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.

Background: Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully.We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. Methods: We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. Results: No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. Conclusion We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.

Purpose: The purpose of this study was to investigate the clinical practice patterns of Korean obstetricians and gynecologists the diagnosis and management of hypertensive disease in pregnant women. Methods: From April 2015 to October 2015, questionnaire was distributed via email to obstetricians who were members of the Society for Maternal and Fetal Medicine. The survey consisted of 37 questions in 6 categories. Responses to the questions on the management of hypertensive disorders of pregnancy, from diagnosis to treatment, were evaluated. Results: A total of 93 obstetricians and gynecologists responded to the survey. High blood pressure was allocated the highest priority as an index mainly used when deciding to hospitalize patients with hypertensive disease during pregnancy, followed by pregnancy symptoms, proteinuria, and blood test results. Calcium channel blocker (CCB) for oral administration and hydralazine for injection were preferred as antihypertensive drugs mainly used to control severe hypertension. Regarding the delivery method for hypertensive disease during pregnancy, in cases of preeclampsia, 63% of the respondents chose the delivery method according to the cervical status, and in cases of hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and eclampsia, which increased in severity, 52% and 31% responded that the delivery method was determined according to the cervical status, respectively. In cases of mild preeclampsia, the 70% of respondents preferred 37–38 weeks of gestation for the delivery time. Regarding the use of aspirin in patient with hypertension during pregnancy, 52% of the respondents occasionally administered aspirin, and in patients with a history of hypertensive disease during pregnancy, only 43% were administered prophylactic aspirin. Conclusion Domestic obstetricians regarded blood pressure as the most meaningful factor when treating women with hypertension during pregnancy and considered blood pressure control as important. The preferred antihypertensive agents were oral CCB and hydralazine injections, and the choice of delivery method was determined according to the condition of the cervix and severity of the disease. Even in women with high risk factors for preeclampsia, prophylactic aspirin was administered in as low as 50%, of patients, possibly may due to the absence of domestic guidelines for aspirin use during pregnancy. Korean guidelines for prophylactic aspirin administration during pregnancy is needed based on additional research on the efficacy of aspirin for domestic women in the future.

Background: Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully.We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. Methods: We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. Results: No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. Conclusion We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.

Purpose: The purpose of this study was to investigate the clinical practice patterns of Korean obstetricians and gynecologists the diagnosis and management of hypertensive disease in pregnant women. Methods: From April 2015 to October 2015, questionnaire was distributed via email to obstetricians who were members of the Society for Maternal and Fetal Medicine. The survey consisted of 37 questions in 6 categories. Responses to the questions on the management of hypertensive disorders of pregnancy, from diagnosis to treatment, were evaluated. Results: A total of 93 obstetricians and gynecologists responded to the survey. High blood pressure was allocated the highest priority as an index mainly used when deciding to hospitalize patients with hypertensive disease during pregnancy, followed by pregnancy symptoms, proteinuria, and blood test results. Calcium channel blocker (CCB) for oral administration and hydralazine for injection were preferred as antihypertensive drugs mainly used to control severe hypertension. Regarding the delivery method for hypertensive disease during pregnancy, in cases of preeclampsia, 63% of the respondents chose the delivery method according to the cervical status, and in cases of hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and eclampsia, which increased in severity, 52% and 31% responded that the delivery method was determined according to the cervical status, respectively. In cases of mild preeclampsia, the 70% of respondents preferred 37–38 weeks of gestation for the delivery time. Regarding the use of aspirin in patient with hypertension during pregnancy, 52% of the respondents occasionally administered aspirin, and in patients with a history of hypertensive disease during pregnancy, only 43% were administered prophylactic aspirin. Conclusion Domestic obstetricians regarded blood pressure as the most meaningful factor when treating women with hypertension during pregnancy and considered blood pressure control as important. The preferred antihypertensive agents were oral CCB and hydralazine injections, and the choice of delivery method was determined according to the condition of the cervix and severity of the disease. Even in women with high risk factors for preeclampsia, prophylactic aspirin was administered in as low as 50%, of patients, possibly may due to the absence of domestic guidelines for aspirin use during pregnancy. Korean guidelines for prophylactic aspirin administration during pregnancy is needed based on additional research on the efficacy of aspirin for domestic women in the future.

