Cisplatin-based chemotherapy has been commonly used as the first-line chemotherapy for metastatic urothelial carcinoma. However, after failure of the first-line cisplatin-based chemotherapy, there is ...no established standard second-line chemotherapy. Starting in 2006, paclitaxel, ifosfamide and nedaplatin chemotherapy has been performed as the second-line chemotherapy in our institution. Here, we report the treatment results of paclitaxel, ifosfamide and nedaplatin chemotherapy.
From 2006 to 2015, 33 patients with metastatic urothelial carcinoma were treated with paclitaxel, ifosfamide and nedaplatin chemotherapy after failure of first-line cisplatin-based chemotherapy in our institution. We retrospectively examined the treatment outcome and predictive factors for therapeutic effects of paclitaxel, ifosfamide and nedaplatin. The median age, treatment cycle and follow-up period were 62.5 years, 3 cycles and 10.4 months, respectively.
The median overall survival and progression-free survival were 10.4 and 3.5 months, respectively. Complete and partial responses were found in 3 and 7 patients, respectively, with an overall response rate of 30%. All patients developed grade 3-4 neutropenia, but there was no treatment-related death. In multivariate analysis, the only prognostic factor for progression-free survival was 24-hour urinary creatinine clearance.
A paclitaxel, ifosfamide and nedaplatin regimen as second-line chemotherapy for metastatic urothelial carcinoma was effective and tolerable. Moreover, paclitaxel, ifosfamide and nedaplatin chemotherapy may be more effective in patients with satisfactory renal function.
A 54‐year‐old man was referred to our hospital because of a suspected esophageal submucosal tumor on upper gastrointestinal radiography. Contrast‐enhanced computed tomography showed a 52 mm ...homogeneous mass attached to the lower thoracic esophagus. Esophagogastroduodenoscopy revealed a 50 mm submucosal tumor in the lower esophagus, and endoscopic ultrasonography (EUS) showed a continuous hypoechoic lesion in the esophageal muscularis propria. Contrast‐enhanced harmonic EUS revealed a non‐echogenic area. T1 and T2 magnetic resonance imaging revealed a high‐signal lesion. Based on imaging studies, an esophageal duplication cyst was diagnosed. Although asymptomatic, the patient underwent video‐assisted thoracic surgery because of the possibility of rupture and the appearance of symptoms due to a future infection or enlargement, although this was not noted before.
In our case, the esophageal duplication cyst appeared as a hypoechoic mass, requiring differentiation from submucosal tumor other than the cyst. Histologically, the cyst was covered by two layers of muscle covered by the chorioepithelial columnar epithelium. EUS fine‐needle aspiration is effective in diagnosing submucosal tumor but also carries the risk of infection. Contrast‐enhanced ultrasonography was used in this case to observe the interior and reach a preoperative diagnosis. Contrast‐enhanced harmonic EUS appears to be effective in examining the interior of submucosal tumor lesions noninvasively.
Background: Constipation causes substantial morbidity worldwide. Methods: This survey assessed constipation-related factors in Japan using the Japanese version of the Irritable Bowel Syndrome Quality ...of Life (IBS-QOL-J) instrument. We also examined the relationship among laxative type, Bristol Stool Form Scale (BSFS) scores, and treatment cost. Finally, we examined differences in satisfaction scores according to laxative type, treatment type, treatment cost, and BSFS score. Results: IBS-QOL-J was higher among those taking salt and/or irritation laxatives. Those paying >JPY 5000 (USD 50.00) had the lowest IBS-QOL-J. IBS-QOL-J was significantly lower among those with a BSFS score of 1 or 2 (severe constipation). Conclusions: This study’s findings suggest that a variety of factors, including treatment type and cost, are associated with defecation satisfaction. Those who had hard stools, used multiple laxatives, or spent more on treatment were less satisfied. Future strategies should target therapies that do not require multiple laxatives with lower treatment costs. Adequate defecation with a small number of appropriate laxatives at minimal cost appears to improve defecation satisfaction. It is desirable to identify appropriate laxatives and improve dietary habits and exercise routines. It is also necessary to stop blindly increasing laxative usage and properly diagnose constipation disorders such as anatomical abnormalities other than functional constipation.
