Sung Chul Park

Healthy range for serum ALT and the clinical significance of "unhealthy" normal ALT levels in the Korean population

Background and Aims:  It remains unclear whether the currently‐used normal range for serum alanine aminotransferase (ALT) levels really reflects a healthy liver. The present study was conducted to evaluate the healthy range of serum ALT in the Korean adult population and to determine the clinical significance of unhealthy levels.

Current and Emerging Biologics for Ulcerative Colitis

Conventional medical treatment for ulcerative colitis can have limited efficacy or severe adverse reactions requiring additional treatment or colectomy. Hence, different biological agents that target specific immunological pathways are being investigated for treating ulcerative colitis. Anti-tumor necrosis factor (TNF) agents were the first biologics to be used for treating inflammatory bowel disease. For example, infliximab and adalimumab, which are anti-TNF agents, are being used for treating ulcerative colitis. Recently, golimumab, another anti-TNF agent, and vedolizumab, an anti-adhesion therapy, have been approved for ulcerative colitis by the U.S. Food and Drug Administration. In addition, new medications such as tofacitinib, a Janus kinase inhibitor, and etrolizumab, another anti-adhesion therapy, are emerging as therapeutic agents. Therefore, there is a need for further studies to select appropriate patient groups for these biologics and to improve the outcomes of ulcerative colitis treatment through appropriate medical usage.

Prevention and management of non-steroidal anti-inflammatory drugs-induced small intestinal injury

Non-steroidal anti-inflammatory drug (NSAID)-induced small bowel injury is a topic that deserves attention since the advent of capsule endoscopy and balloon enteroscopy. NSAID enteropathy is common and is mostly asymptomatic. However, massive bleeding, stricture, or perforation may occur. The pathogenesis of small intestine injury by NSAIDs is complex and different from that of the upper gastrointestinal tract. No drug has yet been developed that can completely prevent or treat NSAID enteropathy. Therefore, a long-term randomized study in chronic NSAID users is needed.

Chemotherapy for advanced gastric cancer: review and update of current practices.

No standard adjuvant or palliative chemotherapy regimen has been internationally approved for patients with advanced gastric cancer. Adjuvant chemoradiotherapy is administered prior to surgery and is used in the Unitied States, and intensified chemotherapy is administered prior to and after surgery and is used in Europe. Limited D1 dissections are also frequently performed in the United States and Europe. In Korea, patients undergoing D2 resection appear to benefit from postoperative adjuvant chemotherapy using S-1 or capecitabine plus oxaliplatin. Fluoropyrimidine, platinum, taxane, epirubicin, and irinotecan may be employed alone or in combination as a first-line therapy in a palliative chemotherapy regimen. In Asia, an orally administered fluoropyrimidine, such as capecitabine or S-1, is favored over the continuous infusion of 5-fluorouracil because of its convenience. Trastuzumab has been integrated into the current standard chemotherapy for human epidermal growth factor receptor 2-overexpressing gastric cancers. There is currently no standard regimen for secondary palliative chemotherapy. Clinical studies of several targeted therapies are ongoing.

The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression

Although coffee is known to have antioxidant, anti-inflammatory, and antitumor properties, there have been few reports about the effect and mechanism of coffee compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Their expression is significantly elevated in many tumors and is accompanied by increased cell proliferation, metastasis and poor response to chemotherapy. In this study, we investigated the cytotoxicity of four bioactive compounds in coffee, namely, caffeine, caffeic acid, chlorogenic acid, and kahweol, in HT-29 human colon adenocarcinoma cells. Only kahweol showed significant cytotoxicity. Specifically, kahweol increased the expression of caspase-3, a pro-apoptotic factor, and decreased the expression of anti-apoptotic factors, such as Bcl-2 and phosphorylated Akt. In addition, kahweol significantly attenuated the expression of HSP70. Inhibition of HSP70 activity with triptolide increased kahweol-induced cytotoxicity. In contrast, overexpression of HSP70 significantly reduced kahweol-induced cell death. Taken together, these results demonstrate that kahweol inhibits colorectal tumor cell growth by promoting apoptosis and suppressing HSP70 expression.

