Safety of pylorus-preserving gastrectomy for gastric cancer combined with antral high-risk lesions: a comparison with endoscopic submucosal dissection.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) is a surgical treatment option for cT1N0M0 gastric cancer located in the middle third of the stomach. However, data for the long-term post-PPG clinical outcomes related to metachronous gastric neoplasms (mGNs) in the residual stomach are currently lacking. Therefore, we aimed to evaluate the safety of PPG by focusing on mGNs. METHODS: In this single-center, retrospective study, we reviewed the data for 362 patients who underwent PPG with a 3-cm antral cuff and 139 who underwent endoscopic submucosal dissection (ESD) for middle-third gastric cancer between January 2013 and December 2015. The histopathologic features of the antrum in the ESD group, which could not be determined in the PPG group, were analyzed to investigate the risk factors for mGNs. The estimated and actual incidence of mGNs in the antrum were compared in the PPG group. RESULTS: The incidence of mGNs was 6.5% (9/139) in the ESD group. The presence of a synchronous adenoma (odds ratio [OR], 8.46; 95% confidence interval [CI], 1.55-46.34), carcinoma (OR, 15.71; 95% CI, 2.67-92.56) and moderate-to-severe intestinal metaplasia (OR, 9.77; 95% CI, 1.14-83.92) were associated with a higher risk of overall mGNs. However, when confined to the antrum, no significant association was observed between these factors and mGNs. In the ESD group, 2 of 9 mGNs (1.4%) were located at the 3-cm antral cuff. In the PPG group, both mGNs (0.6%) were located in the proximal remnant stomach. CONCLUSION: Pylorus-preserving gastrectomy was a safe therapeutic option with regard to the occurrence of metachronous adenomas or carcinomas in our series. Despite the low mGN incidence in the 3-cm antral cuff after PPG, the presence of synchronous neoplasms or moderate-to-severe intestinal metaplasia was a risk factor for mGNs in the ESD group; thus, further studies on longer antral cuffs with long-term follow-up are needed.

Gastric subepithelial tumor: long-term natural history and risk factors for progression.

BACKGROUND: Subepithelial tumors are often detected incidentally during upper gastrointestinal endoscopy. However, their natural history and clinical management have yet to be clearly established. The aim of this study was to evaluate the natural history and risk factors for progression of gastric SETs. METHODS: The study retrospectively reviewed the medical records of patients who were diagnosed with gastric SET using upper gastrointestinal endoscopy between January 2005 and December 2017. Tumor progression was defined by a ≥ 25% increase in diameter. RESULTS: Among 3237 patients, 1859 underwent serial upper gastrointestinal endoscopy for more than six months. Endoscopic ultrasonography was further performed in 733 (39.43%) patients. Resection was performed in 73 (3.93%) patients. Tumor progressed in 138 (7.42%) patients over a mean follow-up period of 59.41 months (range, 5-215 months). In progressed tumors, the mean initial size was 15.01 mm (range, 2-50 mm) and the mean size increment was 12.86 mm (range, 3-50 mm). Large initial tumor size (OR: 1.03, 95% CI: 1.01-1.05), surface ulcer or erosion (OR: 2.47, 95% CI: 1.21-5.06), lobulated shape (OR: 3.76, 95% CI: 2.00-7.06), and middle-third location (OR: 1.65, 95% CI: 1.08-2.52) were significant risk factors for tumor progression. Large SETs had higher rates of progression and tended to grow faster than smaller tumors (r = 0.44, p < 0.001). CONCLUSIONS: The majority of gastric SETs did not increase in size during the long-term follow-up. Serial endoscopy may be sufficient as a follow-up tool for small SETs with intact overlying mucosa without lobulated shape.

Identification of gaze pattern and blind spots by upper gastrointestinal endoscopy using an eye-tracking technique.

BACKGROUND: The lesion detection rate of esophagogastroduodenoscopy (EGD) varies depending on the degree of experience of the endoscopist and anatomical blind spots. This study aimed to identify gaze patterns and blind spots by analyzing the endoscopist's gaze during real-time EGD. METHODS: Five endoscopists were enrolled in this study. The endoscopist's eye gaze tracked by an eye tracker was selected from the esophagogastric junction to the second portion of the duodenum without the esophagus during insertion and withdrawal, and then matched with photos. Gaze patterns were visualized as a gaze plot, blind spot detection as a heatmap, observation time (OT), fixation duration (FD), and FD-to-OT ratio. RESULTS: The mean OT and FD were 11.10 ± 11.14 min and 8.37 ± 9.95 min, respectively, and the FD-to-OT ratio was 72.5%. A total of 34.3% of the time was spent observing the antrum. When observing the body of the stomach, it took longer to observe the high body in the retroflexion view and the low-to-mid body in the forward view. CONCLUSIONS: It is necessary to minimize gaze distraction and observe the posterior wall in the retroflexion view. Our results suggest that eye-tracking techniques may be useful for future endoscopic training and education.

Long-term natural history after endoscopic resection for gastric dysplasia.

BACKGROUND AND STUDY AIMS: Natural history after endoscopic resection (ER) for gastric dysplasia is still unclear. The aim of this study was to evaluate the long-term clinical outcomes and risk factors after ER for gastric dysplasia between control and cases with synchronous or metachronous gastric neoplasm. METHODS: A total of 1090 patients who had undergone ER for gastric dysplasia and been followed up for at least one year from December 2002 to December 2013 were finally analyzed. Risk factors affecting the development of synchronous or metachronous neoplasm (SMN) and long-term clinical outcomes after ER for gastric dysplasia were evaluated. RESULTS: Synchronous and metachronous neoplasms had developed in 126 (11.6%) and 133 patients (12.2%) during the mean follow-up duration of 63.6 months, respectively. Five-year and 10-year risk of metachronous neoplasm were 9.8% and 27.2%, respectively. Median duration to the development of metachronous neoplasm was 103.1 months. While age (P < 0.001) and mucosal atrophy (P = 0.09) of index cases were associated with the development of synchronous neoplasm, age (P = 0.017), incomplete resection (P = 0.025), and intestinal metaplasia (P = 0.017) of background mucosa of index cases were significantly related to the development of metachronous neoplasm in multivariate analysis. Cumulative incidence of SMN was not significantly different among H. pylori negative, eradicated, and persistent group. CONCLUSIONS: Age, incomplete ER, and background intestinal metaplasia of index gastric dysplasia were significantly associated with metachronous recurrence. Endoscopic surveillance for metachronous recurrence after ER for gastric dysplasia is mandatory for longer than 10 years.

Determining the current indications for endoscopic submucosal dissection in patients with Lauren mixed-type early gastric cancer.

BACKGROUND AND AIM: Recent study showed that early gastric cancer (EGC) with Lauren mixed-type (MT) histology is associated with worse prognosis. We aimed to evaluate the clinicopathologic features and prognostic significance of Lauren MT-EGCs that meets the criteria for endoscopic submucosal dissection (ESD). METHODS: We reviewed 2665 patients with EGC who underwent surgery between 2010 and 2015. The clinicopathologic features and invasiveness including lymph node metastasis (LNM) and lymphovascular invasion (LVI) of MT-EGC were compared with those of intestinal type and diffuse type by Lauren histology. RESULTS: Among 2665 patients, EGCs in 241 (9%) patients were classified as MT. Tumor size was larger and depth of invasion was greater than other histology. Among patients with MT-EGC, 16.6% (40/241) showed LNM and 22.8% (55/241) showed lymphatic invasion, which were significantly higher than that of patients with other Lauren types (8.2% and 15.3% in intestinal type and 9.1% and 8.7% in diffuse type, P < 0.001). This finding remained significant even after adjusting for depth of invasion. However, when we analyzed the patient groups who met the absolute or expanded criteria of ESD, no significant difference was observed in the rates of LNM or LVI or cancer mortality by Lauren classification. CONCLUSION: Mixed-type early gastric cancer (MT-EGC) exhibited larger tumor size, greater depth of invasion, and higher risk of LNM and LVI. However, among the patients who met the absolute or expanded criteria of ESD, no significant difference was observed in LNM, LVI, and gastric cancer mortality risk.

Initial overcorrection after surgery for intermittent exotropia in children less than 4 years old: Comparison with older children.

PURPOSE: While initial overcorrection after exotropia-correcting surgery is widely accepted for a favorable long-term outcome, some have not advocated such overcorrection in younger children owing to concerns regarding rapid deterioration of bifixation ability. This study aimed to evaluate the relationship between initial overcorrection after intermittent exotropia surgery and the surgical outcome in patients aged <4 years. METHODS: In this retrospective study, 391 patients who had undergone surgery for intermittent exotropia were classified into two groups according to the age at surgery: <4 years old (group Y [young], 130 patients) and 4-16 years old (group O [old], 261). The patients were subdivided into three groups according to the angle of deviation at postoperative 1 week: esophoria-tropia (ET) ≥10 prism diopters (PD) (subgroup I), ET 1-9 PD (II), and orthotropia or exophoria-tropia (XT) (III). We compared the surgical outcomes between the two groups and among subgroups; then, we analyzed consecutive esotropia patients. RESULTS: The mean exodeviation was smaller in the order of subgroup I, II, and III at every postoperative visit (p<0.05) in group Y but showed no difference among subgroups after 2 years in group O. Consecutive esotropia occurred at 1 month, postoperatively, in 6.9% and 2.6% of the patients in groups Y and O (p = 0.133), respectively. However, it persisted in two and one patient in groups Y and O, respectively, until the last visit. CONCLUSION: Early overcorrection after intermittent exotropia surgery was a safe and desirable result in terms of motor outcome in children aged under 4 years, as well as for children aged between 4-16 years.

Role of Endoscopic Ultrasound in Selecting Superficial Esophageal Cancers for Endoscopic Resection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a curative treatment option for superficial esophageal cancer with a minimal risk for lymph node metastasis. Before ESD, accurate clinical staging is important to select the appropriate candidate. We aimed to estimate the practicality of endoscopic ultrasound (EUS) to select pTis and pT1a. METHODS: We included patients with squamous esophageal cancers who underwent surgical resection or ESD between 2005 and 2018. Pathologic reports were reviewed retrospectively, and pathologic T staging was compared with clinical stage evaluated by EUS. RESULTS: Among 532 patients, 321 had superficial esophageal cancer (pTis: 42; pT1a: 115; and pT1b: 164). Accuracy rates, sensitivity, specificity, positive predicted value, and negative predicted value for selecting cT1a by EUS were 82.3%, 60.5%, 91.5%, 74.8%, and 84.7%, respectively. The rate of overstaged pTis-T1a was 39.5%. Upon multivariable analysis, tumor size (>2 cm), poor differentiation, protruding gross type, and use of conventional EUS (versus miniprobe) were associated factors for overstaging of pTis-T1a. CONCLUSIONS: The accuracy of prediction of EUS for selecting mucosal esophageal cancer that can be treated with ESD was favorable. Target lesions with a large size (>2 cm), poor differentiation, and protruding morphology were related to T overstaging; precaution should be taken when evaluating the clinical stage for cancers with those conditions. Furthermore, miniprobe EUS provides higher accuracy for squamous esophageal cancers confined to mucosa.

Clinical Outcomes of Endoscopic Submucosal Dissection for Early Gastric Cancer in Patients with Comorbidities.

PURPOSE: As the rate of endoscopic resection for early gastric cancer (EGC) has increased in patients with comorbid diseases, it is necessary to elucidate the efficacy of endoscopic submucosal dissection (ESD) for EGC in patients with comorbidities. This study aimed to analyze the clinical outcomes of ESD for EGC in patients with comorbidities. MATERIALS AND METHODS: A total of 969 patients with 1,015 lesions who underwent ESD for EGC at Seoul National University Hospital between 2010 and 2014 were analyzed. The short- and long-term clinical outcomes were evaluated according to the comorbidity status. RESULTS: Comorbidities were observed in 558 patients (57.6%). The comorbidity group had a higher proportion of patients using antithrombotic agents (29.5% vs. 0.9%; P<0.0001). Although procedure-related complications (bleeding and perforation) were not significantly different between the two groups, the length of hospital stay was significantly longer (1.8 vs. 1.4 days, P=0.023), while survival was significantly shorter in the comorbidity group (5-year overall survival rate: 90.5% vs. 97.2%, P<0.0001; 5-year disease-specific survival rate: 97.9% vs. 100%, P=0.018; 5-year disease-free survival rate: 83.4% vs. 89.2%, P=0.007). CONCLUSIONS: Gastric ESD can be performed in patients with comorbidities without increasing the risk of complications.

Use of direct oral anticoagulants does not significantly increase delayed bleeding after endoscopic submucosal dissection for early gastric neoplasms.

Direct oral anticoagulants (DOACs) are widely prescribed for the prevention of stroke in elderly patients with atrial fibrillation and approved indication for DOAC has been expanded. We aimed to evaluate the risk of delayed bleeding in patients who had taken DOAC and underwent endoscopic submucosal dissection (ESD) for gastric neoplasms. We included consecutive patients who underwent ESD between January 2016 and July 2019 in Seoul National University Hospital. Patients were divided into four groups (no med; no medication, DOAC, WFR; warfarin, anti-PLT; anti-platelet agent) according to the medications they had been taken before the procedure. We defined delayed bleeding as obvious post-procedural gastrointestinal bleeding sign including hematemesis or melena combined with hemoglobin drop ≥ 2 g/dL. Among 1634 patients enrolled in this study, 23 (1.4%) patients had taken DOAC and they usually stopped the medication for 2 days before the ESD and resumed within 1 or 2 days. We compared rates of delayed bleeding between groups. Delayed bleeding rates of the groups of no med, DOAC, WFR, and anti-PLT were 2.1% (32/1499) 8.7% (2/23), 14.3% (2/14), 11.2% (11/98), respectively (P < 0.001). However, there was no difference of delayed bleeding rate between no med and DOAC group after propensity score matching (no med vs DOAC, 1.7% vs 10.0%, P = 0.160). Taking DOAC was not associated statistically with post-ESD bleeding when adjusted by age, sex, comorbidities and characteristics of target lesion (Adjusted Odds Ratio: 2.4, 95% Confidence intervals: 0.41-13.73, P = 0.335). Crude rate of bleeding in DOAC users seemed to be higher than no medication group after performing ESD with 2 days of medication cessation. When adjusted by age, sex, and comorbidity, however, this difference seems to be small, which suggests that gastric post-ESD bleeding may be influenced by patients' underlying condition in addition to medication use.

COL8A2 Regulates the Fate of Corneal Endothelial Cells.

Purpose: To investigate the effect of COL8A2 repression on corneal endothelial cells (CECs) in vitro and in vivo. Methods: Cultured human CECs (hCECs) were transfected with COL8A2 siRNA (siCOL8A2), and the cell viability and proliferation rate were measured. The expression of cell proliferation-associated molecules was evaluated by Western blotting and real-time reverse transcription PCR. Cell shape, Wingless-INT (WNT) signaling, and mitochondrial oxidative stress were also measured. For in vivo experiments, siCOL8A2 was transfected into rat CECs (rCECs), and corneal opacity and corneal endothelium were evaluated. Results: After transfection with siCOL8A2, COL8A2 expression was reduced (80%). Cell viability, cell proliferation rate, cyclin D1 expression, and the number of cells in the S-phase were reduced in siCOL8A2-treated cells. The cell attained a fibroblast-like shape, and SNAI1, pSMAD2, and ß-catenin expression, along with mitochondrial mass and oxidative stress levels, were altered. Corneal opacity increased, and the CECs were changed in rats in the siCOL8A2 group. Conclusions: COL8A2 is required to maintain normal wound healing and CEC function.

Endoscopic Submucosal Dissection Versus Surgery for Superficial Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Survival Analysis.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). However, only few studies compared long-term survival outcomes of ESD with surgery. This study compared the overall survival (OS), recurrence-free survival, and complication rates of ESD with those of surgery. METHODS: We reviewed patients who underwent ESD (n = 70) or surgery (n = 114) for SESCC at Seoul National University Hospital from 2011 to 2017. A propensity score-matched analysis was used to reduce selection bias. To increase the precision of our results interpretation, subgroups were analyzed according to the depth of tumor invasion. RESULTS: In the matching study, the ESD group (n = 34) showed comparable survival outcomes with the surgery group (n = 34). The 5-year OS rates were 89.4% vs 87.8% for the ESD and the surgery groups, respectively; similarly, the 5-year recurrence-free survival rates were 90.9% and 91.6%, respectively. The ESD group showed a lower early major complication rate (2.9% [1 of 34] vs 23.5% [8 of 34], P < 0.001) and shorter hospital stay (median, 3.0 days vs 16.5 days, P < 0.001) than the surgery group. In the tumor in situ (Tis)-subgroup, ESD showed better OS than esophagectomy (P = 0.030). Between-group comparisons of survival outcomes in the T1a and T1b subgroups revealed no significant differences. DISCUSSION: Long-term outcomes of ESD are comparable with surgery for patients with SESCC. For early major complications and duration of hospital stay, ESD was associated with better outcomes than radical surgery. These results support ESD as the preferred treatment option for SESCC.

Empiric Versus Clarithromycin Resistance-Guided Therapy for Helicobacter pylori Based on Polymerase Chain Reaction Results in Patients With Gastric Neoplasms or Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Randomized Controlled Trial.

INTRODUCTION: We investigated to compare the effect of empirical therapy vs clarithromycin resistance-guided tailored therapy (tailored therapy) for eradication of Helicobacter pylori. METHODS: In this prospective, single center, open-label randomized controlled trial, we enrolled 72 patients with H. pylori infection from January 2019 through June 2019 in Korea. The patients were randomly assigned to both groups received empirical (n = 36) or tailored therapy (n = 36). Empirical therapy was defined as triple therapy with esomeprazole, amoxicillin, and clarithromycin for 10 days irrespective of clarithromycin resistance. Tailored therapy was triple or quadruple therapy with esomeprazole, metronidazole, tetracycline, and bismuth for 10 days based on genotype markers of resistance determined by gastric biopsy. Resistance-associated mutations in 23S rRNA were confirmed by multiplex polymerase chain reaction. Eradication status was assessed by C-urea breath test, and the primary outcome was eradication rates. RESULTS: H. pylori was eradicated in 27 patients (75.0%), given empirical therapy and 32 patients (88.9%) treated with tailored therapy (P = 0.136) in intention-to-treat analysis. In per protocol analysis, the eradication rate was 97.0% and 81.8% in tailoredvs empirical groups (P = 0.046). Although clarithromycin-resistant H. pylori was eradicated in 3/9 (33.3%) with empirical therapy, it was treated in 11/12 (91.7%) with tailored therapy (P = 0.009). There was no difference in compliance between 2 groups. The rate of adverse events of the tailored group was higher than that of the empirical group (P = 0.036) because quadruple therapy had more side effects than those of triple therapy (P = 0.001). DISCUSSION: Tailored therapy based on polymerase chain reaction is a good alternative to increase eradication rates in a region of high prevalence of clarithromycin resistance (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A342).

Accelerated esterification of free fatty acid using pulsed microwaves.

It was demonstrated that pulsed microwave irradiation is a more effective method to accelerate the esterification of free fatty acid with a heterogeneous catalyst than continuous microwave irradiation. A square-pulsed microwave with a 400 Hz repetition rate and a 10-20% duty cycle with the same energy as the continuous microwave were used in this study. The pulsed microwaves improved the esterification conversion from 39.9% to 66.1% after 15 min in comparison with the continuous microwave under the same reaction conditions. These results indicated that pulsed microwaves with repetitive strong power could enhance the efficiency of biodiesel production relative to the use of continuous microwave with mild power.

Microwave-accelerated energy-efficient esterification of free fatty acid with a heterogeneous catalyst.

This paper shows energy-efficiency of microwave-accelerated esterification of free fatty acid with a heterogeneous catalyst by net microwave power measurement. In the reaction condition of 5 wt% sulfated zirconia and 1:20 M ratio of oil to methanol at 60°C and atmospheric pressure, more than 90% conversion of the esterification was achieved in 20 min by microwave heating, while it took about 130 min by conventional heating. Electric energy consumption for the microwave heating in this accelerated esterification was only 67% of estimated minimum heat energy demand because of significantly reduced reaction time.