Efficacy and safety of MC-003 solution for endoscopic mucosal or submucosal resection: a prospective, multicenter, randomized, triple-blinded, parallel-group, phase III study.

BACKGROUND AND AIMS: The safety and efficacy of solutions for submucosal injection are critical for endoscopic resection of gastric adenomas or early gastric cancers. Although several injectable solutions have been introduced for endoscopic resection, they have some limitations. We aimed to compare the efficacy of the new sodium alginate-based solution MC-003 with that of normal saline (NS; 0.9% sodium chloride). METHODS: In this randomized, triple-blind study, 70 patients were initially enrolled for EMR or endoscopic submucosal dissection (ESD). The main outcomes included the need for additional injections, completion of en bloc resection, and occurrence of adverse events. RESULTS: Each group ultimately included 34 patients. Complete en bloc resections were achieved in all patients (P = 1.000). The MC-003 group had more peri-neoplasm tissue fibrosis (P = .056) and needed fewer additional injections for lesions >15 mm (P = .037), located in the distal portion of the stomach (P = .007), and during ESD procedures (P = .001). The adverse event rate was comparable in both groups. CONCLUSIONS: MC-003 outperformed NS in reducing the need for additional injections during en bloc resection, particularly in larger lesions located in the distal portion of the stomach (where most lesions were found) during ESD procedures, without increasing the incidence of serious adverse events. MC-003 is a promising submucosal injectable solution in real-world clinical settings.

Validation of MELD 3.0 in patients with alcoholic liver cirrhosis using prospective KACLiF cohort.

BACKGROUND AND AIM: The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD-Na, in patients with alcoholic liver cirrhosis. METHODS: This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD-Na, and MELD 3.0, for 30-day and 90-day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes. RESULTS: A total of 1096 patients were included in the study, with a mean age of 53.3 ± 10.4 years, and 82.0% were male. The mean scores for MELD, MELD-Na, and MELD 3.0 at the time of admission were 18.7 ± 7.2, 20.6 ± 7.7, and 21.0 ± 7.8, respectively. At 30 and 90 days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD-Na, and MELD 3.0 at 30 days were 0.823, 0.820, and 0.828; and at 90 days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90-day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels. CONCLUSION: MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant.

The Epidemiology of Hepatitis B Virus Infection in Korea: 15-Year Analysis.

BACKGROUND: The purpose of this study is to investigate the epidemiological changes in chronic hepatitis B (CHB) and assess the impact of coronavirus disease 2019 (COVID-19) over the past 15 years in a region endemic to hepatitis B virus (HBV). METHODS: National Health Insurance Service claims data of hepatitis B patients spanning from 2007 to 2021 was utilized. To compare the characteristics of the hepatitis B group, a control group adjusted for age and gender through propensity score matching analysis was established. RESULTS: The number of patients with CHB has consistently increased over the past 15 years. The average age of the CHB patient group has shown a yearly rise, while the prevalence of male dominance has gradually diminished. The proportions of hepatocellular carcinoma, liver cirrhosis, and decompensation have exhibited a declining pattern, whereas the proportion of liver transplants has continuously risen. Patients with CHB have demonstrated significantly higher medical and medication costs compared to the control group. Moreover, patients with CHB have shown a higher prevalence of comorbidities along with a significantly higher rate of concomitant medication usage. During the COVID period, the HBV group experienced a substantial decrease in the number of outpatient visits and overall medical costs compared to the control group. CONCLUSION: The epidemiology of CHB has undergone significant changes over the past 15 years, encompassing shifts in prevalence, severity, medical costs, and comorbidities. Furthermore, the impact of COVID-19 has been observed to decrease healthcare utilization among patients with CHB when compared to controls.

