Yuan-Ju Lee

Aristolochic acid-induced upper tract urothelial carcinoma in Taiwan: clinical characteristics and outcomes.

Aristolochic acid (AA), a component of all Aristolochia‐based herbal medicines, is a potent nephrotoxin and human carcinogen associated with upper urinary tract urothelial carcinoma (UUC). To investigate the clinical and pathological characteristics of AA‐induced UUC, this study included 152 UUC patients, 93 of whom had been exposed to AA based on the presence of aristolactam‐DNA adducts in the renal cortex. Gene sequencing was used to identify tumors with A:T‐to‐T:A transversions in TP53, a mutational signature associated with AA. Cases with both aristolactam‐DNA adducts and A:T‐to‐T:A transversions in TP53 were defined as AA‐UUC, whereas patients lacking both of these biomarkers were classified as non‐AA‐UUC. Cases with either biomarker were classified as possible‐AA‐UUC. Forty (26%), 60 (40%), and 52 (34%) patients were classified as AA‐UUC, possible‐AA‐UUC and non‐AA‐UUC, respectively. AA‐UUC patients were younger (median ages: 64, 68, 68 years, respectively; p=0.189), predominately female (65%, 42%, 35%, respectively; p=0.011), had more end‐stage renal disease (28%, 10%, 12%, respectively; p=0.055), and were infrequent smokers (5%, 22%, 33%, respectively; p=0.07) compared to possible‐AA‐UUC and non‐AA‐UUC patients. All 14 patients who developed contralateral UUC had aristolactam‐DNA adducts; ten of these also had signature mutations. The contralateral UUC‐free survival period was shorter in AA‐UUC compared to possible‐ or non‐AA‐UUC (p=0.019 and 0.002, respectively), whereas no differences among groups were observed for bladder cancer recurrence. In conclusion, AA‐UUC patients tend to be younger and female, and have more advanced renal disease. Notably, AA exposure was associated with an increased risk for developing synchronous bilateral and metachronous contralateral UUC.

Determining the appropriate length of a double-pigtail ureteral stent by both stent configurations and related symptoms.

PURPOSE To evaluate whether stent length affects the symptoms after stent insertion and to determine the appropriate stent length according to the stent configurations and the related symptoms simultaneously. PATIENTS AND METHODS A total of 87 patients who underwent ureteroscopic lithotripsy (URSL) and double-pigtail ureteral stent (22, 24, or 26 cm) insertion were enrolled. The stent configurations on the images were reviewed to determine whether the length was appropriate. All patients completed a questionnaire to assess the symptoms related to stent insertion. The incidence and severity of the symptoms were compared among the patients with different stent lengths. RESULTS The demographic data were similar among the three groups with different stent lengths (22, 24, or 26 cm). The stent length was associated with the position of the distal loop (P = 0.02), while it was not associated with the position of the proximal loop (P = 0.50). The use of a longer stent was significantly associated with a higher incidence of urinary frequency (P = 0.04) and urgency (P = 0.02). Also, the use of a longer stent was also significantly associated with higher symptom scores of urinary frequency (P < 0.01) and urgency (P < 0.01). CONCLUSIONS The stent length is associated with the position of the distal loop and the related urinary symptoms. A longer stent causes an overlong intravesical segment and more irritative symptoms. On the other hand, the stent length is not associated with either the position of the proximal loop or flank pain. Based on the analysis of both stent configurations on images and related symptoms, a 22-cm stent is more appropriate for those whose height ranges from 149.5 cm to 178.5 cm with a median of 161.9 cm.

Malignant Ureteral Obstruction: Functional Duration of Metallic versus Polymeric Ureteral Stents

