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BACKGROUND: Circulating tumour DNA (ctDNA) has been spotlighted as an attractive biomarker because of its easy accessibility and real-time representation of tumour genetic profile. However, the clinical utility of longitudinal ctDNA monitoring has not been clearly defined. METHODS: Serial blood samples were obtained from metastatic colorectal cancer patients undergoing first-line chemotherapy. ctDNA was sequenced using a targeted next-generation sequencing platform which included 106 genes. Changes in ctDNA profile and treatment outcome were comprehensively analysed. RESULTS: A total of 272 samples from 62 patients were analysed. In all, 90.3% of patients had detectable ctDNA mutation before treatment. ctDNA clearance after chemotherapy was associated with longer progression-free survival which was independent of radiological response (adjusted hazard ratio 0.22, 95% confidence interval 0.10–0.46). Longitudinal monitoring was able to detect ctDNA progression which preceded radiological progressive disease (PD) in 58.1% (median 3.3 months). Diverse resistant mutations (34.9%) and gene amplification (7.0%) at the time of PD were discovered. For 16.3% of the PD patients, the newly identified mutations could be potential candidates of targeted therapy or clinical trial. CONCLUSION: ctDNA profile provided a more accurate landscape of tumour and dynamic changes compared to radiological evaluation. Longitudinal ctDNA monitoring may improve personalised treatment decision-making.

Lymphatic invasion, vascular invasion, and perineural invasion are prognostic factors for colon cancer. However, the prognostic significance of those factors according to the location of permeation (intramural and extramural invasion) in stage II colon cancer is still unclear.This study aims to clarify whether the location of lymphatic invasion, vascular invasion, and perineural invasion could affect survival of stage II colon cancer patients.This was a retrospective cohort study.This study took place at a university teaching hospital.A total of 1130 patients with stage II colon cancers who underwent radical surgery at the Seoul National University Hospital between July 2003 and December 2015 were included.Patients were classified according to the location of lymphatic invasion, vascular invasion, and perineural invasion. Survival outcomes were compared among those without invasion, and those with intramural and extramural invasion. Primary end point is overall survival and secondary end point is disease free survival.Disease-free survival and overall survival of patients with extramural invasion were worse than those of patients without invasion and those with intramural invasion. Multivariate analysis for survival outcomes confirmed that extramural invasion were significant independent prognostic factors. However, both disease free survival and overall survival were not significantly different between patients without invasion and those with intramural invasion.This study was limited by its retrospective design.Extramural invasion was associated with worse prognosis in stage II colon cancer, but intramural invasion was not. Therefore, pathologic reports about the location of lymphatic invasion, vascular invasion, and perineural invasion might be helpful for predicting prognosis and for determining the need of adjuvant chemotherapy in stage II colon cancers. See Video Abstract at http://links.lww.com/DCR/B939.

BACKGROUND: Systemic inflammation is associated with survival outcomes in colon cancer. However, it is not well-known which systemic inflammatory marker is a powerful prognostic marker in patients with colon cancer. METHODS: A total of 4535 colon cancer patients were included in this study. We developed a novel prognostic index using a robust combination of seven systemic inflammation-associated blood features of the discovery set. The predictability and generality of the novel prognostic index were evaluated in the discovery, validation and replication sets. RESULTS: Among all combinations, the combination of albumin and monocyte count was the best candidate expression. The final formula of the proposed novel index is named the Prognostic Immune and Nutritional Index (PINI). The concordance index of PINI for overall and progression-free survival was the highest in the discovery, validation and replication sets compared to existing prognostic inflammatory markers. PINI was found to be a significant independent prognostic factor for both overall and progression-free survival. CONCLUSIONS: PINI is a novel prognostic index that has improved discriminatory power in colon cancer patients and appears to be superior to existing prognostic inflammatory markers. PINI can be utilised for decision-making regarding personalised treatment as the complement of the TNM staging system.

Prognostic role of tumor mutation burden (TMB) stratified by microsatellite instability (MSI) status.

Purpose:Recent sequencing studies revealed that a subset of colorectal cancer harbors a significantly higher number of somatic mutations. These hypermutated tumors show distinct clinicopathologic features. However, the prognostic impact of the hypermutated tumors is not clearly established.Experimental Design:We analyzed tumor mutation burden (TMB) from targeted next-generation sequencing data of 40 major genes in 516 patients with colorectal cancer. TMB was defined as total number of nonsynonymous mutations per tumor. Cutoff value for TMB-high was chosen by which best discriminated relapse-free survival (RFS) using the Contal and O'Quigley method.Results:In the TCGA data, mutation count of the selected 40 genes reflected the whole exome mutation burden (Pearson correlation = 0.873, P < 0.001). In our patient cohort, 8 or more mutations in the 40 genes was defined as TMB-high, which best discriminated RFS. A total of 55 patients (10.7%) had TMB-high. TMB-high tumors were more frequently found in a proximal location (63.6%) and had a higher proportion of N0 disease (30.9%) and MSI-H (49.1%) compared with TMB-low. Most importantly, TMB-high was associated with better 5-year RFS compared with TMB-low (96.3% vs. 79.8%, P = 0.005). Although there was significant overlap between TMB-high and MSI-H, MSI-H status was not significantly associated with RFS. Multivariate analysis revealed TMB-high as an independent positive prognostic factor for RFS [adjusted HR, 0.16 (95% confidence interval, 0.04–0.66), P = 0.011].Conclusions:TMB-high is associated with better prognosis in patients with colorectal cancer treated with curative surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy.

Purpose:Despite the well-known prognostic value of the tumor–immune microenvironment (TIME) in colorectal cancers, objective and readily applicable methods for quantifying tumor-infiltrating lymphocytes (TIL) and the tumor–stroma ratio (TSR) are not yet available.Experimental Design:We established an open-source software-based analytic pipeline for quantifying TILs and the TSR from whole-slide images obtained after CD3 and CD8 IHC staining. Using a random forest classifier, the method separately quantified intraepithelial TILs (iTIL) and stromal TILs (sTIL). We applied this method to discovery and validation cohorts of 578 and 283 stage III or high-risk stage II colorectal cancers patients, respectively, who were subjected to curative surgical resection and oxlaliplatin-based adjuvant chemotherapy.Results:Automatic quantification of iTILs and sTILs showed a moderate concordance with that obtained after visual inspection by a pathologist. The K-means–based consensus clustering of 197 TIME parameters that showed robustness against interobserver variations caused colorectal cancers to be grouped into five distinctive subgroups, reminiscent of those for consensus molecular subtypes (CMS1-4 and mixed/intermediate group). In accordance with the original CMS report, the CMS4-like subgroup (cluster 4) was significantly associated with a worse 5-year relapse-free survival and proved to be an independent prognostic factor. The clinicopathologic and prognostic features of the TIME subgroups have been validated in an independent validation cohort.Conclusions:Machine-learning–based image analysis can be useful for extracting quantitative information about the TIME, using whole-slide histopathologic images. This information can classify colorectal cancers into clinicopathologically relevant subgroups without performing a molecular analysis of the tumors.

