Clinical outcomes and predictors of response for adalimumab in patients with moderately to severely active ulcerative colitis: a KASID prospective multicenter cohort study

Background/Aims@#This study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC). @*Methods@#A prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score. @*Results@#A total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P<0.05). In patients with lower endoscopic activity, higher body mass index, and higher serum albumin levels at baseline, the clinical response rate was higher at week 8. In patients with lower Mayo scores and C-reactive protein levels, clinical responses, and mucosal healing at week 8, the clinical response rate was higher at week 56. Serious adverse drug reactions were identified in 2.8% of patients. @*Conclusions@#ADA is effective and safe for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF-α therapy. The ADA drug level is associated with the efficacy of induction therapy. Patients with better short-term outcomes were predictive of those with an improved long-term response.

Long-term Outcomes after the Discontinuation of Anti-TumorNecrosis Factor-α Therapy in Patients with Inflammatory BowelDisease under Clinical Remission: A Korean Association for the Study of Intestinal Disease Multicenter Study

Background/Aims@#Our study aimed to evaluate the long-term outcomes and risk factors forrelapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established. @*Methods@#A retrospective multicenter cohort study was conducted involving patients with Crohn’s disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued firstline anti-TNF therapy after achieving clinical remission. @*Results@#A total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Coxanalysis revealed that discontinuation owing to the clinician’s decision was associated with lower risk of relapse (vs patient’s preference: hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab: HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing: HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient’s preference (n=6), and other factors (n=4). @*Conclusions@#More than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response.

Long-term Outcomes after the Discontinuation of Anti-TumorNecrosis Factor-α Therapy in Patients with Inflammatory BowelDisease under Clinical Remission: A Korean Association for the Study of Intestinal Disease Multicenter Study

Background/Aims@#Our study aimed to evaluate the long-term outcomes and risk factors forrelapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established. @*Methods@#A retrospective multicenter cohort study was conducted involving patients with Crohn’s disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued firstline anti-TNF therapy after achieving clinical remission. @*Results@#A total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Coxanalysis revealed that discontinuation owing to the clinician’s decision was associated with lower risk of relapse (vs patient’s preference: hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab: HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing: HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient’s preference (n=6), and other factors (n=4). @*Conclusions@#More than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response.

Recurrent Eosinophilic Pneumonia Associated with Mesalazine Suppository in a Patient with Ulcerative Colitis / 대한소화기학회지

Mesalazine suppositories are widely used to treat ulcerative colitis and have a guaranteed safety profile, but although rare, they can cause pulmonary toxicity. A 35-year-old woman with ulcerative colitis was diagnosed to have acute eosinophilic pneumonia after 29 days of oral mesalazine use and improved after mesalazine and corticosteroid were withdrawn. Reintroduction of mesalazine suppositories resulted in acute eosinophilic pneumonia recurrence after 28 days. Mesalazine re-administration (even via a different route) in patients with a history of mesalazine-induced eosinophilic pneumonia should be undertaken cautiously, because eosinophilic pneumonia may recurrence.

Hepatobiliary Manifestation of Inflammatory Bowel Disease / 대한소화기병학회잡지

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.

Hepatobiliary Manifestation of Inflammatory Bowel Disease / 대한소화기학회지

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.

Use of Novel Oral Anticoagulant to Treat Pulmonary Thromboembolism in Patient with Ulcerative Colitis Superinfected Cytomegalovirus Colitis / 대한소화기학회지

Crohn's disease and ulcerative colitis are the two major types of inflammatory bowel disease, and affect mainly the gastrointestinal tract but also have extraintestinal sequelae, such as arterial and venous thromboembolism. Thromboembolic complications, particularly pulmonary thromboembolism, can be life threatening and require prompt management with anticoagulants. Conventional vitamin K antagonists have been used for the treatment of thromboembolic complications, but the development of novel oral anticoagulants has shifted the paradigm. We report a case of a 42-year-old female with ulcerative colitis who experienced an acute flare-up due to cytomegalovirus superinfection with pulmonary thromboembolism. She was treated with oral mesalamine, intravenous steroid and ganciclovir and low-molecular-weight heparin, followed by rivaroxaban, a novel oral anticoagulant. Her symptoms resolved after treatment, and no recurrence was noted during a 6-month post-treatment follow-up.

Dysregulation of MicroRNA-196b-5p and MicroRNA-375 in Gastric Cancer

PURPOSE: Dysregulated microRNAs (miRNAs) can contribute to cancer development by leading to abnormal proliferation of cells, apoptosis, and differentiation. Although several miRNAs that are related to gastric cancer have been identified, the reported results have been inconsistent. The aim of this study was to determine miRNA expression profiles and validate miRNAs up- and down-regulated in gastric cancer. MATERIALS AND METHODS: We evaluated 34 primary gastric cancer tissues and paired adjacent nontumorous gastric tissues. Total RNA was extracted, and low-molecular-weight RNAs (<200 nucleotides) were isolated for further analysis. Two pairs of tissues were processed for GeneChip microarray analysis, and the identified up- and down-regulated miRNAs were validated by real-time quantitative polymerase chain reaction (qPCR). RESULTS: In the set of differentially expressed miRNAs, 5 were overexpressed by more than 2 fold, and 5 were reduced by 2 fold or less in gastric cancer tissues compared with normal gastric tissues. Four of these miRNAs (miR-196b-5p, miR-375, miR-483-5p, and miR-486-5p) were then validated by qPCR, and the relative expression levels of 2 miRNAs (miR-196b-5p and miR-375) were significantly different between cancer and normal tissues. CONCLUSIONS: Our results revealed that the expression of miR-196b-5p and miR-375 significantly correlates with gastric cancer. These miRNAs could therefore serve as diagnostic biomarkers of gastric cancer.

Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease

BACKGROUND/AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Unusual Treatment of Gastric Mucosa Associated Lymphoid Tissue Lymphoma Unresponsive to Helicobacter pylori Eradication

The connection between Helicobacter pylori and mucosa-associated lymphoid tissue (MALT) lymphoma is well established. H. pylori eradication is the initial treatment for MALT lymphoma. However, in H. pylori negative cases or unresponsive patients after successful eradication, radiation, systemic therapies, and surgical resection should be considered. Also local treatment modalities such as endoscopic mucosal resection (EMR) may be a therapeutic option in cases of low grade, localized MALT lymphoma. Herein, we report a case of a 53-year-old man who had a persistent endoscopic mass and tumor cells on histology for 5 months despite H. pylori eradication. Because of no early response to H. pylori eradication, the possibility of the presence of a high-grade lymphoma component, the proximal location of the tumor, and the exophytic nature of the tumor, we decided to perform EMR for complete resection. After EMR, the patient remained in complete remission throughout the 15-month follow up. In our case, endoscopic resection could lead to a more rapid complete remission. Therefore, we suggest that endoscopic resection may be a useful option for low-grade exophytic-type gastric MALT lymphoma treatment with no response to H. pylori eradication.

A Case of a Jejunal Ectopic Pancreas Presenting as Obscure Gastrointestinal Bleeding / 대한소화기학회지

A jejunal ectopic pancreas, where pancreatic tissue is found outside of the usual anatomical location, is a rare submucosal tumor that may cause obscure gastrointestinal (GI) bleeding. After initial negative endoscopic evaluation of the obscure GI bleeding, including colonoscopy and/or upper endoscopy, it is reasonable to proceed with further evaluation of the small bowel. Diagnostic options for the evaluation of the small bowel may include capsule endoscopy, push enteroscopy, or barium contrast small bowel studies. Here, we report a case of obscure GI bleeding caused by a jejunal ectopic pancreas, diagnosed through capsule endoscopy and barium contrast small bowel studies, which was treated successfully with single incision access laparoscopy.

