Therapeutic Drug Monitoring of Biologics for Patients with Inflammatory Bowel Diseases: How, When, and for Whom?

Jia-Feng Wu^1,2

Gut Liver 2022; 16(4):515-524

https://doi.org/10.5009/gnl210262

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Abstract : During the past decade, we have entered an era of biologics for the treatment of Crohn’s disease and ulcerative colitis. The therapeutic goal of inflammatory bowel disease (IBD) management has evolved from symptom control and clinical remission to mucosal healing or even deep remission. Histological remission for ulcerative colitis and transmural healing of Crohn’s disease are potential future goals. With the adoption of the treat-to-target concept, and given the need for tight control of IBD activity, therapeutic drug monitoring (TDM) is an important element of precision medicine. TDM involves the measurement of serum biologics and anti-drug antibodies levels, to confirm whether the right drug with the right dosage was prescribed to reach the right serum levels. TDM may help clinicians adjust biologics based on objective biomarkers instead of using empirical dosage escalation or making symptom-based therapeutic adjustments. Well-established reactive TDM algorithms have been proposed, and emerging evidence supports the clinical application of a proactive TDM strategy to enhance the duration of effective biologics and improve clinical outcomes. Recently, the proactive TDM strategy was shown to avoid the secondary loss of response to biologics, and improve long-term clinical outcomes in IBD patients. This review summarizes data from trials, and practice guidelines, on the clinical application of proactive and reactive TDM strategies for the daily care of biologic-treated IBD patients.

Endoscopic Reintervention for Recurrence of Malignant Biliary Obstruction: Developing the Best Strategy

Mamoru Takenaka , Masatoshi Kudo

Gut Liver 2022; 16(4):525-534

https://doi.org/10.5009/gnl210228

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Abstract : Drainage therapy for malignant biliary obstruction (MBO) includes trans-papillary endoscopic retrograde biliary drainage (ERBD), percutaneous transhepatic biliary drainage (PTBD), and trans-gastrointestinal endoscopic ultrasound-guided biliary drainage (EUS-BD). With the development of chemotherapy, many MBO cases end up needing endoscopic reintervention (E-RI) for recurrent biliary obstruction. To achieve a successful E-RI, it is necessary to understand the various findings regarding E-RI in MBO cases reported to date. Therefore, in this review, we focus on E-RI for ERBD of distal MBO, ERBD of hilar MBO, and EUS-BD. To plan an appropriate E-RI strategy for biliary stent occlusion for MBO, the following must be considered on a case-by-case basis: the urgency of the drainage, the cause of the occlusion, the original route of drainage (PTBD/ERBD/EUS-BD), the initial stent used (plastic stent or self-expandable metallic stent), and in the case of self-expandable metallic stents, the type used (fully covered or uncovered). Regardless of the original method of stent placement, if the inflammation caused by obstructive cholangitis is severe and/or the patient is in shock, PTBD should be considered as the first choice. Finally, it is important to keep in mind that in many cases, performing E-RI will be difficult.

Triple Therapy-Based on Tegoprazan, a New Potassium-Competitive Acid Blocker, for First-Line Treatment of Helicobacter pylori Infection: A Randomized, Double-Blind, Phase III, Clinical Trial

Yoon Jin Choi¹ , Yong Chan Lee¹ , Jung Mogg Kim² , Jin Il Kim³ , Jeong Seop Moon⁴ , Yun Jeong Lim⁵ , Gwang Ho Baik⁶ , Byoung Kwan Son⁷ , Hang Lak Lee⁸ , Kyoung Oh Kim⁹ , Nayoung Kim¹⁰ , Kwang Hyun Ko¹¹ , Hye-Kyung Jung¹² , Ki-Nam Shim¹² , Hoon Jai Chun¹³ , Byung-Wook Kim¹⁴ , Hyuk Lee¹⁵ , Jie-Hyun Kim¹⁶ , Hyunsoo Chung¹⁷ , Sang Gyun Kim¹⁷ , Jae Young Jang¹⁸

Gut Liver 2022; 16(4):535-546

https://doi.org/10.5009/gnl220055

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Abstract : Background/Aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication. Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)- based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases. Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences. Conclusions: TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223).

Long-term Outcomes of Additional Endoscopic Treatments for Patients with Positive Lateral Margins after Endoscopic Submucosal Dissection for Early Gastric Cancer

Tae-Se Kim , Byung-Hoon Min , Yang Won Min , Hyuk Lee , Poong-Lyul Rhee , Jae J. Kim , Jun Haeng Lee

