Potential Value of Visfatin, Omentin-1, Nesfatin-1 and Apelin in Renal Cell Carcinoma (RCC): A Systematic Review and Meta-Analysis.

Renal cell carcinoma (RCC) is the most lethal genitourinary malignancy. Obesity is a risk factor for RCC development. The role of adipokines in the relationship between obesity and RCC requires confirmatory evidence in the form of a systematic review and meta-analysis, specifically for visfatin, omentin-1, nesfatin-1 and apelin. A search of databases up to July 2022 (PubMed, Web of Science and Scopus) for studies reporting the association of these selected adipokines with RCC was conducted. A total of 13 studies fulfilled the selection criteria. Only visfatin (p < 0.05) and nesfatin-1 (p < 0.05) had a significant association with RCC. Meanwhile, apelin and omentin-1 showed no association with RCC. The meta-analysis results of nesfatin-1 showed no association with early-stage (OR = 0.09, 95% CI = −0.12−0.29, p = 0.41), late-stage (OR = 0.36, 95% CI = 0.07−1.89, p = 0.23) and low-grade (OR = 1.75, 95% CI = 0.37−8.27, p = 0.48) RCC. However, nesfatin-1 showed an association with a high grade of the disease (OR = 0.29, 95% CI = 0.13−0.61, p = 0.001) and poorer overall survival (OS) (HR = 3.86, 95% CI = 2.18−6.85; p < 0.01). Apelin showed no association with the risk of RCC development (mean difference = 21.15, 95% CI = −23.69−65.99, p = 0.36) and OS (HR = 1.04, 95% Cl = 0.45−2.41; p = 0.92). Although the number of studies evaluated was limited, analysis from this systematic review and meta-analysis indicate that visfatin and nesfatin-1 were elevated. In summary, these adipokines may play a role in the development and progression of RCC and hence may have potential diagnostic and prognostic capabilities for RCC.

Reduction of pre-procedural anxiety for repeat sessions in extracorporeal shockwave lithotripsy (ESWL) reduces pain intensity: A prospective observational study.

Pain control is a major determinant for successful stone clearance in extracorporeal shockwave lithotripsy (ESWL) for urolithiasis. Pain perception during ESWL may be influenced by patient factors like gender, age, body habitus and anxiety level, and stone related factors like size, laterality and location of stone. We investigated in general, the confounding patient and stone factors influencing pain perception during ESWL with importance given to procedural anxiety in first and the subsequent session of ESWL. This was a prospective observational study of all new consecutive patients who underwent ESWL for a period of 1 year at a tertiary Urological Centre. Demographic and stone anthropometry were analyzed. Pre-procedural anxiety was assessed prior to procedure using hospital anxiety and depression score (HADS) and pain was scored using numerical rating scale-11 at baseline, 30-minutes (i.e., during) and 24 hours after ESWL. Univariate and multivariate analysis for confounding factors included HADs were performed for pain perception. A P value < .05 was considered to be statistically significant. For the study duration, 119 patients were recruited and 72 of them returned for a second session. Procedural anxiety was the only independent factor affecting pain score in ESWL for the first session in multivariate analysis. A statistically significant reduction of mean procedural anxiety score from 6.7 ±â€…4.5 to 3.2 ±â€…2.7 (P < .05) for the second ESWL session was observed (n = 72). This was in conjunction with statistical reduction of mean pain score 30 minutes after ESWL from 5.2 ±â€…2.1 to 4.2 ±â€…2.1 (P < .05). Patients with HADS ≥ 8 had statistically significant higher mean pain score at all 3 intervals in the first ESWL session. This study has shown that pre-procedural anxiety mainly anticipatory, reduces and shows reduction in pain intensity among patients undergoing repeat ESWL. Hence, anxiety reducing methods should be explored in patients undergoing ESWL to avoid unnecessary analgesic use.

Psychological distress among elderly surgical patients who had their surgery postponed during the COVID-19 pandemic.

