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Background/Aims: The treatment of superficial esophageal neoplasms (SENs) in cirrhotic patients is challenging and rarely investigated. We evaluated the outcomes of endoscopic submucosal dissection (ESD) to determine the efficacy and safety of treating SENs in patients with liver cirrhosis.Methods: The baseline characteristics and treatment outcomes of patients who underwent ESD for SENs between November 2005 and December 2017 were retrospectively reviewed.Results: ESD was performed in 437 patients with 481 SENs, including 15 cirrhotic patients with 17 SENs. En bloc resection (88.2% vs. 97.0%) and curative resection (64.7% vs. 78.9%) rates were not different between the cirrhosis and non-cirrhosis groups (p=0.105 and p=0.224, respectively). Bleeding was more common in cirrhotic patients (p=0.054), and all cases were successfully controlled endoscopically. The median procedure and hospitalization duration did not differ between the groups. Overall survival was lower in cirrhotic patients (p=0.003), while disease-specific survival did not differ between the groups (p=0.85).Conclusions: ESD could be a safe and effective treatment option for SENs in patients with cirrhosis. Detailed preprocedural assessments are needed, including determination of liver function, esophageal varix status, and remaining life expectancy, to identify patients who will obtain the greatest benefit.

MicroRNAs (miRNAs), found in blood and body fluids, have emerged as potential non-invasive biomarkers for disease and injury. miRNAs are quantitatively evaluated using typical RNA analysis methods such as the quantitative reverse transcription polymerase chain reaction, microarrays, and Northern blot, all of which require complex procedures and expensive reagents. To utilize miRNAs as practical biomarkers, it will be helpful to develop simple and user-friendly sensors. In this study, a paper-based miRNA sensor was developed by combining two methods: (1) target-recycled DNAzyme (Dz) amplification and (2) graphene oxide-assisted Dz blotting on paper. The Dz spots on paper caused a miRNA-dependent color change in presence of colorimetric reagents and facilitated the quantification of absolute amount of the target miRNA, irrespective of the volume, with high reproducibility. This approach is technologically straightforward and enables quantification of as low as 7.75 fmol miRNA using a portable smartphone.

The biological behavior of sebaceous carcinoma (SeC) is relatively indolent, however, local invasion or distant metastasis is sometimes reported. Nevertheless, a lack of understanding of the genetic background of SeC makes it difficult to apply effective systemic therapy. This study was designed to investigate major genetic alterations in SeCs in Korean patients. A total of 29 samples, including 20 ocular SeCs (SeC-Os) and 9 extraocular SeCs (SeC-EOs), were examined. Targeted next-generation sequencing tests including 171 cancer-related genes were performed. TP53 and PIK3CA genes were frequently mutated in both SeC-Os and SeC-EOs with slight predominance in SeC-Os, whereas the NOTCH1 gene was more commonly mutated in SeC-EOs. In clinical correlation, mutations in RUNX1 and ATM were associated with development of distant metastases, and alterations in MSH6 and BRCA1 were associated with inferior progression-free survival (all p &lt, 0.05). In conclusion, our study revealed distinct genetic alterations between SeC-Os and SeC-EOs and some important prognostic molecular markers. Mutations in potentially actionable genes, including EGFR, ERBB2, and mismatch repair genes, were noted, suggesting consideration of a clinical trial in intractable cases.

Background: Diabetic peripheral neuropathy (DPN), the most common microvascular complication of type-2 diabetes mellitus (T2DM), results in nontraumatic lower-limb amputations. When DPN is not detected early, disease progression is irreversible. Thus, biomarkers for diagnosing DPN are needed. Methods: We analyzed three data sets of T2DM DPN: two for mouse models (GSE70852 and GSE34889) and one for a human model (GSE24290). We found common differentially expressed genes (DEGs) in the two mouse data sets and validated them in the human data set. To identify the phenotypic function of the DEGs, we overexpressed them in zebrafish embryos. Clinical information and serum samples of T2DM patients with and without DPN were obtained from the Korea Biobank Network. To assess the plausibility of DEGs as biomarkers of DPN, we performed an enzyme-linked immunosorbent assay. Results: Among the DEGs, only NPY and SLPI were validated in the human data set. As npy is conserved in zebrafish, its mRNA was injected into zebrafish embryos, and it was observed that the branches of the central nervous system became thicker and the number of dendritic branches increased. Baseline characteristics between T2DM patients with and without DPN did not differ, except for the sex ratio. The mean serum NPY level was higher in T2DM patients with DPN than in those without DPN ( p = 0.0328), whereas serum SLPI levels did not differ ( p = 0.9651). Conclusion: In the pathogenesis of DPN, NPY may play a protective role in the peripheral nervous system and may be useful as a biomarker for detecting T2DM DPN.

Background and Aims: Endoscopic treatment for duodenal neoplasms is associated with a high risk of perforation. This study aimed to determine the feasibility of endoscopic treatment for sporadic nonampullary duodenal adenoma (SNDA). Methods: Consecutive patients undergoing endoscopic treatment for SNDA between January 2005 and December 2015 were included in the study. Clinical characteristics and endoscopic outcomes were analyzed using medical records. Long-term outcome was assessed in patients whose follow-up period was >12 months >1 year. Results: A total of 95 lesions (92 patients) were treated with argon plasma coagulation (APC) ablation (n = 25), endoscopic mucosal resection (EMR, n = 59), or endoscopic submucosal dissection (ESD, n= 11). The median age was 54.9 years, and 63% were male. In patients who underwent EMR and ESD, the en bloc resection rate was 83.1 and 90.0% (p > 0.99); and the complete resection rate was 81.4 and 80% (p > 0.99), respectively. Perforation occurred in 8 patients (8.7%), 4 of whom required surgery. The ESD group showed a significantly higher perforation rate than APC or EMR group (45.5 vs. 0 and 5.1%; p < 0.001). During the median follow-up period of 19 months (range 12–137 months), one patient in the APC ablation group experienced recurrence; no recurrences were seen among EMR and ESD groups. Conclusions: Favorable long-term outcomes indicate that endoscopic treatment is an effective approach for the treatment of SNDA. Considering the high risk of perforation associated with ESD, APC, or EMR may be an acceptable alternative.

Background/Aims Emerging evidence shows that the mechanism of irritable bowel syndrome (IBS) is associated with neurotrophic factors and tight junction proteins (TJPs). It is known that there are sex differences in the pathophysiology of IBS. The aim of the present study is to determine expression levels of neurotrophic factors, TJPs, and cytokines according to IBS subtype and sex. Methods From 59 IBS (33 IBS-constipation, 21 IBS-diarrhea, and 5 IBS-mixed) and 36 control patients, colonic mucosa mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), and various TJPs were assessed by real-time polymerase chain reaction. Western blot was performed to determine levels of zonular occludens-1 (ZO-1). Serum levels of cytokines were measured by enzyme-linked immunosorbent assay. Results TRPV1, GDNF, and NGF mRNA levels were significantly increased in those with IBS-constipation compared to those in controls (all P < 0.05). However, they showed no significant difference between those with IBS-diarrhea and controls. Expression level of TRPV1 correlated with that of GDNF (r = 0.741, P < 0.001) and NGF (r = 0.935, P < 0.001). ZO-1 RNA expression levels were lower (P = 0.021) in female IBS-diarrhea than those in controls, although they showed no significant differences between male IBS-diarrhea and controls. Serum IL-1β levels in female IBS were significantly higher than those of male IBS, especially in IBS-constipation (P < 0.001). Conclusion Our results suggest that neurotrophic factors and IL-1β are closely related to IBS-constipation and that decrease of ZO-1 is an important factor in female with IBS-diarrhea.

