Extrahepatic Malignancies and Antiviral Drugs for Chronic Hepatitis B: A Nationwide Cohort Study.

Background/Aims: Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment. Methods: Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders. Results: The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.1, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88-1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60-0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81-0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62-0.75, P<0.01; E-value for SHR=2.30). Conclusions: TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.

Predicting Helicobacter pylori infection from endoscopic features.

BACKGROUND: Helicobacter pylori infection, prevalent in more than half of the global population, is associated with various gastrointestinal diseases, including peptic ulcers and gastric cancer. The effectiveness of early diagnosis and treatment in preventing gastric cancer highlights the need for improved diagnostic methods. This study aimed to develop a simple scoring system based on endoscopic findings to predict H. pylori infection. METHODS: A retrospective analysis was conducted on 1,007 patients who underwent upper gastrointestinal endoscopy at Asan Medical Center from January 2019 to December 2021. Exclusion criteria included prior H. pylori treatment, gastric surgery, or gastric malignancies. Diagnostic techniques included rapid urease and 13C-urea breath tests, H. pylori culture, and assessment of endoscopic features following the Kyoto gastritis classification. A new scoring system based on endoscopic findings including regular arrangement of collecting venules (RAC), nodularity, and diffuse or spotty redness was developed for predicting H. pylori infection, utilizing logistic regression analysis in the development set. RESULTS: The scoring system demonstrated high predictive accuracy for H. pylori infection in the validation set. Scores of 2 and 3 were associated with 96% and 99% infection risk, respectively. Additionally, there was a higher prevalence of diffuse redness and sticky mucus in cases where the initial H. pylori eradication treatment failed. CONCLUSION: Our scoring system showed potential for improving diagnostic accuracy in H. pylori infection. H. pylori testing should be considered upon spotty redness, diffuse redness, nodularity, and RAC absence on endoscopic findings as determined by the predictive scoring system.

Prediction of immunochemotherapy response for diffuse large B-cell lymphoma using artificial intelligence digital pathology.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and prevalent subtype of aggressive non-Hodgkin lymphoma that poses diagnostic and prognostic challenges, particularly in predicting drug responsiveness. In this study, we used digital pathology and deep learning to predict responses to immunochemotherapy in patients with DLBCL. We retrospectively collected 251 slide images from 216 DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), with their immunochemotherapy response labels. The digital pathology images were processed using contrastive learning for feature extraction. A multi-modal prediction model was developed by integrating clinical data and pathology image features. Knowledge distillation was employed to mitigate overfitting on gigapixel histopathology images to create a model that predicts responses based solely on pathology images. Based on the importance derived from the attention mechanism of the model, we extracted histological features that were considered key textures associated with drug responsiveness. The multi-modal prediction model achieved an impressive area under the ROC curve of 0.856, demonstrating significant associations with clinical variables such as Ann Arbor stage, International Prognostic Index, and bulky disease. Survival analyses indicated their effectiveness in predicting relapse-free survival. External validation using TCGA datasets supported the model's ability to predict survival differences. Additionally, pathology-based predictions show promise as independent prognostic indicators. Histopathological analysis identified centroblastic and immunoblastic features to be associated with treatment response, aligning with previous morphological classifications and highlighting the objectivity and reproducibility of artificial intelligence-based diagnosis. This study introduces a novel approach that combines digital pathology and clinical data to predict the response to immunochemotherapy in patients with DLBCL. This model shows great promise as a diagnostic and prognostic tool for clinical management of DLBCL. Further research and genomic data integration hold the potential to enhance its impact on clinical practice, ultimately improving patient outcomes.

Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evoked a worldwide pandemic. As the emergence of variants has hampered the neutralization capacity of currently available vaccines, developing effective antiviral therapeutics against SARS-CoV-2 and its variants becomes a significant challenge. The main protease (Mpro) of SARS-CoV-2 has received increased attention as an attractive pharmaceutical target because of its pivotal role in viral replication and proliferation. Here, we generated a de novo Mpro-inhibitor screening platform to evaluate the efficacies of Mpro inhibitors based on Mpro cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and Mpro-cleavage sequence, mimicking in vivo viral replication process mediated by Mpro. By measuring the proteolytic activity of Mpro and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of Mpro inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering Mpro inhibitors and may accelerate the development of therapeutics against COVID-19.

