Effectiveness of Decision Aid in Men with Localized Prostate Cancer: a Multicenter Randomized Controlled Trial at Tertiary Referral Hospitals in an Asia Pacific Country.

There are several treatment options for localized prostate cancer with very similar outcome but vary in terms of technique and side effect profiles and risks. Considering the potential difficulty in choosing the best treatment, a patient decision aid (PDA) is used to help patients in their decision-making process. However, the use and applicability of PDA in a country in Asia Pacific region like Malaysia is still unknown. This study aims to evaluate the effectiveness of a PDA modified to the local context in improving patients' knowledge, decisional conflict, and preparation for decision making among men with localized prostate cancer. Sixty patients with localized prostate cancer were randomly assigned to control and intervention groups. A self-administered questionnaire, which evaluate the knowledge on prostate cancer (23 items), decisional conflict (10 items) and preparation for decision-making (10 items), was given to all participants at pre- and post-intervention. Data were analyzed using independent T test and paired T test. The intervention group showed significant improvement in knowledge (p = 0.02) and decisional conflict (p = 0.01) from baseline. However, when compared between the control and intervention groups, there were no significant differences at baseline and post-intervention on knowledge, decisional conflict and preparation for decision-making. A PDA on treatment options of localized prostate cancer modified to the local context in an Asia Pacific country improved patients' knowledge and decisional conflict but did not have significant impact on the preparation for decision-making. The study was also registered under the Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12614000668606 registered on 25/06/2014.

Comparing CxBladder to Urine Cytology as Adjunct to Cystoscopy in Surveillance of Non-muscle Invasive Bladder Cancer-A Pilot Study.

Purpose: Guidelines advocate cystoscopy surveillance (CS) for non-muscle invasive bladder cancer (NMIBC) post-resection. However, cystoscopy is operator dependent and may miss upper tract lesions or carcinoma in-situ (CIS). Urine cytology is a common adjunct but lacks sensitivity and specificity in detecting recurrence. A new mRNA biomarker (CxBladder) was compared with urine cytology as an adjunct to cystoscopy in detecting a positive cystoscopy findings during surveillance cystoscopy in our center. Materials and Methods: Consented patients older than 18, undergoing CS for NMIBC, provide paired urine samples for cytology and CxBladder test. Patients with positive cystoscopy findings would undergo re-Trans Urethral Resection of Bladder Tumor (TURBT). Results: Thirty-five patients were enrolled from April to June 2019. Seven contaminated urine samples were excluded. The remaining cohort of 23 (82%) and 5 (18%) females had a mean age of 66.69 (36-89). Eight (29%) patients with positive cystoscopy finding underwent TURBT. All 8 patients also had positive CxBladder result. This shows that CxBladder has a sensitivity and negative predictive value (NPV) of 100%, specificity of 75% and positive predictive value (PPV) of 62% in predicting a positive cystoscopy finding. TURBT Histo-pathological findings showed Low-grade Ta NMIBC in one patient (4%), and 7 (25%) patients had inflammatory changes. Urine cytology was only positive in one patient with a positive cystoscopy finding. This led to a sensitivity of merely 13% and NPV of 74%, while specificity and PPV was 100% in predicting a positive cystoscopy finding. Conclusion: CxBladder had high NPV and sensitivity which accurately predicted suspicious cystoscopy findings leading to further investigation. It has great potential for use as adjunct to cystoscopy for surveillance of NMIBC.

Polymorphisms in the androgen receptor CAG repeat sequence are related to tumour stage but not to ERG or androgen receptor expression in Malaysian men with prostate cancer.

INTRODUCTION: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene. MATERIALS AND METHODS: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies. RESULTS: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent. CONCLUSIONS: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.

Heterogenous expression of ERG oncoprotein in Malaysian men with adenocarcinoma of the prostate.

INTRODUCTION: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. METHODS: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. RESULTS: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). CONCLUSION: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.

Oral ketamine induced pathological changes of the urinary tract in a rat model.

