Size discrepancy between endoscopic size and pathologic size is not negligible in endoscopic resection for early gastric cancer

Background

Accurate tumor size measurement is critical for selecting proper candidates for endoscopic resection (ER) of early gastric cancer (EGC). However, size discrepancy between endoscopic size and pathologic size often occurs during ER for EGC.

Objective

The purposes of this study were to investigate the clinicopathological characteristics related to size discrepancy and the clinical implications of size discrepancies in terms of therapeutic outcomes.

Methods

Between April 2006 and June 2013, a total of 820 patients with 826 EGCs underwent ER. Enrolled lesions were categorized into the following three groups based on size discrepancy between endoscopic size and pathologic size: well-estimated (N = 308), underestimated (N = 215), or overestimated (N = 303) lesions. The well-estimated group was defined as lesions with a ratio of endoscopic size to pathologic size from 0.7 to 1.3.

Results

The overall median size discrepancy was 5.0 mm (interquartile range 2.0–9.0). Size, location, macroscopic type, primary tumor stage, and histology differed significantly between the three groups. Larger size [odds ratio (OR) 5.07, 95 % confidence interval (CI) 3.38–7.59, p < 0.001], flat/depressed type (OR 1.71, 95 % CI 1.15–2.55, p = 0.008), and undifferentiated histology (OR 2.24, 95 % CI 1.31–3.83, p = 0.003) were independent risk factors for endoscopic size underestimation in multivariate analysis. Smaller size (OR 10.95, 95 % CI 4.64–25.87, p < 0.001) was the only independent predictor for endoscopic overestimation of size. Significantly lower complete resection and curative resection rates were detected in the underestimated group compared with the well-estimated group, while the complete resection rate in the overestimated group tended to be higher than in the well-estimated group. There was no significant difference of curative resection rate between the overestimated and the well-estimated groups.

Conclusions

Larger size, flat/depressed type, and undifferentiated histology of EGC carry a significant risk for endoscopic underestimation of lesion size, which results in the lower rates of complete and curative resections for EGC. Further studies to reduce size discrepancy are warranted.     

Endoscopic stenting for benign upper gastrointestinal strictures and leaks

Background

Self-expandable metal stents (SEMS) and self-expandable plastic stents (SEPS) maybe used for the treatment of benign upper gastrointestinal (GI) leaks and strictures. This study reviewed our experience with stent insertions in patients with benign upper GI conditions.

Methods

Patients who underwent stent placement for benign upper GI strictures and leaks between March 2007 and April 2011 at a tertiary referral academic center were studied using an endoscopic database and electronic patient records. The technical success, complications, and clinical improvement after stent removal were compared according to type of stent. The outcomes measured were clinical response, adverse events, and predictors of stent migration.

Results

Thirty-eight patients (50 % male, mean age = 54 years, range = 12–82) underwent 121 endoscopic procedures. Twenty patients had stents placed for strictures, and 18 had stents placed for leaks. Stent placement was technically successful in all patients. The average duration of stent placement was 54 days (range = 18–118). Clinical improvement immediately after stent placement was seen in 29 of the 38 patients (76.3 %). Immediate post-procedure adverse events occurred in 8 patients. Late adverse events were seen in 18 patients. Evidence of stent migration occurred in 16 patients and was seen in 42 of the 118 successfully placed stents (35.5 %). Migration was more frequent with fully covered SEMS (p = 0.002). After stent removal, 27 patients were evaluable for long-term success (median follow-up time of 283 days, IQR 38–762). Resolution of strictures or leaks was seen in 11 patients (40.7 %). Predictors for long-term success included increasing age and if the stent did not cross the GE junction.

Conclusions

Placement of SEPS and SEMS for benign refractory strictures and fistulas has modest long-term clinical efficacy and is limited by a significant migration rate. Stent migration is common and frequent with fully covered SEMS compared to other types of stents, regardless of indication or location.     

Importance of fat mass and lean mass on bone health in men: the Fourth Korean National Health and Nutrition Examination Survey (KNHANES IV)

Summary

This study was aimed to evaluate the association between body composition and bone health. High lean mass and low fat mass have protective effects on bone health in men representative of the national population.

Introduction

The aim of this study was to evaluate the association between body composition (fat mass and lean mass) and bone health in men.

