Aortic Wall Extracellular Matrix Proteins Correlate with Syntax Score in Patients Undergoing Coronary Artery Bypass Surgery.

AIMS: The SYNTAX score correlate with major cardiovascular events post-revascularization, although the histopathological basis is unclear. We aim to evaluate the association between syntax score and extracellular matrix histological characteristics of aortic punch tissue obtained during coronary artery bypass surgery (CABG). This analysis compares coronary artery bypass surgery patients with High and Low syntax score which were followed up for one year period. METHODS AND RESULTS: Patients with High (score ≥ 33, (n=77)) and Low Syntax Scores (score ≤ 22, (n=71)) undergoing elective CABG were recruited prospectively. Baseline clinical characteristics and surgical risks were well matched. At 1 year, EMACCE (Sum of cardiovascular death, stroke, congestive cardiac failure, and limb, gut and myocardial ischemia) was significantly elevated in the High syntax group (P=0.022). Mass spectrometry (MS)-based quantitative iTRAQ proteomic results validated on independent cohort by immunohistochemistry (IHC) revealed that the High syntax group had significantly upraised Collagen I (P<0.0001) and Elastin (P<0.0001) content in ascending aortic wall. CONCLUSION: This study shows that aortic extracellular matrix (ECM) differ between High and Low syntax groups with up-regulation of Collagen I and Elastin level in High Syntax Score group. This identifies aortic punches collected during CABG as another biomarker source related with atherosclerosis severity and possible clinical outcome.

Sphingosine kinase 1 promotes malignant progression in colon cancer and independently predicts survival of patients with colon cancer by competing risk approach in South asian population.

OBJECTIVES: Sphingosine kinase 1 (SphK1) phosphorylates the membrane sphingolipid, sphingosine, to sphingosine-1-phosphate (S1P), an oncogenic mediator, which drives tumor cell growth and survival. Although SphK1 has gained increasing prominence as an oncogenic determinant in several cancers, its potential as a therapeutic target in colon cancer remains uncertain. We investigated the clinical relevance of SphK1 expression in colon cancer as well as its inhibitory effects in vitro. METHODS: SphK1 expression in human colon tumor tissues was determined by immunohistochemistry and its clinicopathological significance was ascertained in 303 colon cancer cases. The effects of SphK1 inhibition on colon cancer cell viability and the phosphoinositide 3-kinase (PI3K)/Akt cell survival pathway were investigated using a SphK1-selective inhibitor-compound 5c (5c). The cytotoxicity of a novel combination using SphK1 inhibition with the chemotherapeutic drug, 5-fluorouracil (5-FU), was also determined. RESULTS: High SphK1 expression correlated with advanced tumor stages (AJCC classification). Using a competing risk analysis model to take into account disease recurrence, we found that SphK1 is a significant independent predictor for mortality in colon cancer patients. In vitro, the inhibition of SphK1 induced cell death in colon cancer cell lines and attenuated the serum-dependent PI3K/Akt signaling. Inhibition of SphK1 also enhanced the sensitivity of colon cancer cells to 5-FU. CONCLUSION: Our findings highlight the impact of SphK1 in colon cancer progression and patient survival, and provide evidence supportive of further development in combination strategies that incorporate SphK1 inhibition with current chemotherapeutic agents to improve colon cancer outcomes.

Percutaneous coronary intervention in Asians--are there differences in clinical outcome?

BACKGROUND: Ethnic differences in clinical outcome after percutaneous coronary intervention (PCI) have been reported. Data within different Asian subpopulations is scarce. We aim to explore the differences in clinical profile and outcome between Chinese, Malay and Indian Asian patients who undergo PCI for coronary artery disease (CAD). METHODS: A prospective registry of consecutive patients undergoing PCI from January 2002 to December 2007 at a tertiary care center was analyzed. Primary endpoint was major adverse cardiovascular events (MACE) of myocardial infarction (MI), repeat revascularization and all-cause death at six months. RESULTS: 7889 patients underwent PCI; 7544 (96%) patients completed follow-up and were included in the analysis (79% males with mean age of 59 years ± 11). There were 5130 (68%) Chinese, 1056 (14%) Malays and 1001 (13.3%) Indian patients. The remaining 357 (4.7%) patients from other minority ethnic groups were excluded from the analysis. The primary end-point occurred in 684 (9.1%) patients at six months. Indians had the highest rates of six month MACE compared to Chinese and Malays (Indians 12% vs. Chinese 8.2% vs. Malays 10.7%; OR 1.55 95%CI 1.24-1.93, p < 0.001). This was contributed by increased rates of MI (Indians 1.9% vs. Chinese 0.9% vs. Malays 1.3%; OR 4.49 95%CI 1.91-10.56 p = 0.001), repeat revascularization (Indians 6.5% vs. Chinese 4.1% vs. Malays 5.1%; OR 1.64 95%CI 1.22-2.21 p = 0.0012) and death (Indians 11.4% vs. Chinese 7.6% vs. Malays 9.9%; OR 1.65 95%CI 1.23-2.20 p = 0.001) amongst Indian patients. CONCLUSION: These data indicate that ethnic variations in clinical outcome exist following PCI. In particular, Indian patients have higher six month event rates compared to Chinese and Malays. Future studies are warranted to elucidate the underlying mechanisms behind these variations.

Subspecialization and pancreaticoduodenectomy: learning experience from 71 consecutive cases.

BACKGROUND: Pancreaticoduodenectomy (PD) is a major procedure with significant mortality and morbidity. In this study, we reviewed our departmental results with PD as subspecialization for hepatopancreaticobiliary surgery developed, and evaluated the effects on surgical technique and practice. METHODS: Between January 1995 and October 2000, 71 consecutive patients underwent PD for various diseases at our institution. Patients were analysed in two groups according to the 35-month time period in which they underwent surgery: Group A, January 1995 to November 1997 (n = 28), and Group B, December 1997 to October 2000 (n = 43). RESULTS: The two groups were comparable for age, gender distribution, race and associated medical illnesses. Overall 30-day mortality was 5.6% (n = 4); three patients (10.7%) died in Group A and one (2.3%) in Group B. Compared to Group A, there was less surgery-related morbidity (25% vs 16.3%), intraoperative median blood loss (700 mL vs 500 mL), and median intensive-care stay (2 days vs 1 day) in Group B. No significant changes were noted in the overall complication rates (35.7% vs 39.5%), median operating time (4.7 vs 6.1 hours), median blood transfusion requirement (1.46 vs 1.29 units), and median hospital stay (17 vs 18 days). There was a significant shift away from pancreaticojejunostomy (PJ) reconstruction towards pancreaticogastrostomy (PG), especially in Group B. Although preoperative histological confirmation of carcinoma was important in the earlier group, there was less emphasis on this need for a diagnosis before resection in the later period. CONCLUSIONS: Subspecialization in our department has improved the results of PD to an acceptable level, with a mortality of only 2.3%. However, this procedure still causes morbidity, with surgery-related morbidity of 16.3% even with subspecialization. Whether further reductions in morbidity can be achieved with more technical innovations remains to be seen. PG reconstruction was safer than PJ in our practice, with no anastomotic leaks.