Background Interpretation of mediastinal biopsy is often challenging even for experienced pathologists especially when a hematolymphoid neoplasm is suspected. Primary mediastinal large B-cell lymphoma (PMLBCL) and classic Hodgkin lymphoma (CHL) represent two major types of mature B-cell lymphomas of the mediastinum. Although PMLBCL and mediastinal CHL share many clinicopathologic characteristics, their treatment strategies and responses are remarkably different. We therefore aimed to find distinctive histologic or protein markers to better differentiate these two lesions. Methods Search for primary mediastinal B-cell lymphomas found 52 consecutive cases from 3 university hospitals of Korea during 2005 to 2012. Among them, 32 cases that were available for additional immunohistochemistry (IHC) assessment were enrolled in this study. These cases consisted of the following: CHL (N = 13), PMLBCL (N = 16), and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (gray zone lymphoma, N = 3). Along with the clinicopathologic findings, the expression of p63, GATA3 and cyclin E was investigated by IHC in the three categorized lesions mentioned above. Results Most clinical features overlapped between PMLBCL and CHL except for the increased disease progression and mortality found in PMLBCL. In the pathologic review, the presence of epithelioid granuloma favored a diagnosis of CHL, whereas reticulated or alveolar patterns of fibrosis were characteristic of PMLBCL. For protein markers, p63 was predominantly positive in PMLBCL (15/16) compared with CHL (2/13), which indicates that p63 is a marker of the highest diagnostic accuracy when calculated by the area under the ROC curve. GATA3 was expressed in the majority of CHL cases (10/13) compared with PMLBCL (0/16), while the expression of cyclin E was only rarely present in a minor population of PMLBCL. Conclusions P63 expression in tumor cells, even focal expression, and no GATA3 is the most helpful feature in distinguishing PMLBCL from mediastinal CHL.

Background In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC). Methods Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases. Results The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAFV600E mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27). Conclusions The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.

This study was designed to evaluate the preoperative diagnostic categories of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) using thyroid core needle biopsy (CNB) and to analyze its impact on the risk of malignancy (ROM). A total of 2687 consecutive thyroid CNBs were reviewed retrospectively and classified into six diagnostic categories using a standardized reporting system similar to the Bethesda System for Reporting Thyroid Cytopathology. Diagnostic categories of CNBs were compared with the final surgical diagnoses, and the ROM in each category was calculated both before and after excluding NIFTP from malignancy. Of 946 surgically resected cases, 683 were diagnosed as papillary thyroid carcinoma (PTC), and 32 (4.7% of PTC) were reclassified as NIFTP. The CNB diagnostic categories of NIFTP were as follows: follicular neoplasm in 20 (62.5%; 14, with nuclear atypia), indeterminate lesion in 11 (34.4%), and suspicious for malignancy in one (3.1%). When combined, NIFTP and encapsulated follicular variant of PTC (EFVPTC) were more often categorized as follicular neoplasm compared with other PTC variants including infiltrative FVPTC. Exclusion of NIFTP from malignant diagnosis led to a significant decrease in the ROM in follicular neoplasm with nuclear atypia category. Thus, thyroid CNB enables to differentiate NIFTP/EFVPTC from other PTCs, providing a useful guide for optimal treatment in patients with these tumors.

In cases of subepithelial tumors (SETs) located in the cardiac area, a preoperative histologic diagnosis might be helpful in determining the requirement of surgery. To investigate the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in gastric SETs located in the cardia. The data of 107 patients who underwent EUS-FNB, from 2012 to 2017, for tissue sampling of gastric SETs located in the cardia were collected. The clinicopathological data, EUS-related parameters, and surgical outcomes were retrospectively reviewed. The EUS-FNB results were diagnostic in 86.9% (93/107) and nondiagnostic in 13.1% (14/107) of the patients. Immunostaining of the FNB specimens led to the diagnosis of gastrointestinal stromal tumor (GIST) in 25 SETs (23.4%), leiomyoma in 62 SETs (57.9%), heterotopic pancreas in 3 SETs (2.8%), and schwannoma in 2 SETs (1.9%). In the multivariate analysis, patients with GISTs showed significantly more inhomogeneous echogenicity [odds ratio (OR), 8.867], more cystic foci (OR, 26.98), and older age (OR, 1.087). In 26 patients who underwent surgical resection, the agreement between EUS-FNB and surgical pathological findings was 100% with respect to the diagnosis of GISTs (n = 20) and leiomyoma (n = 7). Among these cases, the proportion of high-risk GISTs was 20.0% (4/20), and no leiomyosarcoma was detected. Although a majority of the subepithelial lesions in the cardia of the stomach are benign, 20% of the cases diagnosed with GIST have a high malignant potential. Preoperative EUS-FNB might be a useful tool for decision-making regarding the ultimate management and outcomes of these lesions.

Spontaneous retrograde migration of nasoenteral feeding tubes is common in clinical practice. The aim of the present study was to evaluate the effectiveness of nasoenteral feeding tube tip fixation with hemoclips to prevent tube dislodgement. We retrospectively reviewed patients who underwent insertion of an endoscopic nasoenteral feeding tube with or without tube tip fixation with hemoclips at the Asan Medical Center in Korea from January 2016 to December 2017. We compared the incidence of tube dislodgment and procedure-related complications between the two groups. Of the total 225 procedures, 72 were performed using the clip-assisted method, while 153 were performed using the standard non-clip-assisted method. Tube dislodgement occurred in two (2.8%) cases in the clipping group and in 26 (17.0%) in the non-clipping group (p = 0.003). Non-clipping group had a sevenfold higher risk of tube dislodgement compared to clipping group after adjustments in multivariable logistic regression (adjusted OR 7.97, 95% CI 1.82–35.00). The procedure time was not significantly different between the two groups (17.6 ± 8.5 min in the clipping group vs. 17.8 ± 9.4 min in the non-clipping group, p = 0.872). In addition, procedure-related complications, such as bleeding, aspiration pneumonia, Mallory–Weiss tear, ileus, and tube obstruction, were not different between the two groups. Achieving target calorie intake took 10.4 ± 10.5 days in the clipping group and 7.9 ± 7.9 days in the non-clipping group (p = 0.293). Clip-assisted fixation of nasoenteral feeding tube was effective in preventing tube dislodgement.