Supplementary data

Tumor mutation burden in MSI-H patients

Circulating tumor DNA (ctDNA) may reveal dynamic tumor status during therapy. We conducted serial ctDNA analysis to investigate potential association with clinical outcome in metastatic colorectal cancer (mCRC) patients receiving chemotherapy. Tissue KRAS/NRAS wild-type mCRC patients were enrolled and treated with first-line cetuximab-containing chemotherapy. ctDNA isolated from plasma were analyzed by next generation sequencing (NGS) with 16 targeted gene panel. Among 93 patients, 84 (90.3%) had at least 1 somatic mutation in baseline ctDNA samples (average 2.74). Five patients with KRAS or NRAS hotspot mutation in the ctDNA showed significantly worse progression-free survival (PFS) (p = 0.029). Changes in average variant allele frequency (VAF) in ctDNA showed significant correlation with tumor size change at the time of first response evaluation (p = 0.020) and progressive disease (PD) (p = 0.042). Patients whose average VAF decreased below cutoff (p p = 0.018). At the time of PD, 54 new mutations including KRAS and MAP2K1 emerged in ctDNA. ctDNA sequencing can provide mutation profile that could better reflect tumor mutation status and predict treatment outcome.

Summary Background Laparoscopic surgery has been widely used for rectal cancer; however, its long-term outcomes remain controversial. This study aimed to assess the long-term oncological safety of laparoscopic surgery for rectal cancer using 10-year follow-up data of the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial. Methods The COREAN trial is a, open-label, non-inferiority, randomised controlled trial. Eligible participants were aged 18–80 years, had cT3N0–2M0 middle or low rectal cancer with lesions located within 9 cm of the anal verge, and had been treated with preoperative chemoradiotherapy. Patients were randomly assigned (1:1) to open or laparoscopic surgery with a computer-generated random allocation sequence with a random permuted block design. Neither patients nor clinicians were masked to treatment assignment. Open or laparoscopic total mesorectal excision was done 6–8 weeks after the administration of preoperative concurrent chemoradiotherapy (fluoropyrimidines alone, doublet therapy, or triplet therapy) at a dose of 50·5 Gy over 5·5 weeks. Postoperative adjuvant chemotherapy was administered for 4 months. The primary endpoint of 3-year disease-free survival was published previously. Here, we report 10-year overall survival, disease-free survival, and local recurrence. Analyses were done in the modified intention-to-treat population of all participants who were randomly assigned and provided follow-up data. This study is registered with ClinicalTrials.gov, NCT00470951. Findings Of the 340 patients enrolled in the COREAN trial between April 4, 2006, and Aug 26, 2009 (170 patients in each group), two patients in the laparoscopic surgery group moved abroad and were lost to follow-up, so were not included in this 10-year analysis. The median duration of follow-up was 143 months (IQR 122–156). No differences were observed in 10-year overall survival (74·1% [95% CI 66·8–80·0] in the open surgery group vs 76·8% [69·6–82·5] in the laparoscopic surgery group; p=0·44), 10-year disease-free survival (59·3% [51·1–66·5] vs 64·3% [56·0–71·5]; p=0·20), or 10-year local recurrence (8·9% [5·2–15·0] vs 3·4% [1·4–7·9]; p=0·050) between the open surgery and laparoscopic surgery groups at 10 years after surgery. The stratified hazard ratios, adjusted for ypT and ypN classification and tumour regression grade, for open surgery versus laparoscopic surgery were 0·94 (95% CI 0·63–1·43) for overall survival, 1·05 (0·74–1·49) for disease-free survival, and 2·22 (0·78–6·34) for local recurrence. Interpretation The 10-year follow-up of the COREAN trial confirms the long-term oncological safety of laparoscopic surgery in patients with rectal cancer treated with preoperative chemoradiotherapy. Similar to open surgery, laparoscopic surgery does not compromise long-term survival outcomes in rectal cancer when performed by well trained surgeons. Funding National Cancer Center, Goyang, South Korea.

Exposure to microgravity affects human physiology in various ways, and astronauts frequently report skin-related problems. Skin rash and irritation are frequent complaints during space missions, and skin thinning has also been reported after returning to Earth. However, spaceflight missions for studying the physiological changes in microgravity are impractical. Thus, we used a previously developed 3D clinostat to simulate a microgravity environment and investigate whether physiological changes of the skin can be reproduced in a 3D in vitro setting. Our results showed that under time-averaged simulated microgravity (taSMG), the thickness of the endothelial cell arrangement increased by up to 59.75%, indicating skin irritation due to vasodilation, and that the diameter of keratinocytes and fibroblast co-cultured spheroids decreased by 6.66%, representing skin thinning. The α1 chain of type I collagen was upregulated, while the connective tissue growth factor was downregulated under taSMG. Cytokeratin-10 expression was significantly increased in the taSMG environment. The clinostat-based 3D culture system can reproduce physiological changes in the skin similar to those under microgravity, providing insight for understanding the effects of microgravity on human health before space exploration.

Despite the standard interval of 6-8 weeks between neoadjuvant chemoradiotherapy (nCRT) and surgery, it is debated whether an interval of8 weeks increases the pathologic complete response (pCR) rate. We investigated the interval between nCRT and surgery, and its impact on oncological outcomes and postoperative complications in patients with locally advanced rectal cancer.We retrospectively reviewed patients with rectal cancer who underwent total mesorectal excision after long-course nCRT between 2000 and 2020. They were divided into two groups-those who underwent surgery at 6-8 and8 weeks after nCRT. Surgical outcomes (stoma rate and postoperative complications), pCR, tumor regression grade (TRG), recurrence-free survival (RFS), and overall survival (OS) were compared.We selected 770/1153 patients with rectal cancer, including 502 and 268 patients surgically treated at 6-8 and8 weeks after nCRT, respectively. The pCR rates were similar between the two groups (14.7% vs. 15.3%, p = 0.836), while the TRG was significantly better in the8 weeks group (p = 0.267). Additionally, the postoperative complications, recurrence, 5-year RFS, and OS rates were not significantly different between the two groups.Although tumor regression increased in the8 weeks group, the oncological benefits of surgery8 weeks after nCRT remain uncertain.

Purpose Colorectal cancer (CRC) is the third leading cause of cancer-related mortalities in Korea. It is also the third most frequently diagnosed malignancy worldwide. To significantly improve its oncologic outcome, there is a need to study the diagnosis and treatment strategies further. Methods We established 21 patients-derived organoids from 20 patients with CRC, and characterized their cellular and molecular features. Whole exome sequencing (WES) was performed for these organoids to obtain mutational profiles. It generally took 3 ~ 4 weeks for organoids to grow enough for DNA/RNA extraction and drug screening. The research protocol was reviewed and approved by the institutional review board of the Seoul National University Hospital (IRB No. 1102-098-357). Results Single nucleotide variations, in-frame deletions and insertions, and splice site mutations of CRC related genes were found and classified based on their existing pathogenicity reports from National Center for Biotechnology Information (NCBI). Heterogeneity was confirmed by comparing the expression of each organoid in the major cancer pathway through RNA sequencing. Also, drug sensitivity assay was performed to measure cell viability after treatment with 24 anti-cancer drugs approved by FDA. Conclusion We used the organoid model to identify tumor heterogeneity through various screening. By integrating mutational profiles of WES, RNA-seq, and drug screening results, we could elucidate which mechanism went wrong. Results suggested that tumor heterogeneity should be considered when using organoids as a preclinical model and that organoids are a suitable platform for use in precision medicine. Organoid model is meaningful because we can figure out what therapy will be good for a patient in vitro in a few weeks so that clinical application can be suggested.

