Protective role of kallistatin in renal fibrosis via modulation of Wnt/ß-catenin signaling.

Kallistatin is a multiple functional serine protease inhibitor that protects against vascular injury, organ damage and tumor progression. Kallistatin treatment reduces inflammation and fibrosis in the progression of chronic kidney disease (CKD), but the molecular mechanisms underlying this protective process and whether kallistatin plays an endogenous role are incompletely understood. In the present study, we observed that renal kallistatin levels were significantly lower in patients with CKD. It was also positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with serum creatinine level. Unilateral ureteral obstruction (UUO) in animals also led to down-regulation of kallistatin protein in the kidney, and depletion of endogenous kallistatin by antibody injection resulted in aggravated renal fibrosis, which was accompanied by enhanced Wnt/ß-catenin activation. Conversely, overexpression of kallistatin attenuated renal inflammation, interstitial fibroblast activation and tubular injury in UUO mice. The protective effect of kallistatin was due to the suppression of TGF-ß and ß-catenin signaling pathways and subsequent inhibition of epithelial-to-mesenchymal transition (EMT) in cultured tubular cells. In addition, kallistatin could inhibit TGF-ß-mediated fibroblast activation via modulation of Wnt4/ß-catenin signaling pathway. Therefore, endogenous kallistatin protects against renal fibrosis by modulating Wnt/ß-catenin-mediated EMT and fibroblast activation. Down-regulation of kallistatin in the progression of renal fibrosis underlies its potential as a valuable clinical biomarker and therapeutic target in CKD.

Health-related quality of life of Chinese patients with prostate cancer in comparison to general population and other cancer populations.

PURPOSE: The purpose of this study was to compare the health-related quality of life (HRQOL) of Chinese patients with prostate cancer against the general population and patients with colorectal cancer, breast cancer, nasopharyngeal cancer, and leukemia. METHODS: Chinese male patients (n = 291) with a confirmed diagnosis of prostate cancer were recruited from a urological specialist outpatient clinic in Hong Kong. HRQOL was measured by a condition-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P) and a generic Chinese (HK) SF-12 Health Survey Version 2 (SF-12v2) questionnaire. Mean HRQOL scores of condition-specific and generic questionnaires were compared to available scores derived from other cancers and age-matched male general population, respectively. RESULTS: Chinese patients with prostate cancer had lower general health and vitality domains and lower mental component summary scores than the age-matched Hong Kong normative population. Patients with prostate cancer reported better condition-specific HRQOL (physical well-being, emotional well-being and function well-being) when compared to general cancer population, patients with breast cancer, colorectal cancer, nasopharyngeal cancer, and leukemia in Hong Kong. CONCLUSIONS: Patients with prostate cancer substantially perceived their HRQOL to be better, compared to patients with other cancers, with overall health, energy, and mental health below of Hong Kong general population. Interventions should target at these domains in order to improve the HRQOL of patients with prostate cancer. It is reassuring to find that prostate cancer had less negative impact on HRQOL than other cancer types did.

The internal and external responsiveness of Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Short Form-12 Health Survey version 2 (SF-12 v2) in patients with prostate cancer.

PURPOSE: To examine the responsiveness of Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Short Form-12 Health Survey version 2 (SF-12 v2) in prostate cancer patients because there is a lack of evidence to support their responsiveness in this patient population. METHODS: One hundred sixty-eight subjects with prostate cancer were surveyed at baseline and at 6 months using the SF-12 v2 and FACT-P version 4. Internal responsiveness was assessed using paired t test and generalized estimating equation. External responsiveness was evaluated using receiver operating characteristic curve analysis. RESULTS: The internal responsiveness of the FACT-P and SF-12 v2 to detect positive change was satisfactory. The FACT-P and SF-12 v2 could not detect negative change. The FACT-P and the SF-12 v2 performed the best in distinguishing between improved general health and worsened general health. The FACT-P performed better in distinguishing between unchanged general health and worsened general health. The SF-12 v2 performed better in distinguishing between unchanged general health and improved general health. CONCLUSIONS: Positive change detected by these measures should be interpreted with caution as they might be too responsive to detect "noise," which is not clinically significant. The ability of the FACT-P and the SF-12 v2 to detect negative change was disappointing. The internal and external responsiveness of the social well-being of the FACT-P cannot be supported, suggesting that it is not suitable to longitudinally monitor the social component of HRQOL in prostate cancer patients. The study suggested that generic and disease-specific measures should be used together to complement each other.

