N. Y. Yap

Efficacy of microbial cell preparation in improving chronic constipation: A randomized, double-blind, placebo-controlled trial

BACKGROUND & AIMS Probiotics is an emerging therapeutic agent which may alleviate the symptoms of constipation. We evaluated the effectiveness of microbial cell preparation (Hexbio(®)) containing fructooligosaccharide, Bifidobacterium and Lactobacillus in improving stool frequency and symptoms of chronic constipation. METHODS A total of 120 constipated adults diagnosed using Rome III criteria were randomized and given either microbial cell preparation or placebo to be consumed twice daily. Follow-up was done after a 7-day intervention based on a questionnaire which includes an assessment of symptom profile and a stool diary. RESULTS During the intervention period, the stool frequency was higher (p = 0.001) in the treatment group. Subjects experienced less straining (p = 0.001) and sensation of incomplete evacuation (p < 0.001), as well as improved stool consistency (p < 0.001) compared to the placebo group. While a higher proportion of subjects in the treatment group had a reduction in anorectal blockage sensation and having to defecate by manual maneuvers, the differences were not statistically significant. CONCLUSION The results suggest that microbial cell preparation is effective in improving stool frequency and stool consistency. Furthermore, it could reduce the symptoms of straining and sensation of incomplete evacuation in adults with chronic functional constipation. MREC REG NO 866.59 (IRB, UMMC, Malaysia).

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.

Efficacy, safety, and prognostic indicators of first-line sunitinib in patients with metastatic renal cell carcinoma: A single center experience

Background: We assessed the efficacy and safety of sunitinib as the first-line treatment in metastatic renal cell carcinoma (mRCC) patients. The predictors of survival and efficacy in mRCC as identified from previous studies, including the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic RCC Database Consortium (IMDC) factors, were also evaluated. Patients and Methods: Data from 56 patients with mRCC, treated with sunitinib at our institute (2006–2014), were analyzed retrospectively. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated using univariate and multivariate analyses performed by log-rank test and Cox regression. Results: Fifty-one (91.1%) patients received starting dose of sunitinib of 50 mg/day in 4/2 schedule. The median PFS was 12.7 months (95% confidence interval [CI], 4.5–20.9 months) and the median OS was 16.9 months (95% CI, 3.8–29.9 months). The objective response rate was 27.5%. Dose interruption and reduction due to toxicities were required in 37.5% and 60.7% of patients, respectively. The most common Grades 3–4 toxicities were hand-foot syndrome (HFS) (23.2%), thrombocytopenia (16.1%), and hypertension (14.3%). The Eastern Cooperative Oncology Group performance status ≥2, hemoglobin < lower limit of normal, neutrophil > upper limit of normal (ULN), platelet > ULN, no prior nephrectomy, metastatic sites >:1, liver metastases, lymph node metastases, and development of HFS were independent prognostic factors. Conclusions: Sunitinib treatment has acceptable efficacy and safety profile in Malaysian mRCC patients. The MSKCC and IMDC factors are relevant for predicting survival in our patient cohort while HFS is a promising prognostic predictor which warrants further investigation.

Molecular Characteristics of Renal Cell Carcinoma - a Study Using Traf-1 and a Malaysian Patient Cohort

Aim: Patency after percutaneous balloon angioplasty (PTA) for haemodialysis fistula stenosis is highly variable. This study aimed to assess factors associated with patency following first episode of treatment with PTA. Background: Restenosis recurs commonly after PTA. Previous studies have shown that some intrinsic fistula and biochemical factors may influence patency after PTA. Methods: We retrospectively reviewed all endovascular procedures performed by nephrologists between 2007 and 2012 at a single centre. Anatomical, clinical, biochemical and medication information was subjected to cox regression analysis to identify factors influencing post-intervention patency. Results: 120 patients were identified as having first episode treatment with PTA. During a median follow-up period of 22.66 months (5.24–53 months), 171 follow-up procedures were performed. Post-intervention primary patency rates at 6, 12 and 18 months were 46%, 25% and 15% respectively. Cumulative (functional) patency rates at 6, 12 and 18 months were 97%, 94 and 92% respectively with 1.4 additional procedures per patient. In univariate cox regression analysis, the presence of multiple lesions (p = 0.037) was associated with early restenosis at 6 months, while upper arm fistulae were associated with early restenosis (p = 0.004) and shorter primary patency (p = 0.001). Other anatomical characteristics (fistula age, lesion length, pre-procedure stenosis), clinical history (diabetes, coronary and peripheral artery disease), medications, and biochemical parameters (HbA1c, CRP, albumin and lipids) did not influence patency. Conclusion: Multiple stenoses and upper arm fistulae may be associated with shorter patency after PTA. More large volume prospective studies are required to further assess factors associated with patency after PTA in haemodialysis fistulae, particularly the role of metabolic and inflammatory markers.

Evaluating the characteristics of newly diagnosed renal cell carcinoma to improve patient outcome

Aim: Patency after percutaneous balloon angioplasty (PTA) for haemodialysis fistula stenosis is highly variable. This study aimed to assess factors associated with patency following first episode of treatment with PTA. Background: Restenosis recurs commonly after PTA. Previous studies have shown that some intrinsic fistula and biochemical factors may influence patency after PTA. Methods: We retrospectively reviewed all endovascular procedures performed by nephrologists between 2007 and 2012 at a single centre. Anatomical, clinical, biochemical and medication information was subjected to cox regression analysis to identify factors influencing post-intervention patency. Results: 120 patients were identified as having first episode treatment with PTA. During a median follow-up period of 22.66 months (5.24–53 months), 171 follow-up procedures were performed. Post-intervention primary patency rates at 6, 12 and 18 months were 46%, 25% and 15% respectively. Cumulative (functional) patency rates at 6, 12 and 18 months were 97%, 94 and 92% respectively with 1.4 additional procedures per patient. In univariate cox regression analysis, the presence of multiple lesions (p = 0.037) was associated with early restenosis at 6 months, while upper arm fistulae were associated with early restenosis (p = 0.004) and shorter primary patency (p = 0.001). Other anatomical characteristics (fistula age, lesion length, pre-procedure stenosis), clinical history (diabetes, coronary and peripheral artery disease), medications, and biochemical parameters (HbA1c, CRP, albumin and lipids) did not influence patency. Conclusion: Multiple stenoses and upper arm fistulae may be associated with shorter patency after PTA. More large volume prospective studies are required to further assess factors associated with patency after PTA in haemodialysis fistulae, particularly the role of metabolic and inflammatory markers.