Natural history of gastric leiomyoma.

BACKGROUND: Most gastric leiomyomas are asymptomatic and benign subepithelial tumors (SETs); however, some may increase in size or become symptomatic. Understanding their natural history is therefore important to their management. We investigated the natural history of histologically proven gastric leiomyomas. METHODS: We retrospectively reviewed histologically proven gastric leiomyoma cases at a tertiary center. The baseline characteristics of these cases were analyzed, and those with a follow-up period of at least 12 months without immediate resection were evaluated. The primary outcome was the frequency of size increase of more than 25% during the follow-up period, and the secondary outcome was the histopathologic results in cases that underwent resection. RESULTS: Among the 231 patients with histologically proven gastric leiomyomas, the most frequent location was the cardia (77.1%), and the median size was 3 cm (IQR 2-4 cm). Eighty-four cases were followed up over a median period of 50.8 months (IQR 27.2-91.3 months). During the follow-up period, tumor size increased in two cases (2.4%). Surgical results showed that one case was leiomyoma, and the other was leiomyosarcoma. Among the remaining cases without change in size, 15 underwent surgical resection (n = 10) or endoscopic resection (n = 5), and all cases were confirmed as leiomyoma. CONCLUSIONS: Most gastric leiomyomas are benign SETs, and an increase in size is not frequent, even in large-sized cases. Close monitoring with routine follow-up without resection may be sufficient in cases of histologically proven gastric leiomyoma. However, in cases of ulceration or size increase, resection may be beneficial.

Advancing Korean nationwide registry for hepatocellular carcinoma: a systematic sampling approach utilizing the Korea Central Cancer Registry database.

Hepatocellular carcinoma (HCC) presents a substantial public health challenge in South Korea as evidenced by 10,565 new cases annually (incidence rate of 30 per 100,000 individuals), in 2020. Cancer registries play a crucial role in gathering data on incidence, disease attributes, etiology, treatment modalities, outcomes, and informing health policies. The effectiveness of a registry depends on the completeness and accuracy of data. Established in 1999 by the Ministry of Health and Welfare, the Korea Central Cancer Registry (KCCR) is a comprehensive, legally mandated, nationwide registry that captures nearly all incidence and survival data for major cancers, including HCC, in Korea. However, detailed information on cancer staging, specific characteristics, and treatments is lacking. To address this gap, the KCCR, in partnership with the Korean Liver Cancer Association (KLCA), has implemented a systematic approach to collect detailed data on HCC since 2010. This involved random sampling of 10-15% of all new HCC cases diagnosed since 2003. The registry process encompassed four stages: random case selection, meticulous data extraction by trained personnel, expert validation, anonymization of personal data, and data dissemination for research purposes. This random sampling strategy mitigates the biases associated with voluntary reporting and aligns with stringent privacy regulations. This innovative approach positions the KCCR and KLCA as foundations for advancing cancer control and shaping health policies in South Korea.

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.

Endoscopic resection of gastric gastrointestinal stromal tumor using clip-and-cut endoscopic full-thickness resection: a single-center, retrospective cohort in Korea.

BACKGROUND/AIMS: To overcome the technical limitations of classic endoscopic resection for gastric gastrointestinal stromal tumors (GISTs), various methods have been developed. In this study, we examined the role and feasibility of clip-and-cut procedures (clip-and-cut endoscopic full-thickness resection [cc-EFTR]) for gastric GISTs. METHODS: Medical records of 83 patients diagnosed with GISTs after endoscopic resection between 2005 and 2021 were retrospectively reviewed. Moreover, clinical characteristics and outcomes were analyzed. RESULTS: Endoscopic submucosal dissection (ESD) and cc-EFTR were performed in 51 and 32 patients, respectively. The GISTs were detected in the upper third of the stomach for ESD (52.9%) and cc-EFTR (90.6%). Within the cc-EFTR group, a majority of GISTs were located in the deep muscularis propria or serosal layer, accounting for 96.9%, as opposed to those in the ESD group (45.1%). The R0 resection rates were 51.0% and 84.4% in the ESD and cc-EFTR groups, respectively. Seven (8.4%) patients required surgical treatment (six patients underwent ESD and one underwent cc-EFTR,) due to residual tumor (n=5) and post-procedure adverse events (n=2). Patients undergoing R0 or R1 resection did not experience recurrence during a median 14-month follow-up period, except for one patient in the ESD group. CONCLUSIONS: cc-EFTR displayed a high R0 resection rate; therefore, it is a safe and effective therapeutic option for small gastric GISTs.

