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Inflammatory bowel disease (IBD) has become more common in Asia over the past few decades. The rate of increase in prevalence of the disease varies greatly in Asia, with several countries in East Asia experiencing a more than doubled increase in IBD prevalence over the past decade. Historically, ulcerative colitis (UC) is more common than Crohn's disease (CD) in Asia. However, a reverse trend is beginning to appear in more developed countries in Asia such as Japan, Korea, and Hong Kong. While Asian IBD patients share many similarities with their Western counterparts, there are important differences with significant clinical implications. In Asia, there are more men with CD, more ileo-colonic involvement in CD, less familial aggregation, fewer extra-intestinal manifestations and worse clinical outcomes for older-onset patients with UC. These differences are likely related to the different genetic makeup and environmental exposures in different regions. Evaluation of the differences and rates in epidemiologic trends may help researchers and clinicians estimate disease burden and understand the reasons behind these differences, which may hold the key to unravel the etiology of IBD.
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For the control of Crohn's disease (CD) a thorough assessment of the small intestine is essential; several modalities may be utilized, with cross-sectional imaging being important. Magnetic resonance (MR) enterography, i.e., MRE is recommended as a modality with the highest accuracy for CD lesions. MRE and MR enteroclysis are the two methods performed following distension of the small intestine. MRE has sensitivity and specificity comparable to computed tomography enterography (CTE); although images obtained using MRE are less clear compared with CTE, MRE does not expose the patient to radiation and is superior for soft-tissue contrast. Furthermore, it can assess not only static but also dynamic and functional imaging and reveals signs of CD, such as abscess, comb sign, fat edema, fistula, lymph node enhancement, less motility, mucosal lesions, stricture, and wall enhancement. Several indices of inflammatory changes and intestinal damage have been proposed for objective evaluation. Recently, diffusion-weighted imaging has been proposed, which does not need bowel preparation and contrast enhancement. Comprehension of the characteristics of MRE and other modalities is important for better management of CD.
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The gastrointestinal (GI) tract is colonized by a dense community of commensal microorganisms referred to as the gut microbiota. The gut microbiota and the host have co-evolved, and they engage in a myriad of immunogenic and metabolic interactions. The gut microbiota contributes to the maintenance of host health. However, when healthy microbial structure is perturbed, a condition termed dysbiosis, the altered gut microbiota can trigger the development of various GI diseases including inflammatory bowel disease, colon cancer, celiac disease, and irritable bowel syndrome. There is a growing body of evidence suggesting that multiple intrinsic and extrinsic factors, such as genetic variations, diet, stress, and medication, can dramatically affect the balance of the gut microbiota. Therefore, these factors regulate the development and progression of GI diseases by inducing dysbiosis. Herein, we will review the recent advances in the field, focusing on the mechanisms through which intrinsic and extrinsic factors induce dysbiosis and the role a dysbiotic microbiota plays in the pathogenesis of GI diseases.
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Anti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines.
This cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines.
Thirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (
Exposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion.
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Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy.
Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB.
The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2–36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients.
Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB.
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This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD).
Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220–450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8–26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored.
Mean adalimumab serum concentrations during the induction phase were 13.9–18.1 µg/mL (160/80 mg group) and 7.5−9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups.
Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported.
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Rectal neuroendocrine tumors (NETs) are among the most common of gastrointestinal NETs. Due to recent advances in endoscopy, various methods of complete endoscopic resection have been introduced for small (≤10 mm) rectal NETs. However, there is a debate about the optimal treatment for rectal NETs. In our study, we aimed to evaluate the efficacy and feasibility of endoscopic resection using pneumoband and elastic band (ER-BL) for rectal NETs smaller than 10 mm in diameter.
A total of 55 patients who were diagnosed with rectal NET from January 2004 to December 2011 at Gil Medical Center were analyzed retrospectively. Sixteen patients underwent ER-BL. For comparison, 39 patients underwent conventional endoscopic mucosal resection (EMR).
There was a markedly lower deep margin positive rate for ER-BL than for conventional EMR (6% [1/16] vs. 46% [18/39],
ER-BL is an effective endoscopic treatment with regards to deep margin resection for rectal NET smaller than 10 mm.
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The aim of this study was to evaluate the prevalence of colorectal neoplasia in subjects with fundic gland polyps (FGPs) and the relationship between FGPs and colorectal neoplasia in Korea.
We analyzed 128 consecutive patients with FPGs who underwent colonoscopy between January 2009 and December 2013. For each case, age- (±5 years) and sex-matched controls were identified from among patients with hyperplastic polyps, gastric neoplasms, and healthy controls. Clinical characteristics were reviewed from medical records, colonoscopic findings, pathologic findings, and computed tomography images. The outcome was evaluated by comparison of advanced colonic neoplasia detection rates.
Of the 128 patients, seven (5.1%) had colon cancers and seven (5.1%) had advanced adenomas. A case-control study revealed that the odds of detecting a colorectal cancer was 3.8 times greater in patients with FGPs than in the age- and sex-matched healthy controls (odds ratio [OR], 3.80; 95% confidence interval [CI], 1.09–13.24;
The yield of colonoscopy in colorectal cancer patients with FGPs was substantially higher than that in average-risk subjects. Colonoscopy verification is warranted in patients with FGPs, especially in those 50 years of age or older.
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To prevent the transmission of pathogens by endoscopes, following established reprocessing guidelines is critical. An ideal reprocessing step is simple, fast, and inexpensive. Here, we evaluated and compared the efficacy and safety of two disinfectants, a tertiary amine compound (TAC) and ortho-phthalaldehyde (OPA).
A total of 100 colonoscopes were randomly reprocessed using two same automated endoscope reprocessors, according to disinfectant. The exposure time was 10 minutes for 0.55% OPA (Cidex® OPA, Johnson & Johnson) and 5 minutes for 4% TAC (Sencron2®, Bab Gencel Pharma & Chemical Ind. Co.). Three culture samples were obtained from each colonoscope after reprocessing.
A total of nine samples were positive among the 300 culture samples. The positive culture rate was not statistically different between the two groups (4% for OPA and 2% for TAC,
TAC was non-inferior in terms of reprocessing efficacy to OPA and was safe to use. Therefore, TAC seems to be a good alternative disinfectant with a relatively short exposure time and is also less expensive than OPA.
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Tumor necrosis factor-α inhibitors are now considered as standard therapy for patients with severe inflammatory bowel disease who do not respond to corticosteroids, but they carry a definite risk of reactivation of tuberculosis. We present a case in which a patient with inflammatory bowel disease developed a de novo tuberculosis infection after the start of anti-tumor necrosis factor-α treatment despite showing negative results in tuberculosis screening. Although there are many case reports of pleural, lymph nodal and disseminated tuberculosis following infliximab therapy, we present the first case report of rectal tuberculosis following infliximab therapy.
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Acute cytomegalovirus (CMV) infection occurs commonly in immunocompromised and immunocompetent patients, but is usually asymptomatic in the latter. Vascular events associated with acute CMV infection have been described, but are rare. Hence, such events are rarely reported in the literature. We report a case of pulmonary embolism secondary to acute CMV colitis in an immunocompetent 78-year-old man. The patient presented with fever and diarrhea. Colonic ulcers were diagnosed based on colonoscopy findings, and CMV was the proven etiology on pathological examination. The patient subsequently experienced acute respiratory failure. Pulmonary embolism was diagnosed based on the chest radiography and computed tomography findings. A diagnosis of acute CMV colitis complicated by pulmonary embolism was made. The patient was successfully treated with intravenous administration of unfractionated heparin and intravenous ganciclovir.
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Micronutrient deficiencies in Crohn's disease (CD) patients are not uncommon and usually result in a combination of reduced dietary intake, disease-related malabsorption, and a catabolic state. Decreased serum thiamine levels are often reported in patients with CD. Wernicke's encephalopathy (WE) is a severe form of thiamine deficiency that can cause serious neurologic complications. Although WE is known to occur frequently in alcoholics, a number of non-alcoholic causes have also been reported. Here, we report two cases of non-alcoholic WE that developed in two severely malnourished CD patients who were supported by prolonged total parenteral nutrition without thiamine supplementation. These patients complained of sudden-onset ophthalmopathy, cerebellar dysfunction, and confusion. Magnetic resonance imaging allowed definitive diagnosis for WE despite poor sensitivity. The intravenous administration of thiamine alleviated the symptoms of WE dramatically. We emphasize the importance of thiamine supplementation for malnourished patients even if they are not alcoholics, especially in those with CD.
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