Nucellar embryony, a form of apomixis, is one of the most important traits in citrus breeding. Transposition of a miniature inverted repeat transposable element (MITE) in the promoter of CitRWP gene has been previously reported as the causal mutation. However, features of the MITE such as sequences of terminal inverted repeats (TIRs) and target site duplications (TSDs) remain unclear. An MITE family, DTM10, showing the highest homology was identified from 110 citrus MITE families. At least 80 DTM10 elements were identified from each of 10 genome sequences of Citrinae species. Analysis of 114 sweet orange elements showed that DTM10 contained 56-bp TIRs and mostly 9-bp TSDs. Phylogenetic analyses of DTM10 elements identified from five Citrinae species showed that MITEs in CitRWP might have transposed in a common ancestor of Citrus species. Two inverted MITEs were identified from three mutant alleles analyzed. In addition, three tandem MITEs were identified in the mutant allele of Fortunella CitRWP. A strong DNA secondary structure formed between MITEs was predicted. Due to a strong stem-loop structure, a phenomenon of polymerase jumping was observed during PCR amplification. To develop reliable molecular markers, sequences of mutant and wild-type CitRWP alleles were obtained from diverse citrus accessions. Phylogenetic analysis of CitRWP alleles showed that mutant alleles might have originated from a common ancestor of Citrus species. Based on MITE insertion and a single nucleotide polymorphism in the genic region, three complementary molecular markers were developed. Genotyping results of 241 citrus accessions were found to be identical among three molecular markers.

Endoscopic tattooing is used to mark colorectal lesions for subsequent surgery. As a tattooing agent, India ink has been widely used but is not currently available in Korea. Indocyanine green (ICG) can be applied as an alternative agent. However, studies on colonoscopic tattooing by the direct injection of indocyanine green are lacking. This study aimed to compare the efficacy and safety between an ICG direct injection method and an India ink saline test injection method.A total of 227 patients who underwent preoperative endoscopic tattooing for colorectal neoplasm (149 patients in the ICG direct injection group and 78 patients in the India ink saline test injection group) were included in the study. The efficacy of the two methods was compared by visualization and safety was compared by evaluating the perioperative tattooing complications.The visualization of lesions in the ICG group was not different from that of the India ink group (p=0.42, 96.0% vs 98.7%, respectively). Only one patient in the ICG group had abdominal pain related to tattooing, but no complications developed in the India ink group.Considering the good visualization and low complication rate, the direct injection of ICG can be used as an alternative tattooing method.

This study investigated how the ploidy level of the kiwifruit pollinizer cultivars “CK3” (diploid), “T line” (tetraploid), “Pohwa” (hexaploid) and “Chieftain” (hexaploid) affected fruit set, fruit quality, and seed formation in the tetraploid kiwifruit cultivars “Halla Gold” and “Sweet Gold” cultivated in an unheated greenhouse in Jeju, Korea. Pollen tubes growing in the pistil reached and combined with the ovule 3 days after artificial pollination, and their patterns differed depending on the ploidy level of the pollen parent. The number of pollen tubes observed in “Halla Gold” and “Sweet Gold” pistils was significantly lower following pollination by “CK3” than with the other pollen donors. In all pollen treatments, the fruit set rates were > 90%. The fruit weight of both “Halla Gold” and “Sweet Gold” were high following pollination with “Chieftain” and “Pohwa”. The dry matter content, soluble solids, and acidity were not significantly different among all pollination treatments. Fruit firmness was higher following pollination with “Chieftain” and “Powha.” Colorimeter h˚ values for flesh of “Halla Gold” was low following pollination with “CK3,” but there were no differences for “Sweet Gold” among all pollinations. The number of seeds showed a similar trend to fruit weight, but the 100-seed weight was highest with “T line” as the pollinizer. The results indicate that the ploidy level of the pollen donor affects fruit quality more than fruit set. Also, the pollen most suitable for cultivation of “Halla Gold” and “Sweet Gold” is considered to be tetraploid “T line” and hexaploid “Pohwa” and “Chieftain,” which showed favorable effects on the weight and firmness of fruits, and the number and weight of seeds without adversely influencing fruit set and dry matter content.

Background Smoking is a well‐known risk factor for colorectal cancer incidence; however, the effect of smoking before and after cancer diagnosis on mortality has not been addressed well. Thus, we aimed to evaluate the association of prediagnosis and postdiagnosis smoking status and mortality among colorectal cancer patients. Methods A retrospective cohort consisted of 37,079 male colorectal cancer patients. Smoking status was defined from information within 2 years of colorectal cancer diagnosis for prediagnosis and at least 1 year later for postdiagnosis. The prediagnostic and postdiagnostic smoking status were categorized into four groups (nonsmoker/nonsmoker, nonsmoker/smoker, smoker/nonsmoker, and smoker/smoker). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard model. Results During a median of 6.3 years of follow‐up, a total of 3980 deaths and 2137 deaths from colorectal cancer occurred. The number of prediagnosis smokers were 11,100 and 62.4% of them quitted smoking after the diagnosis. Significantly elevated mortality rate in prediagnosis smokers was observed regardless of postdiagnosis smoking status (smoker/nonsmoker [HR, 1.30; 95% CI, 1.20–1.41] and smoker/smoker [HR, 1.21; 95% CI, 1.09–1.34]). Among patients treated with surgical operation only, those who quit smoking after diagnosis showed lower mortality rates compared to continual smokers (HR, 0.80; 95% CI, 0.67–0.96). Conclusions Smoking before cancer diagnosis rather than postdiagnosis has stronger impact on prognosis colorectal cancer patients, and quitting smoking may improve survival, especially among early stage colorectal cancer patients., This study found that both smoking before and after cancer diagnosis is associated with increased mortality rate among colorectal cancer patient. Quitting smoking after diagnosis was significantly related to diminished mortality among colorectal cancer patients receiving only operation, who is considered as early stage colorectal cancer patients, though smoking cessation after diagnosis among colorectal cancer patients who received radiotherapy or chemotherapy was not associated with significantly decreased mortality.

Purpose There are ongoing investigations to find promising biomarkers for predicting a complete response (CR) after concurrent chemoradiation (CCRT) in rectal cancer. We aimed to find the predictive value in the gut microbiome in terms of response after preoperative CCRT. Methods and Materials We collected a total of 45 fecal samples from patients with rectal cancer before CCRT. Tumor response after CCRT was assessed according to the American Joint Committee on Cancer tumor regression grading system. Analysis of linear discriminant analysis effect size and MetaCyc pathway abundance predictions were performed to compare composition and metabolic function of microbiome between patients with and without CR. We also established a Bayesian network model to identify microbial networks and species to be related with CCRT response. Results Seven patients (15.6%) demonstrated pathologically CR, and 38 patients (84.4%) showed non-CR after preoperative CCRT. Between CR and non-CR patients, there was a significant difference in terms of β-diversity (P = .028), but no difference in α-diversity was found. Bacteroidales (Bacteroidaceae, Rikenellaceae, Bacteroides) were relatively more abundant in patients with non-CR than those with CR. Pathways related to anabolic function predominated in CR patients. According to Bayesian network analysis, Duodenibacillus massiliensis was linked with the improved CR rate. Conclusions From the fecal microbiome using samples obtained before preoperative CCRT, differences in microbial community composition and functions were observed between patients with and without CR in rectal cancer. However, the finding that a specific taxon may be linked with the improved therapeutic response should be verified in a prospective setting.