A Case of a Colon Perforation Due to a Soft Rectal Foreign Body / 대한소화기내시경학회지

Numerous foreign bodies in the rectum have been reported in the literature. Their removal can be challenging depending on the size and shape of the objects and their anatomical location in the rectum. A 64-year-old man presented to the emergency department after inserting a sausage into his rectum. He had some rectal discomfort and lower abdominal pain. There were no signs of bowel perforation. We attempted to extract the sausage impacted in the recto-sigmoid junction by colonoscopy using a snare and grasping forceps but failed to extract the foreign body. Unfortunately, a colon perforation had occurred, and the sausage was eventually extracted by performing a colostomy at the recto-sigmoid junction with primary repair. We report this case of a soft rectal foreign body impacted in the recto-sigmoid colon complicated by a colon perforation with a literature review.

Strongyloidiasis of Gastric and Colonic Mucosa in a Patient with Monoclonal Gammopathy of Undetermined Significance: A Case Report

Here we report a case of Strongyloides stercoralis infection of the gastric and pancolonic mucosa in a 79-year-old female with a monoclonal gammopathy of undetermined significance. Endoscopic biopsies were performed in gastric antrum, cecum, distal ascending colon, and hepatic flexure of the colon. On microscopic examination, there were many adult worms, larvae and eggs in the gastric and colonic mucosa. Worms, larvae, and eggs were located in the crypts and within the lumen of the crypts. The body wall of the adult worm was composed of cuticle and a weak muscle layer. A routine stool examination failed to detect larvae or ova. Based on the histopathologic examination, these parasites were confirmed as S. stercoralis.

Strongyloidiasis of Gastric and Colonic Mucosa in a Patient with Monoclonal Gammopathy of Undetermined Significance: A Case Report

Here we report a case of Strongyloides stercoralis infection of the gastric and pancolonic mucosa in a 79-year-old female with a monoclonal gammopathy of undetermined significance. Endoscopic biopsies were performed in gastric antrum, cecum, distal ascending colon, and hepatic flexure of the colon. On microscopic examination, there were many adult worms, larvae and eggs in the gastric and colonic mucosa. Worms, larvae, and eggs were located in the crypts and within the lumen of the crypts. The body wall of the adult worm was composed of cuticle and a weak muscle layer. A routine stool examination failed to detect larvae or ova. Based on the histopathologic examination, these parasites were confirmed as S. stercoralis.

A Case of Huge Hepatic Recurrence of Low Risk Gastrointestinal Stromal Tumor / 대한내과학회지

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors that express c-kit. The majority of GISTs are located in the stomach and small intestine. The tumors are classified into very-low-risk, low-risk, intermediate-risk, and high-risk categories based on size and mitosis activity. The recurrence of low-risk GIST is extremely rare. We report a hepatic recurrence of a low-risk gastric GIST that had been removed completely 8 years earlier, and presented as a huge hepatic mass. Since recurrent GIST has a poor prognosis, regular long-term follow-up must be considered, although the primary GIST was low risk.

A Case of Strongyloides Stercoralis Concurrently Invading the Stomach and Colon / 대한소화기내시경학회지

Strongyloides stercoralis is a nematode that may involve any segment of the Gl tract or virtually every human organ because of its autoinfection cycle and hyperinfection. It may occur in either immunocompetent or immunocompromised individuals. A 72-year-old woman who had no notable medical history presented with chronic diarrhea and generalized edema and she revealed protein losing eneteropathy. She was diagnosed with Strongyloidiasis infection through EGD and a colonoscopic biopsy specimen at a time when there were rhabditiform larvae present. The patient was treated with albendazole 400 mg/day for three days. At the follow-up three months later, the endoscopic biopsy specimens revealed no evidence of Strongyloidiasis infection and her clinical symptoms had progressively improved. The present case represents a rare report of Strongyloidiasis in a immunocompetent patient diagnosed through EGD and the colonoscopic biopsy specimen concurrently. So, we report on this case along with a review of the relevant literature.

A Case of Spontaneous Hemorrhagic Cholecystitis without Gallstone / 대한소화기학회지

Hemorrhagic acalculous cholecystitis is an extremely rare but potentially fatal disease if detection is delayed. Its risk factors include critical illness, diabetes, malignant disease, uremia, and bleeding diathesis. This is the first case report in which hemorrhagic acalculous cholecystitis not accompanied by any risk factor. We herein present a case of hemorrhagic acalculous cholecystitis in a previously healthy patient who suffered from acute abdomen.

A Case of Gastrointestinal Stromal Tumor with Recurrent Hypoglycemia

Non-islet cell tumor induced hypoglycemia (NICTH) is attributable to overproduction of insulin-like growth factor-II (IGF-II) by solid tumors, and these tumors usually originate from mesenchymal or epithelial cells. Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor and most commonly find in the gastrointestinal tract. It is usually expresses the CD117 (stem cell factor receptor, c-kit) detected by immunohistochemistry. Hypoglycemia associated with GIST is very rare and this has not yet been reported in Korea. A 72-year-old man was hospitalized due to frequent episodes of confusion. It was observed that non-hyperinsulinemic hypoglycemia, an elevated serum IGF-II level and a huge liver mass. The histology of liver mass showed c-kit (CD117) positivity, which was consistent with GIST, but it was surgically unresectable. He was treated with imatinib mesylate. Although he recieved palliative treatment, he still experienced intermittent fasting hypoglycemia. After 2 months, the serum IGF-II level was even higher than before. We changed imatinib mesylate to sunitinib malate and performed radiotherapy on the liver mass. Although the change of the liver mass was not significant, he did not suffer from hypoglycemia for three months afterwards.

Sleep Disorders and Restless Legs Syndrome in Alcohol Dependence Patients / 수면정신생리

OBJECTIVES: We review the sleep problems of the alcohol dependence patients. Especially we are interested in the prevalence, the severity of symptoms, anxiety, depression, and sleep quality of restless legs syndrome (RLS) in the alcohol dependence patients. METHODS: We recruit 86 alcohol dependence patients who were admitted from October 6th, 2008 to October 17th, 2008. We interviewed each patient and evaluated sleep questionnaires such as the Sleep Disorder Questionnaire (SDQ), the Pittsburgh Sleep Quality Index (PSQI) and the International Restless Legs Syndrome Study Group (IRLSSG) rating scale. The presence of RLS and its severity were assessed using the IRLSSG diagnostic criteria and the IRLSSG severity scale, respectively. Depression and anxiety were evaluated by the Beck Depression Inventory (BDI) and the Beck anxiety inventory (BAI). RESULTS: Of all 86 patients, 59 patients have insomnia, 33 patients have RLS, 30 patients have Periodic limb movement disorder (PLMD), 29 patients have nightmare. RLS patients have more high score in the BAI (21.70+/-10.36 vs 14.67+/-11.98), and their sleep quality was poor in the PSQI (11.09+/-4.08 vs 7.92+/-3.91) than non-RLS patients. CONCLUSION: This study shows that alcohol dependence patients show many sleep problems such as insomnia and RLS. So we should notice that the sleep problems of alcohol dependence patients are important in clinical approach and treatment.

A Case of Intramural Duodenal Hematoma after the Use of the Endoscopic Epinephrine Injection Method for Duodenal Ulcer Bleeding in a Chronic Renal Failure Patient undergoing Maintenance Hemodialysis / 대한소화기내시경학회지

An intramural duodenal hematoma has been mostly reported as a consequence of trauma. It can also result from a hematological disorder, anticoagulant drug use and a post-therapeutic endoscopic procedure. Common symptoms of patients with an intramural duodenal hematoma are vomiting and abdominal pain. An intramural duodenal hematoma is rarely accompanied with pancreatitis and cholangitis due to intestinal obstruction. A diagnosis is made by esophagogastroduodenoscopy and the use of an abdominal CT scan. An intramural duodenal hematoma is mainly treated with conservative therapy but it may sometimes be treated with a surgical procedure. We report one case of an intramural duodenal hematoma after performing a therapeutic endoscopic procedure in a chronic renal failure patient undergoing maintenance hemodialysis.