Treatment of Refractory Helicobacter pylori Infection-Tailored or Empirical Therapy

Jyh-Ming Liou , Yi-Chia Lee , and Ming-Shiang Wu et al.

Gut Liver 2022; 16(1):8-18

https://doi.org/10.5009/gnl20330

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Abstract : The treatment of refractory Helicobacter pylori remains challenging in clinical practice. Factors that should be considered in the treatment of refractory H. pylori infection include treatment length, dosage of antibiotics and proton pump inhibitors (PPIs), number of drugs, and the selection of appropriate antibiotics. Extending the treatment length of triple therapy and non-bismuth quadruple therapy to 14 days may increase the eradication rate compared with a shorter period (7 or 10 days). The use of a higher dose of PPIs or vonoprazan may also increase the efficacy of triple therapy. Four-drug therapy, including bismuth or non-bismuth quadruple therapies, usually achieve higher eradication rates than triple therapy. The addition of bismuth or metronidazole to levofloxacin-amoxicillin-PPI therapy may also increase the eradication rate. Therefore, four-drug therapies containing a higher dose of PPIs for 14 days are recommended in the third-line treatment setting for refractory H. pylori infection. The selection of appropriate antibiotics may be guided by susceptibility testing or empirically by medication history. Tailored therapy guided by susceptibility testing or genotypic resistance is recommended whenever possible. However, properly designed empirical therapy based on prior medication history (i.e., avoid the reuse of clarithromycin or levofloxacin empirically) is an acceptable alternative to tailored therapy after considering accessibility, cost, and the preference of the patient.

Systematic Endoscopic Approach for Diagnosing Gastric Subepithelial Tumors

Gwang Ha Kim

Gut Liver 2022; 16(1):19-27

https://doi.org/10.5009/gnl20296

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Abstract : Subepithelial tumors (SETs) are commonly encountered during upper gastrointestinal endoscopy, especially during national gastric cancer screening programs in Korea. Although the majority of SETs are benign, endoscopists harbor concerns regarding whether a SET is benign or malignant because the diagnosis cannot be established on the basis of routine endoscopic biopsy findings. The differential diagnosis of SETs is important, beginning with meticulous endoscopic examination, including the evaluation of the location, macroscopic shape, color, surface characteristics, mobility, consistency, and size of the tumors. The yield of endoscopic biopsy increases with the use of the bite-on-bite technique for SETs without the rolling or tenting sign, with large openings, and with erosion or ulceration. In this review, a systematic approach for the diagnosis of gastric SETs during conventional endoscopy is introduced.

Classification and Diagnostic Criteria for IgG4-Related Sclerosing Cholangitis

Itaru Naitoh and Takahiro Nakazawa

Gut Liver 2022; 16(1):28-36

https://doi.org/10.5009/gnl210116

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Abstract : IgG4-related sclerosing cholangitis (IgG4-SC) can be classified into four types based on cholangiographic findings and regions of biliary stricture. This cholangiographic classification is useful to differentiate IgG4-SC from mimickers including cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic cancer. Autoimmune pancreatitis (AIP) is a valuable clue for the diagnosis of IgG4-SC because the two are frequently found in association with each other. Two sets of diagnostic criteria for IgG4-SC have been proposed. In Japan, the clinical diagnostic criteria 2020 were recently developed. These clinical diagnostic criteria include narrowing of the intrahepatic and/or extrahepatic bile duct, thickening of the bile duct wall, serological findings, pathological findings, other organ involvement, and effectiveness of steroid therapy. When these criteria are applied, IgG4-SC is initially classified as associated or not associated with AIP, and cholangiographic classification is used for differential diagnosis. In most instances, IgG4-SC can be diagnosed on the basis of clinical diagnostic criteria. However, it is challenging to diagnose isolated IgG4-SC or IgG4-SC not associated with AIP. Here, we review the classification and diagnostic criteria for IgG4-SC, specifically focusing on the clinical diagnostic criteria 2020 and a large IgG4-SC case series from a nationwide survey in Japan.

