Outcomes of ulcerative colitis-associated dysplasia patients referred for potential endoscopic submucosal dissection.

BACKGROUND AND AIM: The feasibility of endoscopic submucosal dissection (ESD) as a treatment option for dysplasia in ulcerative colitis (UC) has been reported, but the associated therapeutic decision-making and clinical outcomes have not been extensively investigated. METHODS: We retrospectively reviewed 25 UC patients who were referred for potential ESD of non-polypoid or sessile dysplasia. We analyzed the treatment decisions and the ESD and colectomy outcomes for this patient group. RESULTS: All lesions were located at the colitic segments. The median UC duration was 13.4 years. A colectomy was recommended for 10 patients because of ulceration with indistinct borders (one patient), non-ulceration with indistinct borders (two patients), and non-lifting signs (seven patients). The remaining 15 patients underwent ESD. The en bloc and R0 resection rates were 93.3% and 80%, respectively. The median hospitalization periods were 1 (range, 1-2) day after ESD and 7 (range, 5-30) days after colectomy. No procedure-related complications occurred after ESD, but early and late postoperative complications occurred in two (22.2%) and six (66.7%) of the colectomized patients, respectively. Fourteen ESD cases were followed endoscopically for a median period of 24.7 (range, 5.2-64.8) months. Local recurrence occurred in 2 (14.3%) patients, and metachronous recurrence was identified in two separate patients (14.3%). CONCLUSIONS: Endoscopic submucosal dissection is a feasible endoscopic treatment option for UC-associated dysplasia showing noninvasive pit or vascular patterns, no surface ulceration, distinct borders, and appropriate lifting after submucosal injection. Meticulous endoscopic surveillance is essential to monitor for local or metachronous recurrence of dysplasia after ESD.

Increased Risk of Herpes Zoster Infection in Patients With Inflammatory Bowel Diseases in Korea.

BACKGROUND & AIMS: Few data are available on risk of herpes zoster (HZ) infection in Asian patients with inflammatory bowel diseases (IBD). We investigated whether patients with IBD in Korea have an increased risk of HZ and sought to identify risk factors for infection. METHODS: We performed a nationwide population-based study and a hospital-based, nested case-control study. Using the 2009-2013 data from the Korean national health insurance claims database, we calculated incidence rates and standardized incidence ratios (SIRs) of HZ infection in patients with IBD compared with the entire Korean population. In the nested case-control study, within a hospital-based cohort, 300 patients with IBD and HZ infection were matched with 895 patients with IBD without HZ. RESULTS: In the nationwide population-based study, the incidence rate and SIR of HZ infection in patients with IBD were 18.34/1000 person-years and 1.48 (95% CI, 1.42-1.54), respectively. The SIR for HZ infection was higher in patients with Crohn's disease than in patients with ulcerative colitis (1.90 vs 1.36; P < .001) and higher in male patients than female patients (1.63 vs 1.33; P < .001). The incidence rate of HZ increased with age (P trend < .001), whereas the SIR of HZ infection decreased with age (P trend < .001). In the nested case-control study, corticosteroid use was associated with HZ infection (for ulcerative colitis, adjusted odds ratio, 2.44; 95% CI, 1.18-5.05 and for Crohn's disease, adjusted odds ratio, 2.70; 95% CI 1.25-5.83). CONCLUSIONS: In a population-based study in Korea, we found patients with IBD to have an increased risk for HZ infection-especially among patients who are male, younger, or have Crohn's disease. Corticosteroid use increases risk of HZ infection in patients with IBD.

Clinical characteristics and long-term prognosis of elderly-onset Crohn's disease.

OBJECTIVES: This study aimed to evaluate the clinical characteristics and clinical course of Asian elderly-onset Crohn's disease (EOCD) patients in a large well-defined cohort of South Korean IBD patients. MATERIALS AND METHODS: From the Asan inflammatory bowel disease registry, we identified 29 EOCD patients (diagnosed with CD in age of 60 years or over) out of 2989 CD patients (1.0%). After excluding two patients with unclear data, 27 EOCD were matched with 108 young-onset CD (YOCD) and 108 middle age-onset CD (MOCD) for the interval from symptom onset to diagnosis (±3 years) and follow-up duration (±3 years). RESULTS: Females were predominant in the EOCD group (59.3%) compared to MOCD (31.5%) and YOCD (29.6%) groups (p = .012). In EOCD group, terminal ileal location was the most common (63.0%) at diagnosis, whereas ileocolonic location in other groups (57.4% in MOCD and 78.7% in YOCD, respectively) (p < .001). Patients with perianal fistula at CD diagnosis were less common (14.8% in EOCD vs. 28.7% in MOCD vs. 49.1% in YOCD, p < .001). During follow-up, thiopurines were used less frequently in the EOCD group (48.1% in EOCD vs. 87.0% in MOCD vs. 89.8% in YOCD, p < .001), but the risk for intestinal resection was comparable among three groups (p = .583). CONCLUSIONS: EOCD may have a better clinical course than MOCD and YOCD, as demonstrated by the similar risk for intestinal resection despite the less frequent use of thiopurines.

Fecal Fatty Acid Profiling as a Potential New Screening Biomarker in Patients with Colorectal Cancer.

BACKGROUND: The fatty acid profile of the fecal metabolome and its association with colorectal cancer (CRC) has not been fully evaluated. AIMS: We aimed to compare the fecal fatty acid profiles of CRC patients and healthy controls. METHODS: We enrolled 26 newly diagnosed CRC patients and 28 healthy individuals between July 2014 and August 2014 from our institute. Long- and short-chain fatty acids were extracted from fecal samples and analyzed using gas chromatography-mass spectrometry. RESULTS: Regarding fecal long-chain fatty acids, the levels of total ω-6 polyunsaturated fatty acids and, particularly, of linoleic acid (C18:2ω-6) were significantly higher in male CRC patients than in healthy men (2.750 ± 2.583 vs. 1.254 ± 0.966 µg/mg feces, P = 0.040; 2.670 ± 2.507 vs. 1.226 ± 0.940 µg/mg feces, P = 0.034, respectively). In addition, the levels of total monounsaturated fatty acid and, particularly, of oleic acid (C18:1ω-9) were significantly higher in male CRC patients than in healthy men (1.802 ± 1.331 vs. 0.977 ± 0.625 µg/mg feces, P = 0.027; 1.749 ± 1.320 vs. 0.932 ± 0.626 µg/mg feces, P = 0.011, respectively). However, those differences were not shown in female gender. The level of fecal short-chain fatty acids was not different between CRC patients and healthy controls. CONCLUSIONS: There were changes in the profiles of fecal fatty acid metabolomes in CRC patients compared to healthy controls, implying that fecal fatty acids could be used as a novel screening tool for CRC.

Long-term outcomes of infliximab treatment and predictors of response in 195 patients with ulcerative colitis: a hospital-based cohort study from Korea.

BACKGROUND: Large-scale studies regarding the long-term efficacy of infliximab (IFX) treatment in non-Caucasian patients with ulcerative colitis (UC) are lacking. STUDY: We analyzed the long-term outcomes of IFX in 195 Korean UC patients who received scheduled IFX treatments at Asan Medical Center. IFX failure was defined as IFX discontinuation due to colectomy or non-response to IFX, and additionally UC-related hospitalization or a need for rescue corticosteroids during the course of IFX. RESULTS: Between December 2006 and October 2016, a total of 3101 infusions of IFX were administered to 195 patients over a median period of 21 months. At the end of the follow-up, 86 patients (44.1%) were still receiving IFX without failure. IFX was stopped in 73 (37.4%) patients due to colectomy (23 patients, 11.8%), non-response to IFX (35 patients, 17.9%) or other reasons such as adverse events or patients' preferences (15 patients, 7.7%). An additional 36 (18.5%) patients experienced IFX failure during follow-up due to a need for rescue corticosteroids (13 patients, 6.7%), UC-related hospitalization (8 patients, 4.1%), or both (15 patients, 7.7%). The survival free of IFX failure was 58.1% at 1 year, 50.7% at 3 years and 44.8% at 5 years. In a multivariate regression analysis, cytomegalovirus colitis within 3 months before IFX initiation was a predictor of IFX failure (hazard ratio 1.57; 95% confidence interval 1.04-2.37; p = .032). CONCLUSIONS: The long-term efficacy of IFX in a large, real-life cohort of Korean UC patients appears to be comparable to that in previously published Western studies.

Fecal calprotectin predicts complete mucosal healing and better correlates with the ulcerative colitis endoscopic index of severity than with the Mayo endoscopic subscore in patients with ulcerative colitis.

BACKGROUND: We aimed to evaluate the role of fecal calprotectin (FC) as a noninvasive marker for the disease activity of ulcerative colitis (UC) in a Korean cohort. METHODS: A total of 181 fecal samples were collected from 181 consecutive UC patients between April 2015 and September 2016. FC levels were measured using the Quantum Blue® Calprotectin rapid test. The laboratory test results, partial Mayo Score (pMS), and colonoscopic imaging findings at FC level measurement were retrospectively reviewed. The Mayo endoscopic subscore (MES) and UC endoscopic index of severity (UCEIS) were graded by 2 certified endoscopists after training with 50 other cases. RESULTS: The FC levels were significantly correlated with pMS (Spearman correlation coefficient r = 0.428, p < 0.001), MES (r = 0.304, p < 0.001), UCEIS (r = 0.430, p < 0.001), and CRP (r = 0.379, p < 0.001). FC levels exhibited a significantly better correlation with UCEIS than with MES (Meng's z = - 2.457, p = 0.01). The FC cut-off level of 187.0 mg/kg indicated complete mucosal healing (MES = 0; UCEIS =0) with a sensitivity and specificity of 0.857 and 0.891, respectively (area under the curve, 0.883; 95% confidence interval, 0.772-1.000). CONCLUSION: The FC level is significantly correlated with the clinical disease activity index, endoscopic indices, and serum inflammatory biomarkers in a Korean UC cohort. FC is highly predictive of complete mucosal healing in UC. UCEIS exhibits a stronger correlation with the FC level, as compared to MES. Thus, FC could be used as a reliable noninvasive indicator for evaluating disease activity and mucosal healing in UC.

Long-Term Outcomes of Adalimumab Treatment in 254 Patients with Crohn's Disease: A Hospital-Based Cohort Study from Korea.

BACKGROUND AND AIMS: Large-scale studies regarding the long-term outcomes of adalimumab (ADA) treatment in Asian patients with Crohn's disease (CD) are still scarce. METHODS: We retrospectively analyzed the long-term outcomes of ADA treatment in Korean CD patients who commenced on scheduled ADA treatment at Asan Medical Center between November 2008 and July 2016. Clinical response was defined as maintaining ADA treatment without dose intensification (DI) and/or major abdominal surgery (MAS). RESULTS: Of the 254 patients who received at least two doses of ADA at 2-week intervals as induction therapy, 250 patients (98.4%) showed an initial favorable response by week 4. Among responders, 243 patients were followed up for longer than 4 weeks and were included for further analysis. The median duration of ADA maintenance therapy was 19.4 months. At the last follow-up, 45 patients (18.5%) required DI after a median of 16.8 months and 31 (12.8%) required MAS after a median of 8.9 months. Finally, 161 patients (66.3%) were still receiving ADA without DI and/or MAS. The cumulative probability of maintaining ADA without DI and/or MAS was 81.1% at 1 year, and 36.5% at 5 years. Secondary loss of response to previous infliximab (P = 0.001) and elevated baseline C-reactive protein at starting ADA treatment (P = 0.008) were identified as independent predictors of a poor response to ADA treatment using multivariate regression analysis. CONCLUSIONS: The long-term outcome of ADA treatment in a real-life cohort of Korean patients with CD appears to be comparable to that reported in previously published Western studies.

Insufficient vaccination and inadequate immunization rates among Korean patients with inflammatory bowel diseases.

ABSTRACT: This study aimed to evaluate self-reported vaccination rates, immunity, knowledge of and attitudes toward vaccination among Korean patients with inflammatory bowel disease (IBD) as well as to identify factors associated with proper vaccination.Between November 2013 and February 2015, consecutive patients with IBD were invited to complete a standardized questionnaire on vaccination. Moreover, immune status for common vaccine-preventable diseases was evaluated via serologic tests.A total of 310 patients with IBD were invited to the questionnaire survey and 287 patients (92.6%) who completed the questionnaires were finally enrolled (men, 188 [65.5%], median age at survey, 29.9 years [interquartile range, 22.3-39.2], ulcerative colitis: Crohn disease = 165:122]. Self-reported vaccine uptake rates were as follows: hepatitis A virus (HAV; 13.2%), hepatitis B virus (HBV; 35.2%), seasonal influenza (43.2%), pneumococcus (4.9%). Most of the patients (87.1%) did not know that proper vaccination has been recommended for patients with IBD. Up to 64.8% and 32.8% of patients were negative for IgG anti-HAV antibody and IgG HBV surface antibody, respectively. In a multivariable analysis, newspaper subscription (aOR [adjusted odds ratio] 2.185, 95% confidence interval [CI] 1.136-4.203, P = .019), ever recommendation of vaccination by a physician (aOR 2.456, 95% CI 1.240-4.862, P = .010), and use of anti-tumor necrosis factor agents (aOR 4.966, 95% CI 1.098-22.464, P = .037) showed a significant association with uptake of adult vaccines recommended for patients with IBD.Vaccine uptake rates, positivity of antibody to HAV and HBV, and knowledge of patients with IBD regarding vaccination were not sufficient. Proper educational information and recommendation from physicians could enhance awareness among patients with IBD about the need for vaccination and thereby improve vaccination rates.Trial registration number: NCT01984879.

Changes in prevalence and perception of complementary and alternative medicine use in Korean inflammatory bowel disease patients: results of an 8-year follow-up survey.

BACKGROUND/AIMS: The use of complementary and alternative medicine (CAM) is a global phenomenon, including inflammatory bowel disease (IBD) patients. We aimed to assess the change in prevalence and patterns of CAM use, and attitudes towards CAM over an 8-year time interval (2006 vs. 2014) among IBD patients in Korea. METHODS: A total of 221 IBD patients (CD=142, UC=79) were asked to complete a questionnaire regarding CAM at two time points: at enrollment (2006) and 8 years later (2014/2015). RESULTS: The proportion of patients ever using CAM increased significantly from 60.2% in 2006 to 79.6% in 2014 (P<0.001), while the proportion of current CAM users increased slightly (35.7% to 38.0%, P=0.635); 21.7% used CAM consistently at both time points. The proportion of patients who felt CAM was less effective (P<0.001) and more expensive (P=0.04) than conventional treatments increased over time. Also, the proportion among ever CAM users who perceived a positive effect from CAM significantly decreased in 2014 compared to 2006 (P=0.004). Higher education (adjusted odds ratio [aOR], 2.10), prior side effects to conventional therapies (aOR, 2.23), and prior use of corticosteroids (aOR, 2.51) were associated with CAM use. Interestingly, use of CAM before IBD diagnosis (aOR, 2.73) was significantly associated with consistent CAM use. CONCLUSIONS: Although the attitudes toward CAM have become less favorable, the majority of IBD patients have experienced CAM with an overall increase of current CAM users over time. Moreover, more than half of current CAM users used CAM consistently over time.

Colonic Pseudo-obstruction With Transition Zone: A Peculiar Eastern Severe Dysmotility.

BACKGROUND/AIMS: Previous studies from Korea have described chronic intestinal pseudo-obstruction (CIPO) patients with transition zone (TZ) in the colon. In this study, we evaluated the pathological characteristics and their association with long-term outcomes in Korean colonic pseudo-obstruction (CPO) patients with TZ. METHODS: We enrolled 39 CPO patients who were refractory to medical treatment and underwent colectomy between November 1989 and April 2016 (median age at symptoms onset: 45 [interquartile range, 29-57] years, males 46.2%). The TZ was defined as a colonic segment connecting a proximally dilated and distally non-dilated segment. Detailed pathologic analysis was performed. RESULTS: Among the 39 patients, 37 (94.9%) presented with TZ and 2 (5.1%) showed no definitive TZ. Median ganglion cell density in the TZ adjusted for the colonic circumference was significantly decreased compared to that in proximal dilated and distal non-dilated segments in TZ (+) patients (9.2 vs 254.3 and 150.5, P ＜ 0.001). Among the TZ (+) patients, 6 showed additional pathologic findings including eosinophilic ganglionitis (n = 2), ulcers with combined cytomegalovirus infection (n = 2), diffuse ischemic changes (n = 1), and heterotropic myenteric plexus (n = 1). During follow-up (median, 61 months), 32 (82.1%) TZ (+) patients recovered without symptom recurrence after surgery. The presence of pathological features other than hypoganglionosis was an independent predictor of symptom recurrence after surgery (P = 0.046). CONCLUSIONS: Hypoganglionosis can be identified in the TZ of most Korean CPO patients. Detection of other pathological features in addition to TZ-associated hypoganglionosis was associated with poor post-operative outcomes.

[Clinical Outcomes of Angiography and Transcatheter Arterial Embolization for Acute Gastrointestinal Bleeding: Analyses according to Bleeding Sites and Embolization Types].

Background/Aims: The clinical outcomes of angiography and transcatheter arterial embolization (TAE) for acute gastrointestinal bleeding (GIB) have not been completely assessed, especially according to bleeding sites. This study aimed to assess the efficacy of angiography and safety of TAE in acute GIB. Methods: This was a retrospective study evaluating the records of 321 patients with acute GIB who underwent angiography with or without TAE. Targeted TAE was conducted in 134 patients, in whom angiography showed bleeding sources. Prophylactic TAE was performed in 29 patients when the bleeding source was not detected but a specific vessel was strongly suspected by other examinations. The rate of technical success, clinical success, and complications were analyzed. Results: The detection rate of bleeding source via angiography was 50.8% (163/321), which was not different according to the bleeding sites. The detection rate was higher if the probable bleeding source had already been found by another investigation (59.7% vs. 35.8%, p<0.001). TAE sites were upper GIB in 67, mid GIB in 74, and lower GIB in 22. The technical success rate was 99.3% (133/134), and the clinical success rate was 63.0% (104/163). The prophylactic embolization group showed lower clinical success rate than the targeted embolization group (44.8% vs. 67.9%, p=0.06). The TAE-related complication rate was 12.9% (21/163). Ischemia and/or infarction was more common after TAE for mid and lower GIB than for upper GIB (15.6% vs. 3.0%, p=0.007). Conclusions: Angiography with or without TAE was an effective method for acute GIB. Targeted embolization should be performed if possible given that it has a higher clinical success rate.

Early anti-TNF/immunomodulator therapy is associated with better long-term clinical outcomes in Asian patients with Crohn's disease with poor prognostic factors.

Although early treatment of Crohn's disease (CD) patients with anti-tumor necrosis factor (TNF) agents or immunomodulators (IMs) may improve long-term outcomes, especially those with poor prognostic factors, their effectiveness in Asians remains unclear. In this study, Korean patients with CD naïve to both intestinal surgery and intestinal complications, and with at least two risk factors for progression (diagnosis at age <40 years, systemic corticosteroid treatment <3 months after diagnosis, and perianal fistula at diagnosis) were retrospectively analyzed. Patients were classified into those who started anti-TNFs, or IMs but not anti-TNFs, within 2 years of diagnosis, and those who started anti-TNFs and/or IMs later. Their probabilities of intestinal surgery and intestinal complications were compared. A total of 670 patients were enrolled, 79 in the early anti-TNF, 286 in the early IM, and 305 in the late treatment group. Kaplan-Meier analysis with the log-rank test showed that from starting anti-TNFs/IMs, times to intestinal surgery (P < 0.001), stricturing complications (P = 0.002), and penetrating complications (P < 0.001) were significantly longer in the early anti-TNF/IM groups than in the late treatment group. Multivariate Cox regression analysis showed that, from starting anti-TNFs/IMs, late anti-TNF/IM treatment was independently associated with higher risks of intestinal surgery (adjusted hazard ratio [aHR] 2.321, 95% confidence interval [CI] 1.503-3.584, P < 0.001), behavioral progression (aHR 2.001, 95% CI 1.449-2.763, P < 0.001), stricturing complications (aHR 1.736, 95% CI 1.209-2.493, P = 0.003), and penetrating complications (aHR 3.315, 95% CI 2.094-5.249, P < 0.001) than early treatment. In conclusion, treatment of Asian CD patients having poor prognostic factors with anti-TNFs/IMs within 2 years of diagnosis is associated with better clinical outcomes than later treatment.

Clinical correlations of infliximab trough levels and antibodies to infliximab in South Korean patients with Crohn's disease.

AIM: To investigate the clinical implications of infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATI) levels in Crohn's disease (CD) patients in Asian countries. METHODS: IFX-TL and ATI level were measured using prospectively collected samples obtained with informed consent from CD patients being treated at Asan Medical Center, South Korea. We analyzed the correlations between IFX-TLs/ATI levels and the clinical activity of CD (quiescent vs active disease) based on the CD activity index, C-reactive protein level, and physician's judgment of patients' clinical status at enrollment. The impact of concomitant immunomodulators was also investigated. RESULTS: This study enrolled 138 patients with CD (84 with quiescent and 54 with active disease). In patients with quiescent and active diseases, the median IFX-TLs were 1.423 µg/mL and 0.163 µg/mL, respectively (P < 0.001) and the median ATI levels were 8.064 AU/mL and 11.209 AU/mL, respectively (P < 0.001). In the ATI-negative and -positive groups, the median IFX-TLs were 1.415 µg/mL and 0.141 µg/mL, respectively (P < 0.001). In patients with and without concomitant immunomodulator use, there were no differences in IFX-TLs (0.632 µg/mL and 1.150 µg/mL, respectively; P = 0.274) or ATI levels (8.655 AU/mL and 9.017 AU/mL, respectively; P = 0.083). CONCLUSION: IFX-TL/ATI levels were well correlated with the clinical activity in South Korean CD patients. Our findings support the usefulness of IFX-TLs/ATI levels in treating CD patients receiving IFX in clinical practice.

Chronic intractable diarrhea caused by gastrointestinal mastocytosis.

As mast cells have been highlighted in the pathogenesis of diarrhea-predominant irritable bowel syndrome, a new term "mastocytic enterocolitis" was suggested by Jakate and colleagues to describe an increase in mucosal mast cells in patients with chronic intractable diarrhea and favorable response to treatment with antihistamines. Although it is not an established disease entity, two cases have been reported in the English medical literature. Here, for the first time in Asia, we report another case of chronic intractable diarrhea caused by gastrointestinal mastocytosis. The patient was a 70-year-old male with chronic intractable diarrhea for 3 months; the cause of the diarrhea remained obscure even after exhaustive evaluation. However, biopsy specimens from the jejunum were found to have increased mast cell infiltration, and the patient was successfully treated with antihistamines.

Multiple myeloma in a patient with acromegaly.

Acromegaly is a slowly progressing condition resulting from excess growth hormone (GH), generally caused by a GH-secreting pituitary adenoma. Cancer is the third most common cause of mortality in patients with acromegaly, and insulin-like growth factor 1 (IGF-1) is known to influence tumor formation by increasing cell proliferation and inhibiting apoptosis. Multiple myeloma (MM) is a plasma cell neoplasm, and previous studies have suggested the possible role of IGF-1 in its development of MM. However, no cases of acromegaly accompanied with MM have been reported in Asia to date. We here report the case of a 58-year-old woman with acromegaly accompanied with MM who presented with longstanding acromegalic manifestations resulting from a GH-secreting pituitary adenoma and also exhibited anemia, a reversed albumin/globulin ratio, and plasmacytosis on bone marrow examination. Because IGF-1 has been suggested to play an important role in the development and progression of MM, the patient promptly underwent surgical removal of the pituitary adenoma via a transsphenoidal approach. Since there is currently no consensus on therapeutic guidelines and suggested prognosis for MM with acromegaly, long-term follow-up of such cases is needed.