Association of the leptin to high-molecular-weight adiponectin ratio with metabolic syndrome

Recent studies have reported that leptin and adiponectin are associated with metabolic syndrome. The leptin/adiponectin ratio has been suggested as an atherosclerotic index. The objective of this study was to compare the degree of association of metabolic syndrome with adiponectin levels, leptin levels, leptin/adiponectin ratio, and leptin/high-molecular-weight (HMW) adiponectin ratio. The study population included 3272 Koreans (men: 1915, women: 1357; age, 30-84 years), who had visited the Health Examination Center. Adipokines were divided into quartiles, and metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel-III (NCEP ATP III). A logistic regression model was fitted to establish the association between adipokines and metabolic syndrome. Adipokines, such as adiponectin, HMW adiponectin, and leptin, were found to be statistically related to metabolic syndrome. Compared to the lowest quartile, the leptin/HMW adiponectin ratio in the highest quartile was associated with a 5-fold increase in the probability of prevalent metabolic syndrome, which was independent of age, smoking status, exercise, low-density lipoprotein (LDL) cholesterol, and body mass index. There was a linear increase in the leptin/HMW adiponectin ratio as the number of metabolic syndrome components increased. The leptin/HMW adiponectin ratio had the highest odds ratio in women. In addition, compared to adiponectin or leptin alone, the AUC of the leptin/adiponectin ratio and leptin/HMW adiponectin ratio was higher for metabolic syndrome. We may suggest that the leptin/HMW adiponectin ratio is not superior to other adipokine markers, but is as effective as the leptin/total adiponectin ratio.     

A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics

Metastasis is the major cause of cancer mortality. We aimed to find a metastasis-prone signature for early stage mismatch-repair proficient sporadic colorectal cancer (CRC) patients for better prognosis and informed use of adjuvant chemotherapy. The genome-wide expression profiles of 82 age-, ethnicity- and tissue-matched patients and healthy controls were analyzed using the Affymetrix U133 Plus 2 array. Metastasis-negative patients have 5 years or more of follow-up. A 10 × 10 two-level nested cross-validation design was used with several families of classification models to identify the optimal predictor for metastasis. The best classification model yielded a 54 gene-set (74 probe sets) with an estimated prediction accuracy of 71%. The specificity, sensitivity, negative and positive predictive values of the signature are 0.88, 0.58, 0.84 and 0.65, respectively, indicating that the gene-set can improve prognosis for early stage sporadic CRC patients. These 54 genes, including node molecules YWHAB, MAP3K5, LMNA, APP, GNAQ, F3, NFATC2, and TGM2, integrate multiple bio-functions in various compartments into an intricate molecular network, suggesting that cell-wide perturbations are involved in metastasis transformation. Further, querying the `Connectivity Map’ with a subset (70%) of these genes shows that Gly-His-Lys and securinine could reverse the differential expressions of these genes significantly, suggesting that they have combinatorial therapeutic effect on the metastasis-prone patients. These two perturbagens promote wound-healing, extracellular matrix remodeling and macrophage activation thus highlighting the importance of these pathways in metastasis suppression for early-stage CRC.     

Perianal mucinous adenocarcinoma arising from chronic anorectal fistulae: a review from a single institution

Background Mucinous adenocarcinoma arising from a chronic anorectal fistula is rare, with few reports in the literature. Such lesions present in an innocuous manner and can be mistaken for the more common clinical condition of a benign perianal abscess or fistula. Methods From our prospectively collected database, we identified 4 patients with chronic perianal inflammatory conditions who were subsequently found to have developed perianal mucinous adenocarcinoma on biopsy. We received the symptomatology, subsequent management and further follow-up of each patient. These patients were treated with radical surgery, with or without adjuvant therapy. Results and Conclusions A high index of clinical suspicion is required to make the diagnosis of perianal tumours while assessing patients presenting with perianal inflammatory conditions. Wide excision of the tumour with abdominoperineal resection is the surgical treatment of choice and can provide good long-term results in patients with localized disease.     

