Upper Tract Urothelial Carcinoma (UTUC) Diagnosis and Risk Stratification: A Comprehensive Review.

Diagnosis and risk stratification are cornerstones of therapeutic decisions in the management of patients with upper tract urothelial carcinoma (UTUC). Diagnostic modalities provide data that can be integrated, to provide nomograms and stratification tools to predict survival and adverse outcomes. This study reviews cytology, ureterorenoscopy and the novel tools and techniques used with it (including photodynamic diagnosis, narrow-band imaging, optical coherence tomography, and confocal laser endomicroscopy), and biopsy. Imaging modalities and novel biomarkers are discussed in another article. Patient- and tumor-related prognostic factors, their association with survival indices, and their roles in different scores and predictive tools are discussed. Patient-related factors include age, sex, ethnicity, tobacco consumption, surgical delay, sarcopenia, nutritional status, and several blood-based markers. Tumor-related prognosticators comprise stage, grade, presentation, location, multifocality, size, lymphovascular invasion, surgical margins, lymph node status, mutational landscape, architecture, histologic variants, and tumor-stroma ratio. The accuracy and validation of pre-operative predictive tools, which incorporate various prognosticators to predict the risk of muscle-invasive or non-organ confined disease, and help to decide on the surgery type (radical nephroureterectomy, or kidney-sparing procedures) are also investigated. Post-operative nomograms, which help decide on adjuvant chemotherapy and plan follow-up are explored. Finally, a revision of the current stratification of UTUC patients is endorsed.

Molecular Characteristics of Bladder Tumor: Increased Gene Expression of MAGE-A6 and MAGE-A11 with Decreased MicroRNA-34a and MicroRNA-125b.

Bladder cancer is recognized as one of the top ten most common cancers worldwide. Activation of oncogenes, inactivation of tumor suppressor genes, and dysregulation of androgen signaling pathways are three major pathophysiological causes in the development of bladder tumors. Discovering potential biomarkers is required for the management and immunotherapy of bladder cancer. Melanoma-associated antigen (MAGE)-A6 and MAGE-A11 are two cancer-testis antigens that are potential coregulators of androgen receptors. MicroRNAs, especially miR-34a and miR-125b are two important tumor suppressors that play a critical role in regulating different signaling pathways and inhibiting tumor development. Twenty-nine surgical tissue biopsies were collected from patients with no preoperative chemotherapy or radiotherapy (26 males and, 3 females, mean age±SD: 62.4±13.3 years). Seventeen adjacent uninvolved tissues with no abnormalities upon histological examination were considered normal controls (14 males and, 3 females, mean age±SD: 64.2±7.4 years) . Quantitative PCR was performed to evaluate the gene expression level of MAGE-A6, MAGE-A11, miR-34a, and miR-125b in bladder cancer biopsies. MAGE-A6 and MAGE-A11 expressions were significantly increased in bladder tumors compared with normal tissues. However, the expression levels of miR-34a and miR-125b were significantly downregulated in bladder tumor tissues. Interestingly, the expression level of all these genes was significantly associated with tumor grade, pathological stage (pT), and muscular invasion. MAGE-A6 and MAGE-A11 can be considered potential markers for the diagnosis and immunotherapy of bladder tumors. Furthermore, the modulation of miR-34a and miR-125b gene expression in association with increased MAGE-A6 and MAGE-A11 genes could open a new horizon in the improvement of bladder cancer.

Association Between Preoperative De Ritis (AST/ALT) Ratio and Oncological Outcomes Following Radical Cystectomy in Patients With Urothelial Bladder Cancer.