INTRODUCTION: In recent years, prolonged ketamine abuse has been reported to cause urinary tract damage. However, there is little information on the pathological effects of ketamine from oral administration. We aimed to study the effects of oral ketamine on the urinary tract and the reversibility of these changes after cessation of ketamine intake. METHODS: Rats were fed with illicit (a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg (N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for any potential recovery of pathological changes before being sacrificed for necropsy. Histopathological examination was performed on the kidney and urinary bladder. RESULTS: Submucosal bladder inflammation was seen in 67% of the rats fed with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the control and 100 mg/kg illicit ketamine groups. Renal changes, such as interstitial nephritis and papillary necrosis, were observed in rats given illicit ketamine. After ketamine cessation, no inflammation was observed in the bladder of all rats. However, renal inflammation remained in 60% of the rats given illicit ketamine. No dose-effect relationship was established between oral ketamine and changes in the kidneys. CONCLUSION: Oral ketamine caused pathological changes in the urinary tract, similar to that described in exposure to parenteral ketamine. The changes in the urinary bladder were reversible after short-term exposure.

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.

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 ±â€Š30 versus 54 ±â€Š14 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.

Safety and efficacy of self-expanding removable metal esophageal stents during neoadjuvant chemotherapy for resectable esophageal cancer.

Patients with esophageal cancer may present with dysphagia and weight loss. Resectable lesions require consideration of neoadjuvant chemotherapy, which improves survival but have side effects, which compound already poor intake. Prevention of malnutrition has historically required interventions such as surgical jejunostomy or percutaneous endoscopic gastrostomy, which carry associated morbidity. With established roles in palliation, self-expanding removable metal stents (SERMS) may provide an alternative intervention in resectable disease. We sought to evaluate outcomes from our unit's introduction of SERMS in dysphagic patients prior to esophagectomy. All dysphagic patients presenting with esophageal cancer and considered for curative surgery between April 2006 and November 2008 were offered preoperative treatment of dysphagia with SERMS during neoadjuvant chemotherapy. Baseline and preoperative outcomes assessed included dysphagia score and nutritional markers. Sixteen patients underwent esophageal stenting during neoadjuvant therapy of whom 7/16 (44%) were female with mean age 63 (53-76). In 12/16 (75%), tumors were located in the lower one third of the esophagus. There was a significant fall in mean dysphagia score from 2.5 (range 1-4) to 1.1 (range 0-3) immediately preoperatively. There was no significant change in serum albumin, weight, or body mass index. Stent-related morbidity occurred in 4/16 (25%) patients and stomach migration occurred in 7/16 (43.8%). All were resolved endoscopically and there was no stent-related mortality. Of 10/16 (62.5%) patients ultimately progressing to esophagectomy, 30-day mortality was 6.3%. Anastomotic leak occurred in one patient (10%) and R1 resection rate was 20%. SERMS are a safe and effective intervention in dysphagic patients undergoing neoadjuvant chemotherapy for esophageal cancer. Complications are minor and readily treatable with endoscopy. Objective parameters suggest nutritional status is maintained and symptoms are improved. SERMS do not appear to compromise resection.

PleurX drain use in the management of malignant ascites: safety, complications, long-term patency and factors predictive of success.

OBJECTIVES: The aim of this article was to assess the success, safety, complication profile and factors associated with long-term patency of tunnelled peritoneal drains (PleurX) in the treatment of refractory malignant ascites. METHODS: Over a 4-year period, 28 consecutive patients (32 drain insertions) with refractory malignant ascites were treated with a PleurX drain. The study group comprised 7 males and 21 females (mean age, 61 years). A combination of fluoroscopic and ultrasound guidance was used to insert 4 drains; the remaining 28 drains were inserted under ultrasound guidance alone. Patient history, biochemical profiles, pathological and procedural records and clinical follow-up until death were reviewed. Statistical analysis included multivariate logistic regression analysis and Kaplan-Meier curves (p<0.05 was considered significant). RESULTS: There was a 100% technical success rate for the insertion of the drain; there were no procedure-related deaths and no major complications. Only minor complications were reported: three (10%) immediate; three (10%) early; and two (7%) late. Factors significantly associated with these complications included current chemotherapy, low haemoglobin levels, low albumin levels, high white cell count and high c-reactive protein levels. The length of time the drains remained in situ, and therefore patent, ranged from 5 to 365 days (mean, 113 days). Out of the original 28 tunnelled drains, 24 (86%) remained in situ and functioning until the patients' death. Four (14%) drains dislodged and a subsequent PleurX drain was inserted on the opposite side of the abdominal wall. These new drains remained patent until the patient's death. The annual event rate was 0.45 events per year. A comorbid diagnosis of renal disease or chemotherapy was significantly related to a decreased length of patency. CONCLUSION: The use of tunnelled peritoneal drains is safe and effective and we would advocate their use as a first-line approach in patients with refractory malignant ascites. Care and regular follow-up is indicated following insertion of the drain in all patients, especially those on chemotherapy and those with a pre-procedure diagnosis of renal disease.