BACKGROUND: Many institutions withheld elective lists and triaged surgeries during the peak of coronavirus disease 2019 (COVID-19) pandemic. As a result, older surgical patients have had to wait for rescheduled dates in a long waitlist. This study aimed to identify the psychological impact in these patients when they returned for surgery. METHODS: This was a cross-sectional study which included 153 patients aged ≥ 65 years undergoing elective surgery. Trained interviewers recruited and assessed psychological status pre-operatively with two validated questionnaires - Hospital Anxiety and Depression Scale (HADS) and 36-item Short Form Health Survey (SF-36). Specific questions were asked about their postponed surgeries, appetite and fear. RESULTS: A total of 36 out of 153 (23.5%) patients had their procedures deferred during the first wave of COVID-19 pandemic. Postponed cases were significantly based on the nature of surgery (p = 0.002), cancer diagnosis (p = 0.006) and surgical specialty (p = 0.023). Median HADS scores were higher for patients who were postponed (2.00 versus 4.00 for anxiety, p = 0.180 and 0.00 versus 1.00 for depression, p = 0.424) although no statistical significance was shown. In the whole study population, anxiety was a significant predictor for depression and vice versa (p < 0.001) with other predictive risk factors for anxiety that were age ≥ 85 years old (odds ratio [OR] 6.14, p = 0.018), female (OR 2.41, p = 0.024), cancer (OR 2.19, p = 0.039) and major surgery (OR 2.39, p = 0.023). Similarly, older patients ≥ 85 years old (OR 10.44, p = 0.003) and female (OR 6.07, p = 0.006) had higher risk for depression. Both anxiety and depression were significant risks for loss of appetite (p = 0.005 and 0.001). Lastly, the fear of disease progression due to rescheduling was more frequent in cancer patients (p = 0.035). CONCLUSION: The mental health and disease burden of older surgical patients should be taken into careful consideration when cases need to be postponed in our healthcare system.

Ethnic differences in serum testosterone concentration among Malay, Chinese and Indian men: A cross-sectional study.

OBJECTIVE: To investigate non-urological patients with multiple comorbidities for factors contributing towards differences in testosterone concentration in multiethnic Malaysian men. DESIGN: An observational study. PATIENTS: Sexually active men, ≥40 years, with no known urological problems, were recruited at the phlebotomy clinic at our centre. MEASUREMENTS: A brief history along with latest fasting lipid profile and plasma glucose levels were obtained. An Aging Male Symptoms questionnaire was administered; waist circumference (WC) and serum testosterone concentration were measured. STATSTICAL ANALYSIS: Analysis of testosterone concentration between Malay, Indian and Chinese men was performed. Statistical tests such as analysis of variance, χ2 test, univariate and multivariable regression were performed. Any p < .05 was noted as statistically significant. RESULTS: Among the 604 participants analysed, mean testosterone concentration was significantly lower in Malays (15.1 ± 5.9 nmol/L) compared to the Chinese (17.0 ± 5.9 nmol/L) and Indian (16.1 ± 6.5 nmol/L) participants. The mean WC was also found to be higher among the Malays (96.1 ± 10.9 cm) compared to Chinese (92.6 ± 9.6 cm) and Indians (95.6 ± 9.9 cm). Testosterone concentration tended to be lower with higher age, but this was not statistically significant (p > .05). In the multivariable analysis only Malay ethnicity, WC ≥ 90 cm and low high-density lipoprotein (HDL) were associated with lower testosterone concentration. CONCLUSION: In this study, Malaysian men of Malay origin had lower testosterone concentration compared with Indian and Chinese men. WC and low HDL were also associated with lower testosterone concentrations.

Optimizing outcomes for patients with metastatic prostate cancer: insights from South East Asia Expert Panel.

AIMS: Clinical decision making is challenging in men with metastatic prostate cancer (mPC), as heterogeneity in treatment options and patient characteristics have resulted in multiple scenarios with little or no evidence. The South East Asia Expert Panel 2019 addressed some of these challenges. METHODS: Based on evidence in the literature and expert interviews, 19 statements were formulated for key challenges in the treatment of men with castration-sensitive and -resistant prostate cancer in clinical practice. A modified Delphi process was used to reach consensus among experts in the panel and develop clinical practice recommendations. RESULTS: The majority of the panel preferred a risk-based stratification and recommended abiraterone or enzalutamide as first-line therapy for symptomatic chemotherapy naïve patients. Abiraterone is preferred over enzalutamide as a first-line treatment in these patients. However, the panel did not support the use of abiraterone in high risk lymph-node positive only (N+M0) or in non-metastatic (N0M0) patients. In select patients, low dose abiraterone with food may be used to optimize clinical outcomes. Androgen receptor gene splice variant status may be a useful guide to therapy. In addition, generic versions of approved therapies may improve access to treatment to a broader patient population. The choice of treatment, as well as sequencing are guided by both patient and disease characteristics, preferences, drug access, cost, and compliance. CONCLUSION: Expert recommendations are key to guidance for the optimal management of mPC. Appropriate choice, timing, and sequence of treatment options can help to tailor therapy to maximize outcomes in men with mPC.

Genitourinary extramammary Paget's disease: review and outcome in a multidisciplinary setting.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant disease originating from the apocrine glands involving the perineum, vulva, axilla, scrotum, and penis. OBJECTIVE: To study the clinical presentation, extent of disease, efficacy of treatment, and survival outcomes of the cases in a single institution. METHODS: Retrospective observation data analysis of 19 EMPD cases was performed. Demographic information, clinical management records, and histopathologic data of individual cases were obtained from the inpatient hospital data registry. RESULTS: The mean age (years) at time of diagnosis was 62.4 with equal gender distribution. Synchronous tumors were detected in 6 cases (31.5%). 18 out of 19 patients underwent definitive surgical management in the form of wide local excision (WLE) and reconstructive surgery. Positive margins were found in 11 (68.8%) cases and 7 out of these 11 cases underwent second look surgical intervention to achieve oncological clearance or adjuvant oncology treatment. Follow-up period for living patients varied depending on time of diagnosis and definitive treatment. 10 out 19 cases (52.7%) were alive at the time of the study. Among the 7 cases of mortality from cancer, 5 cases died from progression of underlying associated malignancy and only 2 cases died with advanced stage of EMPD. CONCLUSION: EMPD can be quite aggressive, especially in the secondary form, and surgical management is challenging with a high rate of residual tumor at the surgical margin. EMPD can easily mislead the clinician and patient, leading to unnecessary delay prior to definitive effective management.

A Study on the Immunohistochemical Expressions of Leptin and Leptin Receptor in Clear Cell Renal Cell Carcinoma.

BACKGROUND: The mechanisms that link obesity and cancer development are not well-defined. Investigation of leptin and leptin receptor expressions may help define some of the mechanisms. These proteins are known for associating with the immune response, angiogenesis and, signalling pathways such as JAK2/STAT3, PI3K, and AKT pathways. Tissue proteins can be easily detected with immunohistochemistry (IHC), a technique widely used both in diagnostic and research laboratories. The identification of altered levels of leptin and leptin receptor proteins in tumour tissues may lead to targeted treatment for cancer. OBJECTIVE: The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p < 0.05 was considered significant. RESULTS: There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC. CONCLUSION: In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.

Predictive factors of prostate cancer diagnosis with PSA 4.0-10.0 ng/ml in a multi-ethnic Asian population, Malaysia.

OBJECTIVES: To identify the associated factors determining prostate cancer detection using transrectal ultrasound (TRUS)-guided prostate biopsy, within a multi-ethnic Malaysian population with prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml. METHODS: Study subjects included men with initial PSA between 4.0 and 10.0 ng/ml that have undergone 12-core TRUS-guided prostate biopsy between 2009 and 2016. The prostate cancer detection rate was calculated, while potential factors associated with detection were investigated via univariable and multivariable analysis. RESULTS: A total of 617 men from a multi-ethnic background encompassing Chinese (63.5%), Malay (23.1%) and Indian (13.3%) were studied. The overall cancer detection rate was 14.3% (88/617), which included cancers detected at biopsy 1 (first biopsy), biopsy 2 (second biopsy with previous negative biopsy) and biopsy ≥ 3 (third or more biopsies with prior negative biopsies). Indian men displayed higher detection rate (23.2%) and increased risk of prostate cancer development (OR 1.85, 95% CI 1.03-3.32, p < 0.05), compared to their Malay (9.8%) and Chinese (14.0%) counterparts. Multivariable analysis revealed that ethnicity and PSA density (PSAD) are independent factors associated with overall prostate cancer detection rate. A unit increase of PSAD reflected an increase in PSA after controlling for prostate volume. CONCLUSION: Prostate cancer detection in Malaysia is comparatively lower. Our study suggests that ethnicity and PSA density should be considered when recommending first or repeat TRUS-guided prostate biopsy for prostate cancer detection in a multi-ethnic Malaysian population.

Genome-wide copy number analysis reveals candidate gene loci that confer susceptibility to high-grade prostate cancer.

BACKGROUND: Two key issues in prostate cancer (PCa) that demand attention currently are the need for a more precise and minimally invasive screening test owing to the inaccuracy of prostate-specific antigen and differential diagnosis to distinguish advanced vs. indolent cancers. This continues to pose a tremendous challenge in diagnosis and prognosis of PCa and could potentially lead to overdiagnosis and overtreatment complications. Copy number variations (CNVs) in the human genome have been linked to various carcinomas including PCa. Detection of these variants may improve clinical treatment as well as an understanding of the pathobiology underlying this complex disease. METHODS: To this end, we undertook a pilot genome-wide CNV analysis approach in 36 subjects (18 patients with high-grade PCa and 18 controls that were matched by age and ethnicity) in search of more accurate biomarkers that could potentially explain susceptibility toward high-grade PCa. We conducted this study using the array comparative genomic hybridization technique. Array results were validated in 92 independent samples (46 high-grade PCa, 23 benign prostatic hyperplasia, and 23 healthy controls) using polymerase chain reaction-based copy number counting method. RESULTS: A total of 314 CNV regions were found to be unique to PCa subjects in this cohort (P<0.05). A log2 ratio-based copy number analysis revealed 5 putative rare or novel CNV loci or both associated with susceptibility to PCa. The CNV gain regions were 1q21.3, 15q15, 7p12.1, and a novel CNV in PCa 12q23.1, harboring ARNT, THBS1, SLC5A8, and DDC genes that are crucial in the p53 and cancer pathways. A CNV loss and deletion event was observed at 8p11.21, which contains the SFRP1 gene from the Wnt signaling pathway. Cross-comparison analysis with genes associated to PCa revealed significant CNVs involved in biological processes that elicit cancer pathogenesis via cytokine production and endothelial cell proliferation. CONCLUSION: In conclusion, we postulated that the CNVs identified in this study could provide an insight into the development of advanced PCa.

Genetic polymorphisms in the androgen metabolism pathway and risk of prostate cancer in low incidence Malaysian ethnic groups.

