Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

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.

After publication of the original article the authors found that the following affiliation was incorrect at the time of publication.

PURPOSE: To evaluate the clinical significance of T1 high signal intensity on the globus pallidus as a predictor of severe hepatic encephalopathy in patients with acute-on-chronic liver failure (ACLF), which is a distinct syndrome characterized by multi-organ dysfunction including cerebral failure. MATERIALS AND METHODS: From January 2002 to April 2014, we retrospectively reviewed the magnetic resonance imaging (MRI) findings and clinical and magnetic resonance (MR) features of 74 consecutive patients (44 men and 30 women; mean age, 59.5 years) with liver cirrhosis. The chronic liver failure-sequential organ failure assessment score was used to diagnose ACLF. The pallidal index (PI), calculated by dividing the mean signal intensity of the globus pallidus by that of the subcortical frontal white matter were compared according to ACLF. The PI was compared with the Model for End-Stage Liver Disease (MELD) score in predicting the development of ACLF. RESULTS: Fifteen patients who were diagnosed with ACLF had higher hepatic encephalopathy grades (initial, P = 0.024; follow-up, P = 0.002), MELD scores (P < 0.001), and PI (P = 0.048). In the ACLF group, the mean PI in patients with cerebral failure was significantly higher than that in the patients without cerebral failure (1.33 vs. 1.20, P = 0.039). In patients with ACLF, the area under the curve (AUC) for PI was 0.680 (95% confidence intervals [CI], 0.52–0.85), which was significantly lower than that for the MELD score (AUC, 0.88; 95% CI, 0.77–0.99) (P = 0.04). CONCLUSION: The PI can be an ancillary biomarker for predicting the development of ACLF and severe hepatic encephalopathy.
Acute-On-Chronic Liver Failure ; Female ; Follow-Up Studies ; Globus Pallidus ; Hepatic Encephalopathy* ; Humans ; Liver Cirrhosis ; Liver Diseases* ; Liver* ; Magnetic Resonance Imaging ; Male ; Retrospective Studies ; White Matter