To evaluate the efficacy of selective lateral lymph node dissection (LLND) and the effect of preoperative chemoradiotherapy (PCRT) in patients with LLN ≥ 5 mm. Patients who underwent PCRT for rectal cancer were classified: (A) total mesorectal excision (TME)-only with LLN

This study aimed to evaluate the prevalence of preoperative anemia and impacts of anemia and transfusion on survival in patients undergoing surgery for colorectal cancer. This study included patients who underwent surgery for primary colorectal cancer between 2011 and 2012. The influence of preoperative anemia and postoperative transfusion on recurrence-free survival and overall survival were retrospectively investigated. Anemia was defined as hemoglobin level

OBJECTIVES To investigate the efficacy of health coaching and a web-based program on survivor physical activity (PA), weight, and distress management among stomach, colon, lung and breast cancer patients. METHODS This randomised, controlled, 1-year trial conducted in five hospitals recruited cancer survivors within 2 months of completing primary cancer treatment who had not met ≥1 of these behavioural goals: (i) conducting moderate PA for at least 150 minutes/week or strenuous exercise for over 75 minutes per week or, in the case of lung cancer patients, low or moderate intensity exercise for over 12.5 MET per week, (ii) maintaining normal weight, and (iii) attaining a score >72 in the Post Traumatic Growth Inventory (PTGI). Participants were randomly assigned to one of three groups: the control group, a web-only group, or a health coaching + web group. The primary endpoint was based on a composite of PA, weight, and PTGI score at 12 months. RESULTS Patients in the health coaching + web group (difference = 6.6%, P = .010) and the web-only group (difference = 5.9%, P = .031) had greater overall improvements across the three-outcome composite than the control group. The health coaching + web group had greater overall improvement in PTGI (difference = 12.6%; P

Purpose: Patients who undergo radical surgery for rectal cancer often experience low anterior resection syndrome (LARS). Symptoms of this syndrome include frequent bowel movements, gas incontinence, fecal incontinence, fragmentation, and urgency. The aim of this study was to investigate the convergent validity, discriminative validity, and reliability of the Korean version of the LARS score questionnaire.Methods: The English LARS score questionnaire was translated into Korean using the forward-and-back translation method. A total of 146 patients who underwent radical surgery for rectal cancer answered the Korean version of the LARS score questionnaire including an anchor question assessing the impact of bowel function. Participants answered the questionnaire once more after 2 weeks.Results: The Korean LARS score questionnaire showed high convergent validity in terms of high correlation between the LARS score and quality of life (perfect fit 55.5% vs. moderate fit 37.6% vs. no fit 6.8%, respectively; P < 0.001). The LARS score also showed good discriminative validity between groups of patients differing by sex (29 for males vs. 25 for females; P = 0.014), tumor level (29 for ≤8 cm vs. 24 for >8 cm; P = 0.021), and radiotherapy (32 for yes vs. 24 for no; P = 0.001). The LARS score also demonstrated high reliability at test-retest with no difference between scores at the first and second tests (intraclass correlation coefficient: Q1 = 0.932; Q2 = 0.909, Q3 = 0.944, Q4 = 0.931, and Q5 = 0.942; P < 0.001, respectively).Conclusion: The Korean version of the LARS score questionnaire has proven to be a valid and reliable tool for measuring LARS in Korean patients with rectal cancer.

Colorectal cancer (CRC) represents the third most frequently diagnosed malignancy worldwide and is the second most common cause of tumor-associated mortalities in Korea. Due to the disease’s aggressive behavior, the 5-year survival rate for CRC patients remains unpromising. Well-characterized cell lines have been used as a biological model for studying the biology of cancer and developing novel therapeutics. To assist in vitro studies, 18 CRC cell lines (SNU-1566, SNU-1983, SNU-2172, SNU-2297, SNU-2303, SNU-2353B, SNU-2359, SNU-2373B, SNU-2407, SNU-2423, SNU-2431, SNU-2465, SNU-2493, SNU-2536C, SNU-2621B, SNU-NCC-61, SNU-NCC-376, and SNU-NCC-377) derived from Korean patients were established and characterized in the present study. General characteristics of each cell line including doubling time, in vitro morphology, mutational profiles, and protein expressions of CRC-related genes were described. Whole exome sequencing was performed on each cell line to configure mutational profiles. Single nucleotide variation, frame shift, in-frame deletions and insertions, start codon deletion, and splice stop codon mutation of various genes were found and classified based on their pathogenicity reports. In addition, cell viability was assayed to measure their sensitivities to 24 anti-cancer drugs including anti-metabolites, kinase inhibitors, histone deacetylase inhibitors, alkylating inhibitors, and topoisomerase inhibitors, all widely used for various cancers. On testing, five CRC cell lines showed MSI, of which MLH1 or MSH6 gene was mutated. These newly established CRC cell lines can be used to investigate biological characteristics of CRC, particularly for investigating gene alterations associated with CRC.

Right-sided colonic diverticulitis (RCD) and left-sided colonic diverticulitis (LCD) are considered distinct diseases. However, separate guidelines for RCD do not exist. Since the establishment of RCD management would first require evaluation of disease characteristics and recurrence patterns, this study has aimed to investigate the differences in the clinical characteristics between RCD and LCD and the recurrence patterns of RCD.Patients admitted for colonic diverticulitis between January 2012 and August 2020 were retrospectively reviewed. Clinical characteristics and recurrence rates in RCD and LCD patients, and predictors for recurrence and the recurrence patterns of RCD were analyzed.In total, 446 colonic diverticulitis patients (343 RCD, 103 LCD) were included in this study. RCD patients were more likely to be male, younger, taller, heavier, smoke, drink alcohol, have better physical performance scores, lower modified Hinchey stages and better initial laboratory findings. LCD patients were more likely to receive invasive treatments, have longer fasting and hospital days, higher mortality and cumulative recurrence rates (20.5% vs. 30.4%, P = 0.007). Recurrences in most RCD patients were of similar disease severity and received the same treatments for initial attacks, with rates of recurrence increasing after each recurrence. Predictors of the recurrence of RCD were complicated diverticulitis (hazard ratio[HR] 2.512, 95% confidence interval[CI] 0.127-5.599, p = 0.024) and percutaneous drainage (HR 6.549, 95% CI 1.535-27.930, p = 0.011).RCD is less severe and has a lower recurrence rate than LCD, suggesting that RCD should be treated conservatively. Patients with complicated diseases and those requiring percutaneous drainage are more likely to experience a disease recurrence, suggesting nonsurgical management may be insufficient.

The use of an ostomy for urination and defecation leads to reduced quality of life. Although many ostomy management strategies are needed, such strategies are often implemented by patients. Thus, there is a need for a home health care service platform that can be used in ostomy patient management.We developed an ostomy patient management platform by identifying the needs of patients and medical staff through the Chronic Care Ostomy Self-Management Training Program in the United States and from studies conducted in Korea.The platform encompassed physical management, psychological management, maintenance of social function, spiritual stability, and home medical care. These components were implemented through monitoring, self-care guidance, and a community platform. For the monitoring function, a patient entered their health status in a mobile application (app); the medical staff at the affiliated hospital then monitored the stoma status through a web interface.Our platform allows medical staff to monitor ostomy patients through a web interface and help such patients to fully manage their ostomy at home using an app. We expect that the continued development of patient-oriented functions in our app will allow ostomy patients to experience quality of life improvements.