Methods

Totally, 3,945 men (age ≥20 years) from the fourth Korean National Health and Nutrition Examination Survey of 2008–2009 (KNHANES IV) were included in this study. Body composition and bone mineral densities (BMDs) were measured using dual energy X-ray absorptiometry. Osteopenia or osteoporosis was identified on the basis of the World Health Organization T-score criteria.

Results

Multiple linear regression analyses showed that BMDs of the whole body, femoral neck, and lumbar spine were positively associated with lean mass and negatively associated with fat mass, after controlling for body weight and other potential confounders. Subjects with more fat mass or less lean mass, categorized according to quartiles of fat mass and lean mass, had higher odds of having osteopenia or osteoporosis, as shown by multivariable logistic regression (P for trend <0.001).

Conclusions

High lean mass and low fat mass have protective effects on bone health in a population of Korean adult men. Fat mass appears to exert a detrimental effect on BMD, in contrast with the positive weight-bearing effect. Body composition seems to be a more important determinant for bone health than simple body weight.     

Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes

Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways.     

Antiproliferative Activity of King Cobra (Ophiophagus hannah) Venom l‐Amino Acid Oxidase

King cobra (Ophiophagus hannah) venom l ‐amino acid oxidase (LAAO), a heat‐stable enzyme, is an extremely potent antiproliferative agent against cancer cells when compared with LAAO isolated from other snake venoms. King cobra venom LAAO was shown to exhibit very strong antiproliferative activities against MCF‐7 (human breast adenocarcinoma) and A549 (human lung adenocarcinoma) cells, with an IC₅₀ value of 0.04 ± 0.00 and 0.05 ± 0.00 μg/mL, respectively, after 72‐hr treatment. In comparison, its cytotoxicity was about 3–4 times lower when tested against human non‐tumourigenic breast (184B5) and lung (NL 20) cells, suggesting selective antitumour activity. Furthermore, its potency in MCF‐7 and A549 cell lines was greater than the effects of doxorubicin, a clinically established cancer chemotherapeutic agent, which showed an IC₅₀ value of 0.18 ± 0.03 and 0.63 ± 0.21 μg/mL, respectively, against the two cell lines. The selective cytotoxic action of the LAAO was confirmed by phycoerythrin (PE) annexin V/7‐amino‐actinomycin (AAD) apoptotic assay, in which a significant increase in apoptotic cells was observed in LAAO‐treated tumour cells than in their non‐tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour cells was further demonstrated using caspase‐3/7 and DNA fragmentation assays. We also determined that this enzyme may target oxidative stress in its killing of tumour cells, as its cytotoxicity was significantly reduced in the presence of catalase (a H₂O₂ scavenger). In view of its heat stability and selective and potent cytotoxic action on cancer cells, king cobra venom LAAO can be potentially developed for treating solid tumours.     

Cloning and Characterization of a Unique Cytotoxic Protein Parasporin-5 Produced by Bacillus thuringiensis A1100 Strain

Parasporin is the cytocidal protein present in the parasporal inclusion of the non-insecticidal Bacillus thuringiensis strains, which has no hemolytic activity but has cytocidal activities, preferentially killing cancer cells. In this study, we characterized a cytocidal protein that belongs to this category, which was designated parasporin-5 (PS5). PS5 was purified from B. thuringiensis serovar tohokuensis strain A1100 based on its cytocidal activity against human leukemic T cells (MOLT-4). The 50% effective concentration (EC₅₀) of PS5 to MOLT-4 cells was approximately 0.075 μg/mL. PS5 was expressed as a 33.8-kDa inactive precursor protein and exhibited cytocidal activity only when degraded by protease at the C-terminal into smaller molecules of 29.8 kDa. Although PS5 showed no significant homology with other known parasporins, a Position Specific Iterative-Basic Local Alignment Search Tool (PSI-BLAST) search revealed that the protein showed slight homology to, not only some B. thuringiensis Cry toxins, but also to aerolysin-type β-pore-forming toxins (β-PFTs). The recombinant PS5 protein could be obtained as an active protein only when it was expressed in a precursor followed by processing with proteinase K. The cytotoxic activities of the protein against various mammalian cell lines were evaluated. PS5 showed strong cytocidal activity to seven of 18 mammalian cell lines tested, and low to no cytotoxicity to the others.