After radical nephroureterectomy, substantial numbers of patients with upper tract urothelial carcinoma are ineligible for adjuvant chemotherapy owing to diminished renal function. Accurate ...pre-operative prediction of worse pathological findings in radical nephroureterectomy specimens can guide appropriate patient selection for neoadjuvant chemotherapy. Herein, we evaluated pre-operative voided urine cytology and the additional efficacy of selective ureteral cytology for predicting pathological features in upper tract urothelial carcinoma patients.
This retrospective cohort study comprised 722 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy. Patients with concomitant bladder cancer and those who received neoadjuvant therapy were excluded. Finally, 437 patients with urinary cytology data were enrolled in the study. We assessed the positive voided urine and selective ureteral cytology for predicting higher pathological T stage (≥ pT3), higher tumor grade (3) and positive lymphovascular invasion.
Previous bladder cancer, tumor location, clinical T stage and voided urine cytology (P = 0.029) were independently associated with ≥ pT3, whereas selective ureteral cytology was not. Gender, clinical N category and voided urine cytology (P = 0.017) were independently associated with tumor Grade 3, whereas selective ureteral cytology was not. Hydronephrosis, clinical T stage, clinical N category and voided urine cytology (P = 0.0021) were independently associated with lymphovascular invasion, whereas selective ureteral cytology was not.
Pre-operative positive voided urine cytology was an independent predictor for worse pathological findings in radical nephroureterectomy specimens, while selective ureteral cytology had no additional efficacy. However, further studies with larger numbers of patients and complete data sets are needed to select patients for more aggressive treatments including neoadjuvant chemotherapy.
Background: Endoscopic submucosal dissection (ESD) is widely used for early gastric cancer (EGC) in patients without lymph node metastasis (LNM). Prediction of LNM after ESD is important to determine ...prognosis in patients with EGC. In this regard, the eCura system was applied to predict LNM after noncurative ESD for EGC. This study aimed to identify risk factors for LNM and improve the accuracy of the eCura system for predicting the risk of LNM after ESD. Methods: A total of 150 patients who underwent noncurative resection of EGC by ESD were retrospectively enrolled at five institutions in Japan. All patients underwent additional surgery with lymph node resection after ESD. The risk factors for LNM among clinicopathological parameters were examined and receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff point for predicting high LNM risk using the modified eCura system. Results: Of 150 patients, 19 (13%) had LNM. In the multivariate analysis, lymphatic invasion, and tumor size >30 mm were independent risk factors for LNM. Using a cutoff score of ≥4 for predicting high risk based on the eCura system, the rate of LNM was significantly higher in the high-risk group (4–7 points) than in the low-risk group (0–3 points) (odds ratio 12.0, 95% confidence interval 3.7–54.2, p < 0.0001). Conclusions: An eCura score ≥4 may improve the prediction of LNM risk after ESD in patients with EGC in the intermediate-risk group (2–4 points) of the eCura system, suggesting better treatment strategies for patients. Further prospective and long-term follow-up studies are needed to validate the efficacy of the modified system.
Objective
To investigate if detection of copy number aberrations of chromosomes 3, 7, 9p21, and 17 using multicolour fluorescence in situ hybridization (FISH) predicts patient outcome in ...non‐muscle‐invasive bladder cancer (NMIBC).
Patients and Methods
In all, 118 bladder wash samples were prospectively collected from patients who underwent transurethral resection of bladder tumour (median age 50.5 years, male/female: 91/27, tumour grade 1/2/3: 18/52/42, stage pTis/Ta/T1: 8/62/42) from 2007 to 2010.
The 118 samples were analysed using the UroVysion® kit to detect the copy numbers of chromosomes 3, 7, 9p21, and 17.
