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 α4β7 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.
21 April 2022 in Proceedings of the National Academy of Sciences
Significance: The peristaltic reflex elicits colonic migrating motor complexes (CMMCs) that are thought to be generated by enteric excitatory neurons stimulating smooth muscle cells (SMCs). We found that atropine did not block CMMCs and present a concept showing that poststimulus excitatory responses following nitrergic responses in interstitial cells of Cajal (ICC) are responsible for initiation of CMMCs. Ca 2+ transients in ICC are inhibited by nitrergic stimulation. After the inhibitory period, Ca 2+ transients are increased, activating currents that are conducted to SMCs and initiate propagated contractions. Poststimulus excitation generated by ICC explains the properties of CMMCs. This is important because current therapeutic manipulation of colonic transit is typically directed at strengthening cholinergic responses, whereas targeting nitrergic responses may be more suitable.
18 October 2017 in Journal of Gastrointestinal Surgery
Background: Postoperative minimal residual disease (MRD) detection using circulating-tumour DNA (ctDNA) requires a highly sensitive analysis platform. We have developed a tumour-informed, hybrid-capture ctDNA sequencing MRD assay. Methods: Personalised target-capture panels for ctDNA detection were designed using individual variants identified in tumour whole-exome sequencing of each patient. MRD status was determined using ultra-high-depth sequencing data of plasma cell-free DNA. The MRD positivity and its association with clinical outcome were analysed in Stage II or III colorectal cancer (CRC). Results: In 98 CRC patients, personalised panels for ctDNA sequencing were built from tumour data, including a median of 185 variants per patient. In silico simulation showed that increasing the number of target variants increases MRD detection sensitivity in low fractions (<0.01%). At postoperative 3-week, 21.4% of patients were positive for MRD by ctDNA. Postoperative positive MRD was strongly associated with poor disease-free survival (DFS) (adjusted hazard ratio 8.40, 95% confidence interval 3.49–20.2). Patients with a negative conversion of MRD after adjuvant therapy showed significantly better DFS (P < 0.001). Conclusion: Tumour-informed, hybrid-capture-based ctDNA assay monitoring a large number of patient-specific mutations is a sensitive strategy for MRD detection to predict recurrence in CRC.
10 July 2015 in International Journal of Colorectal Disease
Low anterior resection syndrome (LARS) is the distressful defecatory functional problem after sphincter‐saving surgery for rectal cancer. Although the symptoms of fecal urgency, frequency, and incontinence may develop in most of the patients after surgery, there is no definitive treatments for LARS. Multifactorial etiologies and various risk factors have been identified, but the reduction of storage capacity in the rectum is one of the main reasons for LARS. Anal sphincter muscle or nerve damage during rectoanal resection or anastomosis construction, and intersphincteric resection for low‐lying tumors or hand‐sewing anastomosis, are the absolute risk factors for LARS. Preoperative radiotherapy, postoperative complications, such as anastomosis leakage, or longer duration of stoma, are also risk factors. The severity of LARS can be confirmed using the LARS score questionnaire. The questionnaire has been translated to numerous language versions including Korean and have been validated. Diverse empirical treatments, such as loperamide, fiber, probiotics, or enema, have been tried, but the safety and efficacy have not been verified yet. The 5‐Hydroxytryptamine (5‐HT) receptor antagonist, ramosetron, used for diarrhea‐dominant irritable bowel syndrome, is one potential drug for relieving the symptoms of major LARS. A randomized‐controlled trial suggested the use of ramosetron could be safe and efficacious for patients who have major LARS after sphincter‐saving rectal cancer surgery. Novel techniques or drugs for relieving the symptoms of LARS should be developed more and further studies are necessary.