Background Ureteral obstruction caused by extrinsic compression is often associated with intra-abdominal cancers. Internal drainage with ureteral stents is typically the first-line therapy to relieve such obstructions. Novel designs of ureteral stents made of different materials have been invented to achieve better drainage. In this study, we described the functional outcomes of a Resonance metallic ureteral stent (Cook Medical, Bloomington, Indiana, USA) in patients with malignant ureteral obstruction and compare the functional duration of Resonance stents with regular polymeric stents in the same cohort. Methods Cancer patients who received polymeric stents and subsequent Resonance stents for ureteral obstruction between July 2009 and November 2012 were included in a chart review. Stent failure was detected by clinical symptoms, imaging studies, and renal function tests. The functional durations of each stent were calculated, and possible factors affecting stent patency were investigated. Results A total of 50 stents were successfully inserted into 50 ureteral units in 42 patients with malignant ureteral obstruction. There were 7 antegrade stents and 43 retrograde stents. There were no major complications. Stent-related symptoms were similar in both kinds of stents. After polymeric stents were replaced with Resonance metallic stents, hydronephrosis subsided or remained stable in 90% (45/50) of the ureteral units. Serum creatinine decreased or remained stable in 90% (38/42) of these patients. The Resonance stent exhibited a mean increase in functional duration of 4 months compared with the polymeric stents (p<0.0001), and 50% (25/50) of the Resonance stents exhibited a significant increase in functional duration (more than 3 months). Pre-operative serum creatinine < 2 was associated with a substantial increase in stent duration. Conclusions Resonance stents are effective and safe in relieving malignant ureteral obstructions after polymeric stents failure. Resonance stents can provide a longer functional duration than polymeric stents and should be offered as an option for internal drainage.

Predictive Factors for Ureteral Double-J-Stent-Related Symptoms: A Prospective, Multivariate Analysis

BACKGROUND/PURPOSE Whether the length of stent affects stent-related symptoms after urological procedures remains controversial. We aimed to evaluate the predictive factors for stent-related urinary tract symptoms after uncomplicated ureteroscopic lithotripsy (URSL). METHODS We prospectively recruited a total of 59 patients who underwent URSL and 6-Fr double-J ureteral stent placement. The demographic and perioperative data and stent characteristics, including the length (22, 24 or 26 cm), position of proximal end (upper calyx or pelvis), position of distal end (crossing midline or not), and configurations of both ends (complete or incomplete curl) were recorded. All patients completed a self-administered questionnaire to evaluate the stent-related urinary symptoms, bladder pain, flank pain and hematuria 1 week after the procedure. All variables were analyzed by a proportional odds logistic regression model. RESULTS Twenty-two male (37.3%) and 37 (62.7%) female patients were enrolled in this study. Their mean age was 53.7 ± 12.9 years. The mean body height was 161.9 ± 7.9 cm (range, 145.9-178 cm). In multivariate analysis, the 26-cm stent was independently associated with the severity of frequency, urgency, and nocturia symptoms. Crossing the midline of the distal end was significantly associated with urge incontinence. The 24-cm and 26-cm stents were both very strongly associated with the severity of hematuria. Crossing the midline of the distal end was significantly associated with bladder pain. CONCLUSION The length of stent and crossing the midline of the distal end were significantly associated with stent-related symptoms after URSL. Selection of the proper length of double-J stent is the most important factor in minimizing stent-related symptoms.

Recurrence pattern and TP53 mutation in upper urinary tract urothelial carcinoma

TP53 mutation patterns are associated with prognosis of various cancers. This study was designed to investigate the association between TP53 mutation patterns and recurrence patterns in upper urinary tract urothelial carcinoma (UTUC) patients. A total of 165 consecutive UTUC patients who underwent nephroureterectomies were enrolled for measuring mutation patterns of TP53 gene from exome 2 to 11. Bladder recurrence, contralateral UTUC recurrence, and metastases were compared among groups by using log-rank test and Cox proportional hazard model. Single base substitution as an A:T to T:A transversion was noted in 55 (33.3%) patients (AT group). Forty-two (25.5%) patients had TP53 mutations with only other than A:T to T:A transversion (NAT group), and 68 patients (41.2%) had wide-type TP53 (WT group). AT group was predominately female (64%, 52%, 29%, respectively), had a higher incidence of end-stage renal disease (24%, 14%, 10%, respectively), and had more high-grade tumors (82%, 74%, 62%, respectively) compared to NAT and WT groups. With adjustment of tumor grade/stages, bladder and contralateral UTUC recurrence-free survival duration was shortest in NAT (p < 0.001) and AT group (p < 0.001), respectively. NAT group had a shorter metastasis-free survival duration than the other two groups combined (p = 0.018). As a result, A:T to T:A transversion increased contralateral UTUC recurrence risk, but other mutations in TP53 raised the hazard of bladder recurrence and metastases. Therefore, TP53 mutation pattern may be a useful biomarker to predict recurrence patterns of UTUC patients.