Role of transarterial chemoembolization for hepatocellular carcinoma with extrahepatic metastases in the era of advancing systemic therapy.

Background/Aims: Systemic therapy is the current standard treatment for hepatocellular carcinoma (HCC) with extrahepatic metastases (EHM). However, some patients with HCC and EHM undergo transarterial chemoembolization (TACE) to manage intrahepatic tumors. Herein, we aimed to explore the appropriateness of TACE in patients with HCC and EHM in an era of advanced systemic therapy. Methods: This study analyzed 248 consecutive patients with HCC and EHM (median age 58.5 years, 83.5% male, and 88.7% Child-Pugh A) who received TACE or systemic therapy (83 sorafenib, 49 lenvatinib, 28 immunotherapy-based) between January 2018 and January 2021. Results: Among the patients, 196 deaths were recorded during a median follow-up of 8.9 months. Patients who received systemic therapy had a higher albumin-bilirubin grade, elevated tumor markers, an increased number of intrahepatic tumors, larger-sized tumors, and more frequent portal vein invasion than those who underwent TACE. TACE was associated with longer median overall survival (OS) than sorafenib (15.1 vs. 4.7 months; 95% confidence interval [CI]: 11.1-22.2 vs. 3.7-7.3; hazard ratio [HR] 1.97, P<0.001). After adjustment for potential confounders, TACE was associated with statistically similar survival outcomes to those of lenvatinib (median OS: 8.0 months; 95% CI: 6.5-11.0; HR 1.21, P=0.411) and immunotherapies (median OS: 14.3 months; 95% CI: 9.5-27.0; HR 1.01, P=0.973), demonstrating survival benefits equivalent to these treatments. Conclusion: In patients with HCC and EHM, TACE can provide a survival benefit comparable to that of newer systemic therapies. Accordingly, TACE remains a valuable option in this era of new systemic therapies.

Prevalence and predictors of multidrug-resistant bacteremia in liver cirrhosis.

BACKGROUND/AIMS: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. METHODS: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. RESULTS: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). CONCLUSION: More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

Massive Transfusion Protocol and Outcome of Patients with Acute Variceal Bleeding.

Background/Aims: The massive transfusion protocol (MTP) can improve the outcomes of trauma patients with hemorrhagic shock and some patients with non-traumatic hemorrhagic shock. However, no information is available regarding whether MTP can improve the outcomes of acute variceal bleeding (AVB). This study aimed to determine the effects of MTP on the outcomes of patients with AVB. Methods: Consecutive patients (n = 218) with AVB who did not have current malignancy and visited the emergency room between July 2014 and June 2022 were analyzed. 42-day mortality and failure to control the bleeding were compared between patients with and without MTP activation. Additionally, propensity-score matching was conducted. Results: The amount of blood product transfused was higher in the MTP group. The 42-day mortality rate (42.1% vs. 1.5%, p < 0.001) and the rate of failure to control bleeding (36.8% vs. 0.5%, p < 0.001) were significantly higher in those who received blood transfusions by MTP. MTP was an independent factor associated with 42-day mortality in the multivariable-adjusted analysis (HR 21.05; 95% CI 3.07-144.21, p = 0.002, HR 24.04; 95% CI 3.41-169.31, p = 0.001). The MTP group showed consistently higher 42-day mortality and failure to control bleeding in all subgroup analyses, stratified by systolic blood pressure, hemoglobin level, and the model for end-stage liver disease score. The MTP group also showed higher 42-day mortality (42.9% vs. 0%, p = 0.001) and failure to control bleeding (42.9% vs. 0%, p = 0.001) in a propensity score-matched analysis (n = 52). Conclusions: MTP was associated with poor outcomes in patients with AVB. Further studies are needed to see whether MTP can be an option for patients with massive AVB.

Risk of hepatocellular carcinoma after curative treatment when switching from tenofovir disoproxil fumarate or entecavir to tenofovir alafenamide: A real-world multicenter cohort study.