Evaluating the Diagnostic Potential of Connected Speech for Benign Laryngeal Disease Using Deep Learning Analysis.

OBJECTIVES: This study aimed to evaluate the performance of artificial intelligence (AI) models using connected speech and vowel sounds in detecting benign laryngeal diseases. STUDY DESIGN: Retrospective. METHODS: Voice samples from 772 patients, including 502 with normal voices and 270 with vocal cord polyps, cysts, or nodules, were analyzed. We employed deep learning architectures, including convolutional neural networks (CNNs) and time series models, to process the speech data. The primary endpoint was the area under the receiver's operating characteristic curve for binary classification. RESULTS: CNN models analyzing speech segments significantly outperformed those using vowel sounds in distinguishing patients with and without benign laryngeal diseases. The best-performing CNN model achieved areas under the receiver operating characteristic curve of 0.895 and 0.845 for speech and vowel sounds, respectively. Correlations between AI-generated disease probabilities and perceptual assessments were more pronounced in the connected-speech analyses. However, the time series models performed worse than the CNNs. CONCLUSION: Connected speech analysis is more effective than traditional vowel sound analysis for the diagnosis of laryngeal voice disorders. This study highlights the potential of AI technologies in enhancing the diagnostic capabilities of speech, advocating further exploration, and validation in this field.

Extrahepatic malignancies in metabolic dysfunction-associated fatty liver disease: A nationwide cohort study.

BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes. METHODS: This nationwide cohort study included 9 298 497 patients who participated in a health-screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non-MAFLD, diabetes mellitus (DM)-MAFLD, overweight/obese-MAFLD and lean-MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all-cause and extrahepatic malignancy-related mortality. RESULTS: In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow-up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM-MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11-1.14; p < .001) and the lean-MAFLD (aSHR = 1.12; 95% CI = 1.10-1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non-MAFLD group. However, the overweight/obese-MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non-MAFLD group (aSHR = 1.00; 95% CI = .99-1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM-MAFLD was an independent risk factor for all-cause mortality (adjusted hazard ratio [aHR] = 1.41; 95% CI = 1.40-1.43; p < .001) and extrahepatic malignancy-related mortality (aHR = 1.20; 95% CI = 1.17-1.23; p < .001). CONCLUSION: The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non-MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.

Ensemble Deep Learning Model to Predict Lymphovascular Invasion in Gastric Cancer.

Lymphovascular invasion (LVI) is one of the most important prognostic factors in gastric cancer as it indicates a higher likelihood of lymph node metastasis and poorer overall outcome for the patient. Despite its importance, the detection of LVI(+) in histopathology specimens of gastric cancer can be a challenging task for pathologists as invasion can be subtle and difficult to discern. Herein, we propose a deep learning-based LVI(+) detection method using H&E-stained whole-slide images. The ConViT model showed the best performance in terms of both AUROC and AURPC among the classification models (AUROC: 0.9796; AUPRC: 0.9648). The AUROC and AUPRC of YOLOX computed based on the augmented patch-level confidence score were slightly lower (AUROC: -0.0094; AUPRC: -0.0225) than those of the ConViT classification model. With weighted averaging of the patch-level confidence scores, the ensemble model exhibited the best AUROC, AUPRC, and F1 scores of 0.9880, 0.9769, and 0.9280, respectively. The proposed model is expected to contribute to precision medicine by potentially saving examination-related time and labor and reducing disagreements among pathologists.

Clinical outcomes of argon plasma coagulation for the treatment of gastric low grade dysplasia.

BACKGROUND & AIMS: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low grade dysplasia (LGD) instead of endoscopic resection (ER). Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence. METHODS: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. 112 subjects without any information about H. pylori infection status, 164 subjects who underwent APC for salvage therapy, 5 subjects with high grade dysplasia, and 12 subjects with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed. RESULTS: A total of 618 patients with LGD (median age of 64 years old) were followed up for a median of 30 months and local recurrence has happened in 21 patients (3.4%). Multivariate analysis showed lesion size (hazard ratio 1.06, 95% confidential interval 1.01-1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 cases (2.6%) and local recurrence was in 7 cases (9.5%) of 109 tumors larger than 10 mm (p <0.004). CONCLUSIONS: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of ER. However, when a lesion is larger, APC should be selected carefully with close monitoring.

Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND/AIM: Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT). METHODS: We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1. RESULTS: A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74). CONCLUSION: The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.

Dysphagia associated with esophageal wall thickening in patients with nonspecific high-resolution manometry findings: Understanding motility beyond the Chicago classification version 4.0.

BACKGROUND: Previous studies have demonstrated that 50% of patients with normal high-resolution manometry (HRM) findings or ineffective esophageal motility (IEM) may have abnormal functional luminal imaging probe (FLIP) results. However, the specific HRM findings associated with abnormal FLIP results are unknown. Herein, we investigated the relationship between nonspecific manometry findings and abnormal FLIP results. METHODS: We retrospectively analyzed 684 patients who underwent HRM at a tertiary care center in Seoul, Korea, based on the Chicago Classification version 4.0 protocol. KEY RESULTS: Among the 684 patients, 398 had normal HRM findings or IEM. Of these 398 patients, eight showed esophageal wall thickening on endoscopic ultrasonography or computed tomography; however, no abnormalities were seen during esophagogastroduodenoscopy. Among these eight patients, seven showed repetitive simultaneous contractions (RSCs) in at least one of the two positions: 61% (±29%) in 10 swallows in the supine position and 51% (±30%) in five swallows in the upright position. Four patients who underwent FLIP had a significantly decreased esophagogastric junction distensibility index (1.0 ± 0.5 m m 2 mmHg - 1 at 60 mL). Two of these patients underwent per-oral endoscopic myotomy (POEM) due to a lack of response to medication. Esophageal muscle biopsy revealed hypertrophic muscle with marginal eosinophil infiltration. CONCLUSIONS & INFERENCES: A subset of patients (2%) with normal HRM findings or IEM and RSCs experienced dysphagia associated with poor distensibility of the thickened esophageal wall. FLIP assessment or combined HRM and impedance protocols may help better define these patients who may respond well to POEM.

Artificial Intelligence Model Assisting Thyroid Nodule Diagnosis and Management: A Multicenter Diagnostic Study.

CONTEXT: It is not clear how to integrate artificial intelligence (AI)-based models into diagnostic workflows. OBJECTIVE: To develop and validate a deep-learning-based AI model (AI-Thyroid) for thyroid cancer diagnosis, and to explore how this improves diagnostic performance. METHODS: The system was trained using 19 711 images of 6163 patients in a tertiary hospital (Ajou University Medical Center; AUMC). It was validated using 11 185 images of 4820 patients in 24 hospitals (test set 1) and 4490 images of 2367 patients in AUMC (test set 2). The clinical implications were determined by comparing the findings of six physicians with different levels of experience (group 1: 4 trainees, and group 2: 2 faculty radiologists) before and after AI-Thyroid assistance. RESULTS: The area under the receiver operating characteristic (AUROC) curve of AI-Thyroid was 0.939. The AUROC, sensitivity, and specificity were 0.922, 87.0%, and 81.5% for test set 1 and 0.938, 89.9%, and 81.6% for test set 2. The AUROCs of AI-Thyroid did not differ significantly according to the prevalence of malignancies (>15.0% vs ≤15.0%, P = .226). In the simulated scenario, AI-Thyroid assistance changed the AUROC, sensitivity, and specificity from 0.854 to 0.945, from 84.2% to 92.7%, and from 72.9% to 86.6% (all P < .001) in group 1, and from 0.914 to 0.939 (P = .022), from 78.6% to 85.5% (P = .053) and from 91.9% to 92.5% (P = .683) in group 2. The interobserver agreement improved from moderate to substantial in both groups. CONCLUSION: AI-Thyroid can improve diagnostic performance and interobserver agreement in thyroid cancer diagnosis, especially in less-experienced physicians.

Reappraisal of Portal Vein Tumor Thrombosis as a Prognostic Factor for Patients with Hepatocellular Carcinoma.