BACKGROUND: Radical cystectomy in combination with neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (BC). However, response to treatment varies between patients. Considering the role of hepatic glucose metabolism in urothelial cancer, AST/ALT ratio (De Ritis ratio) has the potential to serve as a prognostic factor for bladder cancer and a predictor for treatment outcome. MATERIALS AND METHODS: We retrospectively analyzed patients who underwent radical cystectomy between March 2016 - March 2019. Patients were classified into 2 groups based on De Ritis ratio (< 1.3 [normal] vs. ≥ 1.3 [high]). Demographics, disease severity, treatment status, and disease outcome (90-day mortality and overall survival [OS]) were compared between 2 groups. RESULTS: A total of 89 patients were included, 62.9% of them having a De Ritis ratio of < 1.3 and 37.1% with a De Ritis ratio of ≥ 1.3. Mean OS was significantly higher in patients with normal De Ritis ratio (40.84 vs. 18.28 months, P < .001), and 90-day mortality rate was lower in these patients (8.9% vs. 36.4%, P = .001). Moreover, De Ritis ratio was the sole independent predictor of OS in multivariable regression analysis. CONCLUSION: De Ritis ratio is an independent prognostic factor in BC patients who underwent radical cystectomy. Furthermore, higher De Ritis ratio is associated with worse OS and a higher 90-day mortality rate after surgery, and therefore, has the potential to serve as a predictor of treatment outcome in BC patients.

Comparing Zonisamide With Sodium Valproate in the Management of Migraine Headaches: Double-Blind Randomized Clinical Trial of Efficacy and Safety.

BACKGROUND: Migraine is one of the most debilitating medical conditions and has a high socioeconomic burden. As conventional therapeutic methods do not entirely alleviate the symptoms, new alternatives are being considered. OBJECTIVES: This study evaluates the efficacy and safety of zonisamide compared with sodium valproate in the management of migraine headaches. PATIENTS AND METHODS: In the current double-blind, parallel, randomized, controlled trial, 96 patients with a migraine diagnosis based on the international headache society (HIS) criteria were selected. They were divided randomly into two groups; the case group was given zonisamide, and sodium valproate was given to a control group. In addition to the side effects of the drugs, the severity, duration, and frequency of migraine attacks were evaluated at baseline and at three months. RESULTS: The 96 selected patients were divided randomly into two treatment groups (zonisamide n = 48, sodium valproate n = 48). Seven patients were excluded from analysis because of early dropout, leaving 89 (n = 45; n = 44) patients for analysis. While using zonisamide, six (13%) patients complained of fatigue, and two (4%) patients encountered noticeable appetite and weight loss. In the control group, five (11%) patients reported dizziness, and four (9%) patients faced obvious appetite and weight gain. Both drugs were considerably efficient in reducing further attacks. There was no statistically significant correlation between frequency or severity of migraine attacks and the drug used for treatment in three months of follow-up. CONCLUSIONS: Both medications are effective in reducing migraine attacks. It will be important to consider the drugs' adverse effects and availability and patients' medical and socioeconomic condition to select the appropriate treatment.

Relation of Stroke Risk Factors with Specific Stroke Subtypes and Territories.

BACKGROUND: Although the risk factors of ischemic strokes are well defined, there is slight information about their relations with the etiologies of ischemic strokes. This study investigated the distribution of ischemic stroke risk factors and their connections to diverse etiologies of cerebrovascular attack (CVA) and specific ischemic regions of brain. METHODS: In this cross sectional study, we analyzed the data of patients with definite diagnosis of CVA, excluding hemorrhagic strokes, registered in Imam Hossein Medical Center in Tehran, Iran. The data were collected from entire archived medical records from March 2010 until September 2012, retrospectively. RESULTS: Out of 1696 cases a total of 1011 subjects, 487 (48.2%) males and 524 (51.8%) females with mean age of 68.91±13.54 yr were included in the study. Patients suffering from atrial fibrillation (AF), valvular heart disease (VHD), and dilated cardiomyopathy were more prone to develop cardioembolic stroke. Those with diabetes mellitus (DM), carotid artery stenosis and dyslipidemia (DLP) had a higher prevalence of macroangiopathic stroke. Ischemic heart disease (IHD), AF, and VHD were associated with stroke in the brain territory supplied by middle cerebral artery (MCA) while DM and carotid artery stenosis were correspondent with posterior cerebral artery (PCA) stroke. CONCLUSION: The diagnosis of the weight of each risk factor of ischemic strokes on different etiologies and territories of ischemia can assist care providers for a more efficient prevention of strokes. The results of this study can also be a basis for further investigations to corroborate the pathophysiology of such relations.