AIM: Antiviral treatment reduces the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. However, there is a lack of high-quality evidence regarding the preventive effects of tenofovir alafenamide (TAF) on HCC. We evaluated the impact of TAF use after curative treatment on HCC recurrence. METHODS: Patients who underwent surgery or radiofrequency ablation as a curative treatment for HCC were selected. Those patients who continued antiviral treatment with nucleos(t)ide analogs (NAs; entecavir [ETV] or tenofovir disoproxil fumarate [TDF]) or switched to TAF were included. The primary outcome was HCC recurrence, and the time-varying effect of NA use on HCC recurrence was analyzed using various statistical methods. RESULTS: Among 2794 consecutive patients with chronic hepatitis B who received curative treatment for HCC, 199 subsequently switched from ETV or TDF to TAF. After a median of 3.0 years, 1303 patients (46.6%) experienced HCC recurrence. After propensity score matching (ratio 1:10), switching to TAF was not associated with an increased HCC recurrence (HR 1.00, 95% CI 0.68-1.47; p = 1.00) by time-varying Cox analysis. Switching to TAF was not associated with HCC recurrence in subgroups of NA (HR 1.06, 95% CI 0.67-1.67; p = 0.81 for TDF, and HR 1.09, 95% CI 0.51-2.33; p = 0.82 for ETV). Kaplan-Meier analysis showed comparable HCC recurrence-free survival between patients who switched to TAF and those who continued with their NA (p = 0.08). Time-varying Cox analyses in various subgroups confirmed the primary findings. CONCLUSIONS: TAF is as effective as TDF and ETV in preventing HCC recurrence after curative treatment.

Ultrasonographic findings of metabolic dysfunction-associated fatty liver disease: A comparative study with non-alcoholic fatty liver disease and clinical characteristics.

PURPOSE: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analyzed the ultrasonographic findings of MAFLD and NAFLD. METHODS: We conducted a retrospective cross-sectional study of subjects aged ≥19 years who underwent a health screening examination, including ultrasonography, (n = 17,066). Patients were separated into one of three groups; pure MAFLD (n = 5304), pure NAFLD (n = 579), and both NAFLD & MAFLD (n = 11,183). The outcomes were the degree of fatty liver disease and liver cirrhosis, defined by ultrasonography. In addition, the risk of ultrasonographic cirrhosis was assessed in the MAFLD group based on clinical characteristics. RESULTS: The pure NAFLD group had a lower risk of severe fatty liver disease than the both NAFLD & MAFLD groups (0.9 % vs. 4.4 %, p < 0.001). Cirrhosis was not diagnosed in the NAFLD group. Cirrhosis was more common in the pure MAFLD group than in the both NAFLD & MAFLD group (0.3 % vs. 0.0 %, p < 0.001). In the MAFLD group, multivariable analysis showed that diagnosis by hepatic steatosis index (Odds ratio [OR], 12.39; 95 % confidence interval [CI], 3.40-45.19; p < 0.001) or significant alcohol intake (OR, 9.58, 95 % CI, 1.93-47.61; p = 0.006) was independently associated with risk of liver cirrhosis on ultrasonography. CONCLUSION: Liver cirrhosis was more frequently identified on ultrasonography in patients with MAFLD than in NAFLD. MAFLD diagnosed using the hepatic steatosis index or significant alcohol intake is a risk factor for liver cirrhosis.

Metabolic dysfunction-associated fatty liver disease and the risk of hepatocellular carcinoma.

Background & Aims: The metabolic dysfunction-associated fatty liver disease (MAFLD) is a new inclusive term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analysed whether hepatocellular carcinoma (HCC) risk differs by MAFLD or NAFLD status in a large sample of asymptomatic adults. Methods: A cohort comprising 73,691 adults were followed up for the development of HCC. NAFLD was diagnosed among participants without other liver diseases (n = 65,992). Results: Participants with MAFLD showed higher incidence of HCC than those without MAFLD (0.37 and 0.24 per 1,000 person-years, respectively; p = 0.006). However, MAFLD was not an independent factor associated with HCC in multivariable adjusted analysis (hazard ratio [HR] 1.21; 95% CI 0.92-1.60). When stratified according to presence of other liver diseases, MAFLD was not associated with HCC in participants with other liver diseases. In participants without other liver diseases, both MAFLD (adjusted HR 1.84; 95% CI 1.09-3.11) and NAFLD (adjusted HR 1.71; 95% CI 1.01-2.90) were independent factors associated with HCC. When stratified according to NAFLD and MAFLD status, there was no HCC development among participants with NAFLD only during 8,936 person-years of follow-up, but this NAFLD-only group comprised 3.4%, and the majority of participants with hepatic steatosis fulfilled both NAFLD and MAFLD criteria. Conclusions: In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. For those without other chronic liver diseases, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC. Impact and Implications: This study investigated the usefulness of newly proposed nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), over non-alcoholic fatty liver disease (NAFLD), in terms of predicting hepatocellular carcinoma. In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. However, for those without chronic liver disease, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC.