Ethanol-induced DNA damage and repair-related molecules in human intestinal epithelial Caco-2 cells

The acute administration of ethanol to intestinal epithelial cells causes increased intestinal permeability and the translocation of endotoxins. The changes caused by ethanol in intestinal cells may be related to oxidative stress and DNA damage. However, DNA damage and repair-related molecules which act against stresses, including ethanol, have not been fully investigated in intestinal cells. Heat shock proteins (Hsps) are involved in the recovery and protection from cell damage and may be associated with DNA repair. Therefore, the aim of our study was to investigate cytotoxicity, DNA damage and the expression of DNA repair-related molecules, antioxidant proteins and Hsps in intestinal cells exposed to ethanol. Human intestinal Caco-2 cells were incubated with 1–8% ethanol for 1 h. Cell viability and DNA damage were determined using the MTT and comet assays, respectively. We measured DNA repair-related molecules, including DNA polymerase β, apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1), growth arrest and DNA damage 45α (GADD45α) and proliferating cell nuclear antigen (PCNA), in Caco-2 cells using western blot analysis. We also measured glutathione peroxidase-1 (GPx-1), peroxiredoxin-1 (PRX-1), superoxide dismutase-2 (SOD-2), Hsp10, Hsp27, Hsp60, heat shock cognate (Hsc)70, Hsp70 and Hsp90. The viability of the Caco-2 cells exposed to ethanol decreased at concentrations ≥7% (P<0.05). The Olive tail moment, indicating DNA damage, increased dose dependently in ≥3% ethanol (P<0.05). Among the DNA repair proteins, the expression of PCNA and APE/Ref-1 increased significantly at 1% ethanol. Antioxidant enzymes, including GPx-1, PRX-1 and SOD-2, had an increased expression at 1% ethanol. Hsp10, Hsp27 and Hsp70 expression also increased significantly at 1% ethanol. In conclusion, the expression of DNA repair molecules, antioxidants and Hsps increased in intestinal Caco-2 cells exposed to low concentrations of ethanol. In particular, PCNA, APE/Ref-1, Hsp10, Hsp27 and Hsp70 were sensitive to low ethanol concentrations, indicating that they may be useful in evaluating the DNA repair and cytoprotective effects of the drug against stress in intestinal cells.

Apocynin Suppresses Lipopolysaccharide‐Induced Inflammatory Responses Through the Inhibition of MAP Kinase Signaling Pathway in RAW264.7 Cells

Apocynin, an inhibitor of NADPH oxidase, exhibits anti‐inflammatory properties in ulcerative colitis. However, the underlying mechanism by which apocynin exerts this effect has not been clearly demonstrated. The objective of this study was to elucidate the anti‐inflammatory mechanism of apocynin in lipopolysaccharide (LPS)‐challenged RAW264.7 macrophage cells. Apocynin inhibited LPS‐induced extracellular secretion of the pro‐inflammatory mediators, nitric oxide (NO) and PGE2 and the expression of inducible nitric oxide synthase and cyclooxygenase‐2. Apocynin also suppressed LPS‐induced secretion of the pro‐inflammatory cytokine, tumor necrosis factor‐α and LPS‐induced degradation of IκB, which retains NF‐κB in the cytoplasm, consequently inhibiting the transcription of pro‐inflammatory genes by NF‐κB in the nucleus. To elucidate the underlying anti‐inflammatory mechanism of apocynin, the involvement of the mitogen‐activated protein (MAP) kinases, c‐jun N‐terminal kinase, extracellular signal‐regulated kinases, and p38 was examined. Apocynin attenuated LPS‐induced activation of all three MAP kinases in a concentration‐dependent manner. The present study demonstrates apocynin exerts anti‐inflammatory activity via the suppression of MAP kinase signaling pathways in LPS‐challenged RAW264.7 macrophage cells. Drug Dev Res, 2016.

