사회간접자본시설에 대한 민간투자법과 관련법률의 체계에 관한 연구(A study on the system of the act on PPI and other relevant laws)

노트 : 이 연구보고서의 내용은 국토연구원의 자체 연구물로서 정부의 정책이나 견해와는 상관없습니다. 특히 법원 등의 판단과 다를 수 있으므로 이 연구보고서의 내용을 신뢰하였기 때문에 발생하였다고 주장하는 어떠한 손해나 불편에 대하여 책임이 없습니다

Single-cell transcriptomics reveals multi-step adaptations to endocrine therapy

Resistant tumours are thought to arise from the action of Darwinian selection on genetically heterogenous cancer cell populations. However, simple clonal selection is inadequate to describe the late relapses often characterising luminal breast cancers treated with endocrine therapy (ET), suggesting a more complex interplay between genetic and non-genetic factors. Here, we dissect the contributions of clonal genetic diversity and transcriptional plasticity during the early and late phases of ET at single-cell resolution. Using single-cell RNA-sequencing and imaging we disentangle the transcriptional variability of plastic cells and define a rare subpopulation of pre-adapted (PA) cells which undergoes further transcriptomic reprogramming and copy number changes to acquire full resistance. We find evidence for sub-clonal expression of a PA signature in primary tumours and for dominant expression in clustered circulating tumour cells. We propose a multi-step model for ET resistance development and advocate the use of stage-specific biomarkers.ope

How Do I Manage Post-Polypectomy Bleeding?

Colonoscopic polypectomy is an effective method for prevention of colorectal cancer and has become one of the most common procedures worldwide. Most colorectal polyps can be removed safely by various polypectomy techniques; however, serious complications can occur. Postpolypectomy bleeding is the most common complication of colonoscopic polypectomy, accounting for 0.3% to 6.1% of polypectomy. This issue summarizes various endoscopic techniques to treat postpolypectomy bleeding.ope

Colorectal stenting: an advanced approach to malignant colorectal obstruction.

Some colorectal cancer (CRC) patients present symptoms of bowel obstruction, which is considered a surgical emergency. Because of poor medical condition and high incidence of post-surgical complications, there has been increasing use of self-expanding metal stents (SEMS) for the purpose of palliation or as a bridge to surgery with some benefits, including shorter hospital stays, lower rates of adverse events, and one-stage surgery. However, with increasing survival of CRC patients, there have been controversial data on clinical outcomes and complications, compared between SEMS use and surgery for treatment of malignant bowel obstruction. We review recent clinical data on clinical outcomes of SEMS use compared to surgery, including complications.ope

Clinical Practice of Surveillance Colonoscopy according to the Classification of Colorectal Intraepithelial Neoplasia in Korea: High-grade Dysplasia/Carcinoma In Situ Versus Intramucosal Carcinoma

Background/Aims : Recent guidelines strongly recommend that the interval of surveillance colonoscopy be determined according to the risk stratification obtained at index colonoscopy. However, because of the differences in perception of the classification of colorectal intraepithelial neoplasia between Asian and Western countries, there is some confusion about surveillance colonoscopy. The aim of the present study was to evaluate the clinicopathological characteristics and the interval of surveillance colonoscopy between patients with high-grade dysplasia/carcinoma in situ and those with intramucosal carcinoma. Methods : From January 2003 to June 2010, 727 patients were included from 8 tertiary centers. Four hundred fifteen patients (57.1%) had high-grade dysplasia/carcinoma in situ (group A), and 312 (43.9%) had intramucosal carcinoma (group B). Clinicopathological data were reviewed retrospectively. Results : Group A had a significantly more frequent family history of colorectal cancer (3.1% vs. 0.6%, P<0.001), smaller polyp size (12 mm vs. 15 mm, P=0.001), and more proximal location (31.1% vs. 21.8%, P=0.005) than did group B. Among 727 patients, surveillance colonoscopy was performed within 6 months in 55.8% of patients and within 12 months in 77.8%. Group B had a significantly shorter interval of surveillance colonoscopy than did group A (P<0.001). There was no difference in detection of advanced neoplasia at surveillance colonoscopy between the 2 groups (6.6% vs. 5.4%, P=0.638). Conclusions : The recommended interval of surveillance colonoscopy is not followed in Korea. More education about post-polypectomy surveillance guidelines is required.ope

대장암 검진 권고안

Colorectal cancer is the third most common cancer in Korea; it is the second most common cancer in men and the third most common in women. The incidence rate in Korea has continuously increased since 1999 when the National Cancer Registry statistics began. Currently; there are several screening modalities; that have been recommended by expert societies, including fecal occult blood test, colonoscopy, computed tomographic colonography The annual fecal immunochemical test (FIT) has been used in adults aged 50 and older as part of the National Cancer Screening Program in Korea since 2004. Although several study results from regional or national colorectal cancer screening programs in other countries have been reported, the National Cancer Screening Program in Korea has not yet been evaluated with evidence-based methods. Herein report the consensus statements on the National Screening Guideline for colorectal cancer developed by a multi-society expert committee in Korea, as follows: 1) We recommend annual or biennial FIT for screening for colorectal cancer in asymptomatic adults, beginning at 45 years of age and continuing until 80 years (recommendation B). 2) There is no evidence for the risks or benefits of FIT in adults older than 80 years (recommendation I). 3) Selective use of colonoscopy for colorectal cancer screening is recommended, taking into consideration individual preference and the risk of colorectal cancer (recommendation C). 4) There is no evidence for the risks or benefits of double-contrast barium enema for colorectal cancer screening in asymptomatic adults (recommendation I). 5) There is no evidence for the risks or benefits of computed tomographic colonography for colorectal cancer screening in asymptomatic adults (recommendation I).ope

Three-year colonoscopy surveillance after polypectomy in Korea: a Korean Association for the Study of Intestinal Diseases (KASID) multicenter prospective study

Background/Aims: Colonoscopic surveillance is currently recommended after polypectomy owing to the risk of newly developed colonic neoplasia. However, few studies have investigated colonoscopy surveillance in Asia. This multicenter and prospective study was undertaken to assess the incidence of advanced adenoma based on baseline adenoma findings at 3 years after colonoscopic polypectomy. Methods: A total of 1,323 patients undergoing colonoscopic polypectomy were prospectively assigned to 3-year colonoscopy surveillance at 11 tertiary endoscopic centers. Relative risks for advanced adenoma after 3 years were calculated according to baseline adenoma characteristics. Results: Among 1,323 patients enrolled, 387 patients (29.3%) were followed up, and the mean follow-up interval was 31.0±9.8 months. The percentage of patients with advanced adenoma on baseline colonoscopy was higher in the surveillance group compared to the non-surveillance group (34.4% vs. 25.7%). Advanced adenoma recurrence was observed in 17 patients (4.4%) at follow-up. The risk of advanced adenoma recurrence was 2 times greater in patients with baseline advanced adenoma than in those with baseline non-advanced adenoma, though the difference was not statistically significant (6.8% [9/133] vs. 3.1% [8/254], P=0.09). Advanced adenoma recurrence was observed only in males and in subjects aged ≥50 years. In contrast, adenoma recurrence was observed in 187 patients (48.3%) at follow-up. Male sex, older age (≥50 years), and multiple adenomas (≥3) at baseline were independent risk factors for adenoma recurrence. Conclusions: A colonoscopy surveillance interval of 3 years in patients with baseline advanced adenoma can be considered appropriate.ope

크론병으로 인한 십이지장-대장 누공의 Endoloop과 Hemoclip을 이용한 수술 전 내시경적 결찰: 증례보고

Duodeno-colonic fistula is an enterocolonic fistula that occurs as a complication of Crohn's disease. Symptoms of duodeno-colonic fistula are similar to those of Crohn's disease, such as weight loss and diarrhea. The treatment of choice is surgery, although medical treatment may also be considered. However, surgery is recommended when all available medical therapies have been ineffective. In this case, we report a secondary duodeno-colonic fistula due to Crohn's disease that was temporarily managed by an endoscopic procedure with a detached endoloop and hemoclips as a bridging therapy to final surgical repair.ope

An unconventional KITENIN/ErbB4-mediated downstream signal of EGF upregulates c-Jun and the invasiveness of colorectal cancer cells

PURPOSE: EGF-stimulated signaling via EGF receptor (EGFR) is important in colorectal tumorigenesis and drug targeting. However, anti-EGFR therapy is not effective in a subset of patients with colorectal cancer, suggesting that unidentified EGF-stimulated pathways might play roles in colorectal cancer. Previously, we identified KAI1 C-terminal interacting tetraspanin (KITENIN) as a metastasis-enhancing gene and found it to be highly expressed in sporadic colorectal cancer tissues. We recently found that EGF further increases KITENIN-induced elevated AP-1 activity. Here we attempted to clarify this novel EGF-stimulated molecular pathway and its roles in colorectal cancer. EXPERIMENTAL DESIGN: We analyzed how EGF modulates the downstream signaling pathway of oncogenic KITENIN in colorectal cancer cells. Biological alterations following EGF treatment were identified in KITENIN-overexpressed colorectal cancer cells with or without alteration of EGFR activity. RESULTS: We identified the KITENIN/ErbB4-Dvl2-c-Jun axis as a novel downstream signal of EGF that is switched on under elevated KITENIN conditions in an EGFR-independent manner. This unconventional EGF signal upregulates c-Jun and enhances invasion and anchorage-independent growth of colorectal cancer cells. In addition, tumor tissues from metastatic patients with colorectal cancer who showed initial poor responses to cetuximab/chemotherapy expressed higher levels of KITENIN than did responders to therapy. CONCLUSIONS: Our results highlight the role of an EGFR-independent EGF signal in mediating the invasiveness and tumorigenesis of colorectal cancer cells. This unconventional pathway might be related to the limited clinical efficacy of anti-EGFR agents in a subset of patients with colorectal cancer.ope

Effects of metformin on colorectal cancer stem cells depend on alterations in glutamine metabolism.

Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells and showed a prominent decrease after metformin treatment in HT29 cells. In glutamine-depleted medium, but not in low-glucose medium, SW620 cells became sensitive to the CSC-suppressing effect of metformin. A combination of metformin and glutaminase C inhibitor (compound 968) suppressed CSCs in SW620 cells and enhanced that effect in HT29 cells. SW620 cells showed higher expression of glutaminase 1 and glutamine transporter (ASCT2) than HT29 cells, especially ASCT2 in CSCs. Knockdown of glutaminase 1, ASCT2, and c-Myc induced significant CSC-suppression and enhanced CSC-suppressing effect of metformin and compound 968. In xenografts and human cancer organoids, combined treatment with metformin and compound 968 showed the same results as those shown in vitro. In conclusion, the effect of metformin on CSCs varies depending on the AMPK-mTOR and glutamine metabolism. The inhibition of glutamine pathway could enhance the CSC-suppressing effect of metformin, overcoming metformin resistance.ope