Appropriate surface designs and precise characterizations of nanoparticles (NPs) are important but as of yet unrealized in biomedical applications of nanomaterials. We report a facile synthetic approach to the preparation of iron oxide (Fe3O4) NPs with different surface charges through exchange with polymeric ligands. An accurate analysis method for characterization of the surface-modified Fe3O4 NPs using a combination of the time-of-flight secondary ion mass spectrometry (ToF-SIMS) and Fourier transform infrared spectroscopy (FT-IR) techniques is demonstrated. A comparison of the spatial distribution of the ligand and core particles with ToF-SIMS and FT-IR verified the successful modification and purification. In addition, the surface was shown to play an important role in interactions with live cells in terms of cytotoxicity, cellular uptake, and even gene transfection. Interestingly, precise control over the surface chemistry of NP enabled efficient transfection of siRNA into suspension type cell, the Jurkat human leukemic T cell line, achieving successful down regulation of NOTCH1 whose signaling pathway is known to be involved in acute leukemia. Our report presents an in-depth study of the interactions between the NPs and cells, as well as their synthesis, characterization, and surface-dependent performance properties.

Background/Aims: Acid suppression therapy is thought to be associated with the topography of Helicobacter pylori and associated gastritis, leading to corpus-predominant gastritis. This study was aimed to investigate the influence of proton pump inhibitor (PPI) treatment on the distribution of H. pylori and associated gastritis in patients with atrophic change. Methods: Patients who underwent endoscopic resection for gastric neoplasms and received PPI for 2 months were prospectively analyzed. Biopsy specimens were obtained from 5 areas in the stomach before, during, and after the treatment with PPI. Histological examination was ­performed using the updated Sydney system, and ­bacterial density of H. pylori was further graded by immunohistochemistry (ClinicalTrials.gov registration number NCT02449941). Results: A total of 15 patients were analyzed, of whom 7 had H. pylori infection. The degree of activity and inflammation were greater in patients with H. pylori infection than in those without H. pylori infection. During the PPI treatment, the density of H. pylori decreased not only in the antrum but also in the corpus. The degree of activity and inflammation improved significantly in the antrum, particularly in the presence of H. pylori infection, while the corpus gastritis was not affected by PPI use. Atrophy and intestinal metaplasia remained unchanged in both regions of the stomach. The observed changes reverted following the discontinuation of PPI treatment. Conclusion: PPI treatment decreased H. pylori both in the antrum and the corpus in patients with atrophic gastritis. Antral gastritis improved during PPI treatment, whereas no changes were found in the corpus.

Upper gastrointestinal bleeding (UGIB) is one of the major manifestations of gastrointestinal stromal tumor (GIST) of the stomach. Several studies have reported that GIST bleeding is associated with poor prognosis. However, only case reports have reported hemostasis modalities for treating hemorrhagic gastric GIST. To identify clinical outcome of gastric GIST bleeding, we analyzed risk factors and prognosis of hemorrhagic GIST evaluating hemostasis methods. Total 697 patients histopathologically diagnosed with primary gastric GIST between January 1998 and May 2015 were enrolled to the study, retrospectively. Of 697 total patients, 46 (6.6%) patients had UGIB. Endoscopic intervention, transarterial embolization, or surgical intervention was performed for initial hemostasis in 15, 2, and 1, respectively. Over a median of 68 months of follow-up, 16 patients in bleeding group and 88 patients in non-bleeding group died; the 5-year survival rate was 79.4% in bleeding group and 91.8% in non-bleeding group (p = 0.004). Multivariate analysis showed that significant risk factors for gastric GIST bleeding included the maximal tumor diameter > 5 cm and Ki-67 positivity. Age ≥ 60 [hazard ratio (HR) = 8.124, p = 0.048], necrosis (HR = 5.093, p = 0.027), and bleeding (HR 5.743, p = 0.034) were significant factors for overall survival of gastric GIST patients. Bleeding risk of gastric GIST was higher when tumor had diameter > 5 cm or Ki-67 positivity. In addition, tumor bleeding, necrosis, and age ≥ 60 years were associated with poor overall survival. Endoscopic intervention can be considered as an effective method for initial hemostasis of hemorrhagic gastric GIST.

Backgrounds/aim We aimed to evaluate the feasibility of endoscopic treatment for gastric epithelial neoplasm in the remnant stomach after distal gastrectomy and compared the clinical outcomes by tumor location and endoscopic treatment modality. Methods We reviewed the data of patients who underwent endoscopic treatment for gastric epithelial neoplasms in the remnant stomach after distal gastrectomy between January 1996 and August 2013. The treatments included endoscopic resection or argon plasma coagulation. Results Herein, 107 patients (median age, 65.1 years; 92 men) encompassing 117 cases of gastric neoplasms in the remnant stomach after distal gastrectomy were endoscopically treated. Forty of these lesions were located at anastomotic sites; they were treated with endoscopic resection in 29 cases (72.5%) and argon plasma coagulation in 11 cases (27.5%). For 77 lesions located on the non-anastomotic site, endoscopic resection was performed in 68 cases (88.4%) and argon plasma coagulation was performed in nine cases (11.7%; p = 0.031). The mean endoscopic resection duration was significantly longer in the anastomotic site group than in the non-anastomotic site group (43.6 vs. 26.3 min, p = 0.018). Recurrence was observed in five (12.8%) patients in the former and in one (1.3%) in the latter (p = 0.015); all the patients were successfully retreated with endoscopic resection or APC. Conclusions Endoscopic treatment for gastric epithelial neoplasm in a remnant stomach after distal gastrectomy is effective and safe. However, closely monitoring for recurrence should be conducted, particularly when the tumor is located at the anastomotic site.

Purpose This study demonstrates that estradiol downregulates inflammation and inhibits colorectal cancer (CRC) development in azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model. Materials and Methods AOM/DSS-treated male and female mice were sacrificed at weeks 2, 10, and 16, to assess estrogen effects on colitis and carcinogenesis. Macroscopic and histologic severity of colitis and Western blot and quantitative real-time polymerase chain reaction were evaluated, to measure inflammatory mediators and cytokines. Results Compared with AOM/DSS-treated male mice (M-AOM/DSS group), AOM/DSS-treated male mice with estradiol administration (M-AOM/DSS+estr group) displayed at week 2 significantly decreased severity of colitis. At weeks 10 and 16, AOM/DSS-treated female mice (F-AOM/DSS group) and the M-AOM/DSS+estr group showed significantly lower tumor multiplicity compared with the M-AOM/DSS group. At week 2, F-AOM/DSS group had a lower level of nuclear factor-κB (NF-κB) expression and higher level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression, compared to the M-AOM/DSS group. At week 2, expression levels of NF-κB and its related mediators decreased in the M-AOM/DSS+estr group, while levels of Nrf2 and Nrf2-related anti-oxidant enzymes increased. In addition, estradiol significantly increased Nod-like receptor protein 3 (NLRP3) inflammasome expressions in AOM/DSS-treated male mice. In contrast, at weeks 10 and 16, Nrf2 and its-related anti-oxidant enzymes and NLRP3 inflammasome were highly expressed in M-AOM/DSS group and in F-AOM/DSS group, who developed cancer. Conclusion The data suggest that estradiol inhibits the initiation of CRC by regulating Nrf2-related pathways. Moreover, these imply the dual role of Nrf2 and NLRP3 inflammasome, including promotion of tumor progression upon tumor initiation.