Spontaneous gastro-pancreatic fistula - a hitherto unknown natural history of IPMN?

Intraductal papillary mucinous neoplasm (IPMN) is a distinct group of benign pancreatic neoplasms often discovered incidentally on imaging. Apart from their malignant potential, little is known about their natural history as most are surgically resected. We report an unusual presentation and possible natural history of IPMN in a patient who refused surgery and hence was on regular follow up.

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.

Granulomatous prostatitis: a reminder to clinicians.

Granulomatous Prostatitis (GnP) is a heterogenous entity classified into specific infections, non-specific infections, post surgical i.e. post-transurethral resection of prostate (TURP) and rare secondary (systemic) causes. A total of 1388 reports of prostatic biopsy and prostatic chips from TURP were reviewed from 1995 and 2007. The results which showed granulomatous prostatitis were analyzed and retrospective data collected from the patient's records. A total of 9 cases with granulomatous prostatitis were identified. There are 3 types of entities which are the non-specific (NSGnP), post-TURP and the specific type. The incidence of GnP in our center is lower than reported by Stillwell et al. The majority of the patients were Malays.

Reliability and validity of the Spielberger State-Trait Anxiety Inventory (STAI) among urological patients: a Malaysian study.

To validate the English version of the Spielberger State-Trait Anxiety Inventory (STAI) in a sample of Malaysia patients with and without urinary symptoms. Validity and reliability were studied in patients with lower urinary tract symptoms (LUTS) and patients without LUTS. Reliability was evaluated using the test-retest method and internal consistency was assessed using Cronbach's alpha. Sensitivity to change was expressed as the effect size in the pre-intervention versus post-intervention score in additional patients with LUTS who underwent transurethral resection of the prostate (TURP). Internal consistency was excellent. A high degree of internal consistency was observed for each of the 40 items with Cronbach's alpha value = 0.38 to 0.89 while the Cronbach's alpha for the total scores was 0.86. Test-retest correlation coefficients for the 40 items score were highly significant. Intraclass correlation coefficient was high (ICC=0.39 to 0.89). A high degree of sensitivity and specificity to the effects of treatment was observed. A high degree of significant level between baseline and post-treatment scores was observed across nearly half of the items in surgical group but not in the non-LUTS group (control subjects). The STAI is reliable, valid and sensitive to clinical change in a sample of Malaysian patients with and without urinary symptoms.

Evaluation of live renal donors with three-dimensional contrast-enhanced magnetic resonance angiography in comparison to catheter angiography.

BACKGROUND: Catheter angiography is traditionally used to determine renal arterial anatomy in live renal donors. Three-dimensional (3D) contrast-enhanced magnetic resonance imaging (MRA) has been suggested as a noninvasive replacement. We assessed the possibility of using MRA in live renal donors in Malaysia. METHODS: Twenty-six consecutive live renal donors were recruited from 2000 to 2002. All potential donors underwent evaluation of the renal arteries using both techniques. Angiographic findings from both modalities were subsequently compared with surgical findings at the time of donor nephrectomy. The total number and diameter of the arteries and the presence of early branching and renal abnormalities were noted. RESULTS: Both angiographic modalities were able to detect multiple renal arteries with catheter angiography having a sensitivity of 100% and MRA a sensitivity of 97%. MRA missed one 1-mm artery due to a low index of suspicion. Renal artery caliber measurements were not significantly different between the two methods. However, both techniques tended to overestimate the caliber of the renal arteries when compared with measurements taken at surgery. Early branching was found in two arteries at the time of surgery, but only one was detected by both techniques. Renal cysts seen on MR were not detected by catheter angiography. CONCLUSIONS: Our findings suggest that noninvasive MRA is a promising substitute for catheter angiography to evaluate the renal arteries of live donors.