Validation of non-invasive diagnosis of CSPH in patients with compensated advanced chronic liver disease according to Baveno VII.

BACKGROUND AND AIMS: Baveno VII consensus introduced the non-invasive criteria of clinically significant portal hypertension (CSPH) using liver stiffness measurement (LSM). We evaluated the usefulness of the Baveno VII criteria to predict the risk of decompensation in patients with compensated advanced chronic liver disease (cACLD). METHODS: We conducted a retrospective cohort study of 1966 patients with cACLD. Patients were categorized into four groups (CSPH excluded (n = 619), grey zone (low risk of CSPH (n = 699), high risk of CSPH (n = 207)), and CSPH included (n = 441)) according to Baveno VII consensus. The risk of events was estimated using a Fine and Gray competing risk regression analysis, with liver transplantation and death as competing events. We calculated standardized hazard ratios (sHR) to assess the relative risk of decompensation. RESULTS: Among 1966 patients, 178 developed decompensations over a median follow-up of 3.06 (IQR: 1.03-6.00) years. Patients with CSPH had the highest decompensation risk, followed by the grey zone high-risk group, grey zone low-risk group, and those without CSPH with 3-year cumulative risks of 22%, 12%, 3.3%, and 1.4% respectively (p < .001). Compared to CSPH excluded group, CSPH included group (sHR: 8.00, 95% CI: 4.00-16.0), grey zone high-risk group (sHR: 6.57, 95% CI: 3.16-13.6), grey zone low-risk group (sHR: 2.15, 95% CI: 1.04-4.41) had significantly higher risk of decompensation (Gray's test p < .01). CONCLUSION: Non-invasive diagnosis of CSPH according to the Baveno VII criteria can stratify the risk of decompensation.

Changes in the prevalence of hepatitis B and metabolic abnormalities among young men in Korea.

Changes in the prevalence of disease over time provide valuable information from a public health perspective. We used data from Korea Military Manpower Administration medical examinations for conscription between 2003 and 2019 (n = 5,355,941), which involved young men aged 19 years, to observe changes in liver disease over time at a population level. Trends in the prevalence of hepatitis B surface antigen (HBsAg), elevated alanine aminotransferase (ALT) levels, the fibrosis-4 (FIB-4) index, obesity, and hypertension were assessed. The prevalence of HBsAg steadily decreased from 3.19% for men born in 1984 to 0.18% for men born in 2000. Among HBsAg-negative subjects, the prevalence of elevated ALT levels increased from 13.15% for men born in 1986 to 16.48% for men born in 2000. The prevalence of obesity, hypertension and the proportion with high FIB-4 scores (≥ 1.45) also increased. This population-based nationwide analysis showed a decreasing trend of HBsAg and increasing trends of possible non-alcoholic fatty liver disease.

Predictors of critical illness among young males with chest pain, abdominal pain, or headaches in the Republic of Korea Army.

Purpose: Chest pain, abdominal pain, and headache are common symptoms associated with critical illness. Here, we aimed to evaluate predictors associated with critical illness in young males of the Republic of Korea Army. Methods: We retrospectively reviewed previously healthy young males with chest pain, abdominal pain, or headaches who visited Armed Forces Seoul District Hospital between January 2019 and December 2020. Critical illness was defined as a condition that required hospitalization, a procedure or surgery, or referral to a tertiary hospital. The symptoms and signs of critical illness were evaluated. Results: Of the 762 enrolled patients, a critical illness was diagnosed in 45 patients (5.9%). Among chest pain signs, palpitation (odds ratio [OR], 22.8; 95% confidence interval [CI], 5.08-102.4; p < 0.001), exertional dyspnea (OR, 16.3; 95% CI, 3.38-78.8; p = 0.001), duration (> 5 minutes) (OR, 7.54; 95% CI, 1.93-29.49; p = 0.004), and squeezing type (OR, 5.28; 95% CI, 1.11-25.11; p = 0.037) were significantly associated with critical illness. Among abdominal pain signs, right-lower-quadrant tenderness (OR, 11.87; 95% CI, 4.671-31.87; p < 0.001) was an alarming sign. For headaches, criticality was low (1.5%), and half of patients with critical illness were diagnosed incidentally regardless of headache. Conclusion: We identified symptoms and signs significantly associated with critical illness in young male patients. This study might serve as a reference for deciding when to transfer soldiers in the field to a rear hospital, thereby contributing to the welfare and combat power of soldiers.