Androgens are involved in prostate cancer (PCa) cell growth. Genes involved in androgen metabolism mediate key steps in sex steroid metabolism. This study attempted to investigate whether single nucleotide polymorphisms (SNPs) in the androgen metabolism pathway are associated with PCa risk in low incidence Asian ethnic groups. We genotyped 172 Malaysian subjects for cytochrome P450 family 17 (CYP17A1), steroid-5-alpha-reductase, polypeptide 1 and 2 (SRD5A1 and SRD5A2), and insulin-like growth factor 1 (IGF-1) genes of the androgen metabolism pathway and assessed the testosterone, dihydrotestosterone and IGF-1 levels. SNPs in the CYP17A1, SRD5A1, SRD5A2, and IGF-1 genes were genotyped using real-time polymerase chain reaction. Although we did not find significant association between SNPs analysed in this study with PCa risk, we observed however, significant association between androgen levels and the IGF-1 and several SNPs. Men carrying the GG genotype for SNP rs1004467 (CYP17A1) had significantly elevated testosterone (P = 0.012) and dihydrotestosterone (DHT) levels (P = 0.024) as compared to carriers of the A allele. The rs518673 of the SRD5A1 was associated with prostate specific antigen (PSA) levels. Our findings suggest CYP17A1 rs1004467 SNP is associated with testosterone and DHT levels indicating the importance of this gene in influencing androgen levels in the circulatory system of PCa patients, hence could be used as a potential marker in PCa assessment.

Managing patients with acute urinary retention.

Acute urinary retention (AUR) is more than ten times more common in men than women. In men it tends to occur in the elderly; the risk of AUR is higher in men > 70 years. The causes in men can be divided into precipitated or occurring spontaneously. These can be further divided according to the mechanism i.e. obstructive, neurological and myogenic. Spontaneous AUR, caused by progression of BPH leading to a mechanical obstruction of the bladder outlet, is the most common cause of AUR. The typical presentation of AUR is a patient complaining of a sudden inability to urinate associated with progressive abdominal distension which is usually painful. The pain increases in intensity with increasing distension of the bladder. An abdominal examination should reveal a distended bladder which can be confirmed by a dull percussion note. A digital rectal examination is vital to gain information on prostatic enlargement (benign or malignant), faecal load in rectum, anal tone and presence of other masses. Urinalysis and culture should be carried out on a sample obtained after catheterisation to rule out infection. Renal function should be assessed to see if there has been damage to the upper tracts. It is better not to perform a PSA test in this situation as it will invariably be raised due to distension of the bladder and catheter insertion. If catheter insertion fails then a urological consultation is required for insertion of a suprapubic catheter. Admission is essential if the patient is: unwell with urosepsis; has abnormal renal function needing investigation and fluid monitoring; has acute neurological problems; or cannot take care of the catheter. Trial without catheter needs to be planned and the ideal time to do this is within 2-3 days so that the patient can pass urine naturally.

The efficacy of periprostatic local anaesthetic infiltration in transrectal ultrasound biopsy of prostate: a prospective randomised control study.

OBJECTIVE: It is still uncertain as to which form of anaesthesia is the optimum. We conducted a study to identify the best location and optimum volume of anaesthetic agent in order to achieve best pain relief and cooperation from our patients. We also assessed the need for local anaesthetic gel for probe lubrication and if the number of cores during biopsy makes a difference in the pain score. MATERIALS AND METHOD: A total of 386 patients were randomised into 4 groups i.e. no anaesthesia (Group A), 10 cc 1% Lignocaine at apical region of prostate (Group B), 5 cc 1% Lignocaine each at both bases (Group C) and lastly, 4 cc at apex and 3 cc each at both bases (Group D). Pain assessment was performed using the 10-point Visual Analog Scale after the procedure with regard to probe insertion and during the biopsy. RESULTS: The groups were comparable in number and mean age. Group B recorded the lowest mean pain score of 2.59. Comparative analysis showed significant pain relief when comparing Group B vs. Group A (P = 0.001). The other groups were not as effective. The overall mean pain score for the probe insertion and the number of cores during biopsy was also not significant. CONCLUSIONS: We suggest that a 10 cc 1% Lignocaine infiltration at the apical region of the prostate be used to obtain best pain relief during this procedure. Plain lubricant jelly is sufficient for probe insertion. There is no need to alter the anaesthetic requirement if number of cores is increased.