Role of Preoperative Colonoscopy in Patients with Gastric Cancer: A Case Control Study of the Prevalence of Coexisting Colorectal Neoplasms

Background

We evaluated the prevalence of coexisting asymptomatic colorectal neoplasm (CRN) in patients with gastric cancer (GC).

Methods

Preoperative colonoscopic examinations were performed in 495 patients with GC who underwent gastrectomy between January 2009 and December 2010. To compare the prevalence of CRN in these patients with that in a normal population, we selected 495 sex- and age-matched persons who underwent colonoscopies for health screening. Risk factors for CRN were evaluated by univariate and multivariate analyses.

Results

The overall incidence of CRN was 41.8 % (414/990). The prevalence of overall CRN, high-risk CRN, and colorectal carcinoma (CRC) were significantly higher in the GC group than in the control group (overall CRN: 48.9 % vs. 34.7 %; high-risk CRN: 28.3 % vs. 13.5 %; CRC: 2.6 % vs. 0.2 %; all P < 0.001). The presence of GC [odds ratio (OR), 1.82; 95 % confidence interval (CI), 1.4–2.38; P < 0.001], age ≥50 years (OR, 2.58; 95 % CI, 1.75–3.81; P < 0.001), and male sex (OR, 2.28; 95 % CI, 1.72–3.02; P < 0.001) were risk factors for overall CRN. In patients with GC, age ≥40 years (OR, 3.22; 95 % CI, 1.24–8.37; P = 0.016) and male sex (OR, 3.21; 95 % CI, 2.17–4.76; P < 0.001) were risk factors for overall CRN.

Conclusions

The prevalence of coexisting CRN, including CRC, was higher in patients with GC than in the normal population. Preoperative colonoscopy is strongly indicated in patients with GC who are male and/or ≥40 years of age.     

Cell membrane and nuclear expression of programmed death ligand-1 in prostate needle biopsy tissue in prostate cancer patients undergoing primary radiation therapy

BackgroundProgrammed death ligand-1 (PD-L1) expression in cancer is often associated with cancer aggressiveness and responsiveness to treatment with PD-1 pathway inhibitors. We conducted a systematic study on the expression of membranous PD-L1 (mPD-L1) and nuclear PD-1-L1 (nPD-L1) in prostate needle biopsy specimens of prostate cancer patients who underwent primary radiotherapy and analyzed the association between PD-L1 expression and clinicopathological characteristics and prognosis of patients.MethodA total of 971 cancer-containing prostate needle biopsy cores from 172 patients were immunohistochemically stained with anti-PD-L1 antibody. The association of PD-L1 expression with Gleason score and tumor volume percentage was evaluated for each biopsy core. Total of 171 patients were divided according to mPD-L1 or nPD-L1 expression, and clinicopathological characteristics were compared between the positive and negative groups. The prognostic significance of mPD-L1, nPD-L1 and common prognostic factors were analyzed in terms of biochemical recurrence.ResultTotal of 15% and 46% of biopsy cores were stained positive for mPD-L1 and nPD-L1, respectively. There was a positive correlation between Gleason score and mPD-L1 and a negative correlation between Gleason score and nPD-L1. Between mPD-L1 and nPD-L1, there was no significant correlation. There was intraindividual heterogeneity in PD-L1 expression among different Gleason scores. For mPD-L1, only pretreatment PSA was significantly higher in the positive group than in the negative, but not Gleason score and T stage. For nPD-L1, Gleason score and T stage were significantly higher in the positive group than in the negative. Both mPD-L1 and nPD-L1 expression were not predictive of BCR-free survival in univariate and multivariate analyses.ConclusionsOur results suggest that PD-1 pathway inhibitor may be a potential therapeutic option in high risk prostate cancer patients as early as neoadjuvant setting. The novel discovery of PD-L1 expression in the nucleus of PC should be subjected to further research.     

Polycythemia is associated with bone loss and reduced osteoblast activity in mice

Summary

Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO).

Introduction

PV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO.

Methods

Bone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2^V617F knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO.

Results

Compared to wt, both JAK2^V617F and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P?<?0.01) suggesting a more severe bone phenotype than JAK2^V617F. Decreased osteoblast numbers and bone formation along with normal osteoclast numbers and activity were found in both mice.

Conclusions

This study indicates that PV is associated with low bone mass and decreased osteoblast activity in mice. Our results support future studies of osteoporosis in affected humans. Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated.

     

Association between serum total bilirubin level and leukoaraiosis in Korean adults

ObjectivesLeukoaraiosis is associated with cerebrovascular microangiopathy. Increasing evidence suggests that bilirubin is a potent cytoprotectant in the development of cardiovascular diseases. This study aimed to determine whether total bilirubin is related to leukoaraiosis.MethodsWe examined the relationship of total bilirubin with leukoaraiosis in 1005 Korean adults. The odds ratios for leukoaraiosis were calculated using multivariate logistic regression across serum total bilirubin tertiles.ResultsIn comparison with the subjects in the reference group (total bilirubin: 15–26 μmol/L), the odds ratio (95% CI) for leukoaraiosis in the 3rd tertile (total bilirubin ≤ 10 μmol/L) was 5.50 (1.24–24.40) in women after adjusting for confounding variables. However, this inverse association between serum total bilirubin and the prevalence of leukoaraiosis was not found in men after adjusting for the same co-variables.ConclusionTotal bilirubin level was inversely associated with leukoaraiosis regardless of classical cardiovascular risk factors in Korean women.     

Effects of the hook of Uncaria rhynchophylla on neurotoxicity in the 6-hydroxydopamine model of Parkinson's disease

Ethnopharmacological relevance

While the hook of Uncaria rhynchophylla (URH) is a traditional herb used in northeast Asia for the treatment of Parkinson's disease (PD)-like symptoms such as tremor, it has not been experimentally evaluated in a PD model.

Aim of the study

We investigated the effects of URH on 6-hydroxydapamine (6-OHDA)-induced neurotoxicity in in vitro and in vivo models of PD.

Materials and methods

The cell viability, anti-oxidative activity, and anti-apoptotic activity of a water extract of URH (URE) were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, reactive oxygen species (ROS), total glutathione (GSH), and caspase-3 assays in PC12 cells stressed by 6-OHDA. We also investigated the behavioral recovery and dopaminergic neuron protection of URE using an apomorphine-induced rotation test and tyrosine hydroxylase immunohistochemistry in the hemi-parkinsonian rat model of the unilateral 6-OHDA lesion of the medial forebrain bundle.

Results

In PC12 cells, URE significantly reduced cell death and the generation of ROS, increased GSH levels, and inhibited caspase-3 activity induced by 6-OHDA. In 6-OHDA-lesioned rats, posttreatment with URE (5 mg/kg/day for 14 days) significantly reduced apomorphine-induced rotation, and it lowered dopaminergic neuronal loss in substantia nigra pars compacta.

Conclusions

URE possesses neuroprotective activity against 6-OHDA-induced toxicity through anti-oxidative and anti-apoptotic activities in PD models.     

Stronger associations of sagittal abdominal diameter with atherogenic lipoprotein subfractions than waist circumference in middle-aged US white and Japanese men

Both sagittal abdominal diameter (SAD) and waist circumference (WC) highly correlate with visceral adipose tissue (VAT) being linked to an atherogenic lipoprotein profile. However, it is uncertain whether SAD is a better correlate of atherogenic lipoprotein subfractions than WC. We examined relative associations of SAD vs WC with lipoprotein subfractions for US white and Japanese men, concurrently examining the associations of VAT vs subcutaneous adipose tissue with lipoprotein subfractions. A population-based sample of 260 white and 282 Japanese men aged 40 to 49 years was examined for VAT and subcutaneous adipose tissue by computed tomography; SAD and WC by a portable sliding-beam caliper and a measuring tape, respectively; and lipoprotein subfractions by nuclear magnetic resonance spectroscopy. Both SAD and WC were significantly and positively associated with large very low-density lipoprotein and total and small low-density lipoprotein particle concentrations, and inversely associated with large high-density lipoprotein particle concentration for both white and Japanese men. In body mass index–adjusted regression models, the significant associations of SAD remained for both white and Japanese men, whereas those of WC became nonsignificant for white men. When SAD and WC were simultaneously included into the body mass index–adjusted models, the associations of SAD remained significant and statistically stronger than those of WC for both white and Japanese men. Furthermore, the pattern of the associations of SAD with those lipoprotein subfractions was comparable to that of the associations of VAT. Sagittal abdominal diameter was comparable to VAT and stronger than WC in the associations with atherogenic lipoprotein subfractions for middle-aged, nondiabetic, white and Japanese men.