Primary Urothelial Carcinoma of the Ureter: 11-Year Experience in Taipei Veterans General Hospital

BackgroundUrothelial carcinoma of the upper urinary tract is relatively rare, occurring in 5% of all urothelial tumors. Ureteral urothelial carcinoma is even less common than that of the renal pelvis, accounting for about 25% of all upper urinary tract tumors. The aim of this study was to evaluate the clinical behavior, survival, recurrence and prognostic information of primary ureteral urothelial carcinoma from our 11 years of experience at the Taipei Veterans General Hospital.MethodsWe retrospectively reviewed 111 patients with ureteral urothelial carcinoma who had been treated in our hospital between January 1993 and December 2003. Tumor staging was according to the 2002 AJCC TNM classification and stage groupings. Patients with stage 0a and stage 0is were categorized as stage 0a/is, and patients with pathologic T stage pTa and pTis were categorized as pTa/is for statistical analysis. The Kaplan-Meier method was used for survival analysis.ResultsThere were 69 males and 42 females, with a mean age of 70.5 ± 9.4 years at diagnosis. Of the 111 patients, 5 presented with stage 0a/is, 38 with stage I, 23 with stage II, 21 with stage III, and 24 with stage IV. Nephroureterectomy with bladder cuff excision was performed in 78 patients, 12 patients received segmental resection of the ureter, 4 received ureteroscopic laser coagulation, and 17 underwent chemotherapy or radiotherapy or both. Tumors were located on the left side in 53 patients, on the right in 53, and bilaterally in 5. The most frequent initial presenting symptom was gross hematuria (65%). The mean postoperative follow-up period was 49.3 months. Disease recurrence in the nephroureterectomy group occurred in 36 patients (46.2%), with 17 (21.8%) at the urinary bladder, 2 (2.6%) at the retroperitoneum, 1 (1.3%) at the contralateral ureter, 6 (7.7%) with distant metastases to the lung, bone, distant lymph nodes or liver, and 10 (12.8%) at multiple sites. The 5-year cancer-specific survival rate was 100% for pTa/is, 95.2% for pT1, 69.4% for pT2, and 43.8% for pT3. All 3 pT4 cases died of cancer in a median of 12 months. Significant prognostic factors for cancer-specific survival by univariate analysis were pT (p = 0.00001), stage (p = 0.00001), type of treatment (p = 0.00001) and grade (p = 0.0001). On multivariate analysis, only stage (p = 0.0001) and grade (p = 0.014) were significant for cancer-specific and overall survival. Stage (p = 0.0001), pT (p =0.0001) and grade (p = 0.026) were also significant prognostic factors of recurrence in multivariate analysis.ConclusionOur experience showed that patients with pTa/is and pT1 tumors treated with radical surgery have excellent prognoses. Tumor stage and grade are the only significant prognostic factors for both cancer-specific and overall survival

Urothelial Inverted Papilloma of the Lower Urinary Tract—A Benign Lesion or a Precursor of Malignancy?

ObjectiveWe investigated the clinical characteristics and follow-up results of patients with a lower urinary tract inverted papilloma (IP) in our hospital, with the intention of clarifying whether certain groups require more aggressive surveillance.Materials and MethodsWe conducted a retrospective study of lower urinary tract IP, using the pathology database of Taipei Veterans General Hospital, from September 1992 to February 2008. In total, 67 patients were enrolled. Patients' clinical characteristics, symptoms, tumor locations, and follow-up data were analyzed.ResultsAmong the 67 patients diagnosed with IP, 59 were male and eight were female, with a mean age of 67.9 ± 12.4 years. Gross hematuria and lower-urinary-tract symptoms were the most common symptoms. All of the patients received transurethral resection as initial treatment. Thirty-eight of these patients were monitored for a median of 21 months (range: 3–168 months). Seven patients had synchronous urothelial malignancies, and one had recurrent IP during follow-up. No patient had subsequent urothelial carcinoma or IP recurrence without a synchronous or previous urothelial malignancy during follow-up.ConclusionThere is a low incidence of developing a subsequent malignancy with a simple IP lesion during follow-up. Rigorous surveillance may be unnecessary in IP patients without a synchronous or previous urothelial malignancy

Optimized ultrasound-assisted extraction of phenolic compounds from Polygonum cuspidatum

In this study the phenolic compounds piceid, resveratrol and emodin were extracted from P. cuspidatum roots using ultrasound-assisted extraction. Multiple response surface methodology was used to optimize the extraction conditions of these phenolic compounds. A three-factor and three-level Box-Behnken experimental design was employed to evaluate the effects of the operation parameters, including extraction temperature (30-70 °C), ethanol concentration (40%-80%), and ultrasonic power (90-150 W), on the extraction yields of piceid, resveratrol, and emodin. The statistical models built from multiple response surface methodology were developed for the estimation of the extraction yields of multi-phenolic components. Based on the model, the extraction yields of piceid, resveratrol, and emodin can be improved by controlling the extraction parameters. Under the optimum conditions, the extraction yields of piceid, resveratrol and emodin were 10.77 mg/g, 3.82 mg/g and 11.72 mg/g, respectively

A Supervised Network Analysis on Gene Expression Profiles of Breast Tumors Predicts a 41-Gene Prognostic Signature of the Transcription Factor MYB