Effect of Sodium Alginate on Gastrointestinal Symptoms after Esophagogastroduodenoscopy with Biopsy: Randomized Controlled Trial

Su Youn Nam , Sang Won Lee , Seong Woo Jeon et al.

Gut Liver 2022; 16(1):37-43

https://doi.org/10.5009/gnl20298

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Abstract : Background/Aims: After esophagogastroduodenoscopy (EGD) with biopsy, some patients experience gastrointestinal symptoms. This study investigated the effect of sodium alginate on biopsy-related gastrointestinal symptoms. Methods: In this open-label, randomized, controlled trial, patients undergoing EGD with biopsy were randomly assigned to a treatment or control group. In the treatment group, sodium alginate was orally administered for 3 days after EGD. Patients completed questionnaires about their gastrointestinal symptoms at baseline (past week), the day after returning home, and after another 3 days. Gastrointestinal symptoms, including abdominal pain, epigastric pain/soreness, heartburn, acid reflux, nausea/vomiting, borborygmus, abdominal distension, and belching, were rated using an upper gastrointestinal symptom rating scale (GSRS). Results: A total of 210 persons (138 men) who underwent EGD with biopsy were enrolled and allocated to the treatment (n=104) or control (n=106) group. At baseline, the demographic factors and GSRS scores were not different between the control and treatment groups. The epigastric pain/soreness score increased in the control group after endoscopic biopsy (+0.056), whereas the score was decreased in the treatment group (–0.067) (p=0.042). In the treatment group, the scores for acid regurgitation and epigastric soreness decreased during follow-up from those at baseline (p

A Novel One-Step Knife Approach Can Reduce the Submucosal Injection Time of Endoscopic Submucosal Dissection: A Single-Blinded Randomized Multicenter Clinical Trials

Hyunil Kim , Jin Woo Kim , Hong Jun Park et al.

Gut Liver 2022; 16(1):44-52

https://doi.org/10.5009/gnl210103

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Abstract : Background/Aims: Endoscopic submucosal dissection (ESD) is a curative treatment modality for early gastric neoplasms; however, ESD can be a time-consuming process. To overcome this pitfall, we developed the one-step knife (OSK) approach, which combines an endoscopic knife and injection needle on a single sheath. We aimed to evaluate whether this approach could reduce the ESD procedure time.Methods: This single-blinded randomized multicenter trial at four tertiary hospitals from June 2019 to June 2020 included patients aged 19 to 85 years undergoing ESD. Patients were randomly assigned to two groups (OSK or conventional knife [CK]). The injection time, total procedure time, resected specimen size, submucosal fluid amount, degree of device satisfaction, and adverse events were evaluated and compared between groups.Results: Fifty-one patients were analyzed (OSK: 25 patients and CK: 26 patients). No baseline differences were observed between groups, with the exception of a higher portion of males in the OSK group. The mean injection time was significantly reduced in the OSK group (39.0 seconds) compared to that in the CK group (87.5 seconds, p

Impact of Visceral Fat on Survival and Metastasis of Stage III Colorectal Cancer

Jung Won Park , Soo Yeon Chang , Joon Seok Lim et al.

Gut Liver 2022; 16(1):53-61

https://doi.org/10.5009/gnl20266

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Abstract : Background/Aims: Previous studies have investigated the relationship between visceral obesity and the risk of colorectal tumors. Visceral obesity may affect the outcome of colorectal cancer (CRC), including survival and metastasis. We investigated the associations between visceral adipose tissue and oncologic outcomes in stage III CRC. Methods: Four hundred seventy-two patients with stage III CRC were identified. Subcutaneous and visceral adipose tissue areas were measured volumetrically via computed tomography for each patient at different levels of the lumbar spine. After adjusting for age, sex, and other clinical factors, the effects of visceral adipose tissue area on mortality and recurrence were assessed using Cox proportional hazard regression. Results: In univariate and multivariate analyses, a higher visceral adipose tissue to total adipose tissue (VT) ratio (hazard ratio [HR], 1.041; 95% CI, 1.008 to 1.075; p=0.015) and higher visceral adipose tissue to subcutaneous adipose tissue (VS) ratio (HR, 1.016; 95% CI, 1.005 to 1.028; p=0.006) were both associated with poor CRC-specific survival. Interestingly, in the evaluation of each site of recurrence, a higher VT ratio (HR, 1.069; 95% CI, 1.010 to 1.131; p=0.020) and higher VS ratio (HR, 1.024; 95% CI, 1.003 to 1.045; p=0.023) were both related to a higher risk of peritoneal seeding and tumor recurrence. The VT ratio at the L3–L4 level was significantly associated with a higher risk of peritoneal seeding and tumor recurrence (HR, 4.969; 95% CI, 1.303 to 18.949; p=0.019), while other levels showed no such relationship. Conclusions: Visceral obesity is closely related to increased risks of CRC-specific mortality and peritoneal seeding metastasis in stage III CRC patients.