Gut Liver 2022; 16(4):547-554

https://doi.org/10.5009/gnl210203

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Abstract : Background/Aims: It is uncertain whether additional endoscopic treatment may be chosen over surgery in patients with positive lateral margins (pLMs) as the only non-curative factor after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to compare the long-term outcomes of additional endoscopic treatments in such patients with those of surgery and elucidate the clinicopathological factors that could influence the treatment selection. Methods: A total of 99 patients with 101 EGC lesions undergoing additional treatment after noncurative ESD with pLMs as the only non-curative factor were analyzed. Among them, 25 (27 lesions) underwent ESD, 29 (29 lesions) underwent argon plasma coagulation (APC), and 45 (45 lesions) underwent surgery. Clinicopathological characteristics and long-term outcomes were compared. Results: Residual tumor was found in 73.6% of cases. The presence of multiple pLMs was associated with higher risk of residual tumor (p=0.046). During a median follow-up of 58.9 months, recurrent or residual lesions after additional ESD and APC were found in 4% (1/25) and 6.8% (2/29) of patients, respectively. However, all were completely cured with surgery or repeated ESD. There were no extragastric recurrences after additional endoscopic treatment. Lymph node metastasis was identified after additional surgery in one (2.2%) patient with an EGC showing histological heterogeneity. Conclusions: Given the favorable long-term outcomes, additional ESD or APC may be an acceptable choice for patients with pLMs as the only non-curative factor after ESD for EGC. However, clincopathological characteristics such as multiple pLMs and histological heterogeneity should be considered in the treatment selection.

Venous Thromboembolism Risk in Asian Patients with Inflammatory Bowel Disease: A Population-Based Nationwide Inception Cohort Study

Su Young Kim¹ , Yeon Seo Cho² , Hyun-Soo Kim¹ , Jung Kuk Lee³ , Hee Man Kim¹ , Hong Jun Park¹ , Hyunil Kim¹ , Jihoon Kim² , Dae Ryong Kang³

Gut Liver 2022; 16(4):555-566

https://doi.org/10.5009/gnl210190

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Abstract : Background/Aims: Inflammatory bowel disease (IBD) is associated with the occurrence of venous thromboembolism (VTE). However, to date, there have been few studies on the risk of VTE in Asian IBD patients. We aimed to estimate the incidence of VTE in Asian IBD patients and to determine if IBD is related to increased VTE risk. Methods: We performed a population-based cohort study between 2004 and 2015 using Korean National Health Insurance data. IBD and VTE were defined by ICD-10 codes. Incidence rates of VTE were calculated among patients with IBD and among age- and sex-matched controls. Hazard ratios were estimated using Cox regression with adjustment for multiple variables. We performed additional analyses stratifying by age, sex, Charlson comorbidity index (CCI) score, and disease type. Results: Among the 45,037 patients with IBD (IBD cohort) and 133,019 matched controls (non-IBD cohort) included in our analysis, 411 IBD patients and 641 controls developed VTE. The IBD cohort had a higher incidence rate ratio and risk of VTE than the non-IBD cohort (incidence rate ratio: 1.92 and hazard ratio: 1.93). Older age, female sex, higher CCI scores, cardiovascular disease, chronic kidney disease, use of steroids, and hospitalization were significant risk factors for VTE in patients with IBD. Conclusions: The IBD patients in this study were approximately two times more likely to develop VTE than the non-IBD individuals. Our findings support the need for thromboprophylaxis in Asian IBD patients with various factors that further increase the risk of VTE.

Risk of Hepatitis B Virus (HBV) Reactivation in Patients with Immune-Mediated Inflammatory Diseases Receiving Biologics: Focus on the Timing of Biologics after Anti-HBV Treatment

Soo Min Ahn¹ , Jonggi Choi² , Byong Duk Ye² , Suk-Kyun Yang² , Ji Seon Oh³ , Yong‑Gil Kim¹ , Chang-Keun Lee¹ , Bin Yoo¹ , Sang Hyoung Park² , Seokchan Hong¹

Gut Liver 2022; 16(4):567-574

https://doi.org/10.5009/gnl210204

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Abstract : Background/Aims: Anti-hepatitis B virus (HBV) therapy is required for patients with HBV infection receiving biologics because of the high risk of HBV reactivation. However, it is unclear when to start biologics after anti-HBV treatment. We investigated the risk of HBV reactivation according to the timing of biologics initiation after anti-HBV treatment in immune-mediated inflammatory disease (IMID) patients with HBV infection. Methods: We retrospectively evaluated the incidence of HBV reactivation in IMID patients who received biologics between July 2005 and April 2020. The patients were divided into two groups (within 1-week and after 1-week) according to the timing of biologics initiation after anti-HBV treatment. The cumulative probabilities and factors associated with HBV reactivation were evaluated. Results: A total of 60 hepatitis B surface antigen-positive patients with IMID received biologics (within 1-week group, n=23 [38%]; after 1-week group, n=37 [62%]). During a median follow-up of 34 months (interquartile range, 20 to 74 months), three patients (5%) developed HBV reactivation. In univariate analysis, the timing of biologics after anti-HBV treatment was not significantly associated with the risk of HBV reactivation (hazard ratio, 0.657; 95% confidence interval, 0.059 to 7.327; p=0.733). The cumulative probabilities of HBV reactivation did not significantly differ according to the timing of biologics (p=0.731). Conclusions: The risk of HBV reactivation was not significantly associated with the timing of biologics administration after anti-HBV treatment. Thus, biologics may be initiated early in patients with IMID undergoing treatment for HBV.