SummaryOver the course of an individual’s lifetime, genomic alterations accumulate in somatic cells. However, the mutational landscape by retrotranspositions of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome, is poorly understood in normal cells. Here, we explored the whole-genome sequences of 892 single-cell clones established from various tissues collected from 28 individuals. Remarkably, 88% of colorectal epithelial cells acquired somatic L1 retrotranspositions (soL1Rs), carrying ∼3 events per cell on average with substantial intra- and inter-individual variances, which was accelerated at least 10-fold during tumourigenesis. Breakpoints of soL1Rs suggested that a few variant mechanisms can be involved in the L1 retrotransposition processes. Fingerprinting of donor L1s using source-specific unique sequences revealed 34 hot L1s, 44% of which were newly discovered in this study, and many ultra-rare hot L1s in the human population showed higher retrotransposition potential in somatic lineages than common sources. Multi-dimensional analysis of soL1Rs with early embryonic developmental relationships, genome-wide methylation, and gene expression profiles of the clones demonstrated that (1) soL1Rs occur from early embryogenesis at a substantial rate, (2) epigenetic activation of hot L1s is stochastically acquired during the wave of early global epigenomic reprogramming, rather than by the sporadic loss-of-methylation at the late stage, and (3) most L1 transcripts in the cytoplasm do not generate soL1Rs in somatic lineages. In summary, this study provides insights into the retrotransposition dynamics of L1s in the human genome and the resultant somatic mosaicism in normal human cells.

Background: Previous studies have suggested the disturbance in the microbial composition followed by dysbiosis contribute to the onset of gastrointestinal malignancies, including colorectal cancer (CRC). However, the impact of microbiome on short-term postoperative complications after CRC surgery is not well investigated. This study aimed to investigate whether the gut microbial diversity and composition in CRC patients were associated with the occurrence of short-term postoperative complications. Methods: We linked the clinical data and preoperative sequencing data of fecal samples of 331 patients who underwent CRC surgery from 2017 to 2019 in Seoul National University Hospital. Short-term postoperative complications were defined as first complications that developed within 30 days of surgery. We used linear discriminant analysis (LDA) of effect size (LEfSe) in the Galaxy webserver to identify enriched bacteria in patients with and without complications. Then, we calculated microbial dysbiosis index (MDI) by each patient and compared them according to the complication status. Wilcoxon rank sum test was conducted to compare the alpha diversity indices according to the complication event. Subgroup analyses according to types of complications were also performed: surgical procedure-related (SP) group and nonsurgical procedure-related (NSP) group. Results: Overall, 84 patients (25%) developed short-term postoperative complications: SP group (n=39) and NSP group (n=45). From the LEfSe analysis, Bacteroides uniformis (LDA score: 3.64, p-value 0.04) and Clostridium colicanis (LDA score: 3.39, p-value 0.01) were enriched in patients who developed short-term complications, whereas Roseburia faecis (LDA score: 3.26, p-value 0.05), Bifidobacterium bifidum (LDA score: 2.98, p-value 0.03), Faecalibacterium sp. (LDA score: 3.12, p-value 0.02) and Prevotella nigrescens (LDA score: 2.87, p-value 0.05) were enriched in patients without complications. When compared with patients without complications, taxa related to class Gammaproteobacteria, genus Clostridium, species Roseburia faecis, and Desulfovibrio D168 were abundant in the SP group. Alpha diversity indices were not significantly different according to the complication status or the type of complication. MDI from the enriched bacteria were significantly higher in patients with complications compared to those without complications (p-value Conclusion: Our study suggests a potential relationship between microbial composition and surgical outcome in CRC patients. No significant difference in alpha diversity was observed according to the occurrence or the type of complication. Further studies are needed to investigate the postoperative changes of microbial features. Citation Format: Hyeree Park, Tung Hoang, Min Jung Kim, Ji Won Park, Seung-Yong Jeong, Aesun Shin. Microbial diversity and composition according to short-term postoperative complication status in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5892.

Background: Gut microbiota has been introduced to involve in the migration and invasion stage of metastasis of colorectal cancer (CRC) cells and interact with both the pharmacokinetics and pharmacodynamics of chemotherapeutic agents and immune checkpoint inhibitors. In this study, we examined microbiome features in association with all-cause mortality of CRC patients and examined their interactions with clinical factors. Methods: We performed 16S rRNA sequencing for 331 preoperative fecal samples of CRC patients at Seoul National University Hospital, Korea. Multiple Cox proportional hazard model was applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of all-cause mortality due to microbiome features (within-sample diversity indices, species patterns, genus abundance, and taxonomic co-occurrence networks) and clinical factors (tumor grade and stage, surgical methods, neoadjuvant and adjuvant therapies, and invasion). We added the multiplicative term into the model to test the interaction between gut microbiota and clinical characteristics. Results: During a median follow-up of 3.7 years, deaths from any causes were reported in 46 patients. From 172 species, the principal component analysis identified 4 patterns, which explained a total 66.1% variation in species abundance. Of 77 genera, 9 co-occurrence networks were identified by the SParse InversE Covariance Estimation for Ecological Association Inference. For genus level, the risk of death was positively associated with Butyricicoccus (HR=1.54, 95% CI=1.17-2.04), but inversely associated with Lactococcus (HR=0.60, 95% CI=0.37-0.95), Acidaminococcus (HR=0.57, 95% CI=0.34-0.96), Megasphaera (HR=0.79, 95% CI=0.64-0.99), Mitsuokella (HR=0.75, 95% CI=0.57-0.99). All-cause mortality was associated with well or moderately differentiated adenocarcinoma (HR=3.84, 95% CI=1.83-8.07), neoadjuvant therapy (HR=4.10, 95% CI=1.40-12.0), tumor stage IV (HR=8.64, 95% CI=3.42-21.8), and presence of venous invasion (HR=2.32, 95% CI=1.08-4.97). Among clinical pathological factors associated with all-cause mortality, Bacteroides abundance significantly interacted with both tumor stage (pinteraction=0.013) and venous invasion (pinteraction=0.001). Conclusion: Our study identified several microbiome features in links with either increasing or decreasing mortality from any causes. Interactions between the gut microbiome and clinical factors might inform insights on how the gut microbiota modulates the effect of clinical factors on CRC prognosis after the curative operation. Further research using postoperative information is needed to confirm our findings. Citation Format: Tung Hoang, Min Jung Kim, Ji Won Park, Seung-Yong Jeong, Aesun Shin. Gut microbiome interacts with clinical characteristics on all-cause mortality of colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2364.

Introduction As total neoadjuvant therapy for locally advanced rectal cancer (LARC) emerged, the possibility of skipping radiotherapy for poorly responsive patients arose. Machine-learning algorithms have focused on the radiopathologic features of tumor segmentation in order to predict responsiveness to radiotherapy. However, in addition to the tumor itself, there are several factors related to responsiveness, such as vasculature affecting hypoxia or MRI-detected extramural vascular invasion status. We aimed to predict poor responders using pretreatment rectal MRI images without segmentation and to identify which factors mainly contribute to the prediction algorithm. Methods Between Jan 1, 2000, and Dec 30, 2020, 689 consecutive patients were retrospectively included in two hospitals. Poor responders were defined by tumor regression grades (TRG) 2 and 3 that were determined through surgical resection. The ResNet-50 model was trained to predict poor responders from pretreatment rectal MRIs (T2-weighted axial, sagittal, and coronal images). We adopted a tenfold cross-validation for training and testing the model and used Gradient-weighted Class Activation Mapping (Grad-CAM) to highlight the important regions in the MRI scans that help predict poor responders. Results The number in each group of TRG was 108 (15.7%), 250 (36.3%), 265 (38.5%), and 66 (9.6%) for TRG0, TRG1, TRG2, and TRG3, respectively. There were 618 patients in the training cohort and 71 patients in the validation cohort. In the training and validation cohort, the accuracy for the prediction of poor responders was 85.6% (area under the curve (AUC) 0.856 [95% CI 0.761-0.950]) and 70.2% (AUC 0.703 [0.682-0.724]), although without segmentation. Our prediction model achieved a sensitivity of 0.724 (95% CI 0.700-0.748), a specificity of 0.684 (0.658-0.710), a positive predictive value of 0.697 (0.656-0.737), and a negative predictive value of 0.708 (0.666-0.751) in the validation cohort. Grad-CAM showed that the most important part of the accurately predicted images to contribute to the prediction was not the tumor (7/355, 1.9%) but the pelvic vasculature (353/355, 99.4%), including iliac vessels, femoral vessels, and presacral plexus, and followed by the mesorectum (38/355, 10.7%). Conclusion The pelvic vasculature contributes more to predicting poor responders to radiotherapy than the tumor itself. Therefore, when creating a prediction model for responsiveness to radiotherapy in LARC, this should be considered. Citation Format: Rumi Shin, Byunho Jo, Inyeop Jang, Cheong-Il Shin, Jin Sun Choi, Seung-Yong Jeong, Seung Chul Heo, Ji Won Park, Min Jung Kim, Tae Hyun Hwang. Why only focus on the tumor?: The crucial role of the extra-tumor environment to predict poor responders for locally advanced rectal cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5374.

