Continuing or stopping 5-aminosalicylates in patients with inflammatory bowel disease on anti-TNF therapy: A nationwide population-based study.

BACKGROUND: The impact of continuing or stopping 5-aminosalicylates (5-ASA) after commencing anti-tumour necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains unclear. AIMS: To compare the outcomes of patients with IBD who stopped or continued 5-ASA after starting anti-TNF therapy. METHODS: We analysed data from the Korean National Health Insurance claims database between 2007 and 2020. We compared the clinical outcomes of patients who stopped or continued 5-ASA within 90 days of anti-TNF initiation. The primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, IBD-related hospitalisation, or intestinal surgery. RESULTS: Among 7442 patients included for analysis (4479 [60.2%] with Crohn's disease [CD] and 2963 [39.8%] with ulcerative colitis [UC]), 1037 (13.9%) discontinued 5-ASA within 90 days of starting anti-TNF therapy. During a median 4.3-year follow-up, discontinuation of 5-ASA was not associated with an increased risk of adverse clinical events (adjusted hazard ratio 1.01, 95% confidence interval 0.93-1.10). The cumulative incidence of each adverse clinical event and the composite outcome were not significantly different between groups (all, p > 0.05). Additionally, separate analyses in CD and UC cohorts revealed no differences in adverse clinical outcomes between the 5-ASA continuation and discontinuation groups. Subgroup analyses by presumed risk factors for disease relapse showed no significant differences in the risk of adverse events between groups. CONCLUSIONS: In this nationwide population-based study, discontinuing 5-ASA after starting anti-TNF therapy was not associated with an increased risk of adverse events in patients with IBD.

Application of clinical decision support tools for predicting outcomes with vedolizumab therapy in patients with inflammatory bowel disease: A KASID multicentre study.

BACKGROUND/AIM: We aimed to validate clinical decision support tools (CDSTs) to predict real-life effectiveness of vedolizumab (VDZ) in patients with inflammatory bowel disease. METHODS: We retrospectively enrolled patients with Crohn's disease (CD) or ulcerative colitis (UC) treated with VDZ at 10 tertiary referral centres in Korea between January 2017 and November 2021. We assessed clinical remission (CREM) and response (CRES), corticosteroid-free clinical remission (CSF-CREM) and response (CSF-CRES), biochemical response based on C-reactive protein (BioRES[CRP]) and faecal calprotectin (BioRES[FC]), endoscopic healing (EH), and the need to optimise or switch drugs based on CDST-defined response groups. Additionally, the area under the receiver operating characteristics curve (AUC) for the CDSTs was calculated. RESULTS: We included 143 patients with CD and 219 with UC. We observed incremental trends on CSF-CRES at week 14 (W14) (ptrend = 0.004) and decreasing trends for the need to optimise or switch drugs (ptrend = 0.016) in CD from the low to high probability groups. Except for CSF-CREM at W54, we noticed incremental trends for all clinical responses at W14, W26 and W54 (ptrend <0.001) in UC. W26 and W54 BioRES[CRP] and W14 EH also showed increasing trends (ptrend <0.05) in UC. With increasing probabilities of response, drug optimisation or switching was less frequently required in UC (ptrend = 0.013). With 26 points cut-off, CDSTs effectively identified W14 CSF-CRES, W26 BioRES[CRP], BioRES[FC] and W54 BioRES[CRP] in UC, all with AUCs >0.600, whereas CDSTs showed poor accuracy in CD. CONCLUSIONS: CDSTs for VDZ had acceptable accuracy in predicting effectiveness outcomes including clinical and biochemical outcomes in UC. However, their utility in CD was limited.

Safety of Biologics and Small Molecules for Inflammatory Bowel Diseases in Organ Transplant Recipients.

PURPOSE: This study aimed to evaluate the safety of biologics and small molecules for the treatment of inflammatory bowel diseases (IBD) in patients receiving antirejection therapies after organ transplants. MATERIALS AND METHODS: We reviewed the medical records of patients with IBD who received organ transplants at the Asan Medical Center between January 1989 and December 2021. We compared the parameters of patients receiving biologics or small molecules to those of patients without those therapies. RESULTS: This study included a total of 53 patients (ulcerative colitis, 41; Crohn's disease, 6; and gastrointestinal Behçet's disease, 6). Among them, 15 patients were receiving biologics or small molecules and 38 were not. During a mean follow-up of 119 months, the proportion of patients experiencing severe infections was significantly higher in those treated with biologics or small molecules than in those not treated. However, other safety outcomes (e.g., malignancies, adverse events, including organizing pneumonia or hepatic failure, and death) were not different between the two groups. Kaplan-Meier curve analysis revealed no significant difference in the safety outcome rate related to the use of biologics or small molecules. During follow-up, eight patients underwent bowel resections for IBD. The rate of bowel resection was not different between the two groups. CONCLUSION: The use of biologics or small molecules for patients with IBD who received organ transplants did not show a significant difference in safety outcomes. However, the possibility of severe infections must be considered.

Optimal Treatment Approaches to Intestinal Behçet's Disease Complicated by Myelodysplastic Syndrome: The KASID and KSBD Multicenter Study.

PURPOSE: Studies on intestinal Behçet's disease (BD) complicated by myelodysplastic syndrome (MDS) are rare, and no established therapeutic guidelines exist. This study aimed to evaluate the clinical presentation and outcomes of patients with intestinal BD complicated by MDS (intestinal BD-MDS) and suggest a treatment strategy. MATERIALS AND METHODS: Data from patients with intestinal BD-MDS from four referral centers in Korea who were diagnosed between December 2000 and December 2022 were retrospectively analyzed. Clinical features and prognosis of intestinal BD-MDS compared with age-, sex-matched intestinal BD without MDS were investigated. RESULTS: Thirty-five patients with intestinal BD-MDS were included, and 24 (70.6%) had trisomy 8. Among the 35 patients, 23 (65.7%) were female, and the median age at diagnosis for intestinal BD was 46.0 years (range, 37.0-56.0 years). Medical treatments only benefited eight of the 32 patients, and half of the patients underwent surgery due to complications. Compared to 70 matched patients with intestinal BD alone, patients with intestinal BD-MDS underwent surgery more frequently (51.4% vs. 24.3%; p=0.010), showed a poorer response to medical and/or surgical treatment (75.0% vs. 11.4%; p<0.001), and had a higher mortality (28.6% vs. 0%; p<0.001). Seven out of 35 patients with intestinal BD-MDS underwent hematopoietic stem cell transplantation (HSCT), and four out of the seven patients had a poor response to medical treatment prior to HSCT, resulting in complete remission of both diseases. CONCLUSION: Patients with intestinal BD-MDS frequently have refractory diseases with high mortalities. HSCT can be an effective treatment modality for medically refractory patients with intestinal BD-MDS.

Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients.

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

Transcriptomic Profiling and Cellular Composition of Creeping Fat in Crohn's disease.

BACKGROUND AND AIMS: Creeping fat [CF] is a poorly understood feature of Crohn's disease [CD], characterized by the wrapping of mesenteric adipose tissue [MAT] around the inflamed intestine. The aim of this study was to investigate the transcriptional profile and compositional features of CF. METHODS: We collected 59 MAT samples: 23 paired samples from patients with CD (CF [CD-CF] and MAT around the uninflamed intestine [CD-MAT]) and 13 MAT samples from non-CD patients [Con-MAT]. Differentially expressed gene [DEG], functional pathway, cell deconvolution, and gene co-expression network analyses were performed. RESULTS: By comparing three different MAT samples, we identified a total of 529 DEGs [|log2FoldChange| > 1.5; false discovery rate < 0.05]. Of these, 323 genes showed an incremental pattern from Con-MAT to CD-MAT, and to CD-CF, while 105 genes displayed a decremental pattern. Genes with an incremental pattern were related to immune cell responses, including B- and T-cell activation, while genes with a decremental pattern were involved in cell trafficking and migration. Cell deconvolution analysis revealed significant changes in cellular composition between the CD-CF and Con-MAT groups, with increased proportions of B-cells/plasma cells [p = 1.16 × 10-4], T-cells [p = 3.66 × 10-3], and mononuclear phagocytes [p = 3.53 × 10-2] in the CD-CF group. In contrast, only the B-cell/plasma cell component showed a significant increase [p = 1.62 × 10-2] in the CD-MAT group compared to Con-MAT. CONCLUSION: The distinct transcriptional profiles and altered cellular components of each MAT found in our study provide insight into the mechanisms behind CF and highlight its possible role in the pathogenesis of CD.

Risk of malignancies and chemopreventive effect of statin, metformin, and aspirin in Korean patients with ulcerative colitis: a nationwide population-based study.

Background/Aims: We investigated the incidences of overall and site-specific malignancies and chemopreventive effects of statin, metformin, and aspirin in patients with ulcerative colitis. Methods: We collected data using the Health Insurance Review and Assessment claims database from January 2007 to April 2020. Results: The overall malignancy risk among the 35,189 ulcerative colitis patients was similar to that of the general population (standardized incidence ratio, 0.94; 95% confidence interval, 0.88-1.00). In male patients, standardized incidence ratios were high for thyroid cancer and low for stomach cancer, colorectal cancer, liver cancer, and lung cancer. Concurrently, standard incidence ratios were high for liver cancer and central nervous system cancer in female patients. While 122 cases of colorectal cancer occurred in the study patients, the standardized incidence ratio was 0.83 (95% confidence interval, 0.69-0.99). Treatment for ulcerative colitis was not associated with an increased adjusted hazard ratio, while comorbidities increased it for all malignancies. Treatment for ulcerative colitis was associated with an increased adjusted hazard ratio, while comorbidities did not increase it for colorectal cancer. After adjusting for age, sex, comorbidities, and ulcerative colitis treatment, statins showed a dose-dependent chemopreventive effect for all malignancies (P=0.002), while metformin and aspirin did not show any. Conclusions: In ulcerative colitis patients, standardized incidence ratios for all malignancies and colorectal cancer did not increase. Adjusted hazard ratios for all malignancies increased with comorbidities and those for colorectal cancer with ulcerative colitis treatment. Statins have a dose-dependent chemopreventive effect for all malignancies.

Efficacy and safety of oral sodium sulfate tablet compared with 1-L polyethylene glycol plus ascorbate: a prospective, randomized, endoscopist-blinded trial.

BACKGROUND AND AIM: Low-volume bowel preparation solutions, including 1-L polyethylene glycol plus ascorbate (PEG-A), have been developed to improve tolerability. The oral sodium sulfate tablet (OST) is a new agent with simethicone as a preloaded component. We investigated the efficacy, safety, and tolerability of OST compared to 1-L PEG-A. METHODS: A single-center, prospective, controlled study was performed with randomization into the OST (group A) and 1-L PEG-A (group B) groups. Bowel preparation efficacy was assessed on the Boston Bowel Preparation Scale (BBPS) and Bubble Scale. Safety and tolerability were evaluated using a questionnaire and laboratory examination. RESULTS: Final analysis was performed on 171 patients (group A: 87, group B: 84). The proportion of bowel preparation success (BBPS ≥ 2 for each colonic segment) in group A was not inferior compared to group B (95.4% vs 96.4%, P = 0.736, 1-sided 97.5% lower confidence limit -7.0%). The adenoma detection rate was not different (59.6% vs 41.9%; P = 0.087). The bubble scale was better in group A (0.2 ± 0.9 vs 1.9 ± 1.7, P < 0.001). All adverse events were mild in both groups. Nausea was less frequent in group A (14.9% vs 38.1%, P = 0.001). Overall satisfaction was better in group A (8.1 ± 2.1 vs 6.4 ± 2.8, P < 0.001). No clinically significant laboratory abnormality developed in both groups. These findings were similarly shown in old patients ≥65 years. CONCLUSIONS: Both OST and 1-L PEG-A were efficacious, safe, and tolerable for bowel preparation of colonoscopy. The OST showed fewer bubbles and slightly better tolerability.

Influence of endoscopists' expertise level on clinical outcomes after bridge-to-surgery stenting in obstructive colorectal cancer.

BACKGROUND AND AIM: This study aimed to investigate the effect of stenting-related factors, including endoscopists' expertise, on clinical outcomes after bridge-to-surgery (BTS) stenting for obstructive colorectal cancer (CRC). METHODS: We analyzed BTS stenting-related factors, including stenting expertise and the interval between stenting and surgery, in 233 patients (63 [13] years, 137 male) who underwent BTS stenting for obstructive CRC. We evaluated the influence of these factors on post-BTS stenting clinical outcomes such as stent-related complications and cancer recurrence. RESULTS: The interval between stenting and surgery was ≤ 7 days in 79 patients (33.9%) and > 7 days in 154 patients (66.1%). BTS stenting was performed by endoscopists with ≤ 50, 51-100, and > 100 prior stenting experiences in 94, 43, and, 96 patients, respectively. The clinical success rate of BTS stenting was 93.1%. Stent-related and postoperative complications developed in 19 (8.2%) and 20 (8.6%) patients, respectively. Cancer recurrence occurred in 76 patients (32.6%). Short BTS interval of ≤ 7 days increased the risk of postoperative complications (odds ratio [OR], 2.61 [1.03-6.75]; P = 0.043). Endoscopists' stenting experience > 100 showed greater clinical success of stenting (OR, 5.50 [1.45-28.39]; P = 0.021) and fewer stent-related complications (OR, 0.26 [0.07-0.80]; P = 0.028) compared with stenting experience ≤ 50. BTS stenting-related factors did not affect long-term oncological outcomes. CONCLUSION: Greater expertise of endoscopists was associated with better short-term outcomes, including high stenting success rate and low rate of stent-related complications after BTS stenting for obstructive CRC. An interval of > 7 days between BTS stenting and surgery was required to decrease postoperative complications.

Adult-onset megacolon with focal hypoganglionosis: A detailed phenotyping and prospective cohort study.

BACKGROUND: In this prospective cohort study, we evaluated features of "adult-onset megacolon with focal hypoganglionosis." METHODS: We assessed the radiologic, endoscopic, and histopathologic phenotyping and treatment outcomes of 29 patients between 2017 and 2020. Data from community controls, consisting of 19,948 adults undergoing health screenings, were analyzed to identify risk factors. Experts reviewed clinical features and pathological specimens according to the London Classification for gastrointestinal neuromuscular pathology. KEY RESULTS: The median age of the patients with adult-onset megacolon with focal hypoganglionosis at symptom onset was 59 years (range, 32.0-74.9 years), with mean symptom onset only 1 year before diagnosis. All patients had focal stenotic regions with proximal bowel dilatation (mean diameter, 78.8 mm; 95% confidence interval [CI], 72-86). The comparison with community controls showed no obvious risk factors. Ten patients underwent surgery, and all exhibited significant hypoganglionosis: 5.4 myenteric ganglion cells/cm (interquartile range [IQR], 3.7-16.4) in the stenotic regions compared to 278 cells/cm (IQR, 190-338) in the proximal and 95 cells/cm (IQR, 45-213) in the distal colon. Hypoganglionosis was associated with CD3+ T cells along the myenteric plexus. Colectomy was associated with significant symptom improvement compared to medical treatment [change in the Global Bowel Satisfaction score, -5.4 points (surgery) vs. -0.3 points (medical treatment); p < 0.001]. CONCLUSIONS AND INFERENCES: Adult-onset megacolon with focal hypoganglionosis has distinct features characterized by hypoganglionosis due to inflammation. Bowel resection appears to benefit these patients.

Investigation of artificial intelligence integrated fluorescence endoscopy image analysis with indocyanine green for interpretation of precancerous lesions in colon cancer.

Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration.

Clinical outcomes of colonoscopic polypectomy with strategic surveillance colonoscopies in patients with 10 or more polyps.

The clinical usefulness of repeat colonoscopic polypectomy in patients with numerous polyps has not been sufficiently determined. We aimed to analyze the clinical outcomes of colonoscopic polypectomy with surveillance colonoscopies in patients with ≥ 10 polyps. We reviewed the medical records of 152 patients who underwent polypectomy of ≥ 10 polyps at the baseline colonoscopy. We investigated polyp number, polyp size, polypectomy method, procedure time, and adverse events of the baseline colonoscopy. We also investigated the frequency and interval of surveillance colonoscopies and their findings. The mean number of polyps detected at the baseline colonoscopy was 20.0, of which 16.0 polyps were endoscopically resected. The mean size of the largest polyp was 13.4 mm. The mean procedure time was 54.9 min. Post-polypectomy bleeding occurred in 6 (3.9%) patients, all of whom were treated conservatively. No patients developed perforation. With an increasing number of surveillance colonoscopies, the number of detected polyps and the procedure time decreased. Surveillance colonoscopies identified colorectal cancer only in three patients (2.0%), all of which were mucosal cancers that could be curatively treated by polypectomy. Colonoscopic polypectomy with repeat surveillance colonoscopies is a clinically effective, efficient, and safe management option in patients with ≥ 10 polyps.

Feasibility of moxifloxacin and proflavine dual fluorescence imaging for detecting gastrointestinal neoplastic lesions: A prospective study.

OBJECTIVES: High-contrast and high-resolution imaging techniques would enable real-time sensitive detection of the gastrointestinal lesions. This study aimed to investigate the feasibility of novel dual fluorescence imaging using moxifloxacin and proflavine in the detection of neoplastic lesions of the human gastrointestinal tract. METHODS: Patients with the colonic and gastric neoplastic lesions were prospectively enrolled. The lesions were biopsied with forceps or endoscopically resected. Dual fluorescence imaging was performed by using custom axially swept wide-field fluorescence microscopy after topical moxifloxacin and proflavine instillation. Imaging results were compared with both confocal imaging with cell labeling and conventional histological examination. RESULTS: Ten colonic samples (one normal mucosa, nine adenomas) from eight patients and six gastric samples (one normal mucosa, five adenomas) from four patients were evaluated. Dual fluorescence imaging visualized detail cellular structures. Regular glandular structures with polarized cell arrangement were observed in normal mucosa. Goblet cells were preserved in normal colonic mucosa. Irregular glandular structures with scanty cytoplasm and dispersed elongated nuclei were observed in adenomas. Goblet cells were scarce or lost in the colonic lesions. Similarity analysis between moxifloxacin and proflavine imaging showed relatively high correlation values in adenoma compared with those in normal mucosa. Dual fluorescence imaging showed good detection accuracies of 82.3% and 86.0% in the colonic and the gastric lesions, respectively. CONCLUSIONS: High-contrast and high-resolution dual fluorescence imaging was feasible for obtaining detail histopathological information in the gastrointestinal neoplastic lesions. Further studies are needed to develop dual fluorescence imaging as an in vivo real-time visual diagnostic method.

Impact of Sarcopenia on Clinical Course of Inflammatory Bowel Disease in Korea.

BACKGROUND AND AIMS: Reduced body muscle mass is a poor prognostic factor for inflammatory bowel disease (IBD). In this study, we investigated the prevalence of sarcopenia at diagnosis and its clinical significance in Korean patients with IBD. METHODS: The prevalence of sarcopenia in IBD patients between June 1989 and December 2016 was investigated using a well-characterized referral center-based cohort. Abdominopelvic computed tomography within six months from IBD diagnosis was used for the evaluation. Sarcopenia was defined as an L3 skeletal muscle index of < 49 cm2/m2 for male and < 31 cm2/m2 for female. The clinical characteristics and outcomes were evaluated with respect to sarcopenia. RESULTS: A total of 1,027 patients (854 Crohn's disease [CD]; 173 ulcerative colitis [UC]) were evaluated. Sarcopenia was found in 56.8% of the population (CD, 57.5%; UC, 53.2%), and male were more likely to be sarcopenic (CD, 94.3%; UC, 91.6%). There were no significant differences in the cumulative risk of using steroids, immunomodulators, biologics, and bowel resections (or colectomy) with or without sarcopenia during follow-up (median: CD, 5.8 years; UC, 3.7 years). In sarcopenic patients with CD, there was a significantly higher cumulative risk of perianal surgeries than in non-sarcopenic patients with CD (Log-rank test; P = 0.001). However, the risk of perianal surgeries was not significant in multivariate analysis (Odds ratio 1.368; 95% confidence interval 0.782-2.391; P = 0.272). CONCLUSION: Sarcopenia at diagnosis may have no significant prognostic value for medical treatment and bowel resection, but it may be associated with perianal CD.

Bronchoesophageal fistula in a patient with Crohn's disease receiving anti-tumor necrosis factor therapy.

Tuberculosis is an adverse event in patients with Crohn's disease receiving anti-tumor necrosis factor (TNF) therapy. However, tuberculosis presenting as a bronchoesophageal fistula (BEF) is rare. We report a case of tuberculosis and BEF in a patient with Crohn's disease who received anti-TNF therapy. A 33-year-old Korean woman developed fever and cough 2 months after initiation of anti-TNF therapy. And the symptoms persisted for 1 months, so she visited the emergency room. Chest computed tomography was performed upon visiting the emergency room, which showed BEF with aspiration pneumonia. Esophagogastroduodenoscopy with biopsy and endobronchial ultrasound with transbronchial needle aspiration confirmed that the cause of BEF was tuberculosis. Anti-tuberculosis medications were administered, and esophageal stent insertion through endoscopy was performed to manage the BEF. However, the patient's condition did not improve; therefore, fistulectomy with primary closure was performed. After fistulectomy, the anastomosis site healing was delayed due to severe inflammation, a second esophageal stent and gastrostomy tube were inserted. Nine months after the diagnosis, the fistula disappeared without recurrence, and the esophageal stent and gastrostomy tube were removed.

Comparative Cost Analysis Between Endoscopic Resection and Surgery for Submucosal Colorectal Cancer.

BACKGROUND: There are few studies analyzing the cost of endoscopic resection and surgical resection in the treatment of submucosal colorectal cancer. OBJECTIVE: The objective was to perform a detailed cost analysis of endoscopic resection and surgical resection for submucosal colorectal cancer. DESIGN: This was a retrospective observational study. SETTING: This study was conducted at a tertiary academic center. PATIENTS: Medical records of 484 patients with submucosal colorectal cancer who underwent endoscopic resection or surgical resection between July 2003 and July 2015 were reviewed. MAIN OUTCOME MEASUREMENTS: The total costs during index admission and follow-up as well as clinical outcomes between the 2 groups were compared in the whole cohort and propensity score-matched cohort. RESULTS: In the propensity score-matched analysis ( n = 155 in each group), the endoscopic resection and surgical resection groups did not show significant differences in the rates of procedure-related adverse events (6.5% vs 3.9%; p = 0.304) and recurrence (0.6% vs 1.3%; p > 0.99). Readmission was more common in the endoscopic resection group (40.6% vs 11.0%; p < 0.001) because 64 (41.3%) patients underwent additional surgery for endoscopic noncurative resection. The endoscopic resection group had a lower cost during the index admission (1335.6 vs 6698.4 USD; p < 0.001), whereas the surgical resection group had a lower cost during follow-up (2488.7 vs 5035.7 USD; p < 0.001). The total cumulative cost was lower in the endoscopic resection group (6371.3 vs 9187.1 USD; p < 0.001). The same trend was observed in the whole cohort without propensity score matching. LIMITATIONS: A limitation of this study was the retrospective nature of analysis. CONCLUSIONS: The total cumulative cost for treatment and follow-up for submucosal colorectal cancer was lower in the endoscopic resection group, which had comparable oncologic outcomes as the surgical resection group. Endoscopic resection can be considered a cost-effective option for initial treatment for submucosal colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B881 . ANLISIS COMPARATIVO DE COSTOS ENTRE LA RESECCIN ENDOSCPICA Y LA CIRUGA PARA EL CNCER COLORRECTAL SUBMUCOSO: ANTECEDENTES: Existen pocos estudios que analizan el costo de la resección endoscópica y la resección quirúrgica en el tratamiento del cáncer colorrectal submucoso.OBJETIVO: El objetivo fue realizar un análisis detallado de costos tanto de la resección endoscópica y la resección quirúrgica para el cáncer colorrectal submucoso.DISEÑO: Este fue un estudio observacional retrospectivo.AJUSTE: Este estudio se realizó en un centro académico terciario.PACIENTES: Se revisaron las historias clínicas de 484 pacientes con cáncer colorrectal submucoso que fueron sometidos a resección endoscópica o resección quirúrgica entre julio de 2003 y julio de 2015.PRINCIPALES MEDICIONES DE RESULTADOS: Los costos totales durante la admisión índice y el seguimiento, así como los resultados clínicos entre los dos grupos, fueron comparados en toda la cohorte y la cohorte emparejada por puntuación de propensión.RESULTADOS: En el análisis emparejado por puntuación de propensión ( n = 155 en cada grupo), los grupos de resección endoscópica y resección quirúrgica no mostraron diferencias significativas en las tasas de eventos adversos relacionados con el procedimiento (6,5% vs 3,9%, p = 0,304) y recurrencia (0,6% vs 1,3%, p > 0,99). La readmisión fue más común en el grupo de resección endoscópica (40,6% vs 11,0%, p < 0,001) porque 64 (41,3%) pacientes fueron sometidos a una cirugía adicional para lograr la resección en aquellos casos en que la resección endoscópica no fue curativa. El grupo de resección endoscópica tuvo un costo menor durante el ingreso índice (1335.6 vs 6698.4 USD, p < 0.001), mientras que el grupo de resección quirúrgica tuvo un costo menor durante el seguimiento (2488.7 vs 5035.7 USD, p < 0.001). El costo total acumulado fue menor en el grupo de resección endoscópica (6371,3 vs 9187,1 USD, p < 0,001). La misma tendencia se observó en toda la cohorte sin emparejamiento por puntuación de propensión.LIMITACIONES: La naturaleza retrospectiva del análisis.CONCLUSIONES: El costo total acumulado para el tratamiento y seguimiento del cáncer colorrectal submucoso fue menor en el grupo de resección endoscópica, que tuvo resultados oncológicos comparables a los del grupo de resección quirúrgica. La resección endoscópica puede considerarse una opción rentable para el tratamiento inicial del cáncer colorrectal submucoso. Consulte Video Resumen en http://links.lww.com/DCR/B881 . (Traducción-Dr Osvaldo Gauto ).

Korean clinical practice guidelines on biologics and small molecules for moderate-to-severe ulcerative colitis.

Ulcerative colitis (UC), a relapsing-remitting chronic inflammatory bowel disease (IBD), has a variable natural course but potentially severe disease course. Since the development of anti-tumor necrosis factor (TNF) agents has changed the natural disease course of moderate-to-severe UC, therapeutic options for patients who failed conventional treatments are expanding rapidly. IBD clinical trials have demonstrated the potential efficacy and safety of novel biologics such as anti-integrin α4ß7 and anti-interleukin-12/23 monoclonal antibodies and small molecules such as a Janus kinase inhibitor. Anti-TNF biosimilars also have been approved and are widely used in IBD patients. Wise drug choices should be made considering evidence-based efficacy and safety. However, the best position of these drugs remains several questions, with limited data from direct comparative trials. In addition, there are still concerns to be elucidated on the effect of therapeutic drug monitoring and combination therapy with immunomodulators. The appropriate treatment regimens in acute severe UC and the risk of perioperative use of biologics are unclear. As novel biologics and small molecules have been approved in Korea, we present the Korean guidelines for medical management of adult outpatients with moderate-to-severe UC and adult hospitalized patients with acute severe UC, focusing on biologics and small molecules.

Risks of colorectal cancer and biliary cancer according to accompanied primary sclerosing cholangitis in Korean patients with ulcerative colitis: a nationwide population-based study.

BACKGROUND/AIMS: We conducted a nationwide population-based study to investigate incidence rates of colorectal and biliary cancers according to accompanying primary sclerosing cholangitis in Korean ulcerative colitis patients. METHODS: We used the Health Insurance Review and Assessment claim database from January 2007 to April 2020. Standardized incidence ratios of colorectal and biliary cancers in ulcerative colitis patients were calculated. RESULTS: Among 35,189 newly diagnosed ulcerative colitis patients, 1,224 patients were diagnosed with primary sclerosing cholangitis. During the study period, 122 and 52 patients were diagnosed with colorectal and biliary cancers, respectively. Incidences of colorectal cancer were not higher in ulcerative colitis patients than those in the general population (standardized incidence ratios, 0.83; 95% confidence interval, 0.69-0.99), regardless of accompanied primary sclerosing cholangitis (standardized incidence ratio, 0.73; 95% confidence interval, 0.24-1.71). While incidences of biliary cancer were not higher in ulcerative colitis patients than those in the general population (standardized incidence ratio, 1.14; 95% confidence interval, 0.80-1.58), these were much higher with accompanied primary sclerosing cholangitis (standardized incidence ratio, 10.07; 95% confidence interval, 5.75-16.36). Cumulative incidences of colorectal and biliary cancers increased in patients who were diagnosed with ulcerative colitis at an older age. CONCLUSIONS: In Korean ulcerative colitis patients, colorectal cancer incidences were not higher than those in the general population regardless of accompanied primary sclerosing cholangitis. However, biliary cancer incidences were much higher in ulcerative colitis patients with primary sclerosing cholangitis than in those without, or in the general population.

Impact of Crohn's Disease on the Survival of Patients with Small-Bowel Adenocarcinoma in Korea: A Bicenter Cohort Study.

Background/Aims: Owing to the low prevalence of small-bowel adenocarcinoma (SBA), data on the impact of Crohn's disease (CD) on the survival of patients with SBA are lacking. Therefore, we investigated this issue in this study. Methods: In this bicenter cohort study, patients with histologically confirmed SBA were retrospectively enrolled and classified into two groups: sporadic SBA and CD-associated SBA. Patients with duodenal SBA were excluded. Overall survival, disease-free survival, and factors associated with survival were analyzed. Results: Of 128 patients with SBA, 115 had sporadic SBA and 13 had CD-associated SBA. Ileal involvement and poorly differentiated tumors were more common in the CD-associated SBA group than in the sporadic SBA group (ileal involvement, 53.8% vs 22.6%; poor differentiation, 46.2% vs 14.8%; both p<0.05). In survival analysis, overall survival showed no statistical difference between the sporadic SBA and CD-associated SBA groups (p=0.370). However, when stratified by stage, the adjusted overall survival of the CD-associated SBA group was lower in patients with an advanced disease stage (p=0.029). Disease-free survival showed the same tendency, albeit without clinical significance (p=0.097). CD (hazard ratio [HR], 2.308; p=0.047), older age (≥65 yr) at SBA diagnosis (HR, 2.766; p=0.001), and stage III/IV disease (HR, 3.151; p<0.001) were factors associated with mortality. Conclusions: The overall survival of patients with CD-associated SBA did not differ from that of patients with sporadic SBA. However, as CD is an independent risk factor for mortality, vigilant surveillance in high-risk patients may be crucial.

Case-case genome-wide association analysis identifying genetic loci with divergent effects on Crohn's disease and ulcerative colitis.

Crohn's disease (CD) and ulcerative colitis (UC), two major subtypes of inflammatory bowel disease, show substantial differences in their clinical course and treatment response. To identify the genetic factors underlying the distinct characteristics of these two diseases, we performed a genome-wide association study (GWAS) between CD (n = 2359) and UC (n = 2175) in a Korean population, followed by replication in an independent sample of 772 CD and 619 UC cases. Two novel loci were identified with divergent effects on CD and UC: rs9842650 in CD200 and rs885026 in NCOR2. In addition, the seven established susceptibility loci [major histocompatibility complex (MHC), TNFSF15, OTUD3, USP12, IL23R, FCHSD2 and RIPK2] reached genome-wide significance. Of the nine loci, six (MHC, TNFSF15, OTUD3, USP12, IL23R and CD200) were replicated in the case-case GWAS of European populations. The proportion of variance explained in CD-UC status by polygenic risk score analysis was up to 22.6%. The area under the receiver-operating characteristic curve value was 0.74, suggesting acceptable discrimination between CD and UC. This CD-UC GWAS provides new insights into genetic differences between the two diseases with similar symptoms and might be useful in improving their diagnosis and treatment.