Multidimensional Nomogram to Predict Postoperative Pancreatic Fistula after Minimally Invasive Pancreaticoduodenectomy.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is an inherently severe risk of pancreatic resection. Previous research has proposed models that identify risk factors and predict CR-POPF, although these are rarely applicable to minimally invasive pancreaticoduodenectomy (MIPD). This study aimed to evaluate the individual risks of CR-POPF and to propose a nomogram for predicting POPF in MIPD. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 429 patients who underwent MIPD. In the multivariate analysis, the Akaike information criterion stepwise logistic regression method was used to select the final model to develop the nomogram. RESULTS: Of 429 patients, 53 (12.4%) experienced CR-POPF. On multivariate analysis, pancreatic texture (p = 0.001), open conversion (p = 0.008), intraoperative transfusion (p = 0.011), and pathology (p = 0.048) were identified as independent predictors of CR-POPF. The nomogram was developed based on patient, pancreatic, operative, and surgeon factors by using the following four additional clinical factors as variables: American Society of Anesthesiologists class ≥ III, size of pancreatic duct, type of surgical approach, and < 40 cases of MIPD experience. CONCLUSIONS: A multidimensional nomogram was developed to predict CR-POPF after MIPD. This nomogram and calculator can help surgeons anticipate, select, and manage critical complications.

Prevalence and trends of multiple antimicrobial resistance of Helicobacter pylori in one tertiary hospital for 20 years in Korea.

BACKGROUND: Failure of Helicobacter pylori (H. pylori) eradication is principally caused by antimicrobial resistance. Nowadays, multidrug resistance could be a major determinant of eradication failure. To assess minimal inhibitory concentration (MIC), antimicrobial resistance rates and trends in H. pylori isolated from patients with upper gastrointestinal disease with long-term period. MATERIALS AND METHODS: Patients who had H. pylori colonies isolated from culture were consecutively enrolled during the period of 2003-2022. From each patient, one to ten isolates were collected from culture of mucosal biopsy. MIC test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin using agar dilution method. Trends in MIC distribution, prevalence of resistances with single and multiple were investigated which were suspected to be related to the failure of empirical H. pylori eradication treatment. RESULTS: From 2003 to 2022, a total of 873 patients were enrolled and 2735 H. pylori isolates were successfully collected. Increase in the primary resistance rate was found in clarithromycin (16.1%-31.0%, p = .022), metronidazole (30.6%-38.1%, p < 0.001), and both of levofloxacin and moxifloxacin (7.3%-35.7%, p < 0.001). The prevalence of multidrug resistance to both clarithromycin and metronidazole (9.2%-37.9%, p < 0.001), clarithromycin and fluoroquinolone (2.8%-41.7%, p < 0.001), and clarithromycin, metronidazole, and fluoroquinolone (1.4%-28.2%, p < 0.001) was found to significantly increase. CONCLUSIONS: The prevalence of multiple resistance against H. pylori in Korea is ongoing. Its trend should be considered when establishing an empirical treatment strategy (ClinicalTrials. gov: NCT05247112).

Ideal Timing of Discontinuation of Antiplatelet Agents Before Gastric Endoscopic Submucosal Dissection for Reducing Delayed Bleeding.

BACKGROUND AND AIMS: This study aimed to evaluate whether the use of antiplatelet agents increases the risk of bleeding after gastric endoscopic submucosal dissection (ESD) and to determine the appropriate time to discontinue antiplatelet agents to minimize complications. METHODS: This retrospective observational study utilized a collected dataset of patients who underwent ESD for gastric adenoma and cancer between January 2010 and December 2020. Patients were classified into three groups according to antiplatelet agent use and discontinuation status. We investigated the risk of post-ESD bleeding with different interruption times and antiplatelet agent types. RESULTS: Of 1879 patients, 1389 were non-users, 190 were in the continuous group, and 203 were in the interrupted group. The rates of overall and delayed bleeding were significantly higher in patients who continued or were interrupted within three days before ESD than in the non-users and interrupted group (6.3% vs. 1.2%, p < 0.001, 6.3% vs. 2.5%, p = 0.01, respectively). Significant differences in delayed bleeding between the continuous and interrupted groups decreased with longer cessation periods. In multivariate analysis, continuous antiplatelet agents were still the strongest risk factor for bleeding (OR 2.81, 95% CI 1.14-6.90). Lower third location and longer procedure times were also independent risk factors for post-ESD bleeding (OR 2.75; 95% CI 1.08-6.97; OR 1.02; 95% CI 1.01-1.02). CONCLUSION: Continuous antiplatelet agent use increases the risk of delayed bleeding after gastric ESD. Therefore, the optimal timing of interruption, rather than the type of antiplatelet agent, should be considered to avoid an additional risk of bleeding and thromboembolism.