Close Observation versus Additional Surgery after Noncurative Endoscopic Resection of Esophageal Squamous Cell Carcinoma.

INTRODUCTION: After noncurative endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma (SESCC), additional esophagectomy is generally recommended. However, considering its high mortality and morbidity, it is uncertain if additional surgery improves the clinical outcomes. This study aimed to compare the clinical outcomes between patients who were observed without additional treatment and those who underwent radical esophagectomy. METHODS: A total of 52 patients with SESCC who underwent complete but noncurative ESD from January 2008 to December 2016 at the Samsung Medical Center and Asan Medical Center in Korea were retrospectively analyzed. Clinicopathologic characteristics and oncologic outcomes were compared between the observation group (n = 23) and the additional surgery group (n = 29). RESULTS: During a mean follow-up of 34.4 and 41.7 months, respectively, the rates of death (observation vs. surgery, 17.4 vs. 10.3%; p = 0.686), recurrence (observation vs. surgery, 13 vs. 17.2%; p = 1.000), and disease-specific death (observation vs. surgery, 4.3 vs. 6.9%; p = 1.000) did not significantly differ between the 2 groups. The 3-year overall survival was 86.3 and 96.4%, respectively (p = 0.776). The 3-year recurrence-free survival (observation vs. surgery, 85.0 vs. 88.7%; p = 0.960) and disease-specific survival (observation vs. surgery, 95.2 vs. 96.4%; p = 0.564) also did not significantly differ. CONCLUSIONS: The clinical outcomes of close observation of noncuratively resected SESCC are comparable to those of additional surgery, at least in the midterm. The wait-and-see strategy could be a feasible management option after noncurative ESD of SESCC in selected patients.

Multiple Opportunistic Infections Related to Hypercortisolemia due to Adrenocortical Carcinoma: A Case Report.

Cushing's syndrome is characterized by excessive cortisol and immuno-suppression. We experienced a case of Cushing's syndrome caused by adrenocortical carcinoma that was complicated by multiple opportunistic infections. A 37-year-old woman with adrenocortical carcinoma (ACC) presented with decreased mental ability and high fever one week after undergoing chemotherapy. Her initial blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA) bacteremia accompanied by septic pneumonia. We admitted her to the intensive care unit and treated her for invasive pulmonary aspergillosis (IPA), Pneumocystis jirovecii pneumonia (PJP), candidemia, and Stenotrophomonas maltophilia pneumonia with broad-spectrum antibiotics and antifungal agents. Nevertheless, her clinical course worsened and she died. Herein, we report a case of Cushing's syndrome associated with cortisol-secreting ACC that presented with multiple opportunistic infections, including MRSA bacteremia, septic pneumonia, candidemia, PJP, and IPA, illuminating a relationship between hypercortisolemia and opportunistic infections.

A comparison of factors associated with the temporal improvement in the overall survival of BCLC stage 0 hepatocellular carcinoma patients.

BACKGROUND: It is uncertain whether the prognosis of Barcelona Clinical Liver Cancer (BCLC) stage 0 hepatocellular carcinoma (HCC) has improved. AIMS: To evaluate whether the outcomes of BCLC stage 0 patients has improved, and if so, what are the reasons behind the noted improved outcome. METHODS: A total of 591 patients with BCLC stage 0 HCC diagnosed at Samsung Medical Center, Seoul, Korea were grouped based on year of diagnosis (earlier cohort; 2007-2009 and later cohort; 2013-2015) and compared. RESULTS: The overall survival (OS) was improved for BCLC stage 0 patients at later cohort (5-year survival rate: 82.1% vs. 92.0% for earlier cohort and later cohort, p = 0.015). However, after adjustment, the treatment period was not an independent factor for OS, especially when the albumin-bilirubin (ALBI) grade was adjusted. The incidence of liver cirrhosis (LC)-related death was increased from 10.4% to 33.3%, while the incidence of HCC-related death decreased from 57.5% to 28.6% in the latter cohort. CONCLUSIONS: The survival improvement of BCLC stage 0 patients was largely explained by better liver function at diagnosis. Mortality from LC-related death was increasing, which calls for careful attention for finding strategies for preserving the liver function for BCLC stage 0 patients.

Risk of domperidone induced severe ventricular arrhythmia.

There has been controversy over the cardiovascular safety of domperidone, attributable to the lack of a well-designed study as well as inconsistent results. This study aimed to examine the risk of severe domperidone-induced ventricular arrhythmia (VA), compared to mosapride, itopride, or non-use of all three prokinetics, in the general population. We conducted a population-based, self-controlled case series analysis. Enrolled subjects were individuals who were diagnosed with severe VA and were prescribed domperidone, mosapride, or itopride from 2003 to 2013 in the National Health Insurance Service-National Sample Cohort. The incidence rate ratio for severe VA was measured during exposure to prokinetics and compared with unexposed periods and itopride (no-proarrhythmic effect)-exposure periods, as control. A total of 2,817 subjects were included. Domperidone, mosapride, or itopride use was associated with increased risk of severe VA, compared with non-use (adjusted incidence rate ratios (IRR) of 1.342 (95% CI 1.096-1.642), 1.350 (95% CI 1.105-1.650), and 1.486 (95% CI 1.196-1.845), respectively). The risk of severe domperidone-induced VA was lower, compared to that of itopride [adjusted IRR of 0.548 (95% CI 0.345-0.870)]. Of the subjects who had been prescribed all three prokinetics, domperidone-exposure was associated with a lower risk of severe VA, compared to itopride-exposure (crude IRR, 0.571; 0.358-0.912). Mosapride-exposure did not show IRR difference for severe VA, compared to itopride-exposure. Domperidone, mosapride, or itopride use is associated with an increased risk of severe VA. However, the magnitude of association was modest and domperidone use does not increase further the risk, compared with other prokinetics.

Changes in Tumor Markers and Their Implications in Selecting Liver Transplantation for Patients With Hepatocellular Carcinoma.

BACKGROUND AND AIM: It has been suggested that tumor markers can provide additional information over tumor size and number-based liver transplantation (LT) criteria. We aimed to assess if changes in tumor markers are associated with the risk of tumor recurrence after LT for hepatocellular carcinoma (HCC) who received loco-regional therapies (LRTs). METHODS: A total of 129 patients who received LT with pre-LT LRTs for HCC were analyzed. Milan criteria and tumor markers, alpha-fetoprotein, and protein induced by vitamin K antagonist II, at diagnosis and at transplant were assessed. The primary outcome was tumor recurrence. RESULTS: When patients were stratified by radiologic criteria, cumulative recurrence rates at 3 years for patients who were not down-staged (outside Milan to outside Milan), progressed (within Milan to outside Milan), down-staged (outside Milan to within Milan), and bridged (within Milan to within Milan) were 66.7%, 58.3%, 18.7%, and 8.5%, respectively (P < .001). Among patients who were transplanted within Milan criteria at transplant (n = 113), cumulative recurrence rates at 3 years were highest for those with persistently high tumor markers (high to high, 21.7%), followed by those with increase in tumor markers (low to high, 11.1%), those with normalization of tumor markers (high to low, 5.6%), and those with persistently low tumor markers (low to low, 0%), respectively, after LRTs (P = .035). CONCLUSIONS: Changes of tumor markers can provide additional information on the risk of recurrence after LT among HCC patients who received LRTs, indicating that they could be used to refine current LT selection criteria.

Detection of Circulating Tumor Cells in Resectable Pancreatic Ductal Adenocarcinoma: A Prospective Evaluation as a Prognostic Marker.