There are limited data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory specimens after resolution of coronavirus disease 2019 (COVID-19)-associated symptoms/signs. We determined duration of SARS-CoV-2 virus shedding in symptomatic patients after remission of symptoms. We investigated the duration of SARS-CoV-2 RNA detection using real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or sputum or saliva. Six patients were included in the final analysis. The median (range) duration of SARS-CoV-2 viral detection after hospitalization was 34 days (22 to 67). After resolution of symptoms/signs, SARS-CoV-2 RNA was detected for median (range) of 26 days (9 to 48). Among the six patients, one had persistent detection of SARS-CoV-2 RNA until day 67 of hospitalization, which was 30 days after symptom resolution. This case represents the longest duration of SARS-CoV-2 detection, and highlights the need for long-term follow up of COVID-19 patients despite resolution of symptoms to confirm SARS-CoV-2 clearance.

Background: Prognosis of patients with diverse chronic diseases is reportedly associated with 25-hydroxyvitamin D levels. In this study, we investigated the potential role of 25-hydroxyvitamin D3 (25[OH]D3) levels in improving the predictive power of conventional prognostic models for patients with liver cirrhosis. Methods: We investigated clinical findings, including serum 25(OH)D3 levels at admission, of 155 patients with cirrhosis who were followed up for a median of 16.9 months. Results: Median 25(OH)D3 levels were significantly different among patients exhibiting Child-Pugh grades A, B, and C. Mortality, including urgent transplantation, was significantly associated with 25(OH)D3 levels in univariate analysis. Severe vitamin-D deficiency (serum 25[OH]D3 level < 5.0 ng/mL) was significantly related to increased mortality, even after adjusting for Child-Pugh and Model for End-stage Liver Disease (MELD) scores. In particular, the presence of severe vitamin D deficiency clearly defined a subgroup with significantly poorer survival among patients with Child-Pugh scores of 5–10 or MELD scores ≤ 20. A new combination model of MELD score and severe vitamin D deficiency showed significantly more accurate predictive power for short- and long-term mortality than MELD scores alone. Additionally, serum 25(OH)D3 levels and new model scores were significantly associated with the development of spontaneous bacterial peritonitis, overt encephalopathy, and acute kidney injury. Conclusion Serum 25(OH)D3 level is an independent prognostic factor for patients with liver cirrhosis and has a differential impact on disease outcomes according to MELD and Child-Pugh scores.

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Liver ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Rectal Neoplasms ; Rectum ; Republic of Korea

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

BACKGROUND: In cirrhotic patients, left ventricular diastolic dysfunction is associated with poor outcomes. Diastolic wall strain (DWS) is a new index of left ventricular diastolic function that correlates with the myocardial stiffness. In this study, we aimed to determine whether DWS calculated from preoperative transthoracic echocardiography can predict the survival of liver transplantation recipients. METHODS: A total of 981 patients who underwent liver transplantation were enrolled. We collected the clinical, laboratory and echocardiographic data retrospectively. The left ventricular posterior wall thickness at end-systole (LVPWs) and end-diastole (LVPWd) were measured using M-mode imaging. DWS was calculated as follows: DWS = (LVPWs – LVPWd) / LVPWs. As previously reported, DWS ≤ 0.33 was defined as low DWS and DWS > 0.33 was defined as normal DWS. The primary outcome of this study was 2-years survival after liver transplantation. RESULTS: The 2-years mortality rate following liver transplantation was higher in low DWS group than normal DWS group (14.6% vs.10.0%, P = 0.038). In univariate Cox regression analysis, age, model for end-stage liver disease score, Child-Turcotte-Pugh score, creatinine, b-type natriuretic peptide, heart rate, left ventricular end-diastolic volume index, left ventricular stroke volume index, left ventricular ejection fraction, E/A ratio, e′, E/e′ ratio, and DWS were associated with 2-years survival after liver transplantation. In multivariate Cox regression analysis, DWS was an independent predictor of 2-years survival after adjusting significant univariate covariates. CONCLUSIONS: This study results indicated that the DWS is an independent prognostic predictor in liver transplantation recipients.
Creatinine ; Diastole ; Echocardiography* ; Heart Rate ; Humans ; Liver Diseases ; Liver Transplantation* ; Liver* ; Mortality ; Natriuretic Peptide, Brain ; Retrospective Studies ; Stroke Volume ; Survival Rate*