The variant fraction (VF; the sum of the non‐modal copy number fraction of each chromosome) was defined as abnormal when the percentage was ≥16%. The percentage deletion of 9p21 (fraction of null or one copy number of the 9p21 locus) was defined as abnormal when the percentage was ≥12%.
Maffezzini risk criteria were also analysed in our cohorts.
Results
There was recurrence in 57 (48.3%) patients and disease progression in 12 (10.1%), with a median follow‐up of 35.7 months.
Multivariate analysis showed that the percentage 9p21 loss (>12%) was an independent prognostic factor for recurrence (P < 0.001, odds ratio OR 3.24, 95% confidence interval CI 1.85–5.62).
For disease progression, tumour grade, positive urine cytology, concurrent carcinoma in situ, and a mean VF of >16% were significant prognostic factors in univariate analysis. In multivariate analysis, a mean VF of >16% was a prognostic factor for disease progression (P = 0.048, OR 6.07, 95% CI 1.02–57.45).
Conclusions
Multicolour‐FISH analysis using a commercially available kit could be a powerful tool not only for diagnosis, but also for prognostication in patients with NMIBC.
Objectives
To determine the feasibility of vesicourethral anastomosis using running suture during retropubic radical prostatectomy and to compare the surgical outcomes of vesicourethral anastomosis ...using running suture with those of the standard interrupted suture technique.
Methods
A total of 60 patients undergoing radical prostatectomy from 2010 to 2012 at the Yamaguchi University Hospital, Japan were included in the present study, and were randomly assigned to vesicourethral anastomosis using running suture (n = 30 patients) or a standard interrupted suture technique group (n = 30 patients). Vesicourethral anastomosis using running suture was carried out with 12‐bite sutures using 3‐0 poliglecaprone. The primary end‐point was the time to catheter removal. Patients' health‐related quality of life was assessed using the Expanded Prostate Cancer Index Composite in 56 patients (28 patients in each group).
Results
No significant difference was found in the median suturing time between the two study groups (both 19 min, P = 0.449). The time to catheter removal was significantly better in the vesicourethral anastomosis using running suture group (hazard ratio 5.23, 95% confidence interval 1.73–17.65, P = 0.003). The pad‐free rate was significantly higher in the vesicourethral anastomosis using running suture group at 1 month after surgery (20.7% vs 3.3%, P = 0.0463); however, there was no significant difference at 3 months and beyond. The Expanded Prostate Cancer Index Composite urinary and bowel summary scores at 1 month were significantly better in the vesicourethral anastomosis using running suture patients (both P < 0.01), though no significant difference was observed thereafter. A vesicourethral anastomosis stricture was noted in three patients (10%) in the standard interrupted suture technique group, and none in the vesicourethral anastomosis using running suture group.
Conclusion
Running suture for vesicourethral anastomosis is feasible during retropubic radical prostatectomy. Furthermore, it offers better outcomes than the conventional standard interrupted suture technique, with a higher likelihood of improvement in patients' health‐related quality of life.
Objectives
To investigate the expression levels of E‐cadherin, Snail, Twist and Bmi‐1 in the human upper tract urothelial carcinoma, and to assess whether these factors could be prognostic markers.
...Methods
Immunohistochemistry was carried out to determine the expression of E‐cadherin, Snail, Twist and Bmi‐1 in upper tract urothelial carcinoma samples from 144 patients that underwent total nephroureterectomy between January 1995 and December 2010. The patient population had a median age of 71 years, and comprised 104 men and 40 women, with a median follow‐up period of 40 months. The prognostic value of these markers was assessed by univariate and multivariate analysis. A risk stratification analysis was carried out.
Results
Snail and Bmi‐1 expression predicted worse overall survival (P = 0.0075 and 0.0035), cancer‐specific survival (P = 0.0919 and 0.0085) and recurrence‐free survival (P = 0.0360 and 0.0817, respectively) compared with tumors that lacked Snail and Bmi‐1 expression. Additionally, clinical parameters, grade, stage and lymphovascular invasion correlated with overall survival, cancer‐specific survival and recurrence‐free survival. Multivariate analysis showed that Bmi‐1 expression was among the most significant factors in predicting cancer‐specific survival (P = 0.0333). The combination of Snail, Bmi‐1 and pathological stage was the most useful prognostic biomarker for upper tract urothelial carcinoma.
