Purpose: Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression. Materials and Methods: Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation, and enrichment analysis were performed. Results: As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in-silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the RhoaR129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked RhoaR129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families. Conclusion The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Background/Aims: Functional dyspepsia (FD) is a chronic upper gastrointestinal symptom complex that routine diagnostic work-up, such as endoscopy, blood laboratory analysis, or radiological examination, fails to identify a cause for. It is highly prevalent in the Korean population, and its response to the various available therapeutic strategies is only modest because of the heterogeneous nature of its pathogenesis. We constituted a guidelines development committee to review the existing guidelines on the management of FD. Methods: This committee drafted statements and conducted a systematic review and meta- analysis of various studies, guidelines, and randomized control trials. External review was also conducted by selected experts. These clinical practice guidelines for FD were developed based on evidence recently accumulated with the revised version of FD guidelines released in 2011 by the Korean Society of Neurogastroenterology and Motility. Results: These guidelines apply to adults with chronic symptoms of FD and include the diagnostic role of endoscopy, Helicobacter pylori screening, and systematic review and meta-analyses of the various treatment options for FD (proton pump inhibitors, Helicobacter pylori eradication, and tricyclic antidepressants), especially according to the FD subtype. Conclusions The purpose of these new guidelines is to aid understanding, diagnosis, and treatment of FD, and the targets of the guidelines are clinicians, healthcare workers at the forefront of patient care, patients, and medical students. The guidelines will continue to be revised and updated periodically.

Background/Aims: Functional dyspepsia (FD) is a chronic upper gastrointestinal symptom complex that routine diagnostic work-up, such as endoscopy, blood laboratory analysis, or radiological examination, fails to identify a cause for. It is highly prevalent in the Korean population, and its response to the various available therapeutic strategies is only modest because of the heterogeneous nature of its pathogenesis. We constituted a guidelines development committee to review the existing guidelines on the management of FD. Methods: This committee drafted statements and conducted a systematic review and meta- analysis of various studies, guidelines, and randomized control trials. External review was also conducted by selected experts. These clinical practice guidelines for FD were developed based on evidence recently accumulated with the revised version of FD guidelines released in 2011 by the Korean Society of Neurogastroenterology and Motility. Results: These guidelines apply to adults with chronic symptoms of FD and include the diagnostic role of endoscopy, Helicobacter pylori screening, and systematic review and meta-analyses of the various treatment options for FD (proton pump inhibitors, Helicobacter pylori eradication, and tricyclic antidepressants), especially according to the FD subtype. Conclusions The purpose of these new guidelines is to aid understanding, diagnosis, and treatment of FD, and the targets of the guidelines are clinicians, healthcare workers at the forefront of patient care, patients, and medical students. The guidelines will continue to be revised and updated periodically.

Functional dyspepsia (FD) is a chronic upper gastrointestinal (GI) symptom complex that routine diagnostic work-up, such as endoscopy, blood laboratory analysis, or radiological examination, fails to identify a cause. It is highly prevalent in the World population, and its response to the various available therapeutic strategies is only modest because of the heterogenous nature of its pathogenesis. Therefore, FD represents a heavy medical burden for healthcare systems. We constituted a guideline development committee to review the existing guidelines on the management of functional dyspepsia. This committee drafted statements and conducted a systematic review and meta-analysis of various studies, guidelines, and randomized control trials. External review was also conducted by selected experts. These clinical practice guidelines for FD were developed based on evidence recently accumulated with the revised version of FD guidelines released in 2011 by the Korean Society of Neurogastroenterology and Motility. These guidelines apply to adults with chronic symptoms of FD and include the diagnostic role of endoscopy, Helicobacter pylori screening, and systematic review and meta-analyses of the various treatment options for FD (proton pump inhibitors, H. pylori eradication, and tricyclic antidepressants), especially according to the FD subtype. The purpose of these new guidelines is to aid the understanding, diagnosis, and treatment of FD, and the targets of the guidelines are clinicians, healthcare workers at the forefront of patient care, patients, and medical students. The guidelines will continue to be revised and updated periodically.

