Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital.

BACKGROUND: While primary intestinal lymphangiectasia (PIL) is considered a rare condition, there have been several reported cases in adults. Nevertheless, the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients. AIM: To enhance understanding by investigating clinical presentation, diagnosis, treatment, complications, and prognoses in adult PIL cases. METHODS: We enrolled adult patients diagnosed with PIL between March 2016 and September 2021. The primary outcome involved examining the diagnosis and treatment process of these patients. The secondary outcomes included identifying complications (infections, thromboembolism) and assessing prognoses (frequency of hospitalization and mortality) during the follow-up period. RESULTS: Among the 12 included patients, peripheral edema (100%) and diarrhea (75%) were the main presenting complaints. Laboratory tests showed that all the patients exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia. Radiologically, the predominant findings were edema of the small intestine (67%) and ascites (58%). The typical endoscopic finding with a snowflake appearance was observed in 75% of patients. Among the 12 patients, two responded positively to octreotide and sirolimus, and eight who could undergo maintenance therapy discontinued subsequently. Complications due to PIL led to infection in half of the patients, thromboembolism in three patients, and one death. CONCLUSION: PIL can be diagnosed in adults across various age groups, with different severity and treatment responses among patients, leading to diverse complications and prognoses. Consequently, tailored treatments will be necessary. We anticipate that our findings will contribute to the management of PIL, an etiology of protein-losing enteropathy.

Incidence of invasive fungal diseases in inflammatory bowel disease patients: A nationwide study in South Korea.

BACKGROUND: Limited reports exist regarding invasive fungal diseases (IFDs) in inflammatory bowel disease (IBD) patients. OBJECTIVES: This study aims to investigate the incidence and risk factors of IFDs, specifically invasive candidiasis, aspergillosis and pneumocystosis, in IBD patients in South Korea using nationwide data. PATIENTS/METHODS: A population-based retrospective cohort of 42,913 IBD patients between January 2010 and December 2018 was evaluated using the Health Insurance Review and Assessment database. The primary outcome was the incidence of IFDs, including invasive candidiasis, aspergillosis and pneumocystosis, while the secondary outcome involved analysing the risk factors associated with each specific infection. RESULTS: The study included a total of 42,913 IBD patients, with 29,909 (69.7%) diagnosed with ulcerative colitis (UC) and 13,004 (30.3%) diagnosed with Crohn's disease (CD). IFDs occurred in 166 IBD patients (0.4%), with 93 cases in UC patients and 73 cases in CD patients. The incidence rates of invasive candidiasis, aspergillosis and pneumocystosis in IBD patients were 0.71 per 1000 person-years (PYs), 0.15 per 1000 PYs and 0.12 per 1000 PYs, respectively. The cumulative incidence of invasive candidiasis (adjusted p-value <.001) and Pneumocystosis (adjusted p-value = .012) was found to be higher in CD patients than in UC patients. Each IFD had different risk factors, including IBD subtypes, age at diagnosis, anti-tumour necrotic factor agents or the Charlson comorbidity index. CONCLUSION: Based on nationwide data in South Korea, this study shows that IFDs occur consistently in patients with IBD, albeit with a low frequency.

Comparison of an Endoscopic Scoring System and the Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn's Disease.

Background/Aims: The newly derived simplified magnetic resonance index of activity (MARIAs) has not been verified in comparison to balloon-assisted enteroscopy (BAE) for patients with small bowel Crohn's disease (CD). We studied the correlation of MARIAs with simple endoscopic scores for CD (SES-CD) of the ileum based on magnetic resonance enterography (MRE) and BAE in patients with small bowel CD. Methods: Fifty patients with small bowel CD who underwent BAE and MRE concurrently within 3 months from September 2020 to June 2021 were enrolled in the study. The primary outcome was the correlation between the active score of ileal SES-CD (ileal SES-CDa)/ileal SES-CD and MARIAs based on BAE and MRE. The cutoff value for MARIAs identifying endoscopically active/severe disease, defined as ileal SES-CDa/ileal SES-CD of 5/7 or more, was analyzed. Results: Ileal SES-CDa/ileal SES-CD and MARIAs showed strong associations (R=0.76, p<0.001; R=0.78, p<0.001). The area under the receiver operating characteristic curve of MARIAs for ileal SES-CDa ≥5 and ileal SES-CD ≥7 was 0.92 (95% confidence interval, 0.88 to 0.97) and 0.92 (95% confidence interval, 0.87 to 0.97). The cutoff value of MARIAs for detecting active/severe disease was 3. A MARIAs index value of ≥3 identified ileal SES-CDa ≥5 with a sensitivity of 85% and specificity of 87% and detected ileal SES-CD ≥7 with a sensitivity of 87% and specificity of 86%. Conclusions: This study validated the applicability of MARIAs compared to BAE-based ileal SES-CDa/SES-CD.