Background and aim Guidelines for selecting the eradication regimen for Helicobacter pylori reinfection remain unclear. This study aimed to evaluate the eradication rate of H. pylori reinfection in patients with a previous infection successfully eradicated with index triple therapy. Methods This was a single-center, retrospective case-control study. A total of 10 468 H. pylori-infected patients treated with proton-pump inhibitor-based triple eradication therapy at a tertiary medical institution between 2005 and 2016 were enrolled. We reviewed the medical records of the enrolled patients and compared the treatment outcomes in those with H. pylori reinfection after a successful eradication. Results Helicobacter pylori infection was successfully eradicated with the index triple therapy in 7770 patients (74.2%). Among 3567 patients followed up for > 1 year, H. pylori reinfection occurred in 420 (11.8%; 3.06% per person-year) during a median follow-up of 39.1 months (interquartile range, 23.5-58.7 months). Of these patients, 164 received eradication therapy for reinfection (triple therapy in 102 and quadruple therapy in 62) and had follow-up data. Triple therapy showed an eradication rate of 78.4% for H. pylori reinfection, which was not significantly different from that of the index triple therapy (P = 0.394). Quadruple therapy for reinfection exhibited a better eradication rate (87.1%) than triple therapy but without statistical significance (P = 0.237). Conclusions Retreatment with triple therapy for H. pylori reinfection after successful eradication of prior infection showed comparable outcomes to the index triple therapy. Bismuth-containing quadruple therapy for reinfection tended to have a better eradication rate than did triple therapy.

17β-estradiol (E2) is known to have a protective effect in colorectal cancer (CRC); thus, E2 may be effective for cancer immunotherapy in CRC. The aim of this study is to evaluate the effect of combination therapy with E2 and anti-programmed cell death receptor-1 ligand (PD-L1) antibodies, and the effects of sex and estrogen on colon tumor growth, PD-L1 expression, and tumor-associated cell populations in an MC38 colon tumor model. Male mice showed increased MC38 colon tumor growth and PD-L1 expression in tumor sections as well as higher proportion of cancer-associated fibroblasts (CD45

Background/Aim: We investigated the oncologic outcomes in elderly patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) by focusing on the impact of comorbidities, sarcopenia, and nutritional status. Methods: Between 2005 and 2016, 280 patients aged ≥ 80 years with 289 EGCs underwent ESD at a tertiary care center. The short- and long-term survival outcomes were assessed. Cox regression analysis was used to identify factors associated with survival, including clinicopathologic factors and abdominal muscle area measured by computed tomography. Results: The rates of en bloc, R0, and, curative resection were 99.3%, 90.0%, and 69.2%, respectively. The rates of post-ESD bleeding and perforation rates were 2.1% and 3.1%, respectively, and no cases showed significant life-threatening adverse events. Over a median follow-up period of 70.5 months, the 3- and 5-year overall survival (OS) rates were 89.5% and 77.1%, respectively, of the114 patients who died, only four (3.5%) were due to gastric cancer. A total of 173 (61.8%) had sarcopenia, and they had lower rates of 3-year (88.4% vs. 91.4%) and 5-year (73.1% vs. 84.0%, p = 0.046) OS than did those without sarcopenia. In multivariable analyses, prognostic nutritional index (hazard ratio [HR], 0.93, 95% confidence interval [CI]: 0.90–0.98, p = 0.002) and Charlson comorbidity index (HR 1.19, 95% CI: 1.03–1.37, p = 0.018) were significant factors associated with overall survival. Conclusions: ESD was a feasible and safe therapeutic method to use in elderly patients, whose long-term survival was significantly associated with nutritional status and comorbidities. These results suggest the need for a possible extension of the curative criteria for ESD in elderly patients with EGC.

The incidence of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) is steadily increasing. However, little is known about the characteristics of these patients or the factors affecting their prognosis. Our aim was to evaluate the pathological prognostic factors associated with survival in NAFLD patients.This was a retrospective cohort study of 575 patients who underwent resection of HCC between January 2004 and December 2018. HCC was associated purely with NAFLD or hepatitis B virus (HBV) based on the pathology and viral markers. The pathological markers of HCC were compared between patients with pure NAFLD and patients with pure HBV.The pathological factors were similar between the two groups. There were no differences in overall survival (OS; P=0.283) or recurrence-free survival (RFS; P=0.990) between the pure NAFLD and pure HBV groups. The NAFLD group had a similar local RFS (P=0.785) but a better systemic RFS compared with the HBV group, (P=0.089). In multivariable analysis using bootstrapping with resampling and replacement of data, no single factor was significantly associated with RFS. However, the Ki-67 labeling index [P=0.022; bootstrap 95% confidence interval (CI): 0.000-0.919] was the only independent factor associated with systemic recurrence in the NAFLD group.In patients with HCC associated with NAFLD, the Ki-67 labeling index determined by immunohistochemistry may predict the risk of systemic recurrence following resection, allowing for stricter monitoring protocols for such patients.

Radiologically identified para-aortic lymph node (PALN) metastasis is contraindicated for pancreatic cancer (PC) surgery. There is no clinical consensus for unexpected intraoperative PALN enlargement. To analyze the prognostic role of unexpected PALN enlargement in resectable PC, we retrospectively reviewed data of 1953 PC patients in a single tertiary center. Patients with unexpected intraoperative PALN enlargement (group A1, negative pathology, n = 59, group A2, positive pathology, n = 13) showed median overall survival (OS) of 24.6 (95% CI: 15.2–33.2) and 13.0 (95% CI: 4.9–19.7) months, respectively. Patients with radiological PALN metastasis without other metastases (group B, n = 91) showed median OS of 8.6 months (95% CI: 7.4–11.6). Compared with group A1, groups A2 and B had hazard ratios (HRs) of 2.79 (95% CI, 1.4–5.7) and 2.67 (95% CI: 1.8–4.0), respectively. Compared with group A2, group B had HR of 0.96 (95% CI: 0.5–1.9). Multivariable analysis also showed positive PALN as a negative prognostic factor (HR 2.57, 95% CI: 1.2–5.3), whereas positive regional lymph node did not (HR 1.32 95% CI: 0.8–2.3). Thus, unexpected malignant PALN has a negative prognostic impact comparable to radiological PALN metastasis. This results suggests prompt pathologic evaluation for unexpected PALN enlargements is needed and on-site modification of surgical strategy would be considered.

Background/aims Postprocedural bleeding is known to be relatively low after argon plasma coagulation (APC) for gastric neoplasms; however, there are few studies proving the effect of antithrombotic agents. This study aimed to analyze the incidence of delayed bleeding (DB) based on antithrombotic agents administered and to identify the risk factors for DB in APC for gastric tumors. Methods A total of 785 patients with 824 lesions underwent APC for single gastric neoplasm between January 2011 and January 2018. After exclusion, 719 and 102 lesions were classified as belonging to the non-antithrombotics (non-AT) and AT groups, respectively. The clinical outcomes were compared between the two groups, and we determined the risk factors for DB in gastric APC. Results Of the total 821 cases, DB occurred in 20 cases (2.4%): 17 cases in the non-AT group and three cases in the AT group (2.4% vs 2.9%, p=0.728). Multivariate analysis of the risk factors for DB confirmed the following significant, independent risk factors: male sex (odds ratio, 7.66; 95% confidence interval, 1.02 to 57.69; p=0.048) and chronic kidney disease (odds ratio, 4.51; 95% confidence interval, 1.57 to 13.02; p=0.005). Thromboembolic events and perforation were not observed in all patients regardless of whether they took AT agents. Conclusions AT therapy is acceptably safe in gastric APC because it does not significantly increase the incidence of DB. However, patients with chronic kidney disease or male sex need to receive careful follow-up on the incidence of post-APC bleeding.