Psychometric properties of Functional Assessment of Cancer Therapy-Prostate (FACT-P) in Chinese patients with prostate cancer.

PURPOSE: The aim of the study was to assess the validity, reliability and sensitivity of the FACT-P (version 4) in Chinese males with prostate cancer. METHODS: Construct validity was assessed using Spearman's correlation test against the 12-item Short Form Health Survey (SF-12v2). Internal consistency and test-retest reliability were assessed using Cronbach's α coefficient and intra-class correlation coefficient, respectively. Sensitivity was determined by performing known-group comparisons by independent t test. RESULTS: FACT-P subscale scores had a moderate correlation with the corresponding SF-12v2 domain score that conceptually measures the similar construct providing evidence for adequate construct validity. Internal consistency was acceptable (α: 0.687-0.900) for all subscales aside from the Prostate Cancer Subscale (α: 0.505) and Trial Outcome Index (α: 0.562). FACT-P subscale and total scores showed good test-retest reliability (range 0.753-0.913). All total scales and most of the subscales were sensitive in detecting differences between patients with different levels of functional impairment but not different cancer stages or levels of prostate-specific antigen. CONCLUSIONS: The measure is a valid and reliable measure to assess the health-related quality of life of Chinese males with prostate cancer. The FACT-P is sensitive to detect difference between patients with varying functional status.

Disease spectrum and treatment patterns in a local male infertility clinic.

OBJECTIVE: To review disease spectrum and treatment patterns in a local male infertility clinic. DESIGN: Case series. SETTING: Male infertility clinic in a teaching hospital in Hong Kong. PATIENTS: Patients who were seen as new cases in a local male infertility clinic between January 2008 and December 2012. INTERVENTION: Infertility assessment and counselling on treatment options. MAIN OUTCOME MEASURES: Disease spectrum and treatment patterns. RESULTS: A total of 387 new patients were assessed in the male infertility clinic. The mean age of the patients and their female partners was 37.2 and 32.1 years, respectively. The median duration of infertility was 3 years. Among the patients, 36.2% had azoospermia, 8.0% had congenital absence of vas deferens, and 48.3% of patients had other abnormalities in semen parameters. The commonest causes of male infertility were unknown (idiopathic), clinically significant varicoceles, congenital absence of vas deferens, mumps after puberty, and erectile or ejaculatory dysfunction. Overall, 66.1% of patients chose assisted reproductive treatment and 12.4% of patients preferred surgical correction of reversible male infertility conditions. Altogether 36.7% of patients required either surgical sperm retrieval or correction of male infertility conditions. CONCLUSIONS: The present study provided important local data on the disease spectrum and treatment patterns in a male infertility clinic. The incidences of azoospermia and congenital absence of vas deferens were much higher than those reported in the contemporary literature. A significant proportion of patients required either surgical sperm retrieval or correction of reversible male infertility conditions.

Risk factors in the prediction of long-term patency of Resonance metallic ureteric stent in malignant ureteric obstruction.

Objectives: Cancer is the second leading cause of death globally in 2018 with an estimated 9.6 million deaths. The costs of managing malignant ureteric obstruction (MUO) is a significant burden to any healthcare system. However, the management of MUO has long been a challenge for urologists. The standard options of percutaneous nephrostomy or polymer double J stents are fraught with problems. We report a large patient series with long-term follow-up in the use of Resonance metallic ureteric stents to relieve MUO, and identification of risk factors associated with stent failure. Patients and methods: All patients with MUO who were arranged to have Resonance metallic ureteric stent insertion at two university hospitals were included in this cohort study, starting from June 2011 to July 2016. Data were retrieved retrospectively. The primary outcome was the total duration of stent patency before stent failure due to malignant disease progression. Stent failure was defined as ureteric obstruction identified on imaging (functional radioisotope scan or antegrade pyelogram), acute renal failure resolved by subsequent percutaneous nephrostomy, or any other cause requiring stent removal prematurely. Secondary outcomes were identification of factors associated with stent failure, grade III or above complication, and development of a risk-adopted model to predict metallic ureteric stent patency rates in MUO patients. Median duration of functioning metallic ureteric stent was determined with Kaplan-Meier survival curve. Results: A total of 124 renal units in 95 patients with MUO were eligible for the study, with a median follow-up period of 22.9 months. About 106 (85.5%) renal units had successful metallic stent insertion, of whom 41 (33.1%) renal units ultimately progressed to ureteric obstruction despite the metallic stents, and required subsequent insertion of nephrostomies. Median duration of functioning metallic ureteric stents was 25 months. Female gender (HR 3.0, 95% CI: 1.3-7.2, P = .014) and suspicious bladder lesion (HR 2.9, 95% CI: 1.4-6.2, P = .005) were independent risk factors for stent failure, respectively. Stratifying patients into low (0 risk factor), intermediate (1 risk factor), and high (2 risk factors) risk groups, we found that this could predict the duration of stent patency in MUO with the metallic stents. (Low risk: 30.3 months vs intermediate group: 17.8 months vs high risk: 4.9 months, P < .001). Conclusion: Resonance metallic ureteral stents are able provide a median of 25 months of ureteric drainage in patients with MUO. Determining whether a patient has one or both risks factors (female gender and bladder lesion) will allow one to estimate the duration of metallic stent patency, which in turn may aid in determining cost-effectiveness in individual patients.