Association between Fecal Calprotectin and Mucosal Healing in Pediatric Patients with Crohn’s Disease Who Have Achieved Sustained Clinical Remission with Anti-Tumor Necrosis Factor Agents

Yoo Min Lee , Sujin Choi , Byung-Ho Choe et al.

Gut Liver 2022; 16(1):62-70

https://doi.org/10.5009/gnl20300

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Abstract : Background/Aims: Although mucosal healing (MH) is acknowledged as the treatment target in the treat-to-target era, there are limitations on repeated endoscopic examinations, especially in pediatric patients. We aimed to investigate whether fecal calprotectin (FC) could serve as a surrogate marker for the assessment of MH in pediatric patients with Crohn’s disease (CD) who have achieved sustained clinical remission (CR) while treated with anti-tumor necrosis factor (TNF) agents. Methods: This multicenter retrospective cross-sectional study included pediatric CD patients who had sustained a CR for at least 6 months with anti-TNF agents and who simultaneously underwent ileocolonoscopy and FC tests during follow-up. MH was defined as the absence of any ulcer on ileocolonoscopy. Results: A total of 131 patients were included in this study. MH was observed in 87 patients (66.7%). The FC level was significantly lower in patients with MH than in those without MH (median 49.0 mg/kg vs 599.0 mg/kg; p

Albumin-to-Globulin Ratio at 1 Year after Anti-Tumor Necrosis Factor α Therapy Can Serve as a Prognostic Biomarker in Pediatric Crohn’s Disease Patients

Eun Sil Kim , Yiyoung Kwon , Yon Ho Choe et al.

Gut Liver 2022; 16(1):71-80

https://doi.org/10.5009/gnl20322

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Abstract : Background/Aims: The efficacy of biologics for the treatment of Crohn’s disease (CD) is affected by the drug concentrations. We aimed to evaluate the importance of albumin and globulin which are known to be associated with drug concentrations as prognostic biomarkers in CD. Methods: In total, 121 pediatric patients with CD who had received anti-tumor necrosis factor (TNF)-α therapy were retrospectively examined between January 2010 and February 2019. Results: Relapse was observed in 48.8% of patients (59/121). The level of calprotectin (odds ratio, 2.13; p=0.03) and the albumin-to-globulin ratio (AGR) at 1 year after anti-TNF-α therapy (odds ratio, 0.0002; p=0.003) were associated with relapse. The AGR at 1 year after anti-TNF-α therapy was the only factor associated with the time-to-relapse (hazard ratio, 0.02; p

Perceptions and Behaviors of Patients with Inflammatory Bowel Disease during the COVID-19 Crisis

Yoo Jin Lee , Kyeong Ok Kim , Min Cheol Kim et al.