Giant cardiac myxoma

Although cardiac myxomas remain an uncommon group of malignancies, they are the most common form of primary cardiac tumour. Clinical presentations can be varied with local cardiac haemodynamic consequences, valvular insufficiency or even embolic phenomena. We present a case of a 46-year-old man with chronic abdominal pain and discuss a number of diagnostic challenges that were confronted up until a definitive diagnosis of cardiac myxoma was made. The resultant outcome was excellent with the patient achieving complete recovery from long term disabling symptoms.     

Meta-analysis of randomized clinical trials comparing drainage alone vs primary sphincter-cutting procedures for anorectal abscess–fistula

Background and aim Concurrent definitive treatment of underlying fistulas from infected anal glands at the time when the anorectal abscesses are drained is controversial as this is associated with a higher incidence of faecal incontinence, failure and recurrence. This meta-analysis was conducted to determine the merits of drainage alone vs primary sphincter-cutting procedures (which includes fistulotomy and fistulectomy) for anorectal abscess–fistula.Methods Medline, Embase and Cochrane Central Register of Controlled Trials database searches identified all randomized controlled trials using the keywords: anorectal abscess, anal sepsis, drainage, fistulotomy, fistulectomy or surgery from 1966 to 2004. The outcome variables analysed were recurrence, faecal continence and wound-healing times.Results Five trials were considered suitable for the meta-analysis, with a total of 405 patients. Sphincter-cutting procedures for anorectal abscesses resulted in 83% reduction in recurrence rate [relative risk (RR) 0.17, 95% confidence interval (CI) 0.09–0.32, p<0.001]. However, there was a tendency to a higher risk of faecal incontinence to flatus and soiling when primary sphincter-cutting procedure was performed (RR 2.46, 95% CI 0.75–8.06, p=0.140).Conclusion There is no conclusive evidence if simple drainage or sphincter-cutting procedure is better in the treatment of anorectal abscess–fistula.     

Manganese intake and cholestatic jaundice in neonates receiving parenteral nutrition: a randomized controlled study

Infants requiring parenteral nutrition (n = 244) were randomized to receive either 1 (group 1, n = 121) or 0.0182 micromol/kg/d (group 2, n = 123) of manganese supplementation. The whole-blood manganese and serum direct bilirubin concentrations of the infants were monitored, as was the development of cholestasis (peak serum direct bilirubin concentration >50 micromol/L). Subgroup analysis was carried out on the data of 78 infants in group 1 and 82 in group 2 who had received manganese supplementation and more than three-quarters of their total daily fluid as parenteral nutrition for >14 d. Of all the infants randomized, the high manganese group (group 1) showed a trend towards developing higher peak whole-blood manganese concentration [group 1 versus group 2: median (interquartile range): 606.0 (421.0; 1005.0) vs 566.0 (336.0: 858.0); p=0.061] and higher peak serum direct bilirubin concentration [37.0 (10.5; 122.5) vs 19.0 (8.0; 112.5); p=0.153], but the differences between the 2 groups did not reach statistical significance. The 2 groups did not differ in terms of the occurrence of cholestasis during parenteral nutrition (63/121 vs 57/123; p=0.444). Subgroup analysis of infants who had received more than three-quarters of their total daily fluid as parenteral nutrition showed, however, that the high manganese group developed significantly higher whole-blood manganese concentration [743.5 (498.0; 1211.0) vs 587.0 (438.0; 982.0); p=0.037] and serum direct bilirubin concentration [84.0 (28.0; 170.0) vs 25.5 (9.0; 117.0): p < 0.001]. Although there was no significant difference in the occurrence of cholestasis (58/78 vs 49/82; p = 0.073), more infants in the high manganese group developed a more severe degree of direct hyperbilirubinaemia, with peak serum direct bilirubin >100 micromol/L (32/78 vs 20/82; p = 0.038). Conclusion: We conclude that the pathogenesis of parenteral nutrition-related cholestasis is probably multifactorial, and that high manganese intake is a significant contributory factor.