Blood Concentrations of Lead, Cadmium, and Mercury Are Associated With Alcohol-Related Liver Disease.

BACKGROUND: An association between environmental pollutants and alcohol-related liver disease (ALD) has not been determined until now. The objectives of this study were to examine the association of the pollutants with ALD, and whether the pollutants together increased the risk of ALD. METHODS: Data were extracted from the Korea National Health and Nutrition Examination Survey (2010-2013 and 2016-2017; n = 11,993). Blood levels of lead, cadmium, and mercury were measured. ALD was defined by a combination of excessive alcohol consumption and ALD/non-alcoholic fatty liver disease index > 0. The aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 score were used to evaluate ALD FIB. RESULTS: The odds ratios (ORs) of ALD for the highest versus the lowest quartiles of exposure were for lead, 7.39 (95% confidence interval [CI], 5.51-9.91); cadmium, 1.68 (95% CI, 1.32-2.14); and mercury, 5.03 (95% CI, 3.88-6.53). Adjusting for age, gender, smoking, occupation, education, and personal income attenuated the associations but indicated significant positive trends (all Ptrend < 0.001). A positive additive interaction between cadmium and lead was observed. The relative excess OR due to the interaction was 0.96 (95% CI, 0.41-1.51); synergy index = 2.92 (95% CI, 0.97-8.80). Among 951 subjects with ALD, advanced FIB was associated with lead and cadmium (OR, 3.46, 95% CI, 1.84-6.53; OR, 8.50, 95% CI, 2.54-28.42, respectively), but not with mercury. The effect estimates for lead and cadmium remained significant even after adjustment for daily alcohol intake. CONCLUSION: Blood levels of lead, cadmium, and mercury were significantly associated not only with the risk of ALD but also with ALD FIB. Cadmium and lead have synergistic effects that increase the risk of ALD.

Can balloon-assisted enteroscopy predict disease outcomes in patients with small-bowel Crohn's disease?

There are limited studies on the endoscopic assessment of disease activity using balloon-assisted enteroscopy (BAE) and its predictive role for long-term outcomes of patients with small bowel Crohn's disease (CD). We sought to investigate the value of BAE as a predictor of long-term outcomes in patients with small-bowel CD. A total of 111 patients with small-bowel CD whose endoscopic disease activity was assessed using BAE based on the small-bowel simple endoscopic score for Crohn's disease (small-bowel SES-CD) at Samsung Medical Center were retrospectively selected from January 2014 to August 2020. The outcome was an evaluation of the risk of surgery according to a small-bowel SES-CD of 0-6 vs. ≥ 7 and endoscopic findings (presence of any ulcer and degree of stricture) using the Cox proportional hazards model. The risk of surgery was significantly increased in patients with a small-bowel SES-CD of ≥ 7 compared to a small-bowel SES-CD of 0-6 [hazard ratio (HR) 6.31; 95% confidence interval (CI) 1.48-26.91; p = 0.013]. In addition, the risk of surgery was significantly increased in patients with stenosis with "cannot be passed" compared to the cases without stenosis (HR 12.34; 95% CI 1.66-91.92; p = 0.014), whereas there was no significance in any ulcer. The present study demonstrated the role of BAE in the endoscopic assessment of disease activity and its predictive value for the risk of surgery in small-bowel CD patients. Further optimization of BAE utilization for the assessment of disease activity is warranted in clinical practice.