Gut Liver 2022; 16(1):81-91

https://doi.org/10.5009/gnl210064

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Abstract : Background/Aims: This study aimed to investigate the perceptions and behaviors of patients with inflammatory bowel disease (IBD) during the early coronavirus disease 2019 (COVID-19) pandemic in the major epidemic area in Korea. Methods: Between April and May 2020, a cross-sectional survey was performed at two tertiary hospitals in Daegu, South Korea, on patients’ experiences, coping strategies and perceptions. Results: Most of the 544 patients participating in the survey strictly adhered to personal protection guidance against COVID-19. In the early COVID-19 crisis, many patients canceled or postponed hospital visits (57.5%) and rescheduled biologics administrations (26.4%). Although 13.6% utilized telemedicine, the frequency of individuals leaving their homes remained unchanged. Although 50.4% were concerned about their susceptibility to COVID-19, 72.2% adhered to their treatment for IBD. In patients taking biologics or Janus kinase inhibitors, 86.8% disagreed that they should discontinue their medication as a preventative measure against COVID-19, but 21.9% actually discontinued their medications. Of those with discordance between the perception of IBD drug adherence and active behaviors, 5.4% of all and 39.4% of biologics or Janus kinase inhibitors withheld drugs specifically due to fear of COVID-19. Only 7% of all patients discussed drug safety with their physicians. The level of concern for COVID-19 depended on the type of drug used. Conclusions: Patients with IBD showed concerns about the increased risk of COVID-19 due to IBD or their medications, and a considerable number of patients withheld their medications without consulting medical staff. Enhanced active communications with patients with IBD and appropriate health-related education should be provided.

Role of Serum Proteinase 3 Antineutrophil Cytoplasmic Antibodies in the Diagnosis, Evaluation of Disease Severity, and Clinical Course of Ulcerative Colitis

So Imakiire , Hidetoshi Takedatsu , Keiichi Mitsuyama et al.

Gut Liver 2022; 16(1):92-100

https://doi.org/10.5009/gnl210211

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Abstract : Background/Aims: Proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a serologic marker for granulomatosis with polyangiitis. However, recent studies have also shown their role as diagnostic markers for ulcerative colitis (UC). This study was performed to investigate the clinical roles of PR3-ANCAs in the disease severity, disease extension, and clinical course of UC.Methods: Serum PR3-ANCAs were measured in 173 UC patients including 77 patients with new-onset patients UC diagnosed within 1 month, 110 patients with Crohn’s disease, 48 patients with other intestinal diseases, and 71 healthy controls. Associations between the PR3-ANCA titer and clinical data, such as disease severity, disease extension, and clinical course, were assessed. The clinical utility of PR3-ANCA measurement was evaluated by receiver operating characteristic (ROC) analysis.Results: PR3-ANCA ≥3.5 U/mL demonstrated 44.5% sensitivity and 95.6% specificity for the diagnosis of UC in all patients. PR3-ANCA positivity was more prevalent in the 77 new-onset UC patients (58.4%). In this group, the disease severity and extension were more severe in PR3-ANCA positive patients than in PR3-ANCA negative group (p

Minimal and Maximal Extent of Band Ligation for Acute Variceal Bleeding during the First Endoscopic Session

Jang Han Jung , Jung Hyun Jo , Sung Eun Kim et al.

Gut Liver 2022; 16(1):101-110

https://doi.org/10.5009/gnl20375

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Abstract : Background/Aims: The appropriate number of band ligations during the first endoscopic session for acute variceal bleeding is debatable. We aimed to compare the technical aspects of endoscopic variceal ligation (EVL) in patients with variceal bleeding according to the number of bands placed per session. Methods: We retrospectively reviewed multicenter data from patients who underwent EVL for acute variceal bleeding. Patients were classified into minimal EVL (targeting only the foci with active bleeding or stigmata of recent bleeding) and maximal EVL (targeting potential bleeding sources in addition to the aforementioned targets) groups. The primary endpoint was 5-day treatment failure. The secondary endpoints were 30-day rebleeding, 30-day mortality, and intraprocedural adverse events. Results: Minimal EVL was associated with lower rates of hypoxia and shock during EVL than maximal EVL (hypoxia, 0.9% vs 2.9%; shock, 1.3% vs 3.4%). However, treatment failure was higher in the minimal EVL group than in the maximal EVL group (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.41). Age ≥60 years, Model for End-Stage Liver Disease score ≥15, Child-Turcotte-Pugh classification C, presence of hepatocellular carcinoma, and systolic blood pressure

Efficacy and Safety of Percutaneous Transhepatic Cholangioscopy with the Spyglass DS Direct Visualization System in Patients with Surgically Altered Anatomy: A Pilot Study

Hyung Ku Chon , Keum Ha Choi , Sang Hyun Seo et al.

Gut Liver 2022; 16(1):111-117

https://doi.org/10.5009/gnl210028

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Abstract : Background/Aims: Percutaneous transhepatic cholangioscopy (PTCS) is used for the diagnosis and treatment of biliary diseases in patients with failed endoscopic retrograde cholangiopancreatography, particularly those with surgically altered anatomy. However, few studies are available on the clinical use of Spyglass DS direct visualization system (SpyDS)-assisted PTCS. This study aimed to assess the efficacy and safety of SpyDS-assisted PTCS in patients with surgically altered anatomy, particularly those with a Roux-en-Y reconstruction. Methods: Thirteen patients (six women, median age 71.4 years [range, 53 to 83 years]) with surgically altered anatomy (four Roux-en-Y choledochojejunostomies, seven Roux-en-Y hepaticojejunostomies, and two Roux-en-Y esophagojejunostomies) who underwent SpyDS-assisted PTCS between January 2019 and August 2020 were included and the data was acquired by retrospectively reviewing electronic medical record. Results: A total of 19 SpyDS-assisted PTCS procedures were performed in the 13 patients: eight had bile-duct stones, and five had biliary strictures. All SpyDS-assisted PTCS procedures were successfully performed. The total procedure time was 42.42±18.0 minutes (mean±standard deviation). Bile duct clearance was achieved in all bile duct stone cases after a median of 2 (range, 1 to 3) procedures. In the five biliary stricture cases, the results of SpyBite forceps-guided targeted biopsy were consistent with adenocarcinoma (100% accuracy). The median hospitalization duration was 20 days (range, 14 to 30 days). No procedure-related morbidity or mortality occurred. Conclusions: SpyDS-assisted PTCS may be a safe, feasible, and effective procedure for the diagnosis and treatment of biliary diseases in patients with surgically altered anatomy, particularly in those with the Roux-en-Y reconstruction requiring a percutaneous approach. However, our findings need to be validated in further studies.

Response to Neoadjuvant Therapy and Prognosis in Patients with Resectable Pancreatic Cancer: A Propensity Score Matching Analysis

Min Sung Yoon , Hee Seung Lee , Chang Moo Kang et al.

Gut Liver 2022; 16(1):118-128

https://doi.org/10.5009/gnl20301

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Abstract : Background/Aims: Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. Methods: We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. Results: Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. Conclusions: We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

Four-Tier Pathologic Tumor Regression Grading System Predicts the Clinical Outcome in Patients Who Undergo Surgical Resection for Locally Advanced Pancreatic Cancer after Neoadjuvant Chemotherapy

Soomin Ahn , Jong-chan Lee , Jaihwan Kim et al.

Gut Liver 2022; 16(1):129-137

https://doi.org/10.5009/gnl20312

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Abstract : Background/Aims: Neoadjuvant chemotherapy is increasingly utilized in patients with borderline or locally advanced pancreatic cancer (LAPC). However, the pathologic evaluation of tumor regression is not routinely performed or well established. We aimed to evaluate the prognostic value of three tumor regression grading systems frequently used in LAPC and to determine the correlation between pathologic and clinical response. Methods: We included a total of 38 patients with LAPC who were treated with neoadjuvant chemotherapy and subsequent resection. Pathologic tumor regression was graded based on the College of American Pathologists (CAP), Evans, and MD Anderson grading systems. Results: One out of 38 patients (2.6%) achieved a pathologic complete response. Unlike other grading systems (Evans, p=0.063; MD Anderson, p=0.110), the CAP grading system was a significant prognostic factor for overall survival (p=0.043). Pathologic N stage (p=0.023), margin status (p=0.044), and radiologic response (p=0.016) correlated with overall survival. In the multivariate analysis, CAP 3 was an independent predictor of shorter overall survival (p=0.026). The CAP grading system correlated with the radiologic response (p=0.007) but not the carbohydrate antigen 19-9 level (p=0.333). Conclusions: The four-tier CAP pathologic tumor regression grading system predicted the clinical outcome in LAPC patients who underwent resection after neoadjuvant chemotherapy. Therefore, a more comprehensive pathologic evaluation is warranted in these patients.