Conclusion
Risk stratification by epithelial–mesenchymal transition and cancer stem cell‐regulated genes, such as Snail and Bmi‐1, might be useful prognostic markers for upper tract urothelial carcinoma.
To date, there are few reliable markers to distinguish tumors with aggressive characteristics in upper tract urothelial carcinoma. The purpose of this study was to identify a biomarker related to ...genetic instability (chromosomal instability or microsatellite instability) with prognostic value, in patients with upper tract urothelial carcinoma.
Expression of chromosomal instability-related markers (BUBR1, p53, polo-like kinase 1) and microsatellite instability-related markers (mismatch repair proteins, MLH1 and MSH2) were assessed by immunohistochemistry in 100 patients who had radical nephroureterectomy for upper tract urothelial carcinoma. Numerical aberrations of chromosomes 7, 9 and 17 were evaluated by fluorescence in situ hybridization, which allowed an estimation of the degree of chromosomal instability. BUB1B copy number was examined by array-based comparative genomic hybridization in 32 patients with upper tract urothelial carcinoma.
BUBR1 status was most significantly correlated with chromosomal instability-related and low mismatch repair parameters, according to the molecular biomarkers examined. Overexpression of BUBR1 is frequently detected in tumors with higher histological grade (P < 0.0001) and is significantly associated with chromosomal instability (P = 0.0071). Array-based comparative genomic hybridization revealed that no tumors (0%) showed BUB1B amplification and gain, indicating that overexpression of BUBR1 was independent of BUB1B copy number. For disease-specific survival, BUBR1 overexpression, lymphovascular invasion, pathological tumor stage, pathological lymph node involvement and low MSH2 expression were significant prognostic factors in univariate analyses. In multivariate analyses, BUBR1 overexpression was an independent prognostic factor for disease-specific survival (P = 0.0483, risk ratio 3.76, 95% confidence interval: 1.01-18.43).
BUBR1 may have significant potential as a biomarker for estimating disease-specific survival in patients with upper tract urothelial carcinoma treated by radical nephroureterectomy.
Background
Currently, there is no consensus regarding which patients with high-risk prostate cancer (PCa) would benefit the most by radical prostatectomy (RP). We aimed to identify patients with ...high-risk PCa who are treatable by RP alone.
Methods
We retrospectively reviewed data on 315 patients with D’Amico high-risk PCa who were treated using RP without neoadjuvant or adjuvant therapy at the institutions of the Yamaguchi Uro-Oncology Group between 2009 and 2013. The primary endpoint was biochemical progression-free survival (bPFS) after RP. Risk factors for biochemical progression were extracted using the Cox proportional hazard model. We stratified the patients with high-risk PCa into 3 subgroups based on bPFS after RP using the risk factors.
Results
At a median follow-up of 49.9 months, biochemical progression was observed in 20.5% of the patients. The 2- and 5-year bPFS after RP were 89.4 and 70.0%, respectively. On multivariate analysis, Gleason score (GS) at biopsy (≥ 8, HR 1.92,
p
< 0.05) and % positive core (≥ 30%, HR 2.85,
p
< 0.005) were independent predictors of biochemical progression. Patients were stratified into favorable- (0 risk factor; 117 patients), intermediate- (1 risk factor; 127 patients), and poor- (2 risk factors; 57 patients) risk groups, based on the number of predictive factors. On the Cox proportional hazard model, this risk classification model could significantly predict biochemical progression after RP (favorable-risk, HR 1.0; intermediate-risk, HR 2.26; high-risk, HR 5.03;
p
< 0.0001).
Conclusion
The risk of biochemical progression of high-risk PCa after RP could be stratified by GS at biopsy (≥ 8) and % positive core (≥ 30%).
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