Gut Microbiota Alteration Influences Colorectal Cancer Metastasis to the Liver by Remodeling the Liver Immune Microenvironment

Na Yuan^1,2,3 , Xiaoyan Li² , Meng Wang⁴ , Zhilin Zhang³ , Lu Qiao² , Yamei Gao² , Xinjian Xu⁵ , Jie Zhi² , Yang Li⁶ , Zhongxin Li⁷ , Yitao Jia^1,2

Gut Liver 2022; 16(4):575-588

https://doi.org/10.5009/gnl210177

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Abstract : Background/Aims:This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniformis were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B. vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions: An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

Metabolic Dysfunction-Associated Fatty Liver Disease Better Predicts Incident Cardiovascular Disease

Seogsong Jeong¹ , Yun Hwan Oh² , Seulggie Choi¹ , Jooyoung Chang¹ , Sung Min Kim¹ , Joung Sik Son³ , Gyeongsil Lee⁴ , Won Kim^5,6 , Sang Min Park^1,4

Gut Liver 2022; 16(4):589-598

https://doi.org/10.5009/gnl210256

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Abstract : Background/Aims: Metabolic dysfunction (MD)-associated fatty liver disease is a new positive diagnostic criterion based on hepatic steatosis and MD. However, a comprehensive evaluation on the association of MD and hepatic steatosis with incident cardiovascular disease (CVD) has yet to be performed. Methods: This retrospective cohort study included 333,389 participants from the Korean National Health Insurance Service database who received a health examination between 2009 and 2010. Hepatic steatosis was defined using the Korean National Health and Nutrition Examination Survey-derived nonalcoholic fatty liver disease scoring system. Cox proportional hazards regression was adopted to determine the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for CVD according to the presence of hepatic steatosis and MD, as well as the composite term. Results: This study included 179,437 men and 153,952 women with a median age of 57 years. Hepatic steatosis with MD (aHR, 2.00; 95% CI, 1.89 to 2.13) and without MD (aHR, 1.30; 95% CI, 1.10 to 1.54) significantly increased the risk of CVD compared to no steatosis without MD (reference). However, steatosis revealed no significant difference in the risk of CVD compared to no steatosis among participants with one MD (aHR, 1.09; 95% CI, 0.91 to 1.30). In participants with steatosis, the presence of one and ≥2 MDs had aHR values of 1.25 (95% CI, 0.87 to 1.79) and 1.71 (95% CI, 1.22 to 2.41), respectively, compared to no MD. Conclusions: Combined consideration of hepatic steatosis and MD was significantly associated with increased CVD risk and showed better predictive performance for CVD than hepatic steatosis or MD alone.

Utility of Direct Peroral Cholangioscopy Using a Multibending Ultraslim Endoscope for Difficult Common Bile Duct Stones

Won Myung Lee¹ , Jong Ho Moon¹ , Yun Nah Lee¹ , Il Sang Shin¹ , Tae Hoon Lee² , Jae Kook Yang² , Sang-Woo Cha³ , Young Deok Cho³ , Sang-Heum Park²

Gut Liver 2022; 16(4):599-605

https://doi.org/10.5009/gnl210355

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Abstract : Background/Aims: Treatment options for difficult bile duct stones are limited. Direct peroral cholangioscopy (POC)-guided lithotripsy may be an option. A newly developed multibending (MB) ultraslim endoscope has several structural features optimized for direct POC. We evaluated the utility of direct POC using an MB ultraslim endoscope for lithotripsy in patients with difficult bile duct stones.Methods: Twenty patients with difficult bile duct stones, in whom stone removal using conventional endoscopic methods, including mechanical lithotripsy, had failed were enrolled from March 2018 to August 2019. Direct POC-guided lithotripsy was performed by electrohydraulic lithotripsy or laser lithotripsy. The primary outcome was complete ductal clearance, defined as the retrieval of all bile duct stones after lithotripsy confirmed by balloon-occluded cholangiography and/or direct POC.Results: The technical success rate of direct POC was 100% (20/20), and the free-hand insertion rate was 95% (19/20). Direct POC-guided lithotripsy, attempted by electrohydraulic lithotripsy in nine patients (45%) and laser lithotripsy in 11 patients (55%), was successful in 95% (19/20) of the patients. Complete ductal clearance after direct POC-guided lithotripsy was achieved in 95% (19/20) of patients. Patients required a median of 2 (range, 1–3) endoscopic retrograde cholangiopancreatography sessions for complete stone removal. Adverse event was observed in one patient (5%) with hemobilia and was treated conservatively.Conclusions: Direct POC using an MB ultraslim endoscope was safe and effective for lithotripsy in patients with difficult bile duct stones.

