Redefining precision and efficiency in orthognathic surgery through virtual surgical planning and 3D printing: a narrative review.

Orthognathic surgery, essential for addressing jaw and facial skeletal irregularities, has historically relied on traditional surgical planning (TSP) involving a series of time-consuming steps including two-dimensional radiographs. The advent of virtual surgical planning (VSP) and 3D printing technologies has revolutionized this field, bringing unprecedented precision and customization to surgical processes. VSP facilitates 3D visualization of the surgical site, allowing for real-time adjustments and improving preoperative stress for patients by reducing planning time. 3D printing dovetails with VSP, offering the creation of anatomical models and surgical guides, enhancing the predictability of surgical outcomes despite higher initial setup and material costs. The integration of VSP and 3D printing promises innovative and effective solutions in orthognathic surgery, surpassing the limitations of traditional methods. Patient-reported outcomes show a positive post-surgery impact on the quality of life, underlining the significant role of these technologies in enhancing self-esteem and reducing anxiety. Economic analyses depict a promising long-term fiscal advantage with these modern technologies, notwithstanding the higher initial costs. The review emphasizes the need for large-scale randomized controlled trials to address existing research gaps and calls for a deeper exploration into the long-term impacts and ethical considerations of these technologies. In conclusion, while standing on the cusp of a technological renaissance in orthognathic surgery, it is incumbent upon the medical fraternity to foster a collaborative approach, balancing innovation with scrutiny to enhance patient care. The narrative review encourages the leveraging of VSP and 3D printing technologies for more efficient and patient-centric orthognathic surgery, urging the community to navigate uncharted territories in pursuit of precision and efficiency in the surgical landscape.

Impact of Coronavirus Disease 2019 on Gastric Cancer Diagnosis and Stage: A Single-Institute Study in South Korea.

PURPOSE: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide. National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. MATERIALS AND METHODS: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the "before COVID" period, and the years 2020 and 2021 as the "during COVID" period. RESULTS: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it. Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. CONCLUSIONS: During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.

Endoscopically injectable and self-crosslinkable hydrogel-mediated stem cell transplantation for alleviating esophageal stricture after endoscopic submucosal dissection.

Esophageal stricture after extensive endoscopic submucosal dissection impairs the quality of life of patients with superficial esophageal carcinoma. Beyond the limitations of conventional treatments including endoscopic balloon dilatation and the application of oral/topical corticosteroids, several cell therapies have been recently attempted. However, such methods are still limited in clinical situations and existing setups, and the efficacies are less in some cases since the transplanted cells hardly remain at the resection site for a long time due to swallowing and peristalsis of the esophagus. Thus, a cell transplantation platform directly applicable with clinically established equipment and enabling stable retention of transplanted cells can be a promising therapeutic option for better clinical outcomes. Inspired by ascidians that rapidly self-regenerate, this study demonstrates endoscopically injectable and self-crosslinkable hyaluronate that allows both endoscopic injection in a liquid state and self-crosslinking as an in situ-forming scaffold for stem cell therapy. The pre-gel solution may compatibly be applied with endoscopic tubes and needles of small diameters, based on the improved injectability compared to the previously reported endoscopically injectable hydrogel system. The hydrogel can be formed via self-crosslinking under in vivo oxidative environment, while also exhibiting superior biocompatibility. Finally, the mixture containing adipose-derived stem cells and the hydrogel can significantly alleviate esophageal stricture after endoscopic submucosal dissection (75% of circumference, 5 cm in length) in a porcine model through paracrine effects of the stem cell in the hydrogel, which modulate regenerative processes. The stricture rates on Day 21 were 79.5% ± 2.0%, 62.8% ± 1.7%, and 37.9% ± 2.9% in the control, stem cell only, and stem cell-hydrogel groups, respectively (p < 0.05). Therefore, this endoscopically injectable hydrogel-based therapeutic cell delivery system can serve as a promising platform for cell therapies in various clinically relevant situations.

Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis.

BACKGROUND: Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner. AIM: To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). METHODS: Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups. RESULTS: Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups. CONCLUSION: Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

Helicobacter pylori promotes epithelial-to-mesenchymal transition by downregulating CK2ß in gastric cancer cells.

Strains of Helicobacter pylori that are positive for the oncoprotein CagA (cytotoxin-associated gene A) are associated with gastric cancer and might be related to the epithelial-to-mesenchymal transition (EMT). Casein kinase 2 (CK2) is a serine/threonine protein kinase that plays a major role in tumorigenesis through signaling pathways related to the EMT. However, the role played by the interaction between CagA and CK2 in gastric carcinogenesis is poorly understood. Although CK2α protein expression remained unchanged during H. pylori infection, we found that CK2α kinase activity was increased in gastric epithelial cells. We also found that the CK2ß protein level decreased in H. pylori-infected gastric cancer cells in CagA-dependent manner and demonstrated that CagA induced CK2ß degradation via HDM2 (human double minute 2; its murine equivalent is MDM2). We observed that CagA induced HDM2 protein phosphorylation and that p53 levels were decreased in H. pylori-infected gastric cancer cells. In addition, downregulation of CK2ß induced AKT Ser473 phosphorylation and decreased the AKT Ser129 phosphorylation level in gastric cancer cells. We also found that the downregulation of CK2ß triggered the upregulation of Snail levels in gastric cancer cells. Furthermore, our in vivo experiments and functional assays of migration and colony formation suggest that CK2ß downregulation is a major factor responsible for the EMT in gastric cancer. Therefore, CK2 could be a key mediator of the EMT in H. pylori-infected gastric cancer and could serve as a molecular target for gastric cancer treatment.

Metabolic alterations of short-chain fatty acids and TCA cycle intermediates in human plasma from patients with gastric cancer.

AIMS: Short-chain fatty acids (SCFAs) are produced by gut microbiota from dietary fiber. Since absorbed SCFAs could be introduced into the tricarboxylic acid (TCA) cycle in host cells, the relationships between SCFAs and TCA cycle intermediates might influence to energy metabolism in the human body. For this reason, information on profile changes between SCFAs and TCA cycle intermediates could help unveil pathological mechanisms of gastric cancer. MAIN METHODS: A gas chromatography-tandem mass spectrometry (GC-MS/MS) method was developed to simultaneously determine SCFAs and TCA cycle intermediates in human plasma from patients with chronic superficial gastritis (CSG), intestinal metaplasia (IM), and gastric cancer. We applied a tetra-alkyl ammonium pairing method to prevent loss of volatile SCFAs and base decarboxylation of TCA cycle intermediates during sample preparation. To assess gastric diseases, metabolic alterations of SCFAs and TCA cycle intermediates in human plasma with gastric disorders were analyzed by their plasma levels. KEY FINDINGS: Significantly different metabolic alterations based on the plasma levels of SCFAs and TCA cycle intermediates were investigated in cancer metabolic pathways. Not only propionate and butyrate, mainly produced by gut microbiota, were significantly decreased, but also cis-aconitate, α-ketoglutarate, and fumarate were significantly increased in plasma with IM or gastric cancer, compared to CSG. Further, based on ratios of product to precursor, three metabolic pathways (succinate/propionate, succinate/α-ketoglutarate, and cis-aconitate/citrate) were supposed to be distorted between gastric diseases. SIGNIFICANCE: In conclusion, propionate, cis-aconitate, α-ketoglutarate, and fumarate could be used to assess the progression of gastric cancer.

Machine Learning Improves the Prediction Rate of Non-Curative Resection of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer.

Non-curative resection (NCR) of early gastric cancer (EGC) after endoscopic submucosal dissection (ESD) can increase the burden of additional treatment and medical expenses. We aimed to develop a machine-learning (ML)-based NCR prediction model for EGC prior to ESD. We obtained data from 4927 patients with EGC who underwent ESD between January 2006 and February 2020. Ten clinicopathological characteristics were selected using extreme gradient boosting (XGBoost) and were used to develop a ML-based model. Dataset was divided into the training and internal validation sets and verified using an external validation set. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were evaluated. The performance of each model was compared by using the Delong test. A total of 1100 (22.1%) patients were identified as being treated non-curatively with ESD. Seven ML-based NCR prediction models were developed. The performance of NCR prediction was highest in the XGBoost model (AUROC, 0.851; 95% confidence interval, 0.837-0.864). When we compared the prediction performance by the Delong test, XGBoost (p = 0.02) and support vector machine (p = 0.02) models showed a significantly higher performance among the NCR prediction models. We developed an ML model capable of accurately predicting the NCR of EGC before ESD. This ML model can provide useful information for decision-making regarding the appropriate treatment of EGC before ESD.

Evaluation of postoperative changes in condylar positions after orthognathic surgery using balanced orthognathic surgery system.

BACKGROUND: Many studies on maintaining the condyle in a normal or anatomical position during orthognathic surgery have been conducted to stabilize surgical outcomes and prevent iatrogenic temporomandibular joint complications. The aim of this study is to evaluate the changes in condylar positions after orthognathic surgery using virtual surgical planning via the balanced orthognathic surgery (BOS) system. METHODS: Postoperative changes in condylar position were retrospectively evaluated in 22 condyles of 11 patients with skeletal class III malocclusion who underwent orthognathic surgery using virtual surgical planning via the BOS system. The center point coordinates of the condylar head before and after orthognathic surgery were analyzed using voxel-based registration. RESULTS: Changes in the condylar position mainly occurred downward in the y-axis (-1.09 ± 0.62 mm) (P < 0.05). The change in the x-axis (0.02 ± 0.68 mm) and z-axis (0.01 ± 0.48 mm) showed no significant difference between before and after orthognathic surgery. CONCLUSION: These results indicate that the changes in the condylar positions after orthognathic surgery using virtual surgical planning via the BOS system mainly occurred downward in the y-axis, with slight changes in the x- and z-axes. The change in the condylar position after orthognathic surgery using the BOS system is clinically acceptable.

Single-cell analysis of gastric pre-cancerous and cancer lesions reveals cell lineage diversity and intratumoral heterogeneity.

Single-cell transcriptomic profiles analysis has proposed new insights for understanding the behavior of human gastric cancer (GC). GC offers a unique model of intratumoral heterogeneity. However, the specific classes of cells involved in carcinogenetic passage, and the tumor microenvironment of stromal cells was poorly understood. We characterized the heterogeneous cell population of precancerous lesions and gastric cancer at the single-cell resolution by RNA sequencing. We identified 10 gastric cell subtypes and showed the intestinal and diffuse-type cancer were characterized by different cell population. We found that the intestinal and diffuse-type cancer cells have the differential metaplastic cell lineages: intestinal-type cancer cells differentiated along the intestinal metaplasia lineage while diffuse-type cancer cells resemble de novo pathway. We observed an enriched CCND1 mutation in premalignant disease state and discovered cancer-associated fibroblast cells harboring pro-stemness properties. In particular, tumor cells could be categorized into previously proposed molecular subtypes and harbored specific subtype of malignant cell with high expression level of epithelial-myofibroblast transition which was correlated with poor clinical prognosis. In addition to intratumoral heterogeneity, the analysis revealed different cellular lineages were responsible for potential carcinogenetic pathways. Single-cell transcriptomes analysis of gastric pre-cancerous lesions and cancer may provide insights for understanding GC cell behavior, suggesting potential targets for the diagnosis and treatment of GC.

Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice.

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota. DESIGN: Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year. RESULTS: The microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation. CONCLUSION: Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.

Efficacy of radiotherapy for gastric bleeding associated with advanced gastric cancer.

BACKGROUND: Gastric bleeding negatively impacts the quality of life of patients with unresectable advanced gastric cancer and is frequently lethal. We investigated the efficacy of RT for palliation of gastric bleeding from gastric cancer and identified an optimal radiotherapy (RT) strategy. METHODS: The study analyzed 57 patients submitted to palliative RT for gastric bleeding associated with gastric cancer between January 2009 and February 2019. Changes in hemoglobin (Hb) levels were analyzed based on measurements taken before and immediately, 1 month, and 2 months after RT. Re-bleeding after RT was identified as either Hb level dropping to < 7.0 g/dL or the administration of a blood transfusion after RT. RESULTS: The median biologically effective dose (α/ß = 10) was 37.5 Gy (range 23.6-58.5). The most common regimen was 25 Gy in five fractions. The mean Hb levels before, immediately after, 1 month, and 2 months after RT (6.6, 9.7, 10.3, and 9.7 g/dL, respectively) were significantly higher than that before RT (all p < 0.001). No significant differences in re-bleeding rates were observed according to total dose, fractional dose, and fraction number. Gastric tumor response evaluated by computed tomography within 2 months after RT showed partial responses were more frequent in patients achieving bleeding control (25.0% vs. 10.8%, p = 0.023) and overall survival was significantly improved for bleeding control within 3 months after RT (median, 15.4 vs. 10.0 weeks, p = 0.048). CONCLUSIONS: RT was an effective modality for gastric bleeding control in gastric cancer, which can be achieved with a short course scheme with five fractions.

WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury.

BACKGROUND & AIMS: WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models. METHODS: Three spasmolytic polypeptide-expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777-treated gastric corpus specimens. RESULTS: Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. CONCLUSIONS: WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.

Profiling of Steroid Metabolic Pathways in Human Plasma by GC-MS/MS Combined with Microwave-Assisted Derivatization for Diagnosis of Gastric Disorders.

Steroid hormones are associated in depth to cellular signaling, inflammatory immune responses, and reproductive functions, and their metabolism alterations incur various diseases. In particular, quantitative profiling of steroids in plasma of patients with gastric cancer can provide a vast information to understand development of gastric cancer, since both sex hormones and glucocorticoids might be correlated with the pathological mechanisms of gastric cancer. Here, we developed a gas chromatography-tandem mass spectrometry-dynamic multiple reaction monitoring (GC-MS/MS-dMRM) method combined with solid-phase extraction (SPE) and microwave-assisted derivatization (MAD) to determine 20 endogenous steroids in human plasma. In this study, MAD conditions were optimized with respect to irradiation power and time. The SPE enabled effective cleanup and extraction for profiling of steroid hormones in human plasma samples. The MAD could improve laborious and time-consuming derivatization procedure, since dielectric heating using microwave directly increase molecular energy of reactants by penetrating through medium. Furthermore, dMRM method provided more sensitive determination of 20 steroids, compared to traditional MRM detection. The limits of quantification of steroids were below 1.125 ng/mL and determination coefficients of calibration curves were higher than 0.9925. Overall precision and accuracy results were below 19.93% and within ±17.04%, respectively. The developed method provided sufficient detection sensitivities and reliable quantification results. The established method was successfully applied to profile steroid metabolism pathways in plasma of patients with chronic superficial gastritis (CSG), intestinal metaplasia (IM), and gastric cancer. Statistical significances of steroid plasma levels between gastric disorder groups were investigated. In conclusion, this method provided comprehensive profiling of 20 steroids in human plasma samples and will be helpful to discover potential biomarkers for the development of gastric cancer and to further understand metabolic syndrome.

Prediction model for bleeding after endoscopic submucosal dissection of gastric neoplasms from a high-volume center.

BACKGROUND AND AIM: Bleeding after endoscopic submucosal dissection (ESD) is a main adverse event. To date, although there have been several studies about risk factors for post-ESD bleeding, there has been few predictive model for post-ESD bleeding with large volume cases. We aimed to design a prediction model for post-ESD bleeding using a classification tree model. METHODS: We analyzed a prospectively established cohort of patients with gastric neoplasms treated with ESD from 2007 to 2016. Baseline characteristics were collected for a total of 5080 patients, and the bleeding risk was estimated using variable statistical methods such as logistic regression, AdaBoost, and random forest. To investigate how bleeding was affected by independent predictors, the classification and regression tree (CART) method was used. The prediction tree developed for the cohort was internally validated. RESULTS: Post-ESD bleeding occurred in 262 of 5080 patients (5.1%). In multivariate logistic regression, ongoing antithrombotic use during the procedure, cancer pathology, and piecemeal resection were significant risk factors for post-ESD bleeding. In the CART model, the decisive variables were ongoing antithrombotic agent use, resected specimen size ≥49 mm, and patient age <62 years. The CART model accuracy was 94.9%, and the cross-validation accuracy was 94.8%. CONCLUSIONS: We developed a simple and easy-to-apply predictive tree model based on three risk factors that could help endoscopists identify patients at a high risk of bleeding. This model will enable clinicians to establish precise management strategies for patients at a high risk of bleeding and to prevent post-ESD bleeding.

Virtually-Planned Orthognathic Surgery Achieves an Accurate Condylar Position.

PURPOSE: Accuracy in orthognathic surgery with virtual planning has been reported, but detailed analysis of accuracy according to anatomic location, including the mandibular condyle, is insufficient. The purpose of this study was to compare the virtual plan and surgical outcomes and analyze the degree and distribution of errors according to each anatomic location. PATIENTS AND METHODS: This retrospective cohort study evaluated skeletal class III patients, treated with bimaxillary surgery. The primary predictor was anatomic locations that consisted of right and left condyles, maxilla, and the distal segment of the mandible. Other variables were age and gender. The primary outcome was surgical accuracy, defined as mean 3-dimensional distance error, mean absolute error, and mean error along the horizontal, vertical, and anteroposterior axes between the virtual plan and surgical outcomes. Landmarks were compared using a computational method based on affine transformation with a 1-time landmark setting. The mean errors were visualized with multidimensional scattergrams. Bivariate and regression statistics were computed. RESULTS: This study included 52 patients, 26 men and 26 women, with a mean age of 21 years and 3 months. The mean 3D distance errors for condylar landmarks, maxillary landmarks, and landmarks on the distal segment of the mandible were 1.03, 1.25, and 2.24 mm, respectively. Condylar landmarks, maxillary landmarks, and the landmarks on the distal segment of the mandible were positioned at 0.49 mm inferior, 0.28 mm anterior, and 1.25 mm inferior, respectively. The landmark errors for the distal segment of the mandible exhibited a wider distribution than those for condylar and maxillary landmarks. CONCLUSIONS: Agreement between the planned and actual outcome aided by virtual surgical planning was highest for the condyles, followed by the maxilla, and the distal segment of the mandible. It is important to consider the tendency for surgical errors in each anatomic location during operations.

Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea 2020.

Helicobacter pylori infection is one of the most common infectious diseases worldwide. Although the prevalence of H. pylori is gradually decreasing, approximately half of the world's population still becomes infected with this disease. H. pylori is responsible for substantial gastrointestinal morbidity worldwide, with a high disease burden. It is the most common cause of gastric and duodenal ulcers and gastric cancer. Since the revision of the H. pylori clinical practice guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin-based triple therapy for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance, especially from clarithromycin. The clinical practice guidelines for the treatment of H. pylori were updated according to evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after an expert consensus on three recommendations regarding the indication for treatment and eight recommendations for the treatment itself. These guidelines were designed to provide clinical evidence for the treatment (including primary care treatment) of H. pylori infection to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards and will be revised if more evidence emerges in the future.

Long-Term Outcomes and Prognostic Factors of Superficial Esophageal Cancer in Patients Aged ≥ 65 Years.

BACKGROUND: The number of elderly patients with superficial esophageal cancer (SEC) is increasing. We aimed to evaluate the clinical outcomes and prognostic factors of overall survival (OS) in elderly patients undergoing endoscopic submucosal dissection (ESD) or surgical resection for SEC. METHODS: Between January 2001 and May 2020, 290 patients aged ≥65 years who underwent ESD or surgical resection for SEC were evaluated. Their clinical outcomes and prognosis were assessed, and independent risk factors for OS were identified. RESULTS: The mean patient age (269 men and 21 women) was 70.9 years (range 65-90 years). En bloc, R0, and curative resections were achieved in 94.5%, 90.0%, and 73.4% of the patients, respectively. During the follow-up [mean: 54.6 months (range: 1-210 months)], 79 patients died. The 3-, 5-, and 10-year OS rates were 82.5, 73.1, and 59.7%, respectively. In multivariate analysis, cancer history of the other organs, American Society of Anesthesiologists performance status, and presence of lymphovascular involvement (hazard ratio = 1.852, 1.656, and 1.943, respectively; all P < 0.05) were independent risk factors for poor OS. The high-risk group (≥2 risk factors) showed a significantly lower OS than the low-risk group (≤ 1 risk factor) (P < 0.001). CONCLUSIONS: The three risk factors could be useful in predicting the long-term prognosis of elderly patients with SEC.

Clinicopathologic Features of Submucosal Papillary Gastric Cancer Differ from Those of Other Differentiated-Type Histologies.

Background/Aims: Papillary gastric cancer (GC) is classified as differentiated adenocarcinoma, together with well-differentiated (WD) and moderately differentiated (MD) adenocarcinoma. This study evaluated the risk of lymph node metastasis (LNM) in submucosal (SM) invasive papillary GC compared with other differentiated early GC types. Methods: This retrospective study involved three tertiary hospitals and enrolled 1,798 lesions with differentiated SM invasive GC treated with curative gastrectomy between March 2001 and December 2012. All pathology slides were reviewed, and clinicopathologic findings associated with LNM, including tumor size, location, gross type, ulceration, depth and width of SM invasion, and lymphovascular invasion (LVI), were analyzed. Results: The proportion of SM papillary GC was 2.8% (n=51). SM papillary GC was associated with larger tumor size and deeper and wider SM invasion than other differentiated GC types. LNM was significantly higher in the papillary type than in the MD and WD types. LNM was found in 27.5% of SM papillary GC patients (WD: 9.0%, MD: 21.2%). LVI was the only significant risk factor for LNM in SM papillary GC. The depth or width of SM invasion was not associated with LNM in papillary GC. Lower third location or elevated gross appearance was significantly associated with LVI. Conclusions: SM papillary GC had the highest LNM rate, with features different from those of other differentiated SM invasive GCs. The treatment strategy for SM papillary GC should be carefully approached, especially for lesions located in the lower third or of the elevated gross type.

Comparison of the Efficacy of Polaprezinc Plus Proton Pump Inhibitor and Rebamipide Plus Proton Pump Inhibitor Treatments for Endoscopic Submucosal Dissection-induced Ulcers.

GOALS: We assessed the efficacy of polaprezinc plus proton pump inhibitor (PPI) treatment for endoscopic submucosal dissection (ESD)-induced ulcer healing compared with rebamipide plus PPI treatment. BACKGROUND: ESD has been widely used as a local treatment option that cures gastric neoplasms. However, it causes large and deep artificial ulcers, and there are no guidelines with regard to the optimal treatment durations and drug regimens for ESD-induced ulcers. Polaprezinc is effective for promoting ulcer healing and helps enhance the quality of ulcer healing. STUDY: Two hundred ten patients with ESD-induced ulcers were randomly allocated to treatment with polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or treatment with rebamipide (300 mg/d) plus pantoprazole (40 mg/d). We evaluated the ulcer healing rate and condition of the ulcer at 4 weeks after dissection. The χ2 or Fisher exact test and the Student t test were used. RESULTS: The ulcer healing rates at 4 weeks after dissection in the polaprezinc plus pantoprazole treatment group were not inferior compared with those in the rebamipide plus pantoprazole treatment group, both in the intention-to-treat analysis (90.3% and 91.4%, respectively, P=0.523) and per-protocol analysis (89.9% and 91.1%, respectively, P=0.531). The short procedure time was an independent predictive factor for a high ulcer healing rate (odds ratio: 0.975; 95% confidence interval: 0.958-0.993; P=0.006). CONCLUSION: The polaprezinc plus PPI treatment showed noninferiority to rebamipide plus PPI treatment in the ulcer healing rate at 4 weeks after ESD.

Long-Term Outcomes and Prognostic Factors of Endoscopic Submucosal Dissection for Early Gastric Cancer in Patients Aged ≥75 Years.

BACKGROUND AND AIMS: The number of elderly patients with early gastric cancer (EGC) who meet the indications for endoscopic submucosal dissection (ESD) is increasing. We aimed to evaluate the clinical outcomes and prognostic factors of overall survival (OS) in elderly patients undergoing ESD for EGC. METHODS: Between January 2006 and December 2018, 439 patients aged ≥75 years who underwent ESD for EGC were analyzed. The clinical outcomes and prognosis were evaluated, and independent risk factors for OS were identified. RESULTS: The mean patient (302 men, 137 women) age was 78.3 (range 75-92) years. En bloc, R0, and curative resections were achieved in 96.8%, 90.7%, and 75.6%, respectively, without severe adverse events. During the follow-up (median 54.2 (range 4.0-159.6) months), 86 patients died (three of gastric cancer). The 3-, 5-, and 10-year OS was 91.2%, 83.5%, and 54.5%, respectively, and the 3-, 5-, and 10-year cancer related survival rate were 99.7%, 99.1% and 97.5%, respectively. In multivariate analysis, smoking, history of cancer of other organs, NLR > 1.6, Charlson comorbidity index ≥ 3, and presence of lymphovascular invasion (hazard ratio = 3.96, 1.78, 1.83, 1.83, and 2.63, respectively, all p < 0.05) were independent five risk factors for poor OS. The high-risk group (≥3 risk factors) showed a significantly lower OS than the low-risk group (<2 risk factors) (p < 0.001). CONCLUSIONS: The five factors could be useful in predicting the long-term prognosis of elderly ESD patients or deciding the therapeutic approaches in case of non-curative resection.