Indirect detection of

Background: There is no study so far that analyzed the patterns of clonal evolution from the initiation of carcinogenesis to distant metastasis in patients with gallbladder adenocarcinoma (GBAC). This study aimed to elucidate the evolutionary trajectories of GBAC using multi-regional and longitudinal tumor samples. Methods: Whole-exome sequencing was conducted on tumors and matched normal samples with the coverage of 300x and 200x, respectively. Using PyClone, CITUP, MapScape, and TimeScape, phylogenetic trees were visualized in each patient considering each tumor’s location and timing of acquisition. Mutational signatures were analyzed using Mutalisk. Results: Between 2013 and 2018, a total of 11 patients (male, 5) including 2 rapid autopsy cases were enrolled. The median age was 70 (range, 59-75) years. The dataset consisted of 11 normal samples, 4 biliary intraepithelial neoplasia (BilIN), 11 primary tumors, and 30 metastatic tumors. The most frequently altered gene was ERBB2 (54.5%), followed by TP53 (45.5%) and FBXW7 (27.3%). Of 6 patients with analyzable tumor ploidy, 2 patients (33.3%) had whole genome doubling (WGD) in both primary and metastatic tumors, and 1 patient (16.7%) had WGD not in the primary tumor but in the liver metastasis. In the BilIN analysis (n=4), most mutations in frequently altered genes in GBAC were detectable from the BilIN stage, but some of them were subclonal. In these 4 patients, the fittest subclone in BilIN underwent linear and branching evolution by acquiring additional subclonal mutations and thus expanded in the primary tumor, suggesting a selective sweep phenomenon. In combined analysis with metastatic tumors (n=11), branching and linear evolution was identified in 9 (81.8%) and 2 (18.2%) patients, respectively. Of the 9 patients with branching evolution, eight (88.9%) had a total of 11 subclones expanded at least 7-fold in regional or distant metastasis. These subclones harbored putative metastasis-driving mutations in tumor suppressor genes such as SMAD4, ROBO1, and DICER1. Metastases were polyclonal in all patients. However, metastatic lesions in the same or adjacent organs showed similar clonal compositions and there was evidence of metastasis-to-metastasis spread. In mutational signature analysis, we identified 6 mutational signatures: signatures 1 (age), 3 (DNA double-strand break-repair), 7 (ultraviolet), 13 (APOBEC), 22 (aristolochic acid), and 24 (aflatoxin) (cosine similarity values ≥ 0.9). Among them, signatures 1 and 13 were dominant at the carcinogenesis stage while signatures 22 and 24 were dominant at the metastasis stage. Conclusions: We have constructed evolutionary trajectories of individual patients, highlighting the role of each clone and the dynamics among clones during carcinogenesis and metastasis. This novel approach may help us move forward to precision medicine that enables early detection of carcinogenesis and metastasis. Citation Format: Minsu Kang, Hee Young Na, Soomin Ahn, Ji-Won Kim, Sejoon Lee, Soyeon Ahn, Ju Hyun Lee, Jeonghwan Youk, Haesook T. Kim, Kui-Jin Kim, Koung Jin Suh, Jun Suh Lee, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Yoo-Seok Yoon, Jee Hyun Kim, Jin-Haeng Chung, Ho-Seong Han, Jong Seok Lee. Evolutionary trajectories during carcinogenesis and metastasis in gallbladder adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6083.

Background: Checking Helicobacter pylori susceptibility tests in the clinical setting before first-line treatment is considered difficult. We compared susceptibility-guided therapy (SGT) with empirical therapy (ET) as a first-line treatment containing clarithromycin and investigated the eradication rate using antimicrobial susceptibility testing (AST). Methods: 257 patients with H. pylori infection, with AST, performed before the eradication of clarithromycin-containing regimens were enrolled and divided into two groups: the SGT and ET groups. Results: Eradication rates in the SGT and ET groups were 85.4% and 58.4% (P &lt, 0.01), respectively. In triple therapy (TT), eradication rates of the SGT and ET groups were 85.1% and 56.6% (P &lt, 0.01), respectively. In sequential therapy (SET), eradication rates of the SGT and ET groups were 86.2% and 65.6% (P = 0.06), respectively. According to AST, TT had an eradication rate of 84.6% with strains susceptible to clarithromycin and amoxicillin and 11.1% with strains resistant to both. SET had an eradication rate of 89.5% with strains susceptible to clarithromycin, amoxicillin, and metronidazole, whereas it was 0% with strains resistant to clarithromycin and metronidazole. Conclusions: SGT as first-line treatment improved eradication rates of TT and SET by 28.5 (P &lt, 0.01) and 20.6 (P = 0.06) percent points, respectively, compared with ET.

Background Endoscopic surveillance after total gastrectomy (TG) for gastric cancer is routinely performed to detect tumor recurrence and postoperative adverse events. However, the reports on the clinical benefits of endoscopic surveillance are ambiguous. We investigated the clinical benefit of endoscopic surveillance after TG for gastric cancer. Methods We analyzed 848 patients who underwent TG with R0 resection for gastric cancer between 2011 and 2012 (380 early gastric cancer and 468 advanced gastric cancer) and underwent regular postoperative surveillance with endoscopy and abdominopelvic computed tomography (CT) with contrast. Results Median follow-up periods were 58 months for both endoscopy (range, 3–96) and abdominopelvic CT (range, 1–96). Tumor recurrence occurred in 167 patients (19.7%), of whom seven (4.2%) were locoregional recurrences in the peri-anastomotic area (n = 5) or regional gastric lymph nodes (n = 2). Whereas the peri-anastomotic recurrences were detected by both endoscopy and abdominopelvic CT, regional lymph node recurrences were only detected by abdominopelvic CT. Out of the 23 events of postoperative adverse events, the majority (87%) were detected by radiologic examinations; three events of benign strictures in the anastomotic site were detected only by endoscopy. Conclusion Endoscopic surveillance did not have a significant role in detecting locoregional tumor recurrence and postoperative adverse events after TG with R0 resection for gastric cancer. Routine endoscopic surveillance after TG may be considered optional and performed according to the capacities of each clinical setting., Graphical Abstract

Background: Periodontitis (PT) is a multifactorial, chronic inflammatory disease that can have heterogeneous clinical presentations. The oral microbiome and its metabolites have been implicated as the causes and regulators of PT pathogenesis. In this study, we assessed the oral microbiome and its metabolome in PT patients to clarify the interactions between the microbiome and its metabolites.Methods: A total of 112 subjects were recruited. Buccal and supragingival samples were collected for microbiome analysis. Saliva samples were collected for metabolomic analyses. Microbiome and metabolome data were analyzed and further integrated for combined analysis using various bioinformatics approaches.Results: Oral metabolomic analysis identified 28 metabolites distinguishing the healthy (H) and PT groups. PT group were further clustered into two subgroups (PT_G1 and PT_G2) depending on metabolite profiles. Oral microbiome analysis revealed discriminatory bacterial species in the H, PT_G1, and PT_G2 microbiota. Interestingly, PT_G2 had significantly higher concentration of short chain fatty acids and higher abundance of pathogenic bacteria. Integrated analysis of the microbiome and metabolome showed close association.Conclusion: Our results provide evidence of a close interplay between the oral microbiome and metabolome. Multi-omics approach including microbiome and microbe-associated metabolites may serve as diagnostic biomarkers and enhance treatment prediction in periodontal disease.

Purpose This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs.Materials and Methods Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included.Results The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS.Conclusion The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.

Although American Thyroid Association guidelines offer a risk stratification scheme for thyroid cancer patients, there is a continuous need for more sophisticated biomarkers that can predict disease progression. In this study, we aim to evaluate the prognostic value of class III beta-tubulin (TUBB3) and uncover the relationship between TUBB3 and invasive potential in thyroid carcinoma. Immunohistochemistry (IHC) for TUBB3 and E-cadherin was performed on a total of 254 cases of thyroid cancer specimens. Tumor budding at the invasive margin was evaluated. In vitro functional studies were also performed, the protein and mRNA levels of TUBB3 were compared among the five cell types at baseline, with transwell invasion and after blocking of TUBB3 by shRNA. IHC revealed that the levels of TUBB3 were higher in conventional papillary carcinomas (cPTCs) and anaplastic thyroid carcinomas (ATCs). In univariate analysis, high tumor budding and TUBB3 expression were associated with inferior progression-free survival in cPTC. The results of a Western blot and RT-PCR agreed with the IHC finding. The results were further validated through data from The Cancer Genome Atlas database. Our results suggest that high expression of TUBB3 in thyroid carcinoma could predict invasive potential and possibly be linked with epithelial&ndash, mesenchymal transition.

The periodontal care can be performed through such method as the non-operative periodontal treatment, operation and scaling...

Background/Aims Data regarding the prognosis of early esophageal cancer are lacking. This study investigated the long-term outcomes and factors affecting the survival of patients with mucosal esophageal squamous cell carcinoma (T1aESCC). Methods We analyzed the clinical and tumor-specific parameters of 263 patients who received surgical resection (SR; n=63) or endoscopic resection (ER; n=200) for T1aESCC. Underlying comorbidities were scored using the Charlson comorbidity index (CCI). Overall survival (OS) was the primary outcome, and multivariate regression analysis was performed to predict factors for OS. Results Of the study patients (age, 64.5±8.0 years), the CCI was 1.0±1.4 in the ER group and 0.6±0.9 in the SR group (p=0.107). The 5-year OS rate during follow-up (54.4±20.4 months) was 85.7% (ER group, 86.8%; SR group, 82.4%; p=0.631). The cumulative 5-year incidence of esophageal cancer recurrence was 10.5% in the ER group (vs 0% in the SR group). The overall mortality rate was 12.9% (ER group, 12.0%; SR group, 15.9%; p=0.399). The most common cause of mortality was second primary cancers in the ER group (75%) and organ dysfunction or postoperative complications in the SR group (70%). According to multivariate analysis, only CCI was significantly associated with OS (p2 and in those with a CCI ≤2 was 60.2% and 88.2%, respectively (p

Downregulation of human leukocyte antigen (HLA) class I has been postulated to be a mechanism of adaptive immune escape in various tumors, especially microsatellite instability–high (MSI‐H) colorectal cancer (CRC). In this study, we aimed to investigate HLA class I and β2‐microglobulin (β2M) expression in MSI‐H and microsatellite‐stable (MSS) CRCs and determine its prognostic impact. The representative areas from the tumor center (TC) and tumor periphery (TP) from 300 CRCs, including 161 MSI‐H and 139 MSS cases, were selected to construct a tissue microarray. Immunohistochemistry (IHC) for HLA A/B/C, β2M, CD3, and CD8 was performed. Reduced HLA A/B/C expression was detected in 113 (70.2%) MSI‐H and 54 (38.8%) MSS cases, while reduced β2M expression was observed in 69 (42.9%) MSI‐H and 17 (12.2%) MSS cases. Although reduced β2M expression was associated with higher pathological tumor (pT) stage in MSI‐H CRC with borderline significance, no association was found between HLA A/B/C and β2M expression and survival. Interestingly, reduced HLA A/B/C expression in MSS was associated with higher stage, and reduced HLA A/B/C and β2M expression was an independent prognostic factor in multivariate analysis. In conclusion, reduced HLA A/B/C and β2M expression was frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitor. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor prognosis in MSS cancers. Overall, IHC for HLA A/B/C and β2M might be a feasible predictive or prognostic tool in CRC., Reduced HLA A/B/C and β2M expression is frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitors. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor survival in MSS cancers, but not in MSI‐H tumors, indicating that cell‐mediated antitumoral immune response may also play an important role in MSS CRC. Together, IHC for HLA A/B/C and β2M can be a predictive or prognostic tool in CRC.

Background Bismuth-containing quadruple therapy is an effective alternative first-line therapy for Helicobacter pylori infection. We evaluated the efficacy and safety of a modified twice-a-day bismuth quadruple regimen (BQT-2) with low-dose (1000 mg total) metronidazole as first-line therapy for the eradication of H pylori. Materials and methods In this prospective pilot study, patients diagnosed with H pylori infection and naive to eradication therapy were included. The modified BQT-2 therapy consisted of rabeprazole 20 mg, amoxicillin 1 g, metronidazole 500 mg, and tripotassium dicitrato bismuthate 600 mg (elemental bismuth 240 mg) twice daily, given 30 minutes before morning and evening meals for 14 days. H pylori eradication was assessed by 13 C-urea breath test conducted at least 4 weeks after therapy completion. Results In 66 patients who received the modified BQT-2 regimen, the compliance rate was 100% and the H pylori eradication rate was 77.3%. H pylori was successfully cultured in 50 (75.8%) patients. The resistance rates to metronidazole and clarithromycin were 30.0% and 22.0%, respectively. Eradication rates were not significantly different according to the resistance to metronidazole (metronidazole-susceptible: 74.3% [26/35], metronidazole-resistant: 73.3% [11/15]; P > .99). Most of the adverse events were mild, with 20 (30%) patients developing nausea, epigastric soreness, loose stool, asthenia, skin rash, dizziness, taste perversion, headache, or dyspepsia. Conclusions Twice-a-day modified BQT-2 regimen with low-dose metronidazole was suboptimal as an alternative first-line therapy for eradicating H pylori, despite high patient compliance.

Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases, but quantitative parameters have not been systemically investigated for this purpose. We aimed to establish objective criteria for adenoma and hyperplasia using the standardized uptake value (SUV) in patients with hyperparathyroidism. Thirty-nine hyperparathyroid patients (male/female: 17/22, age: 58.33 ± 11.69 years) with at least 1 uptake-positive lesion of any degree by visual assessment in preoperative Tc-99m sestamibi quantitative SPECT/CT were included from Oct 2015 to Oct 2017. Pathologically, 44 lesions (32 adenomas and 12 hyperplasia) were identified. All patients experienced normalized levels of intact parathyroid hormone immediately after surgery. Quantitative SPECT/CT was performed at 10 minute and 2 hour post injection of Tc-99m sestabmibi (dose = 740 MBq), and maximum SUV (SUVmax) was measured for the parathyroid lesions. Experienced pathologists evaluated the percentage cellular proportions of chief cells, oxyphil cells, and clear cells. SUVmax (g/mL) of adenomas, hyperplasia, and reference thyroid tissue were 12.92 ± 6.68, 7.90 ± 5.49, and 7.01 ± 2.62 at 10min (early phase), decreasing to 7.46 ± 5.66, 4.65 ± 3.14, and 2.21 ± 1.07 at 2 hour (delayed phase), respectively. The adenomas showed significantly higher SUVmax than both the hyperplasia (P = .0131) and reference thyroid tissue (P

Background and objectives Microsatellite instability (MSI) plays a prognostic and predictive role in colorectal cancer (CRC). Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), a novel type of MSI, was recently identified. Methods A retrospective analysis of a prospective cohort database was performed. Patients who attempted curative surgery for MSI-high (MSI-H) CRC and had available testing results of EMAST were included for analysis. The difference in clinical characteristics, immunohistochemistry profile, and 3-year recurrence-free and overall survival between EMAST-negative and EMAST-positive tumors was measured. Results EMAST status was successfully evaluated in 86 cases among patients who received EMAST testing, and only 16.3% (14/86) of these patients were EMAST-negative/MSI-H. Patients with EMAST-negative tumors were younger; their tumors exhibited well differentiation, less venous invasion, and greater mutS homolog 3 expression. There was no distant metastasis or cancer-specific death among EMAST-negative patients. Yet no statistically significant difference was found between the two groups in 3-year overall or recurrence-free survival. Conclusions Patients with EMAST-negative/MSI-H CRC seem to have different clinicopathological characteristics. Future large-scale studies could clarify the role of EMAST genotype as a sub-classifier of MSI-H CRC.

To evaluate the technical feasibility, safety, and efficacy of a novel full sense device (FSD) for the treatment of obesity in a porcine model. The novel FSD comprised a self-expanding metallic esophageal stent connected to a star-shaped nitinol disk. Three types of FSD were used: fully covered (type A), fully covered with barbs (type B), and uncovered with barbs (type C). Nine juvenile pigs were divided into two groups: FSD (n = 6) and control (n = 3). FSD type A was placed in the FSD group. In case of migration, either FSD type B or type C was then randomly placed. Food intake was monitored daily. Weight changes and ghrelin hormone levels were monitored weekly for 12 weeks. FSD placement was technically successful in all pigs. All FSDs except one migrated to the stomach within 1 week after placement. The pig in which the FSD was retained showed decreased food intake in the first week after FSD placement, and there was a difference in the final weight between the FSD pig and control pigs. The percentage of weight gain was 116.6% in the control group and 105.3% in the FSD pig. FSD placement under fluoroscopic and endoscopic guidance is technically feasible and safe in a porcine model. The uncovered FSD appears to decrease food intake and reduce the rate of weight gain. However, the high FSD migration rate is not encouraging.

BACKGROUND AND AIMS The prognosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is favorable, especially in the absence of lymph node metastasis (LNM). We investigated LNM incidence and location in superficial type gastric MALT lymphoma. METHODS We performed a retrospective analysis of 450 patients newly diagnosed with gastric MALT lymphoma with tumor infiltration confined to the mucosa or submucosa as evidenced by endoscopic ultrasonography. LNM incidence and location were evaluated. RESULTS Of the 450 patients, most patients (434, 96.4%) were initially LNM negative as confirmed by computed tomography (CT) scanning. Sixteen patients (3.6%) were LNM positive. There was no difference in clinical characteristics between the 2 groups except for the extent of lymphoma involvement and endoscopic findings. Among 41 patients undergoing abdominal/pelvic CT (APCT) only, LNM was detected in 1 (2.4%). There were 8 LNM cases among 238 patients undergoing both APCT and chest CT (3.4%). Among 171 patients undergoing APCT, chest CT, and neck CT, 7 cases of LNM were detected (4.1%). The detection rates for each CT were as follows: abdominal CT, 13/450 (2.9%); chest CT, 6/408 (1.5%); and neck CT, 1/171 (0.6%). Among 6 patients with chest CT-positive findings, 3 showed no evidence of LNM on APCT. CONCLUSION LNM was an infrequent finding in gastric MALT lymphoma patients with tumor infiltration confined to the mucosa or submucosa. Besides endoscopy and endoscopic ultrasonography, APCT and chest CT are considered as optimal initial workup modalities in patients with assumed primary superficial gastric MALT lymphoma.

Minimally invasive therapies for obesity are a bridge between lifestyle interventions and bariatric surgery. We developed a novel device to reduce weight gain rate and evaluated its safety and efficacy in juvenile pigs.The intragastric satiety-inducing device (ISD) comprises a self-expandable esophageal metal stent connected to a star-shaped disc placed in the stomach fundus. Eight juvenile pigs were randomized into ISD (n = 5) and control (n = 3) groups. Body weight and serum ghrelin hormone were monitored weekly for 6 weeks. One pig was followed up for 4 additional weeks (rebound pig) after ISD removal. Histological examination and immunohistochemistry for the interstitial cells of Cajal (ICCs) were performed.ISD placement was successful in all pigs. Two ISDs (40%) migrated at 4 and 5 weeks after placement. Weight gain rates were significantly lower in the ISD group than in the control group from week 1 to 6 but were higher in the rebound pig than in a control pig from week 7 to 10. Mean ghrelin hormone level was higher in the control group than in the ISD group from week 1 to 6. ISD induced reversible inflammatory changes in the esophagus and stomach fundus. The number of ICCs was lesser in ISD pigs than in control and rebound pigs.ISD placement is feasible and safe in juvenile pigs. It decreases weight gain rate but induces reversible inflammatory reaction and tissue hyperplasia. Its mechanism may be related to pressure exertion on the stomach fundus or gastric motility alteration.

Background The accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to the rarity of tumor and variable cytologic appearance. The Asian experience with diagnosing MTC by fine-needle aspiration (FNA) was scarcely reported. Methods Cases of MTC with available FNA slides were enrolled from 13 hospitals representing 8 Asia-Pacific countries. Clinicopathological information, including sample preparation technique, staining method, original cytologic diagnosis and review diagnosis were collected. Results Of a total of 145 MTC cases retrospectively recruited, 99 (68.3%) were initially interpreted as MTC/suspicious for MTC (S-MTC). The distribution of original FNA diagnostic categories was not associated with the staining method or sample preparation technique. The staining methods used were Papanicolaou, hematoxylin-eosin and Romanowsky stains. Liquid-based cytology (LBC) was used only in three countries. After reviewing all cases, the diagnostic rate of MTC/S-MTC increased to 91.7% (133/145). Cases with initially unrecognized MTC had either marked pleomorphism or cytology mimicking papillary carcinoma or follicular neoplasm. Although LBC provided certain benefits, there was no significant difference in diagnostic accuracy between conventional smear and LBC. Immunocytochemistry was available in 38 cases (26.2%), all of which were correctly recognized as MTC. Conclusion Our report summarizes how MTC is handled in contemporary Asian thyroid FNA practice. Although the detection rate of MTC by cytology alone is less satisfactory, integration with ancillary tests could achieve an excellent performance. The recognition of constitutive cytomorphologic features is needed for each cytopreparatory method, which may result in a lower threshold to initiate further workup for MTC.

Periodontitis is a chronic and multifactorial inflammatory disease that can lead to tooth loss. At present, the diagnosis for periodontitis is primarily based on clinical examination and radiographic parameters. Detecting the periodontal pathogens at the subgingival plaque requires skilled professionals to collect samples. Periodontal pathogens are also detected on various mucous membranes in patients with periodontitis. In this study, we characterized the oral microbiome profiles from buccal mucosa and supragingival space in a total of 272 healthy subjects as a control group, and periodontitis patients as a disease group. We identified 13 phyla, 193 genera, and 527 species and determined periodontitis-associated taxa. Porphyromonas gingivalis, Tannerella forsythia, Treponema denticolar, Filifactor alocis, Porphyromonas endodontalis, Fretibacterium fastiosum and Peptostreptococcus species were significantly increased in both the buccal mucosa and the supragingival space in periodontitis patients. The identified eight periodontitis-associated bacterial species were clinically validated in an independent cohort. We generated the prediction model based on the oral microbiome profiles using five machine learning algorithms, and validated its capability in predicting the status of patients with periodontitis. The results showed that the oral microbiome profiles from buccal mucosa and supragingival space can represent the microbial composition of subgingival plaque and further be utilized to identify potential microbial biomarkers for the diagnosis of periodontitis. Besides, bacterial community interaction network analysis found distinct patterns associated with dysbiosis in periodontitis. In summary, we have identified oral bacterial species from buccal and supragingival sites which can predict subgingival bacterial composition and can be used for early diagnosis of periodontitis. Therefore, our study provides an important basis for developing easy and noninvasive methods to diagnose and monitor periodontitis.

Background: The increasing prevalence of antimicrobial resistance, together with the lack of novel treatment options, negatively affects successful eradication of Helicobacter pylori. The aim of this study was to investigate genetic mutations in the 23S rRNA genes, which is associated with clarithromycin resistance, and to determine the clinical impact of genotype on phenotypic antimicrobial resistance. Methods: A total of 46 H. pylori strains were obtained from 13 patients, before and after unsuccessful eradication with clarithromycin-based triple therapy. The phenotypic resistance of each H. pylori strain was determined by minimum inhibitory concentration against clarithromycin using the serial two-fold agar dilution method. The genomic sequences of 23S rRNA genes were identified through next-generation sequencing, and nucleotide variants were determined based on comparison with genome sequences of the reference strain H. pylori 26695. Results: Clarithromycin resistance was found in 9 of 13 subjects before treatment and all subjects after unsuccessful eradication. Whole-genome sequencing of the 23S rRNA genes detected 42 mutations on 40 nonidentical loci, including 2147A>G (formerly 2143A>G) and 2146A>G (formerly 2142A>G). All strains with clarithromycin-resistant phenotype had either 2147A>G or 2146A>G mutation. When comparing genotype and phenotype for clarithromycin resistance, there was a significant association between 2147A>G mutation and clarithromycin-resistant phenotype. Conclusions: All clarithromycin-resistant strains had either 2146A>G or 2147A>G mutation, suggesting that tests targeting these two mutations may be enough for the prediction of clarithromycin resistance in this population.

Background Esophageal bolus transit can be assessed using esophagogram or high-resolution impedance manometry (HRIM). The three-dimensional volume of inverted impedance (VII) has been developed to quantify the residual bolus between each swallow through spatiotemporal analysis. However, this novel metric has not been validated against simultaneous esophagogram. Methods A total of nine healthy volunteers (Seven males, aged 19-45 years) were prospectively evaluated with HRIM and barium esophagogram. In addition, 21 symptomatic patients (12 males, aged 20-85 years) without major motility disorder were also included. The VII was estimated from HRIM data using MATLAB program and was compared with residual bolus volume in the esophagus estimated from simultaneous esophagogram. Key results A total of 80 swallows (24 in controls and 56 in patients) were analyzed. Results from the VII method were concordant with the bolus transit pattern estimated from the esophagogram in 91.3% (73/80) of swallows. The correlation between quantitative data from VII and the volume of residual bolus estimated from esophagogram was strong in both groups with a Pearson's correlation coefficient of 0.805 for healthy volunteers and 0.730 for symptomatic patients. The intraclass correlation coefficient of VII between the three swallows within a subject was 0.901 in healthy subjects and 0.705 in patients, indicating a modest reliability of this method. Conclusions and inferences The newly developed VII method is a reliable method in assessing residual bolus volume in the esophagus based on comparison with bolus volume estimated from simultaneous esophagogram.

BACKGROUND Common data models (CDMs) help standardize electronic health record data and facilitate outcome analysis for observational and longitudinal research. An analysis of pathology reports is required to establish fundamental information infrastructure for data-driven colon cancer research. The Observational Medical Outcomes Partnership (OMOP) CDM is used in distributed research networks for clinical data; however, it requires conversion of free text–based pathology reports into the CDM’s format. There are few use cases of representing cancer data in CDM. OBJECTIVE In this study, we aimed to construct a CDM database of colon cancer–related pathology with natural language processing (NLP) for a research platform that can utilize both clinical and omics data. The essential text entities from the pathology reports are extracted, standardized, and converted to the OMOP CDM format in order to utilize the pathology data in cancer research. METHODS We extracted clinical text entities, mapped them to the standard concepts in the Observational Health Data Sciences and Informatics vocabularies, and built databases and defined relations for the CDM tables. Major clinical entities were extracted through NLP on pathology reports of surgical specimens, immunohistochemical studies, and molecular studies of colon cancer patients at a tertiary general hospital in South Korea. Items were extracted from each report using regular expressions in Python. Unstructured data, such as text that does not have a pattern, were handled with expert advice by adding regular expression rules. Our own dictionary was used for normalization and standardization to deal with biomarker and gene names and other ungrammatical expressions. The extracted clinical and genetic information was mapped to the Logical Observation Identifiers Names and Codes databases and the Systematized Nomenclature of Medicine (SNOMED) standard terminologies recommended by the OMOP CDM. The database-table relationships were newly defined through SNOMED standard terminology concepts. The standardized data were inserted into the CDM tables. For evaluation, 100 reports were randomly selected and independently annotated by a medical informatics expert and a nurse. RESULTS We examined and standardized 1848 immunohistochemical study reports, 3890 molecular study reports, and 12,352 pathology reports of surgical specimens (from 2017 to 2018). The constructed and updated database contained the following extracted colorectal entities: (1) NOTE_NLP, (2) MEASUREMENT, (3) CONDITION_OCCURRENCE, (4) SPECIMEN, and (5) FACT_RELATIONSHIP of specimen with condition and measurement. CONCLUSIONS This study aimed to prepare CDM data for a research platform to take advantage of all omics clinical and patient data at Seoul National University Bundang Hospital for colon cancer pathology. A more sophisticated preparation of the pathology data is needed for further research on cancer genomics, and various types of text narratives are the next target for additional research on the use of data in the CDM.