Which one is better? Laparoscopic versus robotic reconstruction in the remnant soft pancreas with a small pancreatic duct following pancreaticoduodenectomy: a multicenter study with propensity score matching analysis.

BACKGROUND: Evidence of the advantages of robotic pancreaticoduodenectomy (RPD) over laparoscopic pancreaticoduodenectomy (LPD) is limited. Thus, this study aimed to compare the surgical outcomes of laparoscopic reconstruction L-recon) versus robotic reconstruction (R-recon) in patients with soft pancreas and small pancreatic duct. METHOD: Among 429 patients treated with minimally invasive pancreaticoduodenectomy (MIPD) between October 2012 and June 2020 by three surgeons at three institutions, 201 patients with a soft pancreas and a small pancreatic duct (< 3 mm) were included in this study. RESULTS: Sixty pairs of patients who underwent L-recon and R-recon were selected after propensity score matching. The perioperative outcomes were comparable between the reconstruction approaches, with comparable clinically relevant postoperative pancreatic fistula (CR-POPF) rates (15.0% [L-recon] vs. 13.3% [R-recon]). The sub-analysis according to the type of MIPD procedure also showed comparable outcomes, but only a significant difference in postoperative hospital stay was identified. During the learning curve analysis using the cumulative summation by operation time (CUSUMOT), two surgeons who performed both L-recon and R-recon procedures reached their first peak in the CUSUMOT graph earlier for the R-recon group than for the L-recon group (i.e., 20th L-recon case and third R-recon case of surgeon A and 43rd L-recon case and seventh R-recon case of surgeon B). Surgeon C, who only performed R-recon, demonstrated the first peak in the 22nd case. The multivariate regression analysis for risk factors of CR-POPF showed that the MIPD procedure type, as well as other factors, did not have any significant effect. CONCLUSION: Postoperative pancreatic fistula rates and the overall perioperative outcomes of L-recon and R-recon were comparable in patients with soft-textured pancreas and small pancreatic duct treated by experienced surgeons.

Is it enough to observe less than 2 cm sized gastric SET?

BACKGROUND AND AIMS: The recent surge in demand for screening endoscopy has led to an increased detection of gastric subepithelial tumors (SETs). According to current guideline, SETs less than 2 cm in size are recommended for periodic surveillance. In light of recent advancement in therapeutic endoscopy in resection of small SET, we analyzed the histopathological features and the effectiveness of endoscopic resection for these small SETs. METHODS: Retrospectively study was performed on 74 patients who underwent endoscopic resection of gastric small (≤ 2 cm) upper gastrointestinal tract SETs. The outcomes including histopathology and en bloc resection were analyzed. RESULTS: The mean SET size was 11.69 ± 5.11 mm. The mean procedure time was 81.26 ± 42.53 min. Of the 74 patients, 28 patients had leiomyomas, 26 had gastrointestinal stromal tumors (GISTs), 14 had ectopic pancreas, 4 had lipomas, and 2 had neuroendocrine tumors. Among those with GIST, two patients exhibited high-risk histology. All patients underwent successful and uneventful endoscopy. CONCLUSIONS: Endoscopic resection can be recommended even for the small gastric SETs. In our study, we found that SETs with a size of less than 2 cm have significant proportion of GISTs which harbor malignant transformation potential.

Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids.

BACKGROUND/AIMS: A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex. METHODS: Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured. RESULTS: HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation. CONCLUSIONS: The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.

Lensless Three-Dimensional Imaging under Photon-Starved Conditions.

In this paper, we propose a lensless three-dimensional (3D) imaging under photon-starved conditions using diffraction grating and computational photon counting method. In conventional 3D imaging with and without the lens, 3D visualization of objects under photon-starved conditions may be difficult due to lack of photons. To solve this problem, our proposed method uses diffraction grating imaging as lensless 3D imaging and computational photon counting method for 3D visualization of objects under these conditions. In addition, to improve the visual quality of 3D images under severely photon-starved conditions, in this paper, multiple observation photon counting method with advanced statistical estimation such as Bayesian estimation is proposed. Multiple observation photon counting method can estimate the more accurate 3D images by remedying the random errors of photon occurrence because it can increase the samples of photons. To prove the ability of our proposed method, we implement the optical experiments and calculate the peak sidelobe ratio as the performance metric.

Besifovir therapy improves hepatic histology and reduces covalently closed circular DNA in chronic hepatitis B patients.

BACKGROUND AND AIM: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. METHODS: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. RESULTS: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). CONCLUSIONS: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients.

Cost-Effectiveness of Empirical Bismuth-Based Quadruple Therapy and Tailored Therapy After Clarithromycin Resistance Tests for Helicobacter pylori Eradication.

BACKGROUND: The eradication rate of clarithromycin-based standard triple therapy (STT) for Helicobacter pylori infection has decreased due to clarithromycin resistance (CR). We evaluated the cost-effectiveness of tailored therapy according to CR test results, and compared the results of STT with those of empirical bismuth quadruple therapy (BQT). METHODS: The prospectively collected data of 490 H. pylori-positive patients with chronic gastritis or peptic ulcer disease were retrospectively analyzed. Among them, 292 patients underwent CR testing using dual-priming oligonucleotide-based polymerase chain reaction. The tailored group (n = 292) consisted of patients treated with STT for 7 days and BQT for 10 days as per their CR test results. The remaining patients were assigned to the empirical group (n = 198) and received BQT for 10 days without a CR test. The eradication rate, adverse events and medical costs associated with H. pylori eradication therapy were investigated. RESULTS: In the tested patients (tailored group), the CR-positive rate was 32.2% (n = 94/292). The eradication rate according to an intention-to-treat analysis was 87.7% in the tailored group and 91.8% in the empirical group (P = 0.124); the respective rates were 94.4% and 97.9% by per-protocol analysis (P = 0.010). The frequency of adverse events was lower in the empirical group than the tailored group (35.1% vs. 52.7%, P < 0.001). Total per capita medical costs were $406.50 and $503.50, respectively. CONCLUSIONS: Ten-day empirical BQT was more effective, safer, and less expensive than tailored therapy based on a CR test for H. pylori eradication.

Prediction model for curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC. METHODS: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model. RESULTS: Endoscopic tumor size 1-2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54-3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81-28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03-2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1-2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673-0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748-0.803). CONCLUSIONS: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC.

Long-term outcomes of endoscopic resection followed by additional surgery after non-curative resection in undifferentiated-type early gastric cancer: a nationwide multi-center study.

BACKGROUND: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. METHODS: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively. CONCLUSIONS: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.

Safety of Gastrointestinal Endoscopy in Korea: A Nationwide Survey and Population-Based Study.

BACKGROUND: Attention should be paid to endoscopy-related complications and safety-related accidents that may occur in the endoscopy unit. This study investigated the current status of complications associated with diagnostic and therapeutic endoscopy in Korea. METHODS: A questionnaire survey on endoscopy-related complications was conducted in a total of 50 tertiary or general hospitals in Korea. The results were compared to the population-level claims data from the Health Insurance Review & Assessment Service (HIRA), which analyzed endoscopy procedures conducted in 2017 in Korea. RESULTS: The incidences of bleeding associated with diagnostic and therapeutic esophagogastroduodenoscopy (EGD) and with diagnostic and therapeutic colonoscopy were 0.224% and 3.155% and 0.198% and 0.356%, respectively, in the 2017 HIRA claims data, compared to 0.012% and 1.857%, and 0.024% and 0.717%, in the 50 hospitals surveyed. The incidences of perforation associated with diagnostic and therapeutic EGD and with diagnostic and therapeutic colonoscopy were 0.023% and 0.613%, and 0.007% and 0.013%, respectively, in the 2017 HIRA claims data compared to 0.001% and 0.325%, and 0.017% and 0.206%, in the 50 hospitals surveyed. In the HIRA claims data, the incidence of bleeding/perforation after diagnostic colonoscopy in clinics, community hospitals, general hospitals, and tertiary hospitals was 0.129%/0.000%, 0.088%/0.004%, 0.262%/0.009%, and 0.479%/0.030% respectively, and the corresponding incidence of bleeding/perforation after therapeutic colonoscopy was 0.258%/0.004%, 0.401%/0.007%, 0.408%/0.024%, and 0.731%/0.055%. CONCLUSION: The incidences of complications associated with diagnostic and therapeutic EGD or colonoscopy tended to increase with the hospital volume in Korea. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0001728.

Effect of antiviral therapy in patients with low HBV DNA level on transarterial chemoembolization for hepatocellular carcinoma.

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low-level viremia HBV-HCC receiving non-curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low-level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV-HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non-antiviral group). The definition of low-level viremia was an HBV DNA level <2000 IU/ml. Kaplan-Meier curves, log-rank tests and Cox regression analysis were used for statistical analyses. The median follow-up duration was 39 months (1-174 months). Overall survival (OS) did not differ between groups (P = .227). Barcelona Clinic Liver Cancer stage (BCLC), Child-Pugh (CP) class and α-fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P = .022) was a prognostic factor for 2-year survival. On subgroup analysis, antiviral therapy improved short-term survival in patients with BCLC stage 0 and A (P = .037) and CP class A (P = .04). In patients with low-level viremia, antiviral therapy yielded short-term survival benefits, particularly in patients with early-stage HCC.

Real-world systemic sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Korea.

Background/Aims Regorafenib has been approved as a second-line systemic therapy for hepatocellular carcinoma (HCC) patients after the phase III RESORCE trial. This study analyzed real-world data to assess the clinical effectiveness and safety of regorafenib compared to the RESORCE trial. Methods This multicenter cohort study included HCC patients treated with regorafenib after sorafenib (n = 133). We evaluated the time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety in patients receiving regorafenib along with the predictors of prognosis. Results The median age was 60 years and 81.2% patients were men. Hepatitis B virus infection (68.4%) was the commonest etiology. Most patients were classified as Child-Pugh A (98.5%) and had extrahepatic metastasis (84%) and vascular invasion (45.1%). This study demonstrated similar characteristics apart from more frequent hepatitis B etiology and more vascular or extrahepatic involvement compared with the RESORCE trial. An objective response rate of 12.5% was obtained for response assessment (n = 112); the disease control rate was 34.8%. Thirty-eight patients died during follow-up. With regorafenib, the median OS, PFS, and TTP were 10.0, 2.7, and 2.6 months, respectively. In the exploratory analysis after sorafenib administration, the median OS was 25.8 months. The rate of response and survival were comparable to those in the RESORCE trial. Child-Pugh score > 5, alpha-fetoprotein > 400 ng/ml, and TTP for sorafenib ≥ median were independently associated with OS. Conclusions This real-word regorafenib study showed comparable effectiveness and safety to the RESORCE trial. Regorafenib improves the prognosis of patients with prolonged TTP during previous sorafenib therapy.

Favorable outcomes of rescue second- or third-line culture-based Helicobacter pylori eradication treatment in areas of high antimicrobial resistance.