Background/Aims: : This study aimed to assess whether hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) could have favorable prognoses with proper treatment under selective conditions. Methods: : This retrospective, single-center study involved 1,168 patients diagnosed with HCC between January 2005 and December 2006, before the introduction of sorafenib. Overall survival (OS) was estimated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify and adjust the variables associated with OS. Results: : In nodular-type HCC, the OS differed significantly according to the presence of PVTT (log-rank p<0.001), and the level of PVTT, not only its presence, was a major independent factor affecting OS. PVTT at the Vp1-3 branch was associated with significantly longer OS than was PVTT at the Vp4 level (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.04 to 3.21). In multivariate analysis, the OS was further stratified according to the PVTT level and tumor type, representing that nodular HCC without PVTT exhibited the best OS, whereas nodular HCC with Vp4 PVTT (adjusted HR, 2.59; 95% CI, 1.57 to 4.28) showed a poor prognosis similar to that of infiltrative HCC. The PVTT level was consistently correlated with OS in patients treated with transarterial chemoembolization. Nodular HCC without PVTT showed the best prognosis, while nodular HCC with Vp1-3 PVTT also exhibited a favorable OS, although inferior to that without PVTT (adjusted HR, 1.47, 95% CI, 0.92 to 2.36). Conclusions: : Active treatment such as transarterial chemoembolization can be considered for selected PVTT cases. The level of PVTT and type of HCC were independent prognostic factors.

Differential Diagnosis of Thickened Gastric Wall between Hypertrophic Gastritis and Borrmann Type 4 Advanced Gastric Cancer.

Background/Aims: : Accurately diagnosing diffuse gastric wall thickening is challenging. Hypertrophic gastritis (HG), while benign, mimics the morphology of Borrmann type 4 advanced gastric cancer (AGC B-4). We compared the features of endoscopy and endoscopic ultrasonography (EUS) between them. Methods: : We retrospectively reviewed patients who underwent EUS for gastric wall thickening between 2000 and 2021, selecting HG and pathologically confirmed advanced gastric cancer cases. Ulceration and antral wall thickening were determined via endoscopy, while EUS assessed the 5-layered gastric wall structure, measuring the proper muscle (PM) layer and total wall thickness. Results: : Male dominance was observed in AGC B-4, and the hemoglobin and albumin levels were significantly lower. The rate of antral wall thickening and presence of ulceration were significantly higher in AGC B-4 cases. Destruction of the PM layers was observed only in AGC B-4 cases, and the PM was significantly thicker in AGC B-4 cases. Forceps biopsy had an excellent success rate in ulcer-present AGC B-4 cases, but only a 42.6% success rate was observed for cases without ulcers, necessitating additional diagnostic modalities. A PM thickness of 2.39 mm distinguished between AGC B-4 and HG effectively. The multivariable analysis showed that a thickened PM layer and the presence of ulceration were significant risk factors for the diagnosis of AGC B-4. Conclusions: : Endoscopic findings of a thickened gastric wall, including antral involvement, and presence of ulcer were significant risk factors for the diagnosis of AGC B-4. EUS findings of destroyed wall layers and a thickened PM of >2.39 mm were the key points of differentiation between HG and AGC B-4.

Comparison of Quality, Antioxidant Capacity, and Anti-Inflammatory Activity of Adlay [Coix lacryma-jobi L. var. ma-yuen (Rom. Caill.) Stapf.] Sprout at Several Harvest Time.

Recently, there has been a growing interest in the consumption of plant-based foods such as vegetables and grains for the purpose of disease prevention and treatment. Adlay seeds contain physiologically active substances, including coixol, coixenolide, and lactams. In this study, adlay sprouts were cultivated and harvested at various time points, specifically at 3, 5, 7, 9, and 11 days after sowing. The antioxidant activity of the extracts was evaluated using assays such as DPPH radical scavenging, ABTS radical scavenging, reducing power, and total polyphenol contents. The toxicity of the extracts was assessed using cell culture and the WST-1 assay. The aboveground components of the sprouts demonstrated a significant increase in length, ranging from 2.75 cm to 21.87 cm, weight, ranging from 0.05 g to 0.32 g, and biomass, ranging from 161.4 g to 1319.1 g, as the number of days after sowing advanced, reaching its peak coixol content of 39.38 mg/g on the third day after sowing. Notably, the antioxidant enzyme activity was highest between the third and fifth days after sowing. Regarding anti-inflammatory activity, the inhibition of cyclooxygenase 2 (COX-2) expression was most prominent in samples harvested from the ninth to eleventh days after sowing, corresponding to the later stage of growth. While the overall production mass increased with the number of days after sowing, considering factors such as yield increase index per unit area, turnover rate, and antioxidant activity, harvesting at the early growth stage, specifically between the fifth and seventh days after sowing, was found to be economically advantageous. Thus, the quality, antioxidant capacity, and anti-inflammatory activity of adlay sprouts varied depending on the harvest time, highlighting the importance of determining the appropriate harvest time based on the production objectives. This study demonstrates the changes in the growth and quality of adlay sprouts in relation to the harvest time, emphasizing the potential for developing a market for adlay sprouts as a new food product.

Risk factors associated with recurrence of gastric hyperplastic polyps: a single-center, long-term, retrospective cohort study.

BACKGROUND: The likelihood of recurrence of gastric hyperplastic polyps (GHPs) following endoscopic resection and the need for long-term follow-up remain unknown. We, therefore, aimed to investigate the factors associated with the recurrence and cumulative incidence of GHPs over a 10-year period. METHODS: Between May 1995 and December 2020, 1,018 GHPs > 1 cm were endoscopically resected from 869 patients. Medical records of these patients were retrospectively reviewed and their clinical features and outcomes were assessed. Groups of GHPs with recurrence and those without recurrence group were compared, and univariate and multivariable analyses were performed to identify the potential risk factors for GHP recurrence. RESULTS: A total of 104 (12.0%) patients who underwent endoscopic removal of GHPs experienced recurrence. Compared to patients without recurrent GHPs, those with recurrent GHPs showed considerably larger median polyp size (28 mm vs. 14 mm, P < 0.001), a higher proportion of multiple polyps (41.3% vs. 29.3%, P = 0.020), polyps with lobulation (63.5% vs. 40.3%, P = 0.001), and exudate (63.5% vs. 46.8%, P = 0.001). Compared to the local recurrence (n = 52) group, the metachronous recurrence (n = 52) group had larger median polyp size (20 mm vs. 16 mm, P = 0.006) as well as higher rates of polyp lobulation (86.5% vs. 40.4%, P < 0.001) and exudate (82.7% vs. 44.4%, P = 0.001). After primary GHP excision, the cumulative incidence of recurrence was 7.2%, 12.7%, and 19.6% at 2 years, 5 years, and 10 years, respectively. CONCLUSION: The incidence of GHP recurrence following endoscopic excision increased as the follow-up period increased, especially in patients whose GHPs were large-sized, multiple, or characterized by surface exudates/lobulations.

A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma.

PURPOSE: Synergistic effect of radiotherapy and immunotherapy for the treatment of hepatocellular carcinoma (HCC) has been reported. This phase I/IIa pilot trial evaluated preliminary efficacy and safety of combination of radioembolization with yttrium-90 microspheres (Y90-radioembolization) and durvalumab in patients with locally advanced unresectable HCC. PATIENTS AND METHODS: Patients with Child-Pugh score ≤ 7 and locally advanced HCC, defined as Barcelona Clinic Liver Cancer (BCLC) stage B HCC or BCLC-C disease without extrahepatic metastases, received Y90-radioembolization followed by intravenous durvalumab 1,500 mg 7 to 14 days after Y90-radioembolization and every 4 weeks thereafter. Primary endpoint was time to progression (TTP) assessed by modified RECIST (mRECIST). Secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) determined by mRECIST, and safety. RESULTS: All 24 patients enrolled received Y90-radioembolization and 23 received at least one dose of durvalumab. Median follow-up duration was 19.0 months (range, 2.2-24.2). Median TTP was 15.2 months [95% confidence interval (CI), 6.1-not estimated]. Median OS was not reached and 18-month OS rate was 58.3% (95% CI, 36.4-75.0). Median PFS was 6.9 months (95% CI, 5.4-15.2). Seven (29.2%) patients had a complete response and 13 (54.2%) had a partial response; ORR was 83.3% (95% CI, 62.6-95.3). Eleven (47.8%) patients experienced any-grade treatment-related adverse events. Two (8.7%) patients had grade 3 treatment-related adverse events (neutropenia and fever). None experienced any treatment-related serious adverse events. CONCLUSIONS: In patients with locally advanced unresectable HCC, the combination of Y90-radioembolization and durvalumab demonstrated promising efficacy and safety, warranting further evaluation in large-scale controlled trials.