Insulin-Like Growth Factor-1 Receptor Targeted Fluorescent Imaging for Gallbladder Cancer in Orthotopic Mouse Models

Jung Ha Choi , Jeong Youp Park

Gut Liver 2022; 16(4):606-612

https://doi.org/10.5009/gnl210164

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Abstract : Background/Aims: Gallbladder cancer is fatal, but fluorescent imaging technology can facilitate timely diagnosis and improve patient outcomes. Fluorophore-conjugated insulin-like growth factor-1 receptor (IGF-1R) targeted antibodies were used to visualize gallbladder cancer in orthotopic tumor mouse models. Methods: Western blotting, flow cytometric analysis, and confocal microscopy detected the expression of IGF-1R in SNU-308, SNU-478, and SNU-1196 bile duct cancer cells. In vivo imaging of SNU-478 and SNU-1196 subcutaneous tumors and orthotopic gallbladder tumor models of SNU-478 were performed after injection with DyLight 650-conjugated IGF-1R antibody. Results: Western blotting and flow cytometric analysis showed that IGF-1R was expressed in bile duct cancer cells, and confocal microscopy demonstrated that IGF-1R antibody was able to bind to IGF-1R on the cell membrane. Fluorescent IGF-1R antibody injected into the mouse tail vein made subcutaneous tumors and orthotopic tumors become fluorescent. The intensity of fluorescence from the tumor was stronger than that from surrounding normal tissues. Histochemical examination confirmed that the tumor was located inside the gallbladder and adjacent liver parenchyma of mice. Conclusions: Our study showed that a fluorescent IGF-1R-targeted antibody could help detect gallbladder tumors. Tumor-specific imaging technology can be applied to endoscopy, laparoscopy, and robotic surgery for better management of gallbladder cancer.

Genetic, Clinicopathological, and Radiological Features of Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation Pattern

Taek Chung¹ , Hyungjin Rhee² , Hyo Sup Shim³ , Jeong Eun Yoo³ , Gi Hong Choi⁴ , Haeryoung Kim⁵ , Young Nyun Park^3,6

Gut Liver 2022; 16(4):613-624

https://doi.org/10.5009/gnl210174

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Abstract : Background/Aims: Intrahepatic cholangiocarcinoma (iCCA) with a ductal plate malformation (DPM) pattern is a recently recognized rare variant. The genomic profile of iCCA with DPM pattern needs to be elucidated. Methods: Cases of iCCA with DPM pattern were retrospectively reviewed based on the medical records, pathology slides, and magnetic resonance imaging (MRI) reports collected between 2010 to 2019 at a single center. Massive parallel sequencing was performed for >500 cancer-related genes. Results: From a total of 175 iCCAs, five (2.9%) cases of iCCA with DPM pattern were identified. All cases were of the small duct type, and background liver revealed chronic B viral or alcoholic hepatitis. Three iCCAs with DPM pattern harbored MRI features favoring the diagnosis of hepatocellular carcinoma, whereas nonspecific imaging features were observed in two cases. All patients were alive without recurrence during an average follow-up period of 57 months. Sequencing data revealed 64 mutated genes in the five cases, among which FGFR and PTPRT were most frequently mutated (three cases each) including an FGFR-TNC fusion in one case. Mutations in ARID1A and CDKN2A were found in two cases, and mutations in TP53, BAP1, ATM, NF1, and STK11 were observed in one case each. No IDH1, KRAS, or PBRM1 mutations were found. Conclusions: iCCAs with DPM pattern have different clinico-radio-pathologic and genetic characteristics compared to conventional iCCAs. Moreover, FGFR and ARID1A variants were identified. Altogether, these findings further suggest that iCCA with DPM pattern represents a specific subtype of small duct type iCCA.

Establishment of Patient-Derived Pancreatic Cancer Organoids from Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsies

Jee Hyung Lee^1,2 , Haeryoung Kim³ , Sang Hyub Lee¹ , Ja-Lok Ku⁴ , Jung Won Chun⁵ , Ha Young Seo⁴ , Soon Chan Kim⁴ , Woo Hyun Paik¹ , Ji Kon Ryu¹ , Sang Kook Lee² , Andrew M. Lowy⁶ , Yong-Tae Kim¹

Gut Liver 2022; 16(4):625-636

https://doi.org/10.5009/gnl210166

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Abstract : Background/Aims: Three-dimensional cultures of human pancreatic cancer tissue also known as “organoids” have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research. Methods: Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays. Results: Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations in KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 which were 93% homologous, and the mean nonreference discordance rate was 5.47%. We observed moderate drug response correlations between the organoids and clinical outcomes in patients who underwent FOLFIRINOX chemotherapy. Conclusions: The established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research.

Diagnostic Concordance and Preoperative Risk Factors for Malignancy in Pancreatic Mucinous Cystic Neoplasms

Ga Hee Kim¹ , Kyu Choi¹ , Namyoung Paik¹ , Kyu Taek Lee¹ , Jong Kyun Lee¹ , Kwang Hyuck Lee¹ , In Woong Han² , Soo Hoon Kang¹ , Jin Seok Heo² , Joo Kyung Park^1,3

Gut Liver 2022; 16(4):637-644

https://doi.org/10.5009/gnl210231

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Abstract : Background/Aims: As pancreatic mucinous cystic neoplasms (MCNs) are considered premalignant lesions, the current guidelines recommend their surgical resection. We aimed to investigate the concordance between preoperative and postoperative diagnoses and evaluate preoperative clinical parameters that could predict the malignant potential of MCNs. Methods: Patients who underwent surgical resection at Samsung Medical Center for pancreatic cystic lesions and whose pathology was confirmed to be MCN, between July 2000 and December 2017, were retrospectively analyzed. Results: Among a total of 132 patients 99 (75%) were diagnosed with MCN preoperatively. The most discordant preoperative diagnosis was an indeterminate pancreatic cyst. The proportion of male patients was higher (24.2% vs 7.1%, p=0.05) in the diagnosis-discordance group and the presence of worrisome features in radiologic imaging studies, such as wall thickening/enhancement (12.1% vs 37.4%, p=0.02) or solid component/mural nodule (3.0% vs 27.3%, p=0.02), was lower in the diagnosis-discordance group. The presence of symptoms (57.7% vs 34.9%, p=0.02), tumor size greater than 4 cm (80.8% vs 55.7%, p=0.04), and radiologic presence of a solid component/mural nodule (42.3% vs 16.0%, p=0.01) or duct dilatation (19.2% vs 6.6%, p=0.01) were significantly associated with malignant MCNs. Conclusions: In our study, the overall diagnostic concordance rate was confirmed to be 75%, and our findings suggest that MCNs have a low malignancy potential when they are less than 4 cm in size, are asymptomatic and lack worrisome features on preoperative images.

CD40 Agonists Alter the Pancreatic Cancer Microenvironment by Shifting the Macrophage Phenotype toward M1 and Suppress Human Pancreatic Cancer in Organotypic Slice Cultures

Chae Yoon Lim¹ , Jae Hyuck Chang² , Won Sun Lee¹ , Jeana Kim³ , Il Young Park⁴

Gut Liver 2022; 16(4):645-659

https://doi.org/10.5009/gnl210311

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Relationship between the High Fatty Liver Index and Risk of Fracture

Min-Ji Kim¹ , Min-Su Kim² , Han-Byul Lee³ , Jae-Hyung Roh² , Jae-Han Jeon⁴

Published online July 27, 2022

https://doi.org/10.5009/gnl210571

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Prolonged QT Interval in Cirrhosis: Twisting Time?

William Lee^1,2 , Bert Vandenberk^1,3 , Satish R. Raj^1,4 , Samuel S. Lee⁵

Published online July 22, 2022

https://doi.org/10.5009/gnl210537

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Real-Time Polymerase Chain Reaction for the Detection of Helicobacter pylori and Clarithromycin Resistance

Jin Hee Noh¹ , Ji Yong Ahn¹ , Jene Choi² , Young Soo Park² , Hee Kyong Na¹ , Jeong Hoon Lee¹ , Kee Wook Jung¹ , Do Hoon Kim¹ , Kee Don Choi¹ , Ho June Song¹ , Gin Hyug Lee¹ , Hwoon-Yong Jung¹ , Jung Mogg Kim³

Published online July 20, 2022

https://doi.org/10.5009/gnl220076

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Comparison of Bilateral and Trisegment Drainage in Patients with High-Grade Hilar Malignant Biliary Obstruction: A Multicenter Retrospective Study

Kazuyuki Matsumoto¹ , Hironari Kato¹ , Kosaku Morimoto¹ , Kazuya Miyamoto² , Yosuke Saragai³ , Hirofumi Kawamoto⁴ , Hiroyuki Okada¹

Published online July 19, 2022

https://doi.org/10.5009/gnl220012

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

National Survey Regarding the Management of Difficult Bile Duct Stones in South Korea

Yoon Suk Lee¹ , Tae Joo Jeon² , Woo Hyun Paik³ , Dong-Won Ahn⁴ , Kwang Hyun Chung⁵ , Byoung Kwan Son⁵ , Tae Jun Song⁶ , Sung-Hoon Moon⁷ , Eaum Seok Lee⁸ , Jae Min Lee⁹ , Seung Bae Yoon¹⁰ , Chang Nyol Paik¹¹ , Yun Nah Lee¹² , Jin-Seok Park¹³ , Dong Wook Lee¹⁴ , Sang Wook Park¹⁵ , Hyung Ku Chon¹⁶ , Kwang Bum Cho¹⁷ , Chang Hwan Park¹⁸ , on behalf of the Committee of Policy and Quality Management in Korean Pancreatobiliary Association

Published online July 19, 2022

https://doi.org/10.5009/gnl220117

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Long-term Effects of the Eradication of Helicobacter pylori on Metabolic Parameters, Depending on Sex, in South Korea

Jaehyung Park¹ , Nayoung Kim^1,2 , Won Seok Kim¹ , Seon Hee Lim³ , Yonghoon Choi¹ , Hyeong Ho Jo¹ , Eunjeong Ji⁴ , Hyuk Yoon¹ , Cheol Min Shin¹ , Young Soo Park¹ , Dong Ho Lee^1,2

Published online June 30, 2022

https://doi.org/10.5009/gnl210588

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

A Randomized, Double-Blind, Active-Control, Noninferiority, Multicenter, Phase 4 Study to Evaluate the Efficacy and Safety of Esomeprazole/Sodium Bicarbonate 20/800 mg in Patients with Nonerosive Gastroesophageal Reflux Disease

Su Hyun Park¹ , Kang Nyeong Lee¹ , Oh Young Lee¹ , Myung Gyu Choi² , Jie-Hyun Kim³ , In-Kyung Sung⁴ , Jae Young Jang⁵ , Kyung Sik Park⁶ , Hoon Jai Chun⁷ , Eun Young Kim⁸ , Jun Kyu Lee⁹ , Jin Seok Jang¹⁰ , Gwang Ha Kim¹¹ , Su Jin Hong¹² , Yong Chan Lee¹³ , Suck-Chei Choi¹⁴ , Hyun Soo Kim¹⁵ , Tae Oh Kim¹⁶ , Gwang Ho Baik¹⁷ , Yong Cheol Jeon¹⁸

Published online June 22, 2022

https://doi.org/10.5009/gnl220023

Abstract  

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Circ_0081143 Contributes to Gastric Cancer Malignant Development and Doxorubicin Resistance by Elevating the Expression of YES1 by Targeting mziR-129-2-3p

Wenting Ou¹, Lin Lin², Rihong Chen², Qingwen Xu², Caijin Zhou²

Published online June 10, 2022

https://doi.org/10.5009/gnl210354

Abstract  

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

TCN1 Deficiency Inhibits the Malignancy of Colorectal Cancer Cells by Regulating the ITGB4 Pathway

Xinqiang Zhu^1,2 , Xuetong Jiang² , Qinglin Zhang³ , Hailong Huang² , Xiaohong Shi⁴ , Daorong Hou⁵ , Chungen Xing¹

Published online June 10, 2022

https://doi.org/10.5009/gnl210494

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

A New Paradigm Shift in Gastroparesis Management

Parit Mekaroonkamol , Kasenee Tiankanon , Rungsun Rerknimitr

Published online June 7, 2022

https://doi.org/10.5009/gnl210309

Abstract  

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Current Status of Opportunistic Infection in Inflammatory Bowel Disease Patients in Asia: A Questionnaire-Based Multicenter Study

Hong Yang¹ , Zhihua Ran² , Meng Jin¹ , Jia-Ming Qian¹

Published online May 25, 2022

https://doi.org/10.5009/gnl210217

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Prognostic Perspectives of STING and PD-L1 Expression and Correlation with the Prognosis of Epstein-Barr Virus-Associated Gastric Cancers

Qi Sun^1,2 , Yao Fu¹ , Xiaobing Chen³ , Lin Li¹ , Hongyan Wu¹ , Yixuan Liu² , Haojun Xu² , Guoren Zhou⁴ , Xiangshan Fan¹ , Hongping Xia^1,2,5

Published online May 25, 2022

https://doi.org/10.5009/gnl210359

Abstract  

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Clinical and Genetic Characteristics of Korean Patients Diagnosed with Chronic Enteropathy Associated with SLCO2A1 Gene: A KASID Multicenter Study

Hee Seung Hong¹ , Jiwon Baek² , Jae Chul Park¹ , Ho-Su Lee² , Dohoon Park² , A-Ran Yoon^1,3 , Soo Jung Park⁴ , Sung Noh Hong⁵ , Seong-Joon Koh⁶ , Chang Kyun Lee⁷ , Bo-In Lee⁸ , Sung Wook Hwang^1,3,9 , Sang Hyoung Park^1,3,9 , Seung-Jae Myung^1,9 , Suk-Kyun Yang^1,3,9 , Kyuyoung Song² , Byong Duk Ye^1,3,9 , on behalf of the IBD Research Group of the Korean Association for the Study of Intestinal Diseases

Published online May 25, 2022

https://doi.org/10.5009/gnl210415

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Joo Hyun Oh^1,2 , Yeon Sil Jang¹ , Danbee Kang^3,4 , Hong Seog Kim⁵ , Eui-Joong Kim⁶ , So-Young Park^7,8 , Cheol-Hyun Kim⁸ , Yang Won Min¹ , Dong Kyung Chang¹

Published online May 25, 2022

https://doi.org/10.5009/gnl210478

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Impact of Evolutionary Changes in Nonalcoholic Fatty Liver Disease on Lung Function Decline

Hyun Woo Lee¹ , Goh Eun Chung² , Bo Kyung Koo³ , Hyungtai Sim⁴ , Murim Choi⁴ , Dong Hyeon Lee⁵ , Seung Ho Choi² , Soo Heon Kwak⁶ , Deog Kyeom Kim^1,7 , Won Kim^5,7 , on behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium

Published online May 25, 2022

https://doi.org/10.5009/gnl210545

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Clinical Significance of Epstein-Barr Virus and Helicobacter pylori Infection in Gastric Carcinoma

