Abbreviations & AcronymsObjectives: To validate the predictive value of Fournier's Gangrene Severity Index in patients with Fournier gangrene and to facilitate patient mortality risk-stratification by simplifying the Fournier's Gangrene Severity Index. Methods: From January 1989 to December 2011, 85 male patients with clinicallydocumented Fournier's gangrene undergoing intensive treatment and with complete medical records were recruited. The demographic information and nine parameters of Fournier's Gangrene Severity Index were compared between survivors and non-survivors. The parameters that showed a significant difference between the two groups were selected to generate a simplified scoring index. Results: Of the 85 patients recruited, 16 patients died of the disease with mortality rate of 18.8%. The Fournier's Gangrene Severity Index score at initial diagnosis was significantly higher in non-survivors than in survivors. Of the nine parameters of Fournier's Gangrene Severity Index, the scores of serum creatinine level, hematocrit level and serum potassium level were significantly different between the two groups. However, the mean body temperatures, heart rate, respiration rate, white blood cell count, serum sodium and bicarbonate levels were non-significantly different. Of the 12 patients with chronic kidney disease or end-stage renal disease, 10 died of severe sepsis. A simplified scoring index including parameters of creatinine, hematocrit and potassium was generated, which provided sensitivity and specificity of 87% and 77% in predicting patient mortality, respectively. The predictive values of this simplified Fournier's Gangrene Severity Index were shown to be non-inferior to Fournier's Gangrene Severity Index in our patients.
Conclusions:The simplified Fournier's Gangrene Severity Index is easy to use at initial diagnosis, and offers a way to compare outcomes in different clinical populations.
Metastatic castration-resistant prostate cancer (mCRPC) is a malignant and lethal disease caused by relapse after androgen-deprivation (ADT) therapy. Since enzalutamide is innovated and approved by US FDA as a new treatment option for mCRPC patients, drug resistance for enzalutamide is a critical issue during clinical usage. Although several underlying mechanisms causing enzalutamide resistance were previously identified, most of them revealed that drug resistant cells are still highly addicted to androgen and AR functions. Due to the numerous physical functions of AR in men, innovated AR-independent therapy might alleviate enzalutamide resistance and prevent production of adverse side effects. Here, we have identified that yes-associated protein 1 (YAP1) is overexpressed in enzalutamide-resistant (EnzaR) cells. Furthermore, enzalutamide-induced YAP1 expression is mediated through the function of chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII) at the transcriptional and the post-transcriptional levels. Functional analyses reveal that YAP1 positively regulates numerous genes related to cancer stemness and lipid metabolism and interacts with COUP-TFII to form a transcriptional complex. More importantly, YAP1 inhibitor attenuates the growth and cancer stemness of EnzaR cells in vitro and in vivo. Finally, YAP1, COUP-TFII, and miR-21 are detected in the extracellular vesicles (EVs) isolated from EnzaR cells and sera of patients. In addition, treatment with EnzaR-EVs induces the abilities of cancer stemness, lipid metabolism and enzalutamide resistance in its parental cells. Taken together, these results suggest that YAP1 might be a crucial factor involved in the development of enzalutamide resistance and can be an alternative therapeutic target in prostate cancer.
The Johnnie Walker position minimizes operative time by eliminating the delay caused by patient positioning and draping changes, allowing better coordination for the surgeon and assistant, and permitting more efficient use of the nondominant hand. The retroperitoneal approach prevents bowel interference in the visual field, making laparoscopic surgery in this modified supine position possible. Nephroureterectomy, bladder cuff resection and endoscopic procedures can be done with ease with the patient in this position.
Objective: To determine the impact of earlier ureteral ligation (EUL) during hand-assisted retroperitoneoscopic nephroureterectomy (HARN) for primary renal pelvis urothelial cancer. Methods: We retrospectively reviewed 240 patients with upper urinary tract urothelial cancer who underwent HARN. Only patients with primary renal pelvis urothelial cancer and complete follow-up with a minimum of 1 year after HARN were enrolled into our study. We defined EUL as ligating the ureter prior to pneumoretroperitoneum and mobilizing the kidney during the surgery. Of these 61 patients, 31 (who composed the study group) underwent EUL, while 30 serving as controls were without ureteral ligation during the surgery. We analyzed intravesical recurrence utilizing log rank testing to assess the significance between the two groups. Results: Clinical parameters were similar between the two groups. The median follow-up after HARN was 39.7 months (range 12-96). There was no significant difference in the rate of intravesical recurrence and cancer-specific survival. However, patients without ligation of the ureter had shorter time to first bladder tumor recurrence (11.7 ± 9.1 months vs. 26.4 ± 19.1 months, p = 0.03). Conclusion: EUL during HARN for primary renal urothelial cancer did not affect intravesical recurrence rate or cancer-specific survival.
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