Background. MYB is predicted to be a favorable prognostic predictor in a breast cancer population. We proposed to find the inferred mechanism(s) relevant to the prognostic features of MYB via a supervised network analysis. Methods. Both coefficient of intrinsic dependence (CID) and Galton Pierson’s correlation coefficient (GPCC) were combined and designated as CIDUGPCC. It is for the univariate network analysis. Multivariate CID is for the multivariate network analysis. Other analyses using bioinformatic tools and statistical methods are included. Results. ARNT2 is predicted to be the essential gene partner of MYB. We classified four prognostic relevant gene subpools in three breast cancer cohorts as feature types I–IV. Only the probes in feature type II are the potential prognostic feature of MYB. Moreover, we further validated 41 prognosis relevant probes to be the favorable prognostic signature. Surprisingly, two additional family members of MYB are elevated to promote poor prognosis when both levels of MYB and ARNT2 decline. Both MYBL1 and MYBL2 may partially decrease the tumor suppressive activities that are predicted to be up-regulated by MYB and ARNT2. Conclusions. The major prognostic feature of MYB is predicted to be determined by the MYB subnetwork (41 probes) that is relevant across subtypes

Comparison and Identification of Estrogen-Receptor Related Gene Expression Profiles in Breast Cancer of Different Ethnic Origins

The interactions between genetic variants in estrogen receptor (ER) have been identified to be associated with an increased risk of breast cancer. Available evidence indicates that genetic variance within a population plays a crucial role in the occurrence of breast cancer. Thus, the comparison and identification of ER-related gene expression profiles in breast cancer of different ethnic origins could be useful for the development of genetic variant cancer therapy. In this study, we performed microarray experiment to measure the gene expression profiles of 59 Taiwanese breast cancer patients; and through comparative bioinformatics analysis against published U.K. datasets, we revealed estrogen-receptor (ER) related gene expression between Taiwanese and British patients. In addition, SNP databases and statistical analysis were used to elucidate the SNPs associated with ER status. Our microarray results indicate that the expression pattern of the 65 genes in ER+ patients was dissimilar from that of the ER- patients. Seventeen mutually exclusive genes in ER-related breast cancer of the two populations with more than one statistically significant SNP in genotype and allele frequency were identified. These 17 genes and their related SNPs may be important in population-specific ER regulation of breast cancer. This study provides a global and feasible approach to study population-unique SNPs in breast cancer of different ethnic origins

Treatment selection for tonsillar squamous cell carcinoma

AbstractBackgroundThe optimal treatment for tonsillar squamous cell carcinoma (SCC) remains controversial. The purpose of this study was to evaluate long-term treatment outcomes of patients with tonsillar SCC, in order to aid in appropriate treatment selection.MethodsWe conducted a retrospective chart review of 105 patients with curatively treated tonsillar SCC between January 1996 and December 2005. Forty-three patients (41.0%) underwent primary surgery with or without adjuvant therapy (primary surgery group), and 62 patients (59.0%) were treated with radiotherapy/chemoradiotherapy (RT/CRT, organ preservation group). Twenty patients (19%) received tumor tonsillectomy before definitive RT/CRT and were grouped into the organ preservation group.ResultsNo significant differences were observed between the primary surgery and organ preservation groups in terms of local control (p = 0.212), regional control (p = 0.684), distant metastasis (p = 0.627), 5-year disease-specific survival (DSS, p = 0.774), and overall survival rates (OS, p = 0.667). The rates of major complication (p = 0.216), long-term dependency on feeding tubes (p = 0.876), and tracheostomy (p = 0.401) were also similar. Advanced T classification (T3–4) was the only factor associated with significantly worse DSS (p = 0.007) and OS (p = 0.012). However, there was also no difference in final treatment outcomes in T3–4 patients regardless of whether they were treated with primary surgery or RT/CRT. In the organ preservation group, tumor tonsillectomy before RT/CRT did not improve local control (p = 0.520) or other treatment outcomes, including 5-year DSS (p = 0.707) and OS (p = 0.745).ConclusionBoth primary surgery and RT/CRT organ preservation are effective treatments for tonsillar SCC. Single modality treatment, either surgery or RT/CRT, can typically be provided for stage I–II diseases. Although RT/CRT organ preservation is used more frequently for stage III–IV tonsillar SCC in recent years, primary surgery combined with adjuvant therapy still achieves equivalent outcomes. Multidisciplinary pretreatment counseling and the facilities and personnel available are therefore important for decision-making. In addition, if RT/CRT organ preservation is selected as the primary treatment, tumor tonsillectomy is not indicated

Major Functional Transcriptome of an Inferred Center Regulator of an ER(−) Breast Cancer Model System

We aimed to find clinically relevant gene activities ruled by the signal transducer and activator of transcription 3 (STAT3) proteins in an ER(−) breast cancer population via network approach. STAT3 is negatively associated with both lymph nodal category and stage. MYC is a component of STAT3 network. MYC and STAT3 may co-regulate gene expressions for Warburg effect, stem cell like phenotype, cell proliferation and angiogenesis. We identified a STAT3 network in silico showing its ability in predicting its target gene expressions primarily for specific tumor subtype, tumor progression, treatment options and prognostic features. The aberrant expressions of MYC and STAT3 are enriched in triple negatives (TN). They promote histological grade, vascularity, metastasis and tumor anti-apoptotic activities. VEGFA, STAT3, FOXM1 and METAP2 are druggable targets. High levels of METAP2, MMP7, IGF2 and IGF2R are unfavorable prognostic factors. STAT3 is an inferred center regulator at early cancer development predominantly in TN