BACKGROUND: Failure of second or third-line eradication treatment against Helicobacter pylori (H. pylori) is principally caused by antimicrobial resistance and reduced treatment adherence. AIMS: To evaluate the efficacy and safety of culture-based rescue eradication treatments in patients who have previously experienced failed eradication treatment. METHODS: Patients who had persistent H. pylori infection following at least one eradication treatment were recommended to undergo culture analysis to determine the minimal inhibitory concentrations of various antimicrobials via endoscopic resection. Consenting patients were assigned one of four therapeutic treatments based on an algorithm determined by antimicrobial resistance. These treatments consisted of 7 or 14-day administration of clarithromycin-containing proton pump inhibitor (PPI) triple therapy; esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy; or lansoprazole, rifabutin, and amoxicillin (RLA) therapy. Eradication efficacy, adherence, and adverse events were assessed aside clinical outcomes. RESULTS: A total of 132 patients were enrolled, with 84 patients completing the study. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 13.1%, 83.3%, 47.6%, and 71.4%, respectively. The patients were allocated to the PPI triple (n = 11), MEA (n = 15), quadruple (n = 53), or RLA triple (n = 5) therapy group. The eradication rates in the intention-to-treat and per-protocol analyses were 90.5% (76 of 84 patients) and 93.8% (76 of 81 patients), respectively. Nausea was the most frequent adverse event (25.0%). CONCLUSIONS: As a rescue therapy, culture-based susceptibility-guided eradication treatment was both effective and safe, even for patients exhibiting high antimicrobial resistance.

Clinical outcomes of endoscopic resection for undifferentiated intramucosal early gastric cancer larger than 2 cm.

BACKGROUND: This study investigated the long-term clinical outcomes of endoscopic resection (ER) for undifferentiated-type (UD) early gastric cancer (EGC), with tumor size > 2 cm as the only non-curative factor. METHODS: From among 1123 patients who underwent ER for UD EGC at 18 tertiary hospitals in Korea between 2005 and 2014, we identified 216 patients with UD intramucosal EGC > 2 cm, which was completely resected, with negative resection margins, and absence of ulceration and lymphovascular invasion. The patients were divided into the additional surgery (n = 40) or observation (n = 176) groups, according to post-ER management and were followed up for a median duration of 59 months for recurrence and 90 months for overall survival. RESULTS: Lymph node (LN) or distant metastasis or cancer-related mortality was not observed in the surgery group. In the observation group, two (1.1%) patients developed LN or distant metastasis with a 5-year cumulative risk of 0.7%, and one (0.6%) patient died of gastric cancer. The 5- and 8-year overall survival rates were 94.1% and 89.9%, respectively, in the observation group and 100.0% and 95.2%, respectively, in the surgery group (log-rank P = 0.159). Cox regression analysis did not reveal an association between the observation group and increased mortality. CONCLUSION: The risk of LN or distant metastasis was not negligible, but as low as 1% for patients undergoing non-curative ER for UD EGC, with tumor size > 2 cm as the only non-curative factor. Close observation may be an alternative to surgery, especially for older patients or those with poor physical status.

Comparison between endoscopic submucosal resection and surgery for the curative resection of undifferentiated-type early gastric cancer within expanded indications: a nationwide multi-center study.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD EGC) has debate due to the risk of lymph node metastasis. We investigated the outcomes of ESD compared to those of surgery for the UD EGC within expanded indication. METHODS: We reviewed 971 UD EGC patients performed ESD across 18 hospitals in Korea and 1812 patients who underwent surgical resection in two hospitals between February 2005 and May 2015. Of these cases, we enrolled a curative resected ESD group of 328 patients and surgery group of 383 cases within an expanded indication. Overall outcomes and one-to-one propensity score-matched (218 ESD group vs 218 surgery group cases) outcomes for these two groups were analyzed. RESULTS: Over the 75.6 month median follow-up period for the 711 enrolled cases, recurrences occurred in 22 patients (6.7%) in the ESD group but not in the surgery group. Overall survival (OS) was higher in the surgery group (p = 0.0316) in all cases, but there was no significant difference after propensity score matching (p = 0.069). According to the histologic type in propensity score matching, the OS of signet ring cell carcinoma and poorly differentiated carcinoma patients did not differ between the ESD and surgery groups (p = 0.1189 and p = 0.3087, respectively). In the surgery group involving expanded criteria, lymph node metastasis was found in six cases (1.56%). CONCLUSIONS: Although ESD shows comparable outcomes to surgery for the UD EGC within expanded indications, appropriate patient selection is needed for the ESD due to the possibility of lymph node metastasis.