Circulating tumor cells (CTCs) are useful biomarkers of many solid tumors, but are infrequently detected in early stage pancreatic ductal adenocarcinomas (PDACs). The first drainage of pancreatic venous blood flow come to portal vein and pass through the liver, and they finally go out for peripheral blood. We thought that comparing CTCs from portal vein and peripheral blood could enable us to understand the clinical meaning of CTCs from each different site in PDACs. Therefore, we aimed to determine 1) whether CTCs could be reliably identified in early stages (operable) of PDACs, 2) if there are any differences in the detected number of CTC in portal vein blood and peripheral blood, and 3) whether CTCs can be sensitive biomarkers for the prognosis of resectable PDAC patients. Newly diagnosed PDAC patients who underwent operation with curative intention between 2013 and 2015 were prospectively enrolled. Blood draws from portal and peripheral vein ran through the microfabricated porous filter, and anti-epithelial cell adhesion molecule (EpCAM) and anti-Plectin-1 antibodies were used for CTC identification. Baseline clinical characteristics, tumor characteristics, treatment, and clinical outcomes were assessed. The clinical stages of the 32 enrolled patients were as follows: IA/IB 1 (3.1%); IIA 9 (28.1%); IIB 17 (53.1%); III 5 (15.6%). Twenty-seven patients (84.4%) received R0 resection, while five patients (15.6%) received R1 resection. EpCAM+ CTCs were detected in 20 portal blood (62.5%) and 22 peripheral blood (68.8%). Plectin-1+ CTCs were identified in 14 portal blood (43.8%) and 16 peripheral blood (50%). Plectin-1-expressing CTCs were picked from CTC platform (microfabricated porous filter) and we could find out all KRAS mutation. Patients with detectable EpCAM+ CTC less than one in peripheral blood showed longer overall survival (OS) compared to patients with detectable CTCs more than one (35.5 months vs. 16.0 months). EpCAM and Plectin-1 successfully identified CTCs at the early stage of PDACs. Also, the number of CTCs could be a prognostic marker for survival in resectable PDACs.

Adjuvant cytokine-induced killer cell immunotherapy for hepatocellular carcinoma: a propensity score-matched analysis of real-world data.

BACKGROUND: Several randomized controlled trials have shown that adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells prolongs recurrence-free survival (RFS) after curative treatment for hepatocellular carcinoma (HCC). We investigated the efficacy of adjuvant immunotherapy with activated CIK cells in real-world clinical practice. METHODS: A total of 59 patients who had undergone curative surgical resection or radiofrequency ablation for stage I or II HCC, and subsequently received adjuvant CIK cell immunotherapy at two large-volume centers in Korea were retrospectively included. Propensity score matching with a 1:1 ratio was conducted to avoid possible bias, and 59 pairs of matched control subjects were also generated. The primary endpoint was RFS and the secondary endpoints were overall survival and safety. RESULTS: The median follow-up duration was 28.0 months (interquartile range, 22.9-42.3 months). In a univariable analysis, the immunotherapy group showed significantly longer RFS than the control group (hazard ratio [HR], 0.42; 95% CI, 0.22-0.80; log-rank P = 0.006). The median RFS in the control group was 29.8 months, and the immunotherapy group did not reach a median RFS. A multivariable Cox proportional hazard analysis showed that immunotherapy was an independent predictor for HCC recurrence (adjusted HR, 0.38; 95% CI, 0.20-0.73; P = 0.004). The overall incidence of adverse events in the immunotherapy group was 16/59 (27.1%) and no patient experienced a grade 3 or 4 adverse event. CONCLUSIONS: The adjuvant immunotherapy with autologous CIK cells after curative treatment safely prolonged the RFS of HCC patients in a real-world setting.

Prognosis and prognostic factors in patients with advanced biliary tract cancer depending on its anatomical location.