Jin Hee Noh¹ , Jun Young Shin² , Jeong Hoon Lee¹ , Young Soo Park² , In-Seob Lee³ , Ga Hee Kim⁴ , Hee Kyong Na¹ , Ji Yong Ahn¹ , Kee Wook Jung¹ , Do Hoon Kim¹ , Kee Don Choi¹ , Ho June Song¹ , Gin Hyug Lee¹ , Hwoon-Yong Jung¹

Published online May 25, 2022

https://doi.org/10.5009/gnl210593

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Trends of Colorectal Cancer Screening Rates in Korea: Korean National Cancer Screening Survey 2005–2020

Bomi Park¹ , Yun Yeong Lee² , Soo Yeon Song² , Hye Young Shin² , Mina Suh^2,3 , Kui Son Choi^2,3 , Jae Kwan Jun^2,3

Published online April 22, 2022

https://doi.org/10.5009/gnl210419

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

The Impact of Socioeconomic Status on Mortality in Patients with Hepatocellular Carcinoma: A Korean National Cohort Study

Woo Jin Yang¹ , Danbee Kang² , Myung Gyu Song¹ , Tae-Seok Seo¹ , Ji Hoon Kim³

Published online April 22, 2022

https://doi.org/10.5009/gnl210567

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

The Korean Hepatitis C Virus Care Cascade in a Tertiary Institution: Current Status and Changes in Testing, Link to Care, and Treatment

Jonggi Choi , Jina Park , Danbi Lee , Ju Hyun Shim , Kang Mo Kim , Young-Suk Lim , Han Chu Lee , Young-Hwa Chung

Published online March 31, 2022

https://doi.org/10.5009/gnl210416

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Fibrotic Burden Determines Cardiovascular Risk among Subjects with Metabolic Dysfunction-Associated Fatty Liver Disease

Eugene Han¹ , Yong-ho Lee^2,3 , Jae Seung Lee^2,4 , Hye Won Lee^2,4 , Beom Kyung Kim^2,4 , Jun Yong Park^2,4 , Do Young Kim^2,4 , Sang Hoon Ahn^2,4 , Byung-Wan Lee^2,3 , Eun Seok Kang^2,3 , Bong-Soo Cha^2,3 , Seung Up Kim^2,4

Published online March 24, 2022

https://doi.org/10.5009/gnl210290

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Clinical Features and Long-term Prognosis of Crohn’s Disease in Korea: Results from the Prospective CONNECT Study

Seung Wook Hong^1,2 , Byong Duk Ye^1,2,3 , Jae Hee Cheon⁴ , Ji Hyun Lee⁵ , Ja Seol Koo⁶ , Byung Ik Jang⁷ , Kang-Moon Lee⁸ , You Sun Kim⁹ , Tae Oh Kim¹⁰ , Jong Pil Im¹¹ , Geun Am Song¹² , Sung-Ae Jung¹³ , Hyun Soo Kim¹⁴ , Dong Il Park¹⁵ , Hyun-Soo Kim¹⁶ , Kyu Chan Huh¹⁷ , Young-Ho Kim¹⁸ , Jae Myung Cha¹⁹ , Geom Seog Seo²⁰ , Chang Hwan Choi²¹ , Hyun Joo Song²² , Gwang Ho Baik²³ , Ji Won Kim²⁴ , Sung Jae Shin²⁵ , Young Sook Park²⁶ , Chang Kyun Lee²⁷ , Jun Lee²⁸ , Sung Hee Jung²⁹ , Yunho Jung³⁰ , Sung Chul Park³¹ , Young-Eun Joo¹⁴ , Yoon Tae Jeen³² , Dong Soo Han³³ , Suk-Kyun Yang^1,2,3 , Hyo Jong Kim²⁷ , Won Ho Kim⁴ , Joo Sung Kim¹¹

Published online March 24, 2022

https://doi.org/10.5009/gnl210299

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Changing Patterns of Causative Pathogens over Time and Efficacy of Empirical Antibiotic Therapies in Acute Cholangitis with Bacteremia

Han Taek Jeong , Jeong Eun Song , Ho Gak Kim , Jimin Han

Published online March 24, 2022

https://doi.org/10.5009/gnl210474

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Forthcoming Step in Gastric Cancer Prevention: How Can Risk Stratification Be Combined with Endoscopic Screening for Gastric Cancer?

Chisato Hamashima

Published online March 22, 2022

https://doi.org/10.5009/gnl210313

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Gastric Outlet Obstruction: Current Status and Future Directions

Ioannis S. Papanikolaou¹ , Peter D. Siersema²

Published online March 22, 2022

https://doi.org/10.5009/gnl210327

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Accuracy of Noninvasive Scoring Systems in Assessing Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Sangsoo Han¹ , Miyoung Choi² , Bora Lee³ , Hye-Won Lee⁴ , Seong Hee Kang⁵ , Yuri Cho⁶ , Sang Bong Ahn⁷ , Do Seon Song⁸ , Dae Won Jun⁹ , Jieun Lee¹⁰ , Jeong-Ju Yoo¹¹

Published online February 23, 2022

https://doi.org/10.5009/gnl210391

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Bismuth-Based Quadruple Therapy versus Metronidazole-Intensified Triple Therapy as a First-Line Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial

Seung In Seo^1,2 , Hyun Lim^2,3 , Chang Seok Bang^2,4 , Young Joo Yang^2,4 , Gwang Ho Baik^2,4 , Sang Pyo Lee^2,5 , Hyun Joo Jang^2,5 , Sea Hyub Kae^2,5 , Jinseob Kim⁶ , Hak Yang Kim^1,2 , Woon Geon Shin^1,2

Published online February 11, 2022

https://doi.org/10.5009/gnl210365

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Improvement in Medication Adherence after Pharmacist Intervention Is Associated with Favorable Clinical Outcomes in Patients with Ulcerative Colitis

Jae Song Kim^1,2 , Min Jung Geum¹ , Eun Sun Son^1,2 , Yun Mi Yu³ , Jae Hee Cheon⁴ , Kyeng Hee Kwon²

Published online February 11, 2022

https://doi.org/10.5009/gnl210371

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Colonic Chicken Skin Mucosa Surrounding Colon Polyps Is an Endoscopic Predictive Marker for Colonic Neoplastic Polyps

Yu Mi Lee^1,2 , Kyung Ho Song³ , Hoon Sup Koo² , Choong-Sik Lee⁴ , Inseok Ko⁵ , Sang Hyuk Lee² , Kyu Chan Huh²

Published online January 7, 2022

https://doi.org/10.5009/gnl210271

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Effects of Reproductive Factors on Lauren Intestinal-Type Gastric Cancers in Females: A Multicenter Retrospective Study in South Korea

Yoon Ju Jung¹ , Hee Jin Kim² , Cho Hyun Park³ , Seun Ja Park⁴ , Nayoung Kim^5,6

Published online January 7, 2022

https://doi.org/10.5009/gnl210293

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Real-World Outcomes of Gemcitabine, Cisplatin, and Nab-Paclitaxel Chemotherapy Regimen for Advanced Biliary Tract Cancer: A Propensity Score-Matched Analysis

Kwangrok Jung , Jaewoo Park , Jae Hyup Jung , Jong-Chan Lee , Jaihwan Kim , Jin-Hyeok Hwang

Published online January 7, 2022

https://doi.org/10.5009/gnl210346

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Effectiveness and Safety of Golimumab in Patients with Ulcerative Colitis: A Multicenter, Prospective, Postmarketing Surveillance Study

Jongwook Yu¹ , Soo Jung Park¹ , Hyung Wook Kim² , Yun Jeong Lim³ , Jihye Park^1,4 , Jae Myung Cha⁵ , Byong Duk Ye⁶ , Tae Oh Kim⁷ , Hyun-Soo Kim⁸ , Hyun Seok Lee^9,10 , Su Young Jung¹¹ , Youngdoe Kim¹¹ , Chang Hwan Choi¹²

Published online December 27, 2021

https://doi.org/10.5009/gnl210335

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Correlation between Surrogate Quality Indicators for Adenoma Detection Rate and Adenoma Miss Rate in Qualified Colonoscopy, CORE Study: KASID Multicenter Study

Jae Hee Han¹ , Hyun Gun Kim¹ , Eu Mi Ahn² , Suyeon Park³ , Seong Ran Jeon¹ , Jae Myung Cha⁴ , Min Seob Kwak⁴ , Yunho Jung⁵ , Jeong Eun Shin⁶ , Hyun Deok Shin⁶ , Young-Seok Cho⁷

Published online December 21, 2021

https://doi.org/10.5009/gnl210287

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Clinical Course of Patients with Intestinal Behçet’s Disease According to Consensus-Based Diagnostic Categories

Yu Young Joo¹ , Bo-In Lee^1,2 , Seung-Jun Kim¹ , Han Hee Lee³ , Jin Su Kim⁴ , Jae Myung Park^1,2 , Young-Seok Cho^1,2 , Kang Moon Lee⁵ , Sang Woo Kim⁶ , Hwang Choi⁷ , Myung-Gyu Choi^1,2

Published online December 17, 2021

https://doi.org/10.5009/gnl210308

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

The Role of Gut Microbiota and Genetic Susceptibility in the Pathogenesis of Pancreatitis

Fumin Xu¹ , Chunmei Yang¹ , Mingcheng Tang¹ , Ming Wang¹ , Zhenhao Cheng¹ , Dongfeng Chen¹ , Xiao Chen² , Kaijun Liu¹

Published online December 16, 2021

https://doi.org/10.5009/gnl210362

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Abstract : Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163⁺ (predominant in M2 macrophages) and FOXP3⁺ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163⁺ expression had shorter overall survival than those with low CD163⁺ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR⁺ (predominant in M1 macrophages) and a decrease in CD163⁺ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR⁺ and decrease CD163⁺ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.