Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the IL-1β-induced mechanical allodynia. In the control group, application of GABA (100 µM) or muscimol (3 µM) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the IL-1β-treated rats. These results suggest that some large myelinated Aβ fibers gain access to the nociceptive system and elicit pain sensation via GABA(A) receptors under inflammatory pain conditions.
Animals ; Bicuculline ; Bumetanide ; Capsaicin ; gamma-Aminobutyric Acid ; Gramicidin ; Humans ; Hyperalgesia* ; Injections, Subcutaneous ; Interleukin-1beta ; Male ; Membranes ; Muscimol ; Myelin Sheath ; Neurons ; Nociceptors ; Rats* ; Rats, Sprague-Dawley ; Receptors, GABA-A ; Sensation

BACKGROUND/AIMS: Gastric pathology and Helicobacter pylori (H. pylori) infection among Asian patients with Crohn's disease (CD) are still unclear. We evaluated gastric histologic features and frequency of H. pylori infection in Korean patients with CD. METHODS: Among 492 patients with CD receiving upper gastrointestinal (GI) endoscopic evaluation in 19 Korean hospitals, we evaluated the endoscopic findings and gastric histopathologic features of 47 patients for our study. Histopathologic classification was performed using gastric biopsy tissues, and H. pylori infection was determined using the rapid urease test and histology. RESULTS: There were 36 men (76.6%), and the median age of patients at the time of upper GI endoscopy was 23.8 years (range, 14.2-60.5). For CD phenotype, ileocolonic disease was observed in 38 patients (80.9%), and non-stricturing, non-penetrating disease in 31 patients (66.0%). Twenty-eight patients (59.6%) complained of upper GI symptoms. Erosive gastritis was the most common gross gastric feature (66.0%). Histopathologically, H. pylori-negative chronic active gastritis (38.3%) was the most frequent finding. H. pylori testing was positive in 11 patients (23.4%), and gastric noncaseating granulomata were detected in 4 patients (8.5%). Gastric noncaseating granuloma showed a statistically significant association with perianal abscess/fistula (P=0.0496). CONCLUSIONS: H. pylori-negative chronic active gastritis appears to be frequent among Korean patients with CD. The frequency of H. pylori infection was comparable with previous studies. An association with perianal complications suggests a prognostic value for gastric noncaseating granuloma in patients with CD.
Asian Continental Ancestry Group ; Biopsy ; Classification ; Crohn Disease* ; Endoscopy ; Gastritis ; Granuloma ; Helicobacter pylori ; Humans ; Korea* ; Male ; Pathology ; Phenotype ; Stomach ; Urease

PURPOSE: Infliximab is currently used for the treatment of active Crohn's disease (CD). We aimed to assess the efficacy and safety of infliximab therapy and to determine the predictors of response in Korean patients with CD. MATERIALS AND METHODS: A total of 317 patients who received at least one infliximab infusion for active luminal CD (n=198) and fistulizing CD (n=86) or both (n=33) were reviewed retrospectively in 29 Korean referral centers. Clinical outcomes of induction and maintenance therapy with infliximab, predictors of response, and adverse events were evaluated. RESULTS: In patients with luminal CD, the rates of clinical response and remission at week 14 were 89.2% and 60.0%, respectively. Male gender and isolated colonic disease were associated with higher remission rates at week 14. In week-14 responders, the probabilities of sustained response and remission were 96.2% and 93.3% at week 30 and 88.0% and 77.0% at week 54, respectively. In patients with fistulizing CD, clinical response and remission were observed in 85.0% and 56.2% of patients, respectively, at week 14. In week-14 responders, the probabilities of sustained response and remission were 94.0% and 97.1%, respectively, at both week 30 and week 54. Thirty-nine patients (12.3%) experienced adverse events related to infliximab. Serious adverse events developed in 19 (6.0%) patients including seven cases of active pulmonary tuberculosis. CONCLUSION: Infliximab induction and maintenance therapy are effective and well tolerable in Korean patients with luminal and fistulizing CD. However, clinicians must be aware of the risk of rare yet critical adverse events.
Colonic Diseases ; Crohn Disease* ; Humans ; Infliximab* ; Male ; Phenobarbital ; Referral and Consultation ; Retrospective Studies ; Tuberculosis ; Tuberculosis, Pulmonary

BACKGROUND/AIMS: Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment. METHODS: This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated. RESULTS: The mean duration of follow-up for the 72 patients was 43.16+/-19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state. CONCLUSIONS: The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation.
Antiviral Agents/*therapeutic use ; Case-Control Studies ; Cohort Studies ; Colectomy/utilization ; Colitis, Ulcerative/complications/*drug therapy ; *Cytomegalovirus ; Cytomegalovirus Infections/complications/*drug therapy ; Ganciclovir/*therapeutic use ; Humans ; Longitudinal Studies ; Remission Induction ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome ; *Virus Activation

BACKGROUND/AIMS: The aim of this study was to analyze the actual application patterns of how Korean diagnostic guidelines for inflammatory bowel disease (IBD) were applied in clinical practice. METHODS: Questionnaires regarding guidelines for ulcerative colitis (UC), Crohn's disease (CD), intestinal Behcet's disease (BD) and intestinal tuberculosis (TB), were distributed during the 2011 Korean Association for the Study of Intestinal Disease annual conference, and e-mail survey was additionally conducted. Forty eight questionnaires were collected. RESULTS: Most of responders (79.2%) were working at secondary (> or =500 beds) or tertiary referral centers. For the necessity of guidelines, 93.8% of responders gave positive answers in UC; 95.8% in CD; 81.3% in BD; 91.7% in TB. Of the clinicians, 95.8%, 91.7%, 64.6%, 77.1% had read UC, CD, BD and TB guideline, and 87.0%, 93.2%, 90.3%, and 92.0% replied that diagnostic guidelines for UC, CD, BD and TB were helpful in practice, respectively. Practice patterns were changed in 39.1%, 33.2%, 41.9%, and 54.1% of responders by UC, CD, BD and TB guidelines, respectively. For the needs of update, 58.7% of responders answered 'yes' in UC, 54.5% in CD, 51.6% in BD and 48.7% in TB. There were differences between recommendations and practice patterns, including colonoscopy surveillance in UC, radiological examinations for small bowel in CD and for intestinal obstruction in UC, or biopsy method in UC, CD and TB, and diagnostic criteria in BD. CONCLUSIONS: Although most of responders perceived the Korean diagnostic guidelines for IBD, there were differences between recommendations of guidelines and actual practice patterns. Therefore, the publicity and revision of diagnostic guidelines are important to reconcile theory and practice.
Asian Continental Ancestry Group ; Behcet Syndrome/diagnosis ; Colitis, Ulcerative/diagnosis ; Colonoscopy ; Crohn Disease/diagnosis ; Humans ; Inflammatory Bowel Diseases/*diagnosis ; *Practice Guidelines as Topic ; Questionnaires ; Republic of Korea ; Tuberculosis, Gastrointestinal/diagnosis

Toremifene is an anti-estrogen which has been shown to be effective in the treatment of breast cancer, and is thought to be a less uterotrophic agent than tamoxifen. The risk assessment concerning endometrial cancer has been inconclusive because of its rare use up to the mid-1990s. We report a case of an adenosarcoma, which is a very rare type of uterine malignancy, after toremifene treatment for 5 years in a breast cancer patient. After 1 year of toremifene use, the patient had a benign Mullerian adenofibroma. After an additional 4 years of toremifene treatment, the endometrial polypoid lesion was transformed into a Mullerian adenosarcoma. Although toremifene is a promising anti-estrogenic agent in the treatment of breast cancer patients, clinicians should not neglect the possibility of a uterine malignancy.
Adenofibroma ; Adenosarcoma ; Breast ; Breast Neoplasms ; Endometrial Neoplasms ; Female ; Humans ; Risk Assessment ; Tamoxifen ; Toremifene

PURPOSE: Respiratory motion is a considerable inhibiting factor for precise treatment with stereotactic radiosurgery using the CyberKnife (CK). In this study, we developed a moving phantom to simulate three-dimensional breathing movement and investigated the distortion of dose profiles between the use of a moving phantom and a static phantom. MATERIALS AND METHODS: The phantom consisted of four pieces of polyethylene; two sheets of Gafchromic film were inserted for dosimetry. Treatment was planned to deliver 30 Gy to virtual tumors of 20, 30, 40, and 50 mm diameters using 104 beams and a single center mode. A specially designed robot produced three-dimensional motion in the right-left, anterior-posterior, and craniocaudal directions of 5, 10 and 20 mm, respectively. Using the optical density of the films as a function of dose, the dose profiles of both static and moving phantoms were measured. RESULTS: The prescribed isodose to cover the virtual tumors on the static phantom were 80% for 20 mm, 84% for 30 mm, 83% for 40 mm and 80% for 50 mm tumors. However, to compensate for the respiratory motion, the minimum isodose levels to cover the moving target were 70% for the 30~50 mm diameter tumors and 60% for a 20 mm tumor. For the 20 mm tumor, the gaps between the isodose curves for the static and moving phantoms were 3.2, 3.3, 3.5 and 1.1 mm for the cranial, caudal, right, and left direction, respectively. In the case of the 30 mm tumor, the gaps were 3.9, 4.2, 2.8, 0 mm, respectively. In the case of the 40 mm tumor, the gaps were 4.0, 4.8, 1.1, and 0 mm, respectively. In the case of the 50 mm diameter tumor, the gaps were 3.9, 3.9, 0 and 0 mm, respectively. CONCLUSION: For a tumor of a 20 mm diameter, the 80% isodose curve can be planned to cover the tumor; a 60% isodose curve will have to be chosen due to the tumor motion. The gap between these 80% and 60% curves is 5 mm. In tumors with diameters of 30, 40 and 50 mm, the whole tumor will be covered if an isodose curve of about 70% is selected, equivalent of placing a respiratory margin of below 5 mm. It was confirmed that during CK treatment for a moving tumor, the range of distortion produced by motion was less than the range of motion itself.
Polyethylene ; Radiosurgery* ; Range of Motion, Articular ; Respiration