Sexual function outcomes following treatment for lower urinary tract symptoms. A one-year study.

The aim of this study was to assess the effects of treating lower urinary tract symptoms (LUTS) on the quality of sexual function in a one-year follow up. A total of 116 patients with LUTS received alpha-blocker treatment, 111 patients underwent transurethral resection of the prostate (TURP) and 70 patients with renal stones, with no or mild symptoms served as a control group. The patients were assessed at baseline, three months, six months and twelve months using the International Index of Erectile Function (IIEF-15). The surgical group exhibited some changes in the domain of IIEF-15. Patients in the medical group showed improvement in erectile function and intercourse satisfaction, while orgasmic, overall sexual satisfaction and sexual drive were relatively unchanged. In contrast, the surgical group suffered retrograde ejaculation and overall sexual dissatisfaction after undergoing TURP. TURP has been found to be associated with retrograde ejaculation intercourse and overall sexual dissatisfaction.

Peritoneal implantation of ureter in a cadaveric kidney transplant recipient.

We report here a case of a kidney transplant recipient in whom the ureter was initially implanted into the peritoneum. Excessive ultrafiltration volume and reversal of serum vs dialysate creatinine ratio when the patient was recommenced on continuous ambulatory peritoneal dialysis first suggested the diagnosis which was subsequently confirmed by a plain abdominal x-ray demonstrating placement of ureteric stent in the peritoneum. This rare complication was successfully corrected with surgical re-implantation of ureter into the bladder and 5 years later, the patient remains well with good graft function.

The sensitivity of the Malay version of Brief Manual of Sexual Function Inventory in assessing erectile dysfunction secondary to benign prostatic hyperplasia.

This study aimed to assess the sensitivity of the Malay version of the Brief Manual Sexual Function Inventory (BMSFI) on patients with and without urinary symptoms in Malaysian population. Validity and reliability were studied in patients with lower urinary tract symptoms (LUTS) and patients without LUTS. Reliability and validity was evaluated by using the test-retest method while internal consistency was assessed by Cronbach's alpha. Sensitivity to change was expressed as the effect size in the pre-intervention versus post-intervention score in patients who underwent transurethral resection of the prostate (TURP). Internal consistency was excellent. A high degree of internal consistency was observed for each of the 11 items and 5 domains (Cronbach's alpha value = 0.67 and higher and 0.73 and higher respectively). Test-retest correlation coefficient for the 11 items scores was highly significant. Intraclass correlation coefficient was high (ICC = 0.68 and above). The sensitivity and specificity showed a high degree of sensitivity and specificity to the effects of treatment. A high degree of significant level between baseline and post-treatment scores were observed across 3 domains in the treatment corresponds cohort but not in the control group. The Mal-BMSFI is a suitable, reliable, valid and sensitive to clinical change in the Malaysian population.

Peritoneal implantation of ureter in a cadaveric kidney transplant recipient

We report here a case of a kidney transplant recipient in whom the ureter was initially implanted into the peritoneum. Excessive ultrafiltration volume and reversal of serum vs dialysate creatinine ratio when the patient was recommenced on continuous ambulatory peritoneal dialysis first suggested the diagnosis which was subsequently confirmed by a plain abdominal x-ray demonstrating placement of ureteric stent in the peritoneum. This rare complication was successfully corrected with surgical re-implantation of ureter into the bladder and 5 years later, the patient remains well with good graft function.

ANCA-associated crescentic IgA glomerulonephritis in pregnancy.

Only a few reports have documented the presence of crescentic IgA nephropathy associated with antineutrophil cytoplasmic antibodies (ANCA), suggesting an overlap that has therapeutic significance as regards the patients' response to treatment. We report a case of rapidly progressive glomerulonephritis with P-ANCA, with biopsyproven crescentic IgA glomerulonephritis in an 11-week pregnant woman who responded very well to cyclophosphamide and prednisone. Her 24-h urine protein dropped from 5400 mg/day to 516 mg/day and serum creatinine from 2.7 mg/dL to 1.4 mg/dL. To the best of our knowledge, this is the first such case reported in pregnancy. Eighteen months after her initial presentation, she has no significant clinical problems and her laboratory work-up shows stable results.