jeju Cancer Rigistry from 1999 to 2012. RESULTS: Cancer incidence in Jeju was increased approximately 2-fold from 1217 cases 1999 to 2376 cases in 1999. Prostate cancer occurred most frequently followed by bladder tumor, and kidney cancer in 2012. In the prostate cancer, incidence was increasing every year from 18 cases in 1999 to 110 cases in 2012. Age-standardized incidence rate (ASR) was approximately four time increased, from 3.0 cases in 1999 and 11.2 cases in 2012. Incidence of bladder cancer were 43 cases in 1999 and 27 cases in 2012, ASR of bladder cancer was increased from 5.0 cases in 1999 to 7.5 cases in 2012. Kidney cancer showed constantly reducing the incidence. Peak is 60 cases in 2009 and recent incidence was 37 cases in 2012. There was no significant change in the incidence of testicular cancer, ureter cancer, renal pelvis cancer from 1999 to 2012. CONCLUSIONS: Incidence of cancer has been increasing in Jeju, similar to other area In Korea. Prostate cancer is the most common urological cancer in Jeju province, and kidney cancer incidence is recently decreasing. We should try to prevent genitourinary tract cancer caused obesity and smoking.

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.

Impact of adjuvant chemotherapy in patients with upper tract urothelial carcinoma and lymphovascular invasion after radical nephroureterectomy

PURPOSE: To evaluate the impact of adjuvant chemotherapy (AC) in patients with upper tract urothelial carcinoma and lymphovascular invasion (LVI) after radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed the clinical records and clinicopatholgic outcomes of patients (n=552) treated with RNU between 1986 and 2013. Patients treated with neoadjuvant chemotherapy and those for whom LVI status was not recorded were excluded. Patients were divided into two groups according to LVI (n=86) or no LVI (n=256). RESULTS: The study included 344 patients (240 men and 104 women) with a median of 53.9 months of follow-up (range, 1-297 months) after RNU. Tumors were organ confined (T2/N0) in 211 (61.3%) and tumor grade high in 291 (84.6%). AC was administered in 64 patients (18.6%). A total of 280 patients (81.4%) were treated with surgery alone. Patients with LVI tended to be older (p=0.049), have a higher pT stage (pT3/T4, p<0.001), be pN+ (p<0.001), have a high tumor grade (p<0.001), and experience recurrence (p<0.001). In the multivariate analysis, LVI was an independent prognostic factor for cancer-specific survival and overall survival (p=0.002 and p<0.001, respectively). The multivariate analysis demonstrated that in the subgroup of patients with LVI, AC was a significant prognostic factor for cancer-specific survival and overall survival (hazard ratio, 0.51; p=0.027 and hazard ratio, 0.50; p=0.025, respectively). CONCLUSIONS: AC does not seem to reduce mortality in patients with advanced upper tract urothelial carcinoma after RNU. In the subgroup of patients with LVI, AC had a positive impact on cancer-specific survival and overall survival. LVI would be helpful for selecting patients who are appropriate for AC.

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.

Prognostic impact of preoperative statin use after radical nephroureterectomy for upper urinary tract urothelial carcinoma

PURPOSE: The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC. CONCLUSIONS: Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC.