Advancements in the Diagnosis of Gastric Subepithelial Tumors

Osamu Goto , Mitsuru Kaise , and Katsuhiko Iwakiri

Gut Liver 2022; 16(3):321-330

https://doi.org/10.5009/gnl210242

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Abstract : A diagnosis of subepithelial tumors (SETs) is sometimes difficult due to the existence of overlying mucosa on the lesions, which hampers optical diagnosis by conventional endoscopy and tissue sampling with standard biopsy forceps. Imaging modalities, by using computed tomography and endoscopic ultrasonography (EUS) are mandatory to noninvasively collect the target’s information and to opt candidates for further evaluation. Particularly, EUS is an indispensable diagnostic modality for assessing the lesions precisely and evaluating the possibility of malignancy. The diagnostic ability of EUS appears increased by the combined use of contrast-enhancement or elastography. Histology is the gold standard for obtaining the final diagnosis. Tissue sampling requires special techniques to break the mucosal barrier. Although EUS-guided fine-needle aspiration (EUS-FNA) is commonly applied, mucosal cutting biopsy and mucosal incision-assisted biopsy are comparable methods to definitively obtain tissues from the exposed surface of lesions and seem more useful than EUS-FNA for small SETs. Recent advancements in artificial intelligence (AI) have a potential to drastically change the diagnostic strategy for SETs. Development and establishment of noninvasive methods including AI-assisted diagnosis are expected to provide an alternative to invasive, histological diagnosis.

Postinfection Irritable Bowel Syndrome

Uday C Ghoshal

Gut Liver 2022; 16(3):331-340

https://doi.org/10.5009/gnl210208

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Abstract : Following acute gastroenteritis (AGE) due to bacteria, viruses, or protozoa, a subset of patients develop new onset Rome criteria positive irritable bowel syndrome (IBS), called postinfection IBS (PI-IBS). The pooled prevalence of PI-IBS following AGE was 11.5%. PI-IBS is the best natural model that suggests that a subset of patients with IBS may have an organic basis. Several factors are associated with a greater risk of development of PI-IBS following AGE including female sex, younger age, smoking, severity of AGE, abdominal pain, bleeding per rectum, treatment with antibiotics, anxiety, depression, somatization, neuroticism, recent adverse life events, hypochondriasis, extroversion, negative illness beliefs, history of stress, sleep disturbance, and family history of functional gastrointestinal disorders (FGIDs), currently called disorder of gut-brain interaction. Most patients with PI-IBS present with either diarrhea-predominant IBS or the mixed subtype of IBS, and overlap with other FGIDs, such as functional dyspepsia is common. The drugs used to treat non-constipation IBS may also be useful in PI-IBS treatment. Since randomized controlled trials on the efficacy of drugs to treat PI-IBS are rare, more studies are needed on this issue.

2021 Korean Society of Gastrointestinal Endoscopy Clinical Practice Guidelines for Endoscopic Sedation

Hong Jun Park , Byung-Wook Kim , Jun Kyu Lee et al.

Gut Liver 2022; 16(3):341-356

https://doi.org/10.5009/gnl210530

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Abstract : Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Such cardiopulmonary complications are usually temporary, and most patients recover without sequelae. However, these events may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.

Type 2 Autoimmune Pancreatitis: Consensus and Controversies

Yoh Zen

Gut Liver 2022; 16(3):357-365

https://doi.org/10.5009/gnl210241

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Abstract : Autoimmune pancreatitis (AIP) has attracted much attention in the last two decades, and due to the diagnostic value of immunoglobulin G4 (IgG4), the number of cases diagnosed in clinical practice has markedly increased. However, in contrast to prototypic IgG4-related type 1 AIP, a minor subtype of AIP, referred to as type 2 AIP, is less widely known and has thus not yet been characterized in detail. Type 2 AIP is unrelated to IgG4 and is a completely distinct entity from type 1 AIP. One confusing factor is that the two types of AIP share patterns of clinical presentation (e.g., acute pancreatitis and painless jaundice) and imaging abnormalities (e.g., diffuse or segmental enlargement). Since there are currently no established serum markers, the diagnosis of type 2 AIP is highly challenging and requires the tissue confirmation of neutrophilic injury to the pancreatic ducts, a finding designated as a granulocytic epithelial lesion. Approximately one-third of cases are associated with inflammatory bowel disease, particularly ulcerative colitis; however, the pathological relationship between these two conditions has not yet been clarified. Unanswered questions relate to its pathophysiology, the potential development of a similar granulocytic injury in other organs, and the characteristics of pediatric cases. This review summarizes consensus and controversies surrounding type 2 AIP, with the aim of increasing awareness and highlighting the unmet needs of this underrecognized condition.

The Incidence and Risk Factors for Metachronous Gastric Cancer in the Remnant Stomach after Gastric Cancer Surgery

Yonghoon Choi , Nayoung Kim , Hyuk Yoon et al.

Gut Liver 2022; 16(3):366-374

https://doi.org/10.5009/gnl210202

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Abstract : Background/Aims: Less invasive surgical treatment is performed in East Asia to preserve postoperative digestive function and reduce complications such as postgastrectomy syndromes, but there is an issue of metachronous gastric cancer (GC) in the remaining stomach. This study aimed to analyze the incidence of metachronous GC and its risk factors in patients who had undergone partial gastrectomy. Methods: A total of 3,045 GC patients who had undergone curative gastric partial resection at Seoul National University Bundang Hospital were enrolled and analyzed retrospectively for risk factors, including age, sex, smoking, alcohol, Helicobacter pylori status, family history of GC, histological type, and surgical method. Results: Metachronous GC in the remaining stomach occurred in 35 of the 3,045 patients (1.1%): 23 in the distal gastrectomy group (18 with Billroth-I anastomosis, five with Billroth-II anastomosis), seven in the proximal gastrectomy (PG) group, and five in the pylorus-preserving gastrectomy (PPG) group. Univariate and multivariate Cox regression analyses showed that age ≥60 years (p=0.005) and surgical method used (PG or PPG, p

Seronegative Celiac Disease in Patients with Isolated Refractory Dyspepsia and Gastroesophageal Reflux Disease

Salih Tokmak , Baris Boral , and Yuksel Gumurdulu

Gut Liver 2022; 16(3):375-383

https://doi.org/10.5009/gnl210382

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Abstract : Background/Aims: To investigate the presence of seronegative celiac disease in patients with isolated refractory dyspepsia and gastroesophageal reflux disease (GERD)-related complaints. Methods: This was a single-center, prospective study performed at a tertiary care referral hospital. Among 968 consecutive patients, 129 seronegative patients with tissue damage consistent with Marsh IIIa classification or above were included. The patients were divided into two groups: dyspepsia (n=78) and GERD (n=51). Biopsies were taken from the duodenum regardless of endoscopic appearance, and patients with Marsh IIIa or above damage were advised to consume a gluten-free diet. The Glasgow Dyspepsia Severity (GDS) score, Reflux Symptom Index (RSI), and Biagi score were calculated at baseline and every 3 months. Control endoscopy was performed every 6 months during follow-up. Results: The median follow-up time was 19.9 months (range, 6 to 24 months) in the dyspepsia group and 19.2 months (range, 6 to 24 months) in the GERD group. All the patients were positive for the HLA-DQ2 and DQ8 haplotypes. The differences between the mean GDS scores (14.3±2.1 vs 1.1±0.2, respectively, p

Quality of Life in Newly Diagnosed Moderate-to-Severe Ulcerative Colitis: Changes in the MOSAIK Cohort Over 1 Year

Ik Hyun Jo , Kang-Moon Lee , Dae Bum Kim et al.

Gut Liver 2022; 16(3):384-395

https://doi.org/10.5009/gnl210141

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Abstract : Background/Aims: Improving quality of life has been gaining importance in ulcerative colitis (UC) management. The aim of this study was to investigate changes in health-related quality of life (HRQL) and related factors in patients with moderate-to-severe UC. Methods: A multicenter, hospital-based, prospective study was performed using a Moderate-to-Severe Ulcerative Colitis Cohort in Korea (the MOSAIK). Changes in HRQL, evaluated using the 12-Item Short Form Health Survey (SF-12) and Inflammatory Bowel Disease Questionnaire (IBDQ), were analyzed at the time of diagnosis and 1 year later. Results: In a sample of 276 patients, the mean age was 38.4 years, and the majority of patients were male (59.8%). HRQL tended to increase in both the IBDQ and SF-12 1 year after diagnosis. A higher partial Mayo score was significantly related to poorer HRQL on the IBDQ and SF-12 in a linear mixed model (p<0.01). Inflammatory markers such as C-reactive protein (CRP) or erythrocyte sedimentation rate also showed a negative correlation on HRQL (p<0.05). Patients whose IBDQ score improved by 16 or more (71.2%) in 1 year were younger, tended to be nonsmokers, and had a lower partial Mayo score and CRP than those whose IBDQ score did not. There was no significant association between HRQL and disease extent, treatments at diagnosis, or the highest treatment step during the 1-year period. Conclusions: Optimally controlled disease status improves HRQL in patients with moderate-to-severe UC. The partial Mayo score and inflammatory markers may be potential indicators reflecting the influence of UC on patient`s daily lives.

Clinical Course of Hepatitis B Viral Infection in Patients Undergoing Anti-Tumor Necrosis Factor α Therapy for Inflammatory Bowel Disease

Ji Min Lee , Shu-Chen Wei , Kang-Moon Lee et al.

Gut Liver 2022; 16(3):396-403

https://doi.org/10.5009/gnl210081

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Abstract : Background/Aims: Little is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy. Methods: This retrospective multinational study involved multiple centers in Korea, China, Taiwan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients’ medical records were reviewed, and data were collected using a web-based case report form. Results: Overall, 191 patients (77 ulcerative colitis and 114 Crohn’s disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis. Conclusions: Liver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

The Influence of Face Shields on the Quality of Colonoscopy in the Era of the COVID-19 Pandemic

Jin Wook Lee , Hyo Jeong Lee , Dae Sung Kim et al.

Gut Liver 2022; 16(3):404-413

https://doi.org/10.5009/gnl210063

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Abstract : Background/Aims: The worldwide coronavirus disease 2019 pandemic has led endoscopists to use personal protective equipment (PPE) for infection prevention. This study aimed to investigate whether wearing a face shield as PPE affects the quality of colonoscopy.Methods: We reviewed the medical records and colonoscopy findings of patients who underwent colonoscopies at Asan Medical Center, Korea from March 10 to May 31, 2020. The colonoscopies in this study were performed by five gastroenterology fellows and four expert endoscopists. We compared colonoscopy quality indicators, such as withdrawal time, adenoma detection rate (ADR), mean number of adenomas per colonoscopy (APC), polypectomy time, and polypectomy adverse events, both before and after face shields were added as PPE on April 13, 2020.Results: Of the 1,344 colonoscopies analyzed, 715 and 629 were performed before and after the introduction of face shields, respectively. The median withdrawal time was similar between the face shield and no-face shield groups (8.72 minutes vs 8.68 minutes, p=0.816), as was the ADR (41.5% vs 39.8%, p=0.605) and APC (0.72 vs 0.77, p=0.510). Polypectomy-associated quality indicators, such as polypectomy time and polypectomy adverse events were also not different between the groups. Quality indicators were not different between the face shield and no-face shield groups of gastroenterology fellows, or of expert endoscopists.Conclusions: Colonoscopy performance was not unfavorably affected by the use of a face shield. PPE, including face shields, can be recommended without a concern about colonoscopy quality deterioration.

Continued Postoperative Use of Tumor Necrosis Factor-α Inhibitors for the Prevention of Crohn’s Disease Recurrence

Jongwook Yu , Hye Kyung Hyun , Jihye Park et al.

Gut Liver 2022; 16(3):414-422

https://doi.org/10.5009/gnl210062

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Abstract : Background/Aims: Many patients with Crohn’s disease (CD) undergo intestinal resection during the disease course. Despite surgery, postoperative recurrence (POR) commonly occurs. Although postoperative use of tumor necrosis factor α (TNF-α) inhibitors is known to be effective in preventing POR, few studies have evaluated the effectiveness of continuing the same TNF-α inhibitors postoperatively in patients who received TNF-ɑ inhibitors before surgery.Methods: This retrospective observational study was performed in a single tertiary medical center. We retrospectively reviewed patients who had undergone the first intestinal resection due to CD and divided them into two groups: TNF-α inhibitor users in both the preoperative and postoperative periods, and TNF-α inhibitor users in only the preoperative period. We compared the clinical outcomes between these two groups.Results: In total, 45 patients who used TNF-α inhibitors preoperatively were recruited. Among them, TNF-α inhibitors were used postoperatively in 20 patients (44.4%). The baseline characteristics except age at diagnosis were similar in both groups. The rates of surgical and endoscopic recurrence were not different between the two groups, but the cumulative clinical recurrence rate was significantly lower in the postoperative TNF-α inhibitors group (log-rank p=0.003). In multivariate Cox regression analysis, postoperative TNF-α inhibitors use was significantly associated with a decreased risk of clinical recurrence (adjusted hazard ratio, 0.204; 95% confidence interval, 0.060 to 0.691; p=0.011).Conclusions: Continuing TNF-α inhibitors postoperatively in patients who were receiving TNF-α inhibitors before surgery significantly reduced the rate of clinical recurrence. For patients with CD who received TNF-α inhibitors preoperatively, continuing their use after surgery could be recommended.

Fasting Blood Glucose Variability and Unfavorable Trajectory Patterns Are Associated with the Risk of Colorectal Cancer

Hyoju Jun , Jieun Lee , Hye Ah Lee et al.

Gut Liver 2022; 16(3):423-432

https://doi.org/10.5009/gnl210048

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Abstract : Background/Aims: The relationship between fasting blood glucose (FBG) variability and colorectal cancer (CRC) remains ill-defined. This study aimed to evaluate the association of FBG variability with CRC risk in the healthy population without overt diabetes. Methods: In the data from the Korean National Health Insurance Service-Health Screening Cohort, we included individuals examined by FBG testing at least 3 times between 2002 and 2007. FBG variability was calculated using standard deviation (SD) and coefficient of variation (CV). Results: Regarding FBG variability, an increase in the quintile of SD or CV was independently associated with CRC risk (all p for trend

Metabolic Dysfunction-Associated Fatty Liver Disease Predicts Long-term Mortality and Cardiovascular Disease

Joon Ho Moon , Won Kim , Bo Kyung Koo et al.

Gut Liver 2022; 16(3):433-442

https://doi.org/10.5009/gnl210167

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Abstract : Background/Aims: We investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study. Methods: Individuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions: overweight/obesity (body mass index ≥23 kg/m²), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis. Results: Among 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85). Conclusions: MAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.

Circulating Cancer Stem Cells Expressing EpCAM/CD90 in Hepatocellular Carcinoma: A Pilot Study for Predicting Tumor Recurrence after Living Donor Liver Transplantation

Hyeo Seong Hwang , Jeong Eun Yoo , Dai Hoon Han et al.

Gut Liver 2022; 16(3):443-455

https://doi.org/10.5009/gnl210162

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Abstract : Background/Aims: Circulating tumor cells (CTCs) with cancer stemness have been demonstrated to be a direct cause of tumor recurrence, and only few studies have reported the role of CTCs in liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods: Epithelial cell adhesion molecule+ (EpCAM+), cluster of differentiation 90+ (CD90+) and EpCAM+/CD90+ CTCs were sorted via fluorescence-activated cell sorting, and transcripts level of EpCAM, K19 and CD90 in the peripheral blood were analyzed via real-time polymerase chain reaction preoperatively and on postoperative days 1 and 7 in 25 patients who underwent living donor liver transplantation (LDLT) for HCC. EpCAM protein was assessed in HCC tissue using immunohistochemical staining. The median follow-up duration was 40 months. Results: HCC after LDLT recurred in four out of 25 patients. Detection of EpCAM+ or CD90+ CTCs correlated well with their messenger RNA levels (p

Metabolic Risk Factors Are Associated with the Disease Severity and Prognosis of Hepatitis B Virus-Related Acute on Chronic Liver Failure

Lu Chen , Jinjin Dai , Qing Xie et al.

Gut Liver 2022; 16(3):456-464

https://doi.org/10.5009/gnl210449

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Abstract : Background/Aims: Metabolic risk factors could accelerate hepatitis B virus (HBV)-related mortality; however, their impacts on disease severity in HBV-related acute on chronic liver failure (HBV-ACLF) patients remain unexplored. In this study, we assessed the effects of metabolic risk factors on the outcome of HBV-ACLF patients. Methods: This study retrospectively enrolled antiviral therapy naïve HBV-ACLF patients from a single center in China. Patients were evaluated according to Child-Turcotte-Pugh score, Model for End-Stage Liver Disease (MELD) score, 30-day, 90-day mortality and survival rate to estimate the prognosis of HBV-ACLF. The impacts of different metabolic risk factors were further analyzed. Results: A total of 233 patients, including 158 (67.8%) with metabolic risk factors and 75 (32.2%) without metabolic risk factors, were finally analyzed. Patients with metabolic risk factors had significantly higher MELD score (22.6±6.1 vs 19.8±3.8, p

Increased Risk of Cancer after Cholecystectomy: A Nationwide Cohort Study in Korea including 123,295 Patients

Yoon Jin Choi , Eun Hyo Jin , Joo Hyun Lim et al.

Gut Liver 2022; 16(3):465-473

https://doi.org/10.5009/gnl210009

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Abstract : Background/Aims: Contradictory findings on the association between cholecystectomy and cancer have been reported. We aimed to investigate the risk of all types of cancers or site-specific cancers in patients who underwent cholecystectomy using a nationwide dataset. Methods: Subjects who underwent cholecystectomy from January 1, 2007, to December 31, 2014, who were older than 20 years and who underwent an initial baseline health check-up within 2 years were enrolled. Those who were diagnosed with any type of cancer before the enrollment or within 1 year after enrollment were excluded. Ultimately, patients (n=123,295) who underwent cholecystectomy and age/sex matched population (n=123,295) were identified from the database of the Korean National Health Insurance Service. The hazard ratio (HR) and 95% confidence interval (CI) for cancer were estimated, and Cox regression analysis was performed. Results: The incidence of cancer in the cholecystectomy group was 9.56 per 1,000 person-years and that in the control group was 7.95 per 1,000 person-years. Patients who underwent cholecystectomy showed an increased risk of total cancer (adjusted HR, 1.19; 95% CI, 1.15 to 1.24; p

Prognosis and Clinical Characteristics of Patients with Pancreatic Ductal Adenocarcinoma Diagnosed by Endoscopic Ultrasonography but Indeterminate on Computed Tomography

Sung Woo Ko , Tae Hyeon Kim , Tae Jun Song et al.

Gut Liver 2022; 16(3):474-482

https://doi.org/10.5009/gnl210123

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Abstract : Background/Aims: Endoscopic ultrasonography (EUS) provides high-resolution images and is superior to computed tomography (CT) scan in diagnosing small pancreatic ductal adenocarcinoma (PDAC). As a result, the use of EUS for early detection of PDAC has attracted attention. This study aimed to identify the clinical and radiological characteristics of patients with PDAC diagnosed by EUS but not found on CT scan. Methods: The medical records of patients diagnosed with PDAC at 12 tertiary referral centers in Korea from January 2003 to April 2019 were reviewed. This study included patients with pancreatic masses not clearly observed on CT scan but identified on EUS. The clinical characteristics and radiological features of the patients were analyzed, and survival analysis was performed. Results: A total of 83 patients were enrolled. The most common abnormal CT findings other than a definite mass was pancreatic duct dilatation, which was identified in 61 patients (73.5%). All but four patients underwent surgery. The final pathologic stages were as follows: IA (n=31, 39.2%), IB (n=8, 10.1%), IIA (n=20, 25.3%), IIB (n=17, 21.5%), III (n=2, 2.5%), and IV (n=1, 1.4%). The 5-year survival rate of these patients was 50.6% (95% confidence interval, 38.8% to 66.7%). Elevated liver function testing and R1 resection emerged as significant predictors of mortality in the multivariable Cox regression analysis. Conclusions: This multicenter study demonstrated favorable long-term prognosis in patients with PDAC diagnosed by EUS but indeterminate on CT scan. EUS should be considered for patients with suspected PDAC but indeterminate on CT scan.

Pyloric Gland Adenoma of the Esophagus Treated by Endoscopic Submucosal Dissection: A Case Report

Kwangbeom Park , Do Hoon Kim , Sung Duck Lee et al.

Gut Liver 2022; 16(3):483-486

https://doi.org/10.5009/gnl210357

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Abstract : A pyloric gland adenoma is a rare neoplasm that occurs most frequently in the stomach and should be removed because of its precancerous potential. Although there have been case reports of pyloric gland adenomas in extragastric areas such as the duodenum, pancreas, and bile duct, esophageal pyloric gland adenoma has never been reported in Korea. Herein, we report a case of esophageal pyloric gland adenoma that was successfully treated by endoscopic submucosal dissection.