Electrolyte changes after bowel preparation for colonoscopy: A randomized controlled multicenter trial

AIM To investigate the electrolyte changes between 2-L polyethylene glycol with ascorbic acid 20 g (PEG-Asc) and 4-L PEG solutions. METHODS From August 2012 to February 2013, a total of 226 patients were enrolled at four tertiary hospitals. All patients were randomly allocated to a PEG-Asc group or a 4-L PEG. Before colonoscopy, patients completed a questionnaire to assess bowel preparation-related symptoms, satisfaction, and willingness. Endoscopists assessed the bowel preparation using the Boston Bowel Preparation Scale (BBPS). In addition, blood tests, including serum electrolytes, serum osmolarity, and urine osmolarity were evaluated both before and after the procedure. RESULTS A total of 226 patients were analyzed. BBPS scores were similar and the adequate bowel preparation rate (BBPS ≥ 6) was not different between the two groups (PEG-Asc vs 4-L PEG, 73.2% vs 76.3%, P = 0.760). Bowel preparation-related symptoms also were not different between the two groups. The taste of PEG-Asc was better (41.1% vs 16.7%, P < 0.001), and the willingness to undergo repeated bowel preparation was higher in the PEG-Asc group (73.2% vs 59.3%, P = 0.027) than in 4-L PEG. There were no significant changes in serum electrolytes in either group. CONCLUSION In this multicenter trial, bowel preparation with PEG-Asc was better than 4-L PEG in terms of patient satisfaction, with similar degrees of bowel preparation and electrolyte changes.

Occult gastric cancer with distant metastasis proven by random gastric biopsy

Krukenberg tumor, a rare metastatic ovarian tumor arising from gastrointestinal adenocarcinoma mainly, tends to occur in premenopausal females. Finding the origin of a Krukenberg tumor is crucial for determining prognosis. In Eastern countries, the most common origin of Krukenberg tumor is stomach cancer, which is generally diagnosed via endoscopic biopsy to investigate an abnormal mucosal lesion. Here, we describe a case of huge adnexal mass in a 33-year-old woman who presented with abdominal distension. Two independent endoscopic examinations performed by experts in two tertiary university hospitals revealed no abnormal mucosal lesion. The patient was diagnosed with a Krukenberg tumor according to findings from random endoscopic biopsies taken from normal-looking gastric mucosa in our hospital. It is very rare to be diagnosed via a random biopsy in cases where three well-trained endoscopists had not found any mucosal lesion previously. Thus, in this case, random biopsy was helpful in finding the origin of a Krukenberg tumor.

Job Stress and Job Satisfaction among Health-Care Workers of Endoscopy Units in Korea.

Background/Aims: The management of job-related stress among health-care workers is critical for the improvement of healthcare services; however, there is no existing research on endoscopy unit workers as a team. Korea has a unique health-care system for endoscopy unit workers. In this study, we aimed to estimate job stress and job satisfaction among health-care providers in endoscopy units in Korea. Methods: We performed a cross-sectional survey of health-care providers in the endoscopy units of three university-affiliated hospitals in Korea. We analyzed the job stress levels by using the Korean occupational stress scale, contributing factors, and job satisfaction. Results: Fifty-nine workers completed the self-administered questionnaires. The job stress scores for the endoscopy unit workers (46.39±7.81) were relatively lower compared to those of the national sample of Korean workers (51.23±8.83). Job stress differed across job positions, with nurses showing significantly higher levels of stress (48.92±7.97) compared to doctors (42.59±6.37). Job stress and job satisfaction were negatively correlated with each other (R2=0.340, p<0.001). Conclusions: An endoscopy unit is composed of a heterogeneous group of health-care professionals (i.e., nurses, fellows, and professors), and job stress and job satisfaction significantly differ according to job positions. Job demand, insufficient job control, and job insecurity are the most important stressors in the endoscopy unit.