BACKGROUND: Postoperative nausea and vomiting (PONV) frequently occurs following bimaxillary orthognathic surgeries. Compared to opioids, Nefopam is associated with lower incidences of PONV, and does not induce gastrointestinal tract injury, coagulopathy, nephrotoxicity, or fracture healing dysfunction, which are common side effects of Nonsteroidal anti-inflammatory drugs. We compared nefopam- and fentanyl-induced incidence of PONV in patients with access to patient-controlled analgesia (PCA) following bimaxillary orthognathic surgeries. METHODS: Patients undergoing bimaxillary orthognathic surgeries were randomly divided into nefopam and fentanyl groups. Nefopam 120 mg or fentanyl 700 µg was mixed with normal saline to a final volume of 120 mL. Patients were given access to nefopam or fentanyl via PCA. Postoperative pain intensity and PONV were measured at 30 minutes and 1 hour after surgery in the recovery room and at 8, 24, 48, and 72 hours after surgery in the ward. The frequency of bolus delivery was compared at each time point. RESULTS: Eighty-nine patients were enrolled in this study, with 48 in the nefopam (N) group and 41 in the fentanyl (F) group. PONV occurred in 13 patients (27.7%) in the N group and 7 patients (17.1%) in the F group at 8 hours post-surgery (P = 0.568), and there were no significant differences between the two groups at any of the time points. VAS scores were 4.4 ± 2.0 and 3.7 ± 1.9 in the N and F groups, respectively, at 8 hours after surgery (P = 0.122), and cumulative bolus delivery was 10.7 ± 13.7 and 8.6 ± 8.5, respectively (P = 0.408). There were no significant differences in pain or bolus delivery at any of the remaining time points. CONCLUSION: Patients who underwent bimaxillary orthognathic surgery and were given nefopam via PCA did not experience a lower rate of PONV compared to those that received fentanyl via PCA. Furthermore, nefopam and fentanyl did not provide significantly different postoperative pain control.
Analgesia, Patient-Controlled ; Analgesics, Opioid ; Fentanyl ; Fracture Healing ; Gastrointestinal Tract ; Humans ; Incidence ; Nefopam ; Orthognathic Surgery ; Pain, Postoperative ; Passive Cutaneous Anaphylaxis ; Postoperative Nausea and Vomiting ; Prospective Studies ; Recovery Room

OBJECTIVE: The aim of this study was to examine the validity of the Korean version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood disorder patients. METHODS: A total of 454 patients who diagnosed as mood disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32-R2 (KHCL-32-R2). RESULTS: The KHCL-32-R2 showed a three-factorial structure (eigenvalue >2) that accounted for 43.26% of the total variance. Factor 1 was labeled “active/elated” and included 16 items; factor 2, “irritable/distractible” and included 9 items; and factor 3 was labeled “risk-taking/indulging” and included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score distinguished between BD and MDD, which yielded a sensitivity of 70% and a specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15 with maximized sensitivity (0.67) and specificity (0.66). Cronbach’s alpha of KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79, respectively. Correlations between KHCL-32-R2 and Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder Questionnaire were −0.66 (p=0.41), −0.14 (p=0.9), and 0.61 (p < 0.001), respectively. CONCLUSION: The KHCL-32-R2 may be a useful tool in distinguishing between bipolar and depressive patients in clinical settings.
Bipolar Disorder ; Depression ; Depressive Disorder, Major ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Mood Disorders* ; Psychometrics* ; Sensitivity and Specificity

Ursolic acid (UA) supplementation was previously shown to improve skeletal muscle function in resistance-trained men. This study aimed to determine, using the same experimental paradigm, whether UA also has beneficial effects on exercise-induced skeletal muscle damage markers including the levels of cortisol, B-type natriuretic peptide (BNP), myoglobin, creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) in resistance-trained men. Sixteen healthy participants were randomly assigned to resistance training (RT) or RT+UA groups (n=8 per group). Participants were trained according to the RT program (60~80% of 1 repetition, 6 times/week), and the UA group was additionally given UA supplementation (450 mg/day) for 8 weeks. Blood samples were obtained before and after intervention, and cortisol, BNP, myoglobin, CK, CK-MB, and LDH levels were analyzed. Subjects who underwent RT alone showed no significant change in body composition and markers of skeletal muscle damage, whereas RT+UA group showed slightly decreased body weight and body fat percentage and slightly increased lean body mass, but without statistical significance. In addition, UA supplementation significantly decreased the BNP, CK, CK-MB, and LDH levels (p<0.05). In conclusion, UA supplementation alleviates increased skeletal muscle damage markers after RT. This finding provides evidence for a potential new therapy for resistance-trained men.
Adipose Tissue ; Body Composition ; Body Weight ; Creatine ; Creatine Kinase ; Healthy Volunteers ; Humans ; Hydrocortisone ; L-Lactate Dehydrogenase ; Male ; Muscle, Skeletal* ; Myoglobin ; Natriuretic Peptide, Brain ; Pilot Projects* ; Resistance Training*

PURPOSE: This study was conducted to identify the effectiveness of a preoperative comprehensive geriatric assessment (CGA) for predicting postoperative morbidity in elderly patients who underwent surgery for colorectal cancer. METHODS: Elderly patients (≥70 years old) who underwent surgery for colorectal cancer at a tertiary hospital in Korea were identified, and their cases were analyzed using data from a prospectively collected database to establish an association between major postsurgical complications and 'high-risk' patient as defined by the CGA. RESULTS: A total of 240 patients, with a mean age of 76.7 ± 5.2 years, were enrolled. Ninety-five patients (39.6%) were classified as "high-risk" and 99 patients (41.3%) as having postoperative complications. The univariate analysis indicated that risk factors for postoperative complications were age, American Society of Anesthesiologists physical status classification, serum hemoglobin, carcinoembryonic antigen, cancer stage, and "high-risk" status. The multivariable analyses indicated that "high-risk" status (odds ratio, 2.107; 95% confidence interval, 1.168–3.804; P = 0.013) and elevated preoperative carcinoembryonic antigen (odds ratio, 2.561; 95% confidence interval, 1.346–4.871, P = 0.004) were independently associated with postoperative complications. A multivariable analysis of the individual CGA domains indicated that high comorbidities and low activities of daily living were significantly related with postoperative complications. CONCLUSION: A preoperative CGA indicating "high-risk" was associated with major postoperative complications in elderly patients who underwent surgery for colorectal cancer. Thus, using the CGA to identify elderly colorectal-cancer patients who should be given more care during postoperative management may be clinically beneficial.
Activities of Daily Living ; Aged* ; Carcinoembryonic Antigen ; Classification ; Colorectal Neoplasms* ; Comorbidity ; Geriatric Assessment* ; Humans ; Korea ; Postoperative Complications ; Prospective Studies ; Risk Factors ; Tertiary Care Centers

PURPOSE: Pharmacologic thromboprophylaxis is routinely recommended for Western cancer patients undergoing major surgery for prevention of venous thromboembolism (VTE). However, it is uncertainwhetherroutine administration of pharmacologic thromboprophylaxis is necessary in all Asian surgical cancer patients. This prospective study was conducted to examine the incidence of and risk factors for postoperative VTE in Korean colorectal cancer (CRC) patients undergoing major abdominal surgery. MATERIALS AND METHODS: This study comprised two cohorts, and none of patients received perioperative pharmacologic thromboprophylaxis. In cohort A (n=400), patients were routinely screened for VTE using lower-extremity Doppler ultrasonography (DUS) on postoperative days 5-14. In cohort B (n=148), routine DUS was not performed, and imaging was only performed when there were symptoms or signs that were suspicious for VTE. The primary endpoint was the VTE incidence at 4 weeks postoperatively in cohort A. RESULTS: The postoperative incidence of VTE was 3.0% (n=12) in cohort A. Among the 12 patients, eight had distal calf vein thromboses and one had symptomatic thrombosis. Age ≥ 70 years (odds ratio [OR], 5.61), ≥ 2 comorbidities (OR, 13.42), and white blood cell counts of > 10,000/μL (OR, 17.43) were independent risk factors for postoperative VTE (p < 0.05). In cohort B, there was one case of VTE (0.7%). CONCLUSION: The postoperative incidence of VTE, which included asymptomatic cases, was 3.0% in Korean CRC patients who did not receive pharmacologic thromboprophylaxis. Perioperative pharmacologic thromboprophylaxis should be administered to Asian CRC patients on a risk-stratified basis.
Asia ; Asian Continental Ancestry Group ; Cohort Studies ; Colorectal Neoplasms* ; Colorectal Surgery ; Comorbidity ; Humans ; Incidence* ; Leukocyte Count ; Prospective Studies* ; Risk Factors ; Thrombosis ; Ultrasonography, Doppler ; Veins ; Venous Thromboembolism*