Teng Aik Ong

Cardiovascular risk factors and ethnicity are independent factors associated with lower urinary tract symptoms.

Objectives To determine the lower urinary tract symptoms (LUTS) profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in a multiethnic Asian setting. Materials and Methods We conducted a cross-sectional study of 1021 men aged 40–79 years with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The severity of LUTS was assessed using the International Prostate Symptom Score (IPSS). Potential factors associated with LUTS including age, ethnicity, education, history of hypertension, diabetes and hypercholesterolemia, height, weight, and prostate volume were evaluated using univariable and multivariable analyses. Results There were 506 (50%) men found to have moderate-to-severe LUTS attaining an IPSS above 7. Overall, nocturia (45.5%) was the most frequently reported symptom. Multivariable analysis showed that age, ethnicity, prostate volume and history of hypertension and hypercholesterolemia were independent factors associated with severity of LUTS (p < 0.05). Considering individual lower urinary tract symptoms, we found a strong association of storage symptom with history of hypertension and hypercholesterolemia. Malay men were significantly bothered by post micturition symptom compared to their Chinese and Indian counterparts. Stratified analyses of LUTS demonstrated a mutually exclusive cardiovascular risk factors profile defined by ethnicity. Conclusion Severity of LUTS varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity and cardiovascular risk factors including hypertension and hypercholesterolemia may also need to be taken into account in managing men with LUTS.

Ethnicity is an independent determinant of age-specific PSA level: findings from a multiethnic Asian setting.

Objectives To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting. Materials and Methods We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis. Results There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05). Conclusion These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population.

Acute Anuric Renal Failure Following Jering Bean Ingestion

Djenkol beans or jering (Pithecellobium jeringa) is a traditional delicacy consumed by the local population in Malaysia. Jering poisoning or djenkolism is characterized by spasmodic pain, urinary obstruction and acute renal failure. The underlying pathology is an obstructive nephropathy, which is usually responsive to aggressive hydration and diuretic therapy. We present a case of djenkolism following ingestion of jering. The patient required urgent bilateral ureteric stenting following the failure of conservative therapy. Healthcare providers need to recognize djenkolism as a cause of acute renal failure and the public educated on this potential health hazard.

Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction

Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg(-1)·day(-1) ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis.

Clinical Prognostic Factors and Survival Outcome in Renal Cell Carcinoma Patients - A Malaysian Single Centre Perspective

BACKGROUND This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms. MATERIALS AND METHODS The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis. RESULTS The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, 9.5±4.3cm, was larger than non palpable masses, 5.3±2.7cm (p<0.001). CONCLUSIONS This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.

Hook Wire Localization for Testis Sparing Surgery

OBJECTIVE To describe a novel technique for localizing small testicular mass during testicular-sparing surgery (TSS). METHODS AND RESULTS A 20-year-old man presented with bilateral testicular masses. Both alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (BHCG) levels were raised. Clinical and imaging studies revealed a 2.7 cm and 0.7 cm mass in the right and left testis, respectively. No metastatic disease was detected on staging scans. Right inguinal total orchiectomy was performed. For the left testis, the inguinal approach was used to deliver the testis to the surgical wound. Vascular clamping and cooling of the testis were performed. A hook wire (Ghiatas Beaded Breast Localization Wire, 20G) was then inserted through the small testicular tumor with the aid of on-table ultrasound imaging. Testicular-sparing surgery (TSS) was easily performed with the aid of the hook wire. Postoperative recovery was uneventful. The histology report revealed a mixed germ cell tumor with clear margin. Tumor markers returned to normal after surgery. Serum testosterone level was also within normal range. Follow-up ultrasound scan showed a viable left testis with normal vascularity. CONCLUSION Hook wire localization of a small testicular mass under ultrasound guidance is an easy-to-perform technique that facilitates TSS in selected patients. This technique allows TSS to be performed in a more controlled and confident manner.

Assessment and Clinical Significance of Haematuria in Malaysian Patients - Relevance to Early Cancer Diagnosis

AIM To study the causes and significance of both microscopic and macroscopic haematuria in adult patients and assess possible relevance to early detection of urological cancers. METHODS 417 patients presenting with haematuria were assessed in our Urology Unit. Following confirmation of haematuria, these patients were subjected to imaging techniques and flexible cystoscopy. Parameters analysed included clinical characteristics, imaging results, flexible cystoscopy findings, time delay to diagnoses and eventual treatment and final diagnoses of all cases. RESULTS 390 haematuria cases were analysed from 417 consecutive patients with haematuria. After 27 cases were excluded as they had previous history, 245 microscopic and 145 macroscopic. Age range was 17 to 95 years old with predominance of 152 females to 239 males. The racial distribution included 180 Chinese, 100 Indians,95 Malays and 15 other races. The final diagnoses were benign prostatic hyperplasia (22.6%), no cause found (22.3%), other causes (18.7%), urolithiasis (11.5%), urinary tract infection UTI (10.8%), non specific cystitis (10.3%), bladder tumours (2.8%) and other genitourinary tumours (1%). 11 new cases (2.8%) of bladder cancers were diagnosed, with a mean age of 59 years. Only 3 of 245 (1.2%) patients with microscopic haematuria had newly diagnosed bladder tumour compared with 8 of 145 (5.5%) patients with frank haematuria (p=0.016). Mean time taken from onset of symptoms to diagnosis of bladder cancer was 53.3 days with definitive treatment (TURBT) in 20.1 days from diagnosis. CONCLUSION - This study has highlighted the common causes of haematuria in our local setting. We recommend that full and appropriate investigations be carried out on patients with frank haematuria especially those above 50 years old in order to provide earlier detection and prompt management of bladder diseases especially tumours.