Background: One of the major topics about colorectal cancer (CRC) is the core role of various immune cells against cancer cells. To comprehensively understand genetic basis of immune system underlying CRC progression, association of single-nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) of immune-related genes were investigated with colorectal cancer survival. Methods: CRC patients enrolled in the Seoul National University Hospital with prospective follow-up were included in the study. From blood-derived DNA from CRC patients, genome-wide SNPs were genotyped by using the Korea Biobank Array (KoreanChip). 2,729 immune-related genes were selected from Ensembl, Gene Ontology (GO), and KEGG database and 37,398 mapped SNPs were extracted. SNP or PRS-based Cox proportional hazard models were fit for events of overall survival (OS) and progression-free survival (PFS) estimating effect sizes with hazard ratios (HRs). PRS was calculated as effect size weighted sum of risk alleles of individual patients and categorized into tertiles. To investigate enriched pathways, protein-protein interaction networks analysis was conducted. Bonferroni-corrected p-value (1.3 × 10−6) was used as statistically significance threshold. Results: Among 960 CRC patients, 154 (16.0%) occurred events of death and 245 (25.5%) of progression during the follow-up (median=1,698 days, range=7-2,563 days). For OS, a statistically significant associations were mapped to ACTR3B, ST6GAL1, COTL1, PRKCZ, and CAMK1D genes with the strongest SNP rs14808985 (HR=3.07, P=1.87 × 10−7). For PFS, marginal association was mapped to MECOM gene with the strongest SNP rs16854234 (HR=1.48, P=6.13 × 10−6). In PRS analysis, the highest tertile group showed the prominently increased risk for OS (HR=25.0, P Conclusions: We identified novel predictive biomarker genetic variants in ACTR3B and MECOM genes associated with OS and PFS, respectively, among CRC patients. Additionally, we presented PRS as a useful biomarker for survival outcomes and suggested enriched biological pathways involved in CRC progression. These knowledges can promote the understanding of CRC survival and the development of immune-related therapeutic interventions for CRC patients in the future. Citation Format: Dabin Yun, Nan Song, Jin-Ah Sim, Min Jung Kim, Ji Won Park, Seung Yong Jeong, Aesun Shin. Novel predictive biomarker SNPs and polygenic risk scores of immune-related genes for colorectal cancer survival in Korea. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5234.

Backgrounds: Colorectal cancer (CRC) is one of the most common cancers in the world, and recently in South Korea, the incidence rates are increasing. CRC patients have a high prevalence of depression and experience various symptoms such as bowel problems. However, previous studies analyzing network analysis has not yet been conducted to understand the association between symptoms with chronic anxiety and depression. Methods: In this study, symptom network and centrality analysis were conducted to confirm the interaction between symptoms and functioning (e.g., pain, fatigue, physical functioning, etc.) of patients diagnosed with CRC according to the higher risk of anxiety and depressive groups ahead of surgical treatment. In this study, symptom and functioning variables in a total of 939 CRC patients were measured using EORTC QLQ-C30 and EORTC QLQ-CR29. Network analysis, visualization, and centrality analysis were performed to determine the connectivity between anxiety, depression, and other correlated symptoms amongst CRC patients using the qgraph R package. Results: As a result of confirming the difference in anxiety and depression according to socio-demographic characteristics, there was a significant difference in the education level in the group with anxiety(Ps Conclusion: In conclusion, the study compared and analyzed symptom networks to confirm the interaction between symptoms of CRC patients according to anxiety and depression. The symptom network of CRC patients showed different patterns according to anxiety and depression. Pain appeared as a central symptom in both the anxious and depressed groups. This indicates that pain is a key role because it is related to other symptoms and affects the flow of the symptom network the most. Therefore, intensive pain management is expected to be important in treating CRC patients with anxiety and depression. It is expected that the basis for the management of colorectal cancer patients and survivors can be prepared toward the long term of cancer treatment and survival. Citation Format: Jinah Sim, Ji Won Yu, Nan Song, Ae Sun Shin, Ji Won Park, Seung Yong Jeong. Symptom network identification from anxious and depressive groups in colorectal cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4368.

Background Lateral pelvic lymph node dissection (LPLND) is an option in the treatment of rectal cancer and may reduce local recurrence/improve disease-free survival. Advancements in minimally invasive technology have improved the ability to identify anatomy and neurovascular structures that may help in LPLND. The aim of this retrospective study was to evaluate the technical feasibility and oncological safety of laparoscopic LPLND compared with the open LPLND. Method Between July 2010 and July 2019, patients from three tertiary referral hospitals who underwent LPLND with total mesorectal excision for primary rectal cancer were included. Baseline patient characteristics, perioperative outcomes, pathologic results, recurrence, and survival were compared between the laparoscopic and open groups. Results There were 126 and 70 patients in the laparoscopic and open groups respectively. The laparoscopic group had less estimated blood loss (100 ml versus 300 ml, P Conclusion Laparoscopic LPLND was associated with improved perioperative outcomes and non-inferior oncological outcomes.

Due to the increasing tendency to construct taller and more slender buildings, the need to address aerodynamic and induced dynamic forces (inertial forces) under both service and strength-l...

Background Tumor budding is associated with lymph node (LN) metastasis in submucosal colorectal cancer (CRC). However, the rate of LN metastasis associated with the number of tumor buds is unknown. Here, we determined the optimal tumor budding cut-off number and developed a composite scoring system (CSS) for estimating LN metastasis of submucosal CRC. Methods In total, 395 patients with histologically confirmed T1N0–2M0 CRC were evaluated. The clinicopathological characteristics were subjected to univariate and multivariate analyses. The Akaike information criterion (AIC) values of the multivariate models were evaluated to identify the optimal cut-off number. A CSS for LN metastasis was developed using independent risk factors. Results The prevalence of LN metastasis was 13.2%. Histological differentiation, lymphatic or venous invasion, and tumor budding were associated with LN metastasis in univariate analyses. In multivariate models adjusted for histological differentiation and lymphatic or venous invasion, the AIC value was lowest for five tumor buds. Unfavorable differentiation (odds ratio [OR], 8.16; 95% confidence interval [CI], 1.80–36.89), lymphatic or venous invasion (OR, 5.91; 95% CI, 2.91–11.97), and five or more tumor buds (OR, 3.01; 95% CI, 1.21–7.69) were independent risk factors. In a CSS using these three risk factors, the rates of LN metastasis were 5.6%, 15.5%, 31.0%, and 52.4% for total composite scores of 0, 1, 2, and ≥ 3, respectively. Conclusions For the estimation of LN metastasis in submucosal CRC, the optimal tumor budding cut-off number was five. Our CSS can be utilized to estimate LN metastasis.