The Activation of the LIMK/Cofilin Signaling Pathway via Extracellular Matrix-Integrin Interactions Is Critical for the Generation of Mature and Vascularized Cardiac Organoids.

The generation of mature and vascularized human pluripotent stem cell-derived cardiac organoids (hPSC-COs) is necessary to ensure the validity of drug screening and disease modeling. This study investigates the effects of cellular aggregate (CA) stemness and self-organization on the generation of mature and vascularized hPSC-COs and elucidates the mechanisms underlying cardiac organoid (CO) maturation and vascularization. COs derived from 2-day-old CAs with high stemness (H-COs) and COs derived from 5-day-old CAs with low stemness (L-COs) were generated in a self-organized microenvironment via Wnt signaling induction. This study finds that H-COs exhibit ventricular, structural, metabolic, and functional cardiomyocyte maturation and vessel networks consisting of endothelial cells, smooth muscle cells, pericytes, and basement membranes compared to L-COs. Transcriptional profiling shows the upregulation of genes associated with cardiac maturation and vessel formation in H-COs compared with the genes in L-COs. Through experiments with LIMK inhibitors, the activation of ROCK-LIMK-pCofilin via ECM-integrin interactions leads to cardiomyocyte maturation and vessel formation in H-COs. Furthermore, the LIMK/Cofilin signaling pathway induces TGFß/NODAL and PDGF pathway activation for the maturation and vascularization of H-COs. The study demonstrates for the first time that LIMK/Cofilin axis activation plays an important role in the generation of mature and vascularized COs.

The optimal surgery timing after stenting in colorectal cancer patients with malignant obstruction: additionally compared with emergency surgery.

BACKGROUND: This study aimed to determine short-term and long-term outcomes according to time intervals after stenting and compared them with those of emergency surgery (ES) in colorectal cancer (CRC) with malignant obstruction. METHODS: CRC with malignant obstructions was reviewed retrospectively between January 2008 and July 2018. Of a total of 539 patients who visited the emergency room and underwent ES, 133 were enrolled in the ES group. Of a total of 567 patients who initially received stenting and subsequently underwent elective surgery, 220 were enrolled in the SEMS group. The interval between SEMS placement and elective surgery was classified as < 11 days, 11-17 days, and > 17 days. RESULTS: For those who received SEMS (n = 220), those with a time interval of 11-17 days (n = 97) had fewer hospital days than those with a time interval of < 11 days (n = 68) (8 days vs. 15 days) and less stoma formation than those with a time interval of > 17 days (n = 55) (1.0% vs. 14.6%). Multivariable analysis revealed a decreased risk of death for the group with a time interval of 11-17 days (20.6%) compared to the ES group (31.6%) (hazard ratio: 0.48; 95% confidence interval: 0.24-0.97). Disease-free survival was comparable between the SEMS and ES groups regardless of the time interval (log-rank p = 0.52). CONCLUSIONS: The time interval of 11-17 days after stenting to elective surgery appeared to be associated with the most favorable outcomes.

Phlebosclerotic Colitis in a Healthy Young Female with Long-term Herbal Medicine Use.

Phlebosclerotic colitis is a rare form of intestinal ischemia. It is caused by calcified peripheral mesenteric veins and a thickened colonic wall. These characteristic findings can be identified on CT and colonoscopy. A 37-year-old female with a history of long-term herbal medicine use presented with acute lower abdominal pain and vomiting of sudden onset. Colonoscopic findings showed dark-blue discolored edematous mucosa and multiple ulcers from the ascending colon to the sigmoid colon. Abdominal CT findings showed diffuse thickening of the colonic wall and calcifications of the peripheral mesenteric veins from the ascending colon to the sigmoid colon. Based on these findings, the patient was diagnosed with phlebosclerotic colitis. We report this rare case of phlebosclerotic colitis in a healthy young female patient with a history of long-term herbal medicine use and include a review of the relevant literature.

Comparison of Clinical and Imaginal Features According to the Pathological Grades of Dysplasia in Branch-Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN) for Personalized Medicine.

Background: In patients with BD-IPMN, surgical indications have been focused on finding malignant lesions (HGD, high-grade dysplasia/IC, invasive carcinoma). The aim of this study was to compare the preoperative factors that distinguish HGD from LGD (low-grade dysplasia) and HGD from IC to find the optimal pathologic target for surgery according to individuals, considering surgical risks and outcomes. Methods: We retrospectively analyzed 232 patients with BD-IPMN diagnosed based on pathology after surgery and preoperative images. The primary outcome was identifying preoperative factors distinguishing HGD from LGD, and HGD from IC. Results: In patients with LGD/HGD, a solid component or an enhancing mural nodule ≥ 5 mm (OR = 9.29; 95% CI: 3.3−54.12; p < 0.000) and thickened/enhancing cyst walls (OR = 6.95; 95% CI: 1.68−33.13; p = 0.008) were associated with HGD. In patients with malignant lesions (HGD/IC), increased serum CA 19-9 (OR = 12.59; 95% CI: 1.81−87.44; p = 0.006) was associated with IC. Conclusions: The predictive factors for HGD were the presence of a solid component or an enhancing mural nodule ≥ 5 mm and thickened/enhancing cyst walls compared with LGD, and if accompanied by increased CA 19-9, it might be necessary to urgently evaluate the lesion due to the possibility of progression to IC. Based on this finding, we need to find HGD as the optimal pathologic target for surgery to improve survival in low-surgical-risk patients, and IC could be assumed to be the optimal pathologic target for surgery in high-surgical-risk patients because of high morbidity and mortality associated with surgery.

A Machine Learning-Based Diagnostic Model for Crohn's Disease and Ulcerative Colitis Utilizing Fecal Microbiome Analysis.

Recent research has demonstrated the potential of fecal microbiome analysis using machine learning (ML) in the diagnosis of inflammatory bowel disease (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC). This study employed the sparse partial least squares discriminant analysis (sPLS-DA) ML technique to develop a robust prediction model for distinguishing among CD, UC, and healthy controls (HCs) based on fecal microbiome data. Using data from multicenter cohorts, we conducted 16S rRNA gene sequencing of fecal samples from patients with CD (n = 671) and UC (n = 114) while forming an HC cohort of 1462 individuals from the Kangbuk Samsung Hospital Healthcare Screening Center. A streamlined pipeline based on HmmUFOTU was used. After a series of filtering steps, 1517 phylotypes and 1846 samples were retained for subsequent analysis. After 100 rounds of downsampling with age, sex, and sample size matching, and division into training and test sets, we constructed two binary prediction models to distinguish between IBD and HC and CD and UC using the training set. The binary prediction models exhibited high accuracy and area under the curve (for differentiating IBD from HC (mean accuracy, 0.950; AUC, 0.992) and CD from UC (mean accuracy, 0.945; AUC, 0.988)), respectively, in the test set. This study underscores the diagnostic potential of an ML model based on sPLS-DA, utilizing fecal microbiome analysis, highlighting its ability to differentiate between IBD and HC and distinguish CD from UC.

Risk of prostate cancer in patients with inflammatory bowel disease: a nationwide cohort study in South Korea.

Background: Several studies have suggested an association between inflammatory bowel disease (IBD) and the risk of prostate cancer development. However, these findings are inconsistent, and studies based on Asian populations are limited. Objectives: We compared the risk of prostate cancer according to IBD status using the Korean National Health Insurance Service database. Design: A population-based retrospective cohort of age-matched 59,044 non-IBD patients and 14,761 IBD patients between January 2009 and December 2011 was analyzed up to December 2017. Methods: The risk of prostate cancer was compared between patients with IBD and controls using the Cox proportional hazards regression model and Kaplan-Meier survival analysis. Results: During a median follow-up of 6 years, the incidence rate of prostate cancer was 264 per 100,000 person-years in non-IBD patients and 242 per 100,000 person-years in patients with IBD. IBD status was not associated with the risk of prostate cancer compared to non-IBD [adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI): 0.80-1.08, p = 0.32). The cumulative incidence of prostate cancer did not differ by IBD status (non-IBD patients versus IBD patients: log-rank p = 0.27; non-IBD patients versus ulcerative colitis versus Crohn's disease: log-rank p = 0.42). In multivariate analysis, age was an independent risk factor for the development of prostate cancer (HR 1.03, 95% CI: 1.02-1.03, p < 0.001). Conclusion: In our population-based study, IBD status was not associated with the risk of prostate cancer.

Utility of a deep learning model and a clinical model for predicting bleeding after endoscopic submucosal dissection in patients with early gastric cancer.

BACKGROUND: Bleeding is one of the major complications after endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) patients. There are limited studies on estimating the bleeding risk after ESD using an artificial intelligence system. AIM: To derivate and verify the performance of the deep learning model and the clinical model for predicting bleeding risk after ESD in EGC patients. METHODS: Patients with EGC who underwent ESD between January 2010 and June 2020 at the Samsung Medical Center were enrolled, and post-ESD bleeding (PEB) was investigated retrospectively. We split the entire cohort into a development set (80%) and a validation set (20%). The deep learning and clinical model were built on the development set and tested in the validation set. The performance of the deep learning model and the clinical model were compared using the area under the curve and the stratification of bleeding risk after ESD. RESULTS: A total of 5629 patients were included, and PEB occurred in 325 patients. The area under the curve for predicting PEB was 0.71 (95% confidence interval: 0.63-0.78) in the deep learning model and 0.70 (95% confidence interval: 0.62-0.77) in the clinical model, without significant difference (P = 0.730). The patients expected to the low- (< 5%), intermediate- (≥ 5%, < 9%), and high-risk (≥ 9%) categories were observed with actual bleeding rate of 2.2%, 3.9%, and 11.6%, respectively, in the deep learning model; 4.0%, 8.8%, and 18.2%, respectively, in the clinical model. CONCLUSION: A deep learning model can predict and stratify the bleeding risk after ESD in patients with EGC.

Machine Learning Model to Stratify the Risk of Lymph Node Metastasis for Early Gastric Cancer: A Single-Center Cohort Study.

Stratification of the risk of lymph node metastasis (LNM) in patients with non-curative resection after endoscopic resection (ER) for early gastric cancer (EGC) is crucial in determining additional treatment strategies and preventing unnecessary surgery. Hence, we developed a machine learning (ML) model and validated its performance for the stratification of LNM risk in patients with EGC. We enrolled patients who underwent primary surgery or additional surgery after ER for EGC between May 2005 and March 2021. Additionally, patients who underwent ER alone for EGC between May 2005 and March 2016 and were followed up for at least 5 years were included. The ML model was built based on a development set (70%) using logistic regression, random forest (RF), and support vector machine (SVM) analyses and assessed in a validation set (30%). In the validation set, LNM was found in 337 of 4428 patients (7.6%). Among the total patients, the area under the receiver operating characteristic (AUROC) for predicting LNM risk was 0.86 in the logistic regression, 0.85 in RF, and 0.86 in SVM analyses; in patients with initial ER, AUROC for predicting LNM risk was 0.90 in the logistic regression, 0.88 in RF, and 0.89 in SVM analyses. The ML model could stratify the LNM risk into very low (<1%), low (<3%), intermediate (<7%), and high (≥7%) risk categories, which was comparable with actual LNM rates. We demonstrate that the ML model can be used to identify LNM risk. However, this tool requires further validation in EGC patients with non-curative resection after ER for actual application.

LEFTY-PITX2 signaling pathway is critical for generation of mature and ventricular cardiac organoids in human pluripotent stem cell-derived cardiac mesoderm cells.

The generation of mature ventricular cardiomyocytes (CMs) resembling adult CMs from human pluripotent stem cells (hPSCs) is necessary for disease modeling and drug discovery. To investigate the effect of self-organizing capacity on the generation of mature cardiac organoids (COs), we generated cardiac mesoderm cell-derived COs (CMC-COs) and CM-derived COs (CM-COs) and evaluated COs. CMC-COs exhibited more organized sarcomere structures and mitochondria, well-arranged t-tubule structures, and evenly distributed intercalated discs. Increased expressions of ventricular CM, cardiac metabolic, t-tubule formation, K+ ion channel, and junctional markers were confirmed in CMC-COs. Mature ventricular-like function such as faster motion vector speed, decreased beats per min, increased peak-to-peak duration, and prolonged APD50 and APD90 were observed in CMC-COs. Transcriptional profiling revealed that extracellular matrix-integrin, focal adhesion, and LEFTY-PITX2 signaling pathways are upregulated in CMC-COs. LEFTY knockdown affected ECM-integrin-FA signaling pathways in CMC-COs. Here, we found that high self-organizing capacity of CMCs is critical for the generation of mature and ventricular COs. We also demonstrated that LEFTY-PITX2 signaling plays key roles for CM maturation and specification into ventricular-like CM subtype in CMC-COs. CMC-COs are an attractive resource for disease modeling and drug discovery.

Transplantation of 3D bio-printed cardiac mesh improves cardiac function and vessel formation via ANGPT1/Tie2 pathway in rats with acute myocardial infarction.

A novel tissue engineering strategy using 3D bio-print technology has become a promising therapeutic method for acute myocardial infarction (AMI) in an animal model. However, the application of 3D bio-printed tissue remains limited due to poor graft survival. Therefore, it is a scientific priority to enhance graft survival by precisely adjusting the 3D environment of encapsulated cells. In this study, novel transplantable 3D cardiac mesh (cMesh) tissue with a porous mesh structure was presented using human cardiomyocytes, human cardiac fibroblasts, and gelatin-methacryloyl-collagen hydrogel. Cardiomyocytes and cardiac fibroblasts were well spreaded. The cardiomyocytes were connected with a gap junction channel in bio-printed cMesh and a 3D cardiac patch with an aggregated structure. Porous cMesh demonstrated structural advantages by increased phosphorylation of mTOR, AKT, and ERK signals associated with cell survival. Transplanted cMesh in rats with AMI improved long-term graft survival, vessel formation, and stabilization, reduced fibrosis, increased left ventricle thickness, and enhanced cardiac function. Our results suggest that porous cMesh provides structural advantages and a positive therapeutic effect in an AMI animal model.

Efficacy of entecavir versus tenofovir in preventing hepatocellular carcinoma in patients with chronic hepatitis B with maintained virologic response.

BACKGROUND & AIMS: Several studies suggested that efficacy of tenofovir in reducing the risk of the development of hepatocellular carcinoma (HCC) might be better than that of entecavir. It remains unknown whether a change in therapy can further reduce the risk of HCC in patients receiving entecavir therapy and achieved goal of antiviral therapy, a maintained undetectable hepatitis B virus (HBV) DNA level in the serum. METHODS: A total of 1336 treatment-naïve chronic HBV mono-infected adult patients, who started entecavir or tenofovir treatment and achieved a maintained virologic response during follow-up were analysed. RESULTS: During a median 4.4 years of follow-up (range, 1.0-7.4 years) after achieving virologic response, 99 patients developed HCC. The 5-year cumulative HCC incidence rate was 7.3% and 6.3% for the entecavir and tenofovir groups, respectively, with similar risk of HCC between the two groups (adjusted HR, 0.82; 95% CI, 0.52-1.29; p = 0.3). The risk of HCC was similar in the propensity score-matched cohort (HR, 1.02; 95% CI, 0.68-1.52; p = 0.94) and inverse probability treatment weighting analysis (HR, 1.11; 95% CI, 0.74-1.66; p = 0.62). In the subgroup analysis, HCC risk was similar between the two drugs in both patients with and without cirrhosis. DISCUSSION: In patients showing maintained virologic response, no difference in the risk of HCC between entecavir and tenofovir was observed. This indicates entecavir might be as effective as tenofovir in the prevention of HCC among those patients and suggest that a change in therapy in anticipation of further reducing the risk of HCC might not be necessary for patients receiving entecavir and showing virologic response.

Clinical feasibility and oncologic safety of primary endoscopic submucosal dissection for clinical submucosal invasive early gastric cancer.

PURPOSE: This study aimed to evaluate the clinical feasibility and oncologic safety of primary endoscopic submucosal dissection for cT1bN0M0 gastric cancer by identifying patients who had undergone curative resection after endoscopic submucosal dissection and patients who had undergone primary surgery but could be treated with endoscopic submucosal dissection. METHODS: A single-center retrospective cohort study was conducted on patients with cT1bN0M0 gastric cancer (size: ≤ 30 mm) and differentiated histology from January 2007 to May 2017. Submucosal invasion was evaluated using conventional endoscopy and endoscopic ultrasonography. Patients were divided into the primary endoscopic submucosal dissection and primary surgery groups according to initial treatment. RESULTS: Curative resection rate was 65.0% (91/140) in the primary endoscopic submucosal dissection group. Of patients in the primary surgery group, 49.1% (82/167) were considered eligible for endoscopic submucosal dissection. No differences in en bloc resection rate were observed between pT1a and pT1b gastric cancers after endoscopic submucosal dissection (97.8 vs. 97.9%). However, the negative horizontal margin rate was higher in pT1a gastric cancer than pT1b gastric cancer (98.9 vs. 91.3%). There was no difference in overall survival among the curative treatment groups (log rank P = 0.310). CONCLUSION: In this study, 173 (56.4%) out of 307 patients with cT1bN0M0 gastric cancer could avoid unnecessary surgery if primary endoscopic submucosal dissection was used. Based on these findings, it is necessary to add an appropriate indication for endoscopic submucosal dissection in patients with cT1b gastric cancer. Further management could be determined based on pathologic findings after primary endoscopic submucosal dissection.

Long-Term Safety of Delayed Surgery After Upfront Endoscopic Resection for Early Gastric Cancer: A Propensity Matched Study.

BACKGROUND: When non-curative resection is confirmed after endoscopic resection (ER) of early gastric cancer (EGC), delayed surgery is recommended because it provides favorable survival outcomes. Long-term outcome after surgery of EGC with or without previous ER has not been evaluated. OBJECTIVE: The aim of this study was to compare the long-term oncologic safety between primary surgery and delayed surgery after ER. METHODS: Patients who had undergone curative surgery (R0) for EGC were included and were divided into primary and delayed surgery groups. Primary surgery was defined as gastrectomy without ER for EGC, whereas delayed surgery was defined as additional curative gastrectomy due to non-curative resection after ER; an average delay of 21.5 days (range 1-195) was observed. Propensity score matching was performed. The primary outcome was overall survival (OS) and the secondary outcomes were cancer-specific survival (CSS) and disease-free survival (DFS). RESULTS: After propensity score matching, 1439 patients were included, of whom 1042 (72.4%) were in the primary surgery group and 397 (27.6%) were in the delayed surgery group. The OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.59-1.27; p = 0.459), CSS (HR 0.47, 95% CI 0.15-1.47; p = 0.196), and DFS (HR 0.54, 95% CI 0.15-1.90; p = 0.334) were not different. CONCLUSIONS: The long-term outcomes of delayed surgery after non-curative ER for EGC were non-inferior to primary surgery. Therefore, an attempt for ER of EGC that satisfies the absolute and expanded indication seems justified for preventing gastrectomy. In case of non-curative resection after ER, additional delayed surgery should be performed.

Comparison of ICC patients with hepatitis B infection to those with no major risk factors for HCC.

BACKGROUND: There has been renewed interest in HBV-associated ICC, because it could share a common carcinogenesis disease process with HCC. We investigated whether there is a difference in clinical outcome between ICC patients with HBV infection and those without any major risk factors for HCC. METHODS: A total of 253 curatively resected, surgically diagnosed ICC patients were analyzed and divided into two groups according to the presence or absence of major risk factors for HCC: an HBV group (n = 45) and a non-HCC-risk (NHR) group (n = 208). RESULTS: Lymph node metastasis was more frequently observed in the NHR group (HBV vs. NHR: 8.89% vs. 24.52%, P = 0.027). Patients in the HBV group demonstrated more favorable survival than those in the NHR group. However, this difference was not statistically significant (5-year survival rate, 54.7% vs. 42.3%, P = 0.128). Cumulative recurrence rate in the HBV group was 62.2%, which was not significantly different from 63.0% in the NHR group (P = 1.000). CONCLUSION: This study found that while ICC patients with HBV infection showed some favorable tumor characteristics, patients' stage-specific survival and recurrence rates were not significantly different compared to those without any major risk factors for HCC.

Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling.

Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells, including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson's disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD.