Purpose: Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and Methods: Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results: Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.

The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.

PURPOSE: Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection. MATERIALS AND METHODS: This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomywith orwithout adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values. RESULTS: Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis. CONCLUSION: This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.
Biomarkers ; Capecitabine ; Chemotherapy, Adjuvant ; Disease-Free Survival ; DNA Repair ; Humans ; Immunohistochemistry ; Prognosis ; Prospective Studies ; Recurrence ; Stomach Neoplasms ; Thymidylate Synthase

PURPOSE: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. MATERIALS AND METHODS: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.
Anemia ; Capecitabine ; Chemotherapy, Adjuvant* ; Cisplatin ; Disease-Free Survival ; Follow-Up Studies ; Gastrectomy ; Hand-Foot Syndrome ; Humans ; Korea ; Lymph Node Excision ; Mucositis ; Neutropenia ; Stomach Neoplasms*

OBJECTIVE: This study was conducted to demonstrate the temporal trends in perinatal outcomes of triplet pregnancies over the last two decades. METHODS: The medical records of patients with triplet pregnancies at two Korean tertiary-care hospitals from 1992 to 2012 were retrospectively reviewed in regard to maternal and neonatal outcomes. The study was divided into two periods for analysis: period I (1992–2001) and period II (2003–2012). RESULTS: Over a 21-year period, 65 women with triplet pregnancies and 185 neonates were analyzed. Period II, when compared with period I, was associated with improved maternal outcomes, characterized by a decreased incidence of preeclampsia (31.8% vs. 2.3%, P=0.002) and anemia (68.2% vs. 30.2%, P=0.003) during pregnancy. Regarding neonatal aspects, the composite morbidity of period II was significantly decreased compared with that of period I, as assessed with a generalized estimating equation for logistic regression (26.2% vs. 8.1%, P=0.03). Multivariable analysis revealed that the gestational age at delivery and the period were significantly associated with the composite neonatal morbidity (P<0.001 and 0.007, respectively). CONCLUSION: Improved neonatal morbidity was associated with a higher gestational age at delivery and with the more recent decade.
Anemia ; Female ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Logistic Models ; Medical Records ; Pre-Eclampsia ; Pregnancy ; Pregnancy Outcome ; Pregnancy, Triplet ; Premature Birth ; Retrospective Studies ; Triplets

In Korea, the Hospice, Palliative Care, and Life-sustaining Treatment Decision-making Act was enacted in February 2016 in order to ensure that the patient's self-determination in end-of-life care processes is respected. To enhance physicians' understanding of this act and to provide proper criteria for medical judgment in variety of clinical settings, consensus guidelines were published in November 2016. In this article, the characteristics of these guidelines and related issues regarding the definitions of ‘the end stage of disease’ and ‘last days of life’ and the criteria for medical judgment are presented and summarized. According to the guidelines, the term ‘end stage of disease’ refers to a state in which there is no possibility of a fundamental recovery and the symptoms are expected to worsen within months. The terms ‘the last days of life’ and ‘the final days of life’ refer to a state in which, despite treatment, the patient's condition is worsening and death is impending, with no possibility of recovery. The attending physician and another relevant specialist should both judge a patient's medical condition as either ‘end stage of disease’ for hospice/palliative care or ‘the last days of life’ for dying patient care according to the law. Caregivers should provide appropriate medical information to eligible patients for palliative or ‘end stage of disease’ care through advance care planning. Therefore, it is critically necessary that caregivers understand the legitimate process of hospice/palliative and dying patient care based on the patient's wishes and best interests. Physicians should apply these consensus guidelines to eligible patients considering their clinical course and the patients' wishes.
Advance Care Planning ; Caregivers ; Consensus ; Hospices ; Humans ; Judgment ; Jurisprudence ; Korea ; Palliative Care ; Patient Care ; Specialization

In Korea, the Hospice, Palliative Care, and Life-sustaining Treatment Decision-making Act was enacted in February 2016 in order to ensure that the patient's self-determination in end-of-life care processes is respected. To enhance physicians' understanding of this act and to provide proper criteria for medical judgment in variety of clinical settings, consensus guidelines were published in November 2016. In this article, the characteristics of these guidelines and related issues regarding the definitions of ‘the end stage of disease’ and ‘last days of life’ and the criteria for medical judgment are presented and summarized. According to the guidelines, the term ‘end stage of disease’ refers to a state in which there is no possibility of a fundamental recovery and the symptoms are expected to worsen within months. The terms ‘the last days of life’ and ‘the final days of life’ refer to a state in which, despite treatment, the patient's condition is worsening and death is impending, with no possibility of recovery. The attending physician and another relevant specialist should both judge a patient's medical condition as either ‘end stage of disease’ for hospice/palliative care or ‘the last days of life’ for dying patient care according to the law. Caregivers should provide appropriate medical information to eligible patients for palliative or ‘end stage of disease’ care through advance care planning. Therefore, it is critically necessary that caregivers understand the legitimate process of hospice/palliative and dying patient care based on the patient's wishes and best interests. Physicians should apply these consensus guidelines to eligible patients considering their clinical course and the patients' wishes.

BACKGROUND AND OBJECTIVES: Preoperative identification of intimal tear site in acute type A dissection will help procedural planning. The objective of this study was to determine the key findings of computed tomography (CT)-based prediction for tear site and compare the accuracy between radiologists and surgeons. SUBJECTS AND METHODS: Multi-detector CT (MDCT) images from 50 patients who underwent surgical repair of type A aortic dissection were retrospectively reviewed by 4 cardiac surgeons with limited experience or by 3 radiologists specialized in cardiovascular imaging. Surgical findings of intimal tear site were used as references. RESULTS: In surgical findings, the locations of intimal tear that were identified in 43 patients included aorta (n=25), ascending with arch (n=7), and arch only (n=11). The rest were retrograde dissections from the tear of descending aorta. Key CT findings that were most frequently found were defect in the intimal flap shadow (30.0+/-4.0 patients/reviewer, accuracy 87.0+/-11.7%) and differential filling of false lumen by phase and location (9.4+/-2.9 patients/reviewer, 84.8+/-10.4%). Surgeons predicted tear site (75.0+/-7.7% vs. 86.7+/-1.2%, p=0.055) and specified flap defect (80.5+/-10.3% vs. 95.7+/-7.4%, p=0.073) with lower accuracy than radiologists. CONCLUSIONS: With MDCT imaging, well-educated surgeons could be accurate in three fourths of cases. There was room for improvement through experience. Considering the substantial possibility of inaccuracy, critical decisions on CT images should be made through thorough reviewing by as many experienced radiologists and surgeons as possible.
Aorta ; Aorta, Thoracic ; Humans ; Retrospective Studies ; Tears*

Congenital chloride diarrhea (CCD) is a rare autosomal recessive disease, which is characterized by electrolyte absorption defect due to impaired function of the Cl-/HCO3 - exchanger in the ileum and the colon. Its main features are profuse watery diarrhea, high fecal chloride concentration, and failure to thrive. Profuse watery diarrhea characterized by a high concentration of chloride in stools results in hypochloremia, hyponatremia, and dehydration with metabolic alkalosis. Early detection and therapeutic intervention can prevent life-threatening symptoms of CCD and growth failure. Recently, several therapies, such as proton pump inhibitors and butyrate, have been suggested for amelioration of diarrhea. Here, we report a case of CCD in a preterm male infant who was successfully treated with an oral proton pump inhibitor.
Absorption ; Alkalosis ; Butyrates ; Colon ; Dehydration ; Diarrhea* ; Failure to Thrive ; Humans ; Hyponatremia ; Ileum ; Infant ; Male ; Omeprazole ; Proton Pump Inhibitors ; Proton Pumps* ; Protons*