We aimed to compare the short- and long-term outcomes of simultaneous laparoscopic, hybrid, and open resection for colorectal cancer and synchronous liver metastases. We retrospectively analyzed the data of 647 patients with simultaneous resection of colorectal cancer and liver metastases between January 2006 and December 2018 at three tertiary referral hospitals. Patient’s baseline characteristics, perioperative outcomes, pathological examination results, liver-specific recurrence rate and survivals were compared between the propensity score-matched groups. Forty-two and 81 patients were selected for the laparoscopic vs. hybrid groups, and 48 and 136 patients for laparoscopic vs. open groups, respectively. The laparoscopic group had fewer wound complications (2.1 vs. 13.2%; p = 0.028) than the open group, and a shorter postoperative hospital stay than the hybrid and open groups (8 vs. 11 days, p

BACKGROUND Obtaining an accurate pedigree is the first step in recognizing a patient with hereditary nonpolyposis colorectal cancer, or Lynch syndrome. However, lack of standardization of the degree of relationship included in the pedigrees generally limits obtaining a complete and/or accurate pedigree. DESIGN This study analyzed the extent of pedigree required to screen for colorectal cancer and to diagnose Lynch syndrome. SETTINGS The study was conducted at 2 tertiary care centers. PATIENTS A detailed family history was obtained from patients undergoing surgery for colorectal cancer from 2003 to 2016. A simplified pedigree that included only first-degree relatives was obtained and compared with the extended pedigree. MAIN OUTCOME MEASURES The eligibility of the 2 pedigrees was assessed for each proband. The proportion of patients who would be missed using a simplified rather than an extended pedigree was calculated based on the American Cancer Society guidelines for recommending screening for colorectal cancer, on the revised Bethesda guidelines and the revised suspected hereditary nonpolyposis colorectal cancer criteria for screening for hereditary colorectal cancer, and on the Amsterdam II criteria for diagnosis of Lynch syndrome. RESULTS The study examined 2015 families, including 41,826 individuals. Use of simplified and extended pedigrees was comparable in screening for colorectal cancer, with ratios of 183 of 185 (98.9%) for American Cancer Society guidelines, 295 of 295 (100%) for revised Bethesda guidelines, and 60 of 60 (100%) for revised suspected hereditary nonpolyposis colorectal cancer criteria. However, the use of simplified pedigrees missed a definitive diagnosis of Lynch syndrome in 6 of 10 patients fulfilling Amsterdam II criteria based on extended pedigrees. The mean ages at diagnosis of the 4 probands included and the 6 missed using simplified pedigrees differed significantly (60.8 vs 38.2 y). LIMITATIONS The study was limited by its recall bias, cross-sectional nature, lack of germline testing, and potential inapplicability to the general population. CONCLUSIONS A simplified pedigree is acceptable for selecting candidates to screen for hereditary colorectal cancer, whereas an extended pedigree is still required for a more precise diagnosis of Lynch syndrome, especially in younger patients. See Video Abstract at http://links.lww.com/DCR/B97. EXTENSION DE PEDIGREE REQUERIDO EN LA DETECCION Y DIAGNOSTICO DE CANCER COLORRECTAL HEREDITARIO SIN POLIPOSIS: COMPARACION DE LOS PEDIGREES SIMPLIFICADO Y EL EXTENDIDO: La obtencion de un Pedigree exacto es el primer paso para reconocer un paciente con cancer colorrectal hereditario sin poliposis o sindrome de Lynch. Sin embargo, la falta de estandarizacion del grado de relacion incluido en los Pedigrees generalmente limita la obtencion de un Pedigree completo y / o preciso.Este estudio analizo el grado de Pedigree requerido para detectar el cancer colorrectal y diagnosticar el sindrome de Lynch.Se obtuvo una historia familiar detallada de pacientes sometidos a cirugia por cancer colorrectal desde 2003 hasta 2016. Se obtuvo tambien un Pedigree simplificado que incluia solo familiares de primer grado y se comparo con el Pedigree extendido.La elegibilidad de los dos Pedigrees se evaluo para cada sujeto de prueba (proband). La proporcion de pacientes que se perderian usando un Pedigree simplificado en lugar de extendido se calculo en base a las guias de la Sociedad Americana del Cancer y sus recomendaciones en la deteccion de cancer colorrectal, en las pautas revisadas de Bethesda y en los criterios revisados de cancer colorrectal hereditario sin poliposis para la deteccion hereditaria de cancer colorrectal y segun las normas de Amsterdam II para el diagnostico del sindrome de Lynch.El estudio examino a 2.015 familias, incluidas 41.826 personas. El uso de Pedigree simplificado y extendido fue comparable en la deteccion del cancer colorrectal, con proporciones de 183/185 (98,9%) comparadas con las recomendaciones de la American Cancer Society, 295/295 (100%) para las pautas revisadas de Bethesda y 60/60 (100%) para los criterios revisados de sospecha de cancer colorrectal hereditario sin poliposis. Sin embargo, el uso de Pedigree simplificado omitio un diagnostico definitivo del sindrome de Lynch en 6 de diez pacientes que cumplian las normas de Amsterdam II basados en Pedigrees extendidos. Las edades medias al diagnostico de los cuatro sujetos de prueba incluidos y los seis perdidos usando el Pedigree simplificado diferian significativamente (60.8 vs. 38.2 anos).Un Pedigre simplificado es aceptable en la seleccion de candidatos para la deteccion de cancer colorrectal hereditario, mientras que aun se requiere un Pedigree extendido para un diagnostico mas preciso de sindrome de Lynch, especialmente en pacientes mas jovenes. Consulte Video Resumen en http://links.lww.com/DCR/B97. (Traduccion-Dr. Edgar Xavier Delgadillo).

Gravity is omnipresent for all objects on Earth. However, in an environment of different gravitational stress (e.g., microgravity or partial gravity), cells and organs show different biological responses. So, researchers have attempted to achieve micro- or partial gravity on Earth through various approaches, such as parabolic flight or free fall. However, the duration of such ground experiments is highly limited, making it very difficult to conduct time-consuming tasks, such as cell culture. Thus, a three-dimensional (3D) clinostat is utilized as an alternative for experiments on the International Space Station. It provides time-averaged simulated micro- and partial gravity by using mechanical frames with two rotating actuators. This study proposes novel control algorithms for simulating micro- and partial gravity and validates them by applying it to the control of a manufactured 3D clinostat. First, the novel algorithm for time-averaged simulated microgravity (taSMG) provided a more uniformly distributed gravity field by reducing two poles the gravity-concentrated areas. The taSMG with reduced poles provides isotropic gravitational patterns, from which it is possible to minimize the unnecessary effect due to nonuniformity of the gravity vector direction. Second, the other suggested novel algorithm for time-averaged simulated partial gravity (taSPG) controls the pole sizes asymmetrically to generate the intended size of partial gravity. The suggested algorithms are based on mathematical models rather than totally randomized motions. Therefore, the convergence of gravity values, in the rotating frame over time, can be analytically predicted with improved accuracy compared with previously reported algorithms. The developed 3D clinostat hardware and algorithms will effectively provide well-validated taSMG and taSPG for cell growth experiments in future studies for space medicine.