Is prostate specific antigen (PSA) density necessary in selecting prostate cancer patients for active surveillance and what should be the cutoff in the Asian population?

BACKGROUND: To investigate the role of Prostate Specific Antigen density (PSAD) in selecting prostate cancer patients for active surveillance (AS) and to determine a cutoff PSAD in identifying adverse pathological outcomes. METHODS: Data from 287 patients who underwent radical prostatectomy for prostate cancer were retrospectively reviewed. Six different AS protocols, the University of Toronto; Royal Marsden; John Hopkins; University of California San Francisco (UCSF); Memorial Sloan Kettering Cancer Center (MSKCC) and Prostate Cancer Research International: Active Surveillance (PRIAS), were applied to the cohort. Pre-operative demographics and pathological outcomes were analysed. Statistical analyses on the predictive factors of adverse pathological outcomes and significance of PSAD were performed. A cutoff PSAD with best balance between sensitivity and specificity in identifying adverse pathological outcome was determined. RESULTS: PSAD predicted adverse pathological outcomes better than Prostate Specific Antigen (PSA) level alone. The PSAD was significantly lower (0.12-0.13 ng/dl/ml) in protocols including PSAD (the John Hopkins and PRIAS) compared with the other four protocols not including PSAD as a selection criteria (0.21-0.25 ng/dl/dl, P = 0.00). PSAD predicted adverse pathological outcomes in all protocols not incorporating PSAD as an inclusion criteria (P = 0.00-0.02). By the receiver operator characteristics curve analysis, it was found that a PSAD level of 0.19 ng/ml/ml had the best balance between sensitivity and specificity in predicting pathological adverse disease (Area under curve = 0.63, P = 0.004). CONCLUSION: PSAD is necessary in selecting prostate cancer patients for active surveillance. It predicts adverse pathological outcomes in patients eligible for active surveillance better than PSA level alone. A PSAD cutoff at 0.19 ng/ml/ml has the best balance between sensitivity and specificity in predicting pathological adverse disease. We recommend using AS protocol incorporating PSAD as a selection criteria (in particular the PRIAS protocol with a cutoff PSAD at 0.2 ng/ml/ml) when recruiting prostate cancer patients for AS.

Surgical treatment of infected aneurysms and pseudoaneurysms of the thoracic and abdominal aorta.

BACKGROUND: To review the outcome of infected aneurysms and pseudoaneurysms of the thoracic and abdominal aorta treated in a major teaching hospital. METHODS: Between December 1994 and January 2003, 13 infected aortic aneurysms and pseudoaneurysms (5 thoracic, 4 paravisceral, 4 infrarenal) in 10 consecutive patients were treated surgically. Aortic debridement with in situ reconstruction is our standard practice. Endovascular repair was offered to suitable patients with thoracic aortic involvement. RESULTS: There were six men and four women with a mean age of 63 years. The commonest pathogen was Salmonella species, accounting for 50% of the cases. Aortic debridement with in situ revascularization was performed for six patients with visceral reconstruction in four of them. One patient with aortic bifurcation involvement and gross purulent infection had ligation and debridement followed by right axillobifemoral bypass. Four infected thoracic aortic pseudoaneurysms in three other patients underwent endovascular repair. There was no hospital death, limb loss, renal failure, or intestinal ischemia. There were two late deaths from sepsis and pneumonia at 3 months and 77 months after operation. Eight patients were alive after a mean follow-up of 36 months and no late graft infection was evident. CONCLUSIONS: Surgical treatment for infected aortic aneurysms with in situ reconstruction is associated with favorable outcome and good long-term result. Endovascular repair has a potential role.