Tumour necrosis factor receptor-associated factor-1 (TRAF-1) expression is increased in renal cell carcinoma patient serum but decreased in cancer tissue compared with normal: potential biomarker significance

Summary Renal cell carcinoma (RCC) generally has a poor prognosis because of late diagnosis and metastasis. We have previously described decreased tumour necrosis factor receptor-associated factor-1 (TRAF-1) in RCC compared with paired normal kidney in a patient cohort in Australia. In the present study, TRAF-1 expression in clear cell RCC (ccRCC) and normal kidney was again compared, but in a cohort from University Malaya Medical Centre. Serum TRAF-1 was also evaluated in RCC and normal samples. Immunohistochemistry with automated batch staining and Aperio ImageScope morphometry was used to compare TRAF-1 in 61 ccRCC with paired normal kidney tissue. Serum from 15 newly diagnosed and untreated ccRCC and 15 healthy people was tested for TRAF-1 using ELISA. In this cohort, TRAF-1 was highly expressed in proximal tubular epithelium of normal kidney, and significantly decreased in ccRCC tissue (p < 0.001). Conversely, TRAF-1 in serum from ccRCC patients was significantly increased over control serum (132 ± 30 versus 54 ± 14 pg/mL, respectively; p = 0.013). Decreased TRAF-1 in RCC tissue, reported previously, was confirmed. This, along with significantly increased serum TRAF-1 may indicate the protein is actively secreted during development and progression of ccRCC. Therefore, the increased serum TRAF-1 may be a useful non-invasive indicator of RCC development.

Short-Term Survival in Breast Cancer: The Experience of the University of Malaya Medical Centre

OBJECTIVE To study the impact of various clinicopathological factors on short-term survival in a cohort of breast cancer patients treated at the University of Malaya Medical Centre (UMMC). METHODS All cases of breast cancer treated at UMMC from January 1999 to June 2001, except for stage IV disease, were included in the study. Survival analysis was carried out using Kaplan-Meier for univariate analysis and Cox regression for multivariate analysis. The log-rank test was used to test the significance of differences between the different survival curves. RESULTS A total of 385 patients were included. The mean patient age at presentation was 50.3 years (SD, 11.4); 198 (51.4%) patients had lymph node-positive disease, and 187 (48.6%) had node-negative disease. The mean follow-up period was 18.7 months (SD, 8.8). The Malay ethnic group, tumours of larger size, node-positive disease, more than five positive lymph nodes, oestrogen receptor (ER) negativity and the presence of lymphovascular invasion were significant prognostic factors for shorter recurrence-free survival (RFS) in the univariate analysis. In the multivariate analysis, ER negativity was the only independent adverse prognostic factor for RFS. For overall survival (OS), tumours of larger size, node-positive disease, more than five positive lymph nodes, ER negativity and high grade tumours were associated with significantly shorter OS. However, more than five positive lymph nodes was the only independent prognostic factor for shorter OS in the multivariate analysis. Further multivariate analysis of the patients with node-positive disease showed that the Malay ethnic group, ER negativity and more than five positive lymph nodes were independent prognostic factors for shorter RFS. On the other hand, ER negativity and more than five positive lymph nodes were independent negative prognostic factors for OS in this subgroup of patients. CONCLUSION The evaluation of various prognostic factors would provide useful information on disease progression in local patients, especially for the planning of adjuvant therapies and follow-up protocols. Differences in the pattern of breast cancer among the different ethnic groups in Malaysia warrant further studies.

Asia prostate cancer study (A-CaP Study) launch symposium

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The A-CaP Study is scheduled to begin in 2016, when each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognosis investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. The inaugural Board Meeting of A-CaP was held on December 11, 2015 at the Research Center for Advanced Science and Technology, The University of Tokyo, attended by representatives of all participating countries and regions, who signed a memorandum of understanding concerning registration for A-CaP. Following the Board Meeting an A-CaP Launch Symposium was held. The symposium was attended by representatives of countries and regions participating in A-CaP, who gave presentations. Presentations and a keynote address were also delivered by representatives of the University of California San Francisco, USA, and the Peter MacCallum Cancer Centre, Australia, who provided insight and experience on similar databases compiled in their respective countries.