Objective: Previous studies have revealed that biliary tract cancer (BTC) has different clinical characteristics depending on its anatomical location. However, clinical studies about the prognosis of BTC according to its anatomical location are lacking. We aimed to compare the prognosis of BTC according to its anatomical location. Methods: We retrospectively reviewed records of 311 patients with advanced BTC who received gemcitabine based palliative chemotherapy from January 2006 to December 2015 at Samsung medical Center. Results: During median follow-up of 7.67 months, the median overall survival (OS) times for patients with gallbladder (GB) cancer, intrahepatic cholangiocellular carcinoma (ICCC) and extrahepatic cholangiocellular carcinoma (ECCC) were 8.1 months, 7.7 months and 13.4 months, respectively. Median progression free survival (PFS) times for those with GB cancer, ICCC and ECCC were 4.1 months, 5.4 months and 7.2 months respectively. In multivariate analysis, anatomical location of cancer was a statistically significant factor for OS and PFS (p < .001). Prognostic factors associated with OS were also different according to the anatomical location of cancer: CA 19-9 and chemotherapy response for GB cancer; disease status, albumin and chemotherapy response for ICCC; performance status and chemotherapy response for ECCC. Conclusions: Prognosis and prognostic factors of BTC were significantly different depending on its anatomical location.

Combined Multichannel Intraluminal Impedance and High-resolution Manometry Improves Detection of Clinically Relevant Esophagogastric Junction Outflow Obstruction.

BACKGROUND/AIMS: Esophagogastric junction outflow obstruction (EGJOO) is a diagnostically heterogeneous group with variable clinical relevance. We studied whether evaluation of bolus transit by multichannel intraluminal impedance (MII) is useful for discriminating clinically relevant EGJOO. METHODS: A total 169 patients diagnosed as having EGJOO between June 2011 and February 2018 were analyzed. All the patients received a combined MII and high-resolution manometry (CMII-HRM). MII was reported as having abnormal liquid bolus transit (LBT) if ＜ 80% of swallows had complete bolus transit. EGJOO was defined as a median integrated relaxation pressure of ＞ 20 mmHg and when the criteria for achalasia were not met. Patients who progress to achalasia, show significant passage disturbance, or require pneumatic dilatation were defined as having a clinically relevant EGJOO. RESULTS: Among the patients with EGJOO (n = 169), the clinically relevant group (n = 10) is more likely to have dysphagia (100% vs 25.2%, P ＜ 0.001), compartmentalized pressurization (CP; 90.0% vs 22.0%, P ＜ 0.001), and abnormal LBT (100% vs 66.7%, P = 0.032) compared to the non-relevant group (n = 159). The combination of dysphagia, CP, and abnormal LBT showed the best predictive power for clinically relevant EGJOO (sensitivity 90%, specificity 92.5%, positive predictive value 42.9%, negative predictive value 99.3%, positive likelihood ratio 11.9, and negative likelihood ratio 0.1). When CMII-HRM was used, an additional 8.3% of clinically relevant EGJOO cases were identified as compared with HRM alone. CONCLUSION: Clinically relevant EGJOO can be predicted using CMII-HRM.

Endoscopic submucosal dissection under general anesthesia for superficial esophageal squamous cell carcinoma is associated with better clinical outcomes.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been widely accepted for treating superficial esophageal squamous cell carcinoma (SESCC). The aim of this study was to evaluate the efficacy and safety of ESD for SESCC and the effect of different sedation methods on their clinical outcomes. METHODS: We retrospectively analyzed a total of 169 patients (175 lesions) who underwent ESD for SESCC at Samsung Medical Center, Seoul, South Korea. Short-term and long-term clinical outcomes were evaluated and compared according to the sedation method (conscious sedation [CS] vs general anesthesia [GA]). RESULTS: En bloc resection, complete resection, and curative resection (CuR) were achieved in 93.7, 74.9, and 58.9% of cancers, respectively. Perforation and stricture occurred in 8.0 and 12.0% of lesions, respectively. During a mean follow-up period of 33.7 months for survival, 3 (3.0%) patients died without evidence of recurrence after achieving CuR. During a mean follow-up period of 32.5 months for recurrence, 1 (1.0%) patient experienced lymph node metastasis. Synchronous and metachronous cancer were found in 1.0% and in 3.0% of patients, respectively. Multivariate analysis revealed that GA was associated with a higher complete resection rate and a lower perforation rate as compared to CS (odds ratio 3.401, 95% confidence interval 1.317-8.785, P = 0.011 and odds ratio 0.067, 95% confidence interval 0.006-0.775, P = 0.030, respectively). CONCLUSIONS: ESD is an oncologically effective treatment modality for SESCC, particularly when CuR is achieved. Applying GA for esophageal ESD could improve the clinical outcomes of ESD in patients with SESCC.