Purpose: Recent sequencing studies revealed that a subset of colorectal cancer harbors a significantly higher number of somatic mutations. These hypermutated tumors show distinct clinicopathologic features. However, the prognostic impact of the hypermutated tumors is not clearly established. Experimental Design: We analyzed tumor mutation burden (TMB) from targeted next-generation sequencing data of 40 major genes in 516 patients with colorectal cancer. TMB was defined as total number of nonsynonymous mutations per tumor. Cutoff value for TMB-high was chosen by which best discriminated relapse-free survival (RFS) using the Contal and O'Quigley method. Results: In the TCGA data, mutation count of the selected 40 genes reflected the whole exome mutation burden (Pearson correlation = 0.873, P < 0.001). In our patient cohort, 8 or more mutations in the 40 genes was defined as TMB-high, which best discriminated RFS. A total of 55 patients (10.7%) had TMB-high. TMB-high tumors were more frequently found in a proximal location (63.6%) and had a higher proportion of N0 disease (30.9%) and MSI-H (49.1%) compared with TMB-low. Most importantly, TMB-high was associated with better 5-year RFS compared with TMB-low (96.3% vs. 79.8%, P = 0.005). Although there was significant overlap between TMB-high and MSI-H, MSI-H status was not significantly associated with RFS. Multivariate analysis revealed TMB-high as an independent positive prognostic factor for RFS [adjusted HR, 0.16 (95% confidence interval, 0.04–0.66), P = 0.011]. Conclusions: TMB-high is associated with better prognosis in patients with colorectal cancer treated with curative surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and represents the second most common cause of all cancer-related deaths in Korea. Although epidemiological data indicate a sharp increase in the incidence of CRC among individuals older than 50 years, more than 10% of CRCs occur before reaching 50. These are known as early-onset CRCs (EOCRCs) and are likely to be suggestive of hereditary predisposition. However, known familial CRC syndromes account for only 20% of genetic aberrations of EOCRC, and the remaining 80% are still in question. Therefore, we aimed to establish reproducible biological resources and contribute to expand the mutation database of EOCRC. Four cell lines derived from the original tumor mass of CRC patients diagnosed under age 30 years were established, and next-generation sequencing technique was used to identify the genetic features of EOCRC. We have identified one novel fusion gene, FAM174A-WWC1, and analyzed its functional role. The induction of FAM174A-WWC1 to normal fibroblast caused alternations in cellular morphology as well as intercellular expression of E-cadherin and N-cadherin. Moreover, WWC1 carrying the fused FAM174A domain not only abrogated the membrane expression of YAP1 but also significantly increased the levels of nucleic YAP1. As a result, the FAM174A-WWC1 expression increased the oncogenic capacity and invasiveness of normal fibroblasts, which suggests its role as a potential driver mutation of EOCRC.

Rectal preservation against medical advice after neoadjuvant chemoradiotherapy for rectal cancer may increase oncologic uncertainty. This study aimed to compare the oncologic outcomes of patients undergoing rectal preservation as intended by the surgeon, and the outcomes of patients refusing rectal resection against medical advice. The study population consisted of patients in whom the rectum was preserved after neoadjuvant chemoradiotherapy for clinical stage I–III mid or low rectal cancer between May 2003 and August 2017 (n = 2883); these patients were divided into those in whom rectal preservation was intended by their surgeon (intended rectal preservation, group A, n = 41) and those in whom the rectum was not resected against medical advice (unintended rectal preservation, group B, n = 101), defined as non-operative management or local excision. The tumor distance, age, and performance status of patients were not significantly different between the groups, while the clinical T stage before chemoradiotherapy was lower in group A than in group B (P

To date, the effect of adjuvant chemotherapy after curative resection in patients with stage II colon cancer remains controversial. Still, little is known about the effects of adjuvant chemotherapy in patients with stage II colon cancer who are older than 70 years, as most studies did not focus on this population. This study aimed to investigate the oncologic outcomes of elderly patients with stage II colon cancer who underwent curative resection with or without postoperative adjuvant chemotherapy. We retrospectively reviewed medical records of patients older than 70 years who underwent curative resection of stage II primary colon cancer during 2002–2015. Patients were classified into surgery alone (SA) and adjuvant chemotherapy (AC) groups and propensity score-matched at a 1:1 ratio using a logistic regression. The end points were recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Of the 623 patients who met the criteria, 145 were assigned to each arm after propensity score matching. The mean ages of the SA and AC groups were 74.3 and 74.0 years, respectively. A log-rank test revealed no significant inter-group differences in RFS (p = 0.202), CSS (p = 0.486) or OS (p = 0.299). In a Cox regression analysis, adjuvant chemotherapy was not found to be an independent factor affecting RFS (p = 0.206), CSS (p = 0.487) or OS (p = 0.301). Adjuvant chemotherapy does not appear to yield survival benefits in elderly patients with stage II colon cancer.

Purpose The purpose of this study was to evaluate treatment response to neoadjuvant chemoradiotherapy (CRT) with regard to mucin status in pathology and pretreatment magnetic resonance imaging (MRI) in locally advanced rectal cancer. Materials and Methods Between 2003 and 2011, 306 patients with locally advanced rectal cancer received neoadjuvant CRT followed by surgery, and mucinous adenocarcinoma (MAC) was found in 27 (8.8%). All MAC patients had MRI before and after CRT and mucin proportion at MRI was measured. Therapeutic response was assessed by pathology after total mesorectal excision. To determine the optimal cut-off for mucin proportion in predicting good CRT response (near total or total regression) and negative circumferential resection margin (CRM), the receiver-operating characteristic analysis was performed. Results After neoadjuvant CRT, overall downstaging occurred in 44.4% of MAC and 72.4% of non-MAC (p=0.001), and positive CRM (≤1 mm) was observed more frequently in MAC (p

Performance-based wind design (PBWD) allowing inelastic behavior under extreme wind load has only been recently considered for design of high-rise buildings. Unlike performance-based seismi...

Simple Summary We have developed and analytically validated the Korean Pan-cancer Companion Diagnostic (CDX) Panel to apply targeted anticancer drugs to Korean patients based on the molecular characteristics of tumors using tumor samples without matched patient normal samples. The panel included 31 genes with reported single nucleotide variants, 9 genes with reported copy number variations, and 15 genes with predictive responses to targeted drugs under clinical testing, enabling the panel to be analyzed for the targets of 30 targeted anticancer drugs. It is cost-effective and optimized for cancer type-specific therapy in Korean cancer patients across solid cancer types while minimizing the limitations of existing approaches. This gene screening method is expected to reduce test turnaround time and cost, making it a balanced approach to investigate solid cancer-related gene regions. Abstract Recently, several panels using two representative targeting methods have been developed but they do not reflect racial specificity, especially for Asians. We have developed and analytically validated the Korean Pan-cancer Companion Diagnostic (CDX) Panel to apply targeted anticancer drugs to Korean patients based on the molecular characteristics of tumors using tumor samples without matched patient normal samples. The panel included 31 genes with reported single nucleotide variants, 9 genes with reported copy number variations, and 15 genes with predictive responses to targeted drugs under clinical testing, enabling the panel to be analyzed for the targets of 30 targeted anticancer drugs. It is cost-effective and optimized for cancer type-specific therapy in Korean cancer patients across solid cancer types while minimizing the limitations of existing approaches. In addition, the optimized filtering protocol for somatic variants from tumor-only samples enables researchers to use this panel without matched normal samples. To verify the panel, 241 frozen tumor tissues and 71 formalin-fixed paraffin-embedded (FFPE) samples from several institutes were registered. This gene screening method is expected to reduce test turnaround time and cost, making it a balanced approach to investigate solid cancer-related gene regions.