Network pharmacology and molecular docking analysis based on mechanism of Huangqin Tang in treatment of colorectal cancer / 吉林大学学报(医学版)

Objective:To analyze the potential therapeutic targets of Huangqin Tang in treatment of colorectal cancer(CRC)by network pharmacology and molecular docking techniques,and to clarify the related molecular mechanism.Methods:The active component and target dataset for Huangqin Tang were constructed based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP);the CRC-disease related target dataset was built by Databases such as GeneCards,Online Mendelian Inheritance in Man(OMIM),and pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB).Drug-disease target intersect,Huangqin Tang herbal formula network,and protein-protein interaction(PPI)networks were built by R software,Cytoscape software,and STRING Database;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted by R software and Metascape platform;molecular docking validation was performed with AutoDock and PyMOL software to assess the ligand-receptor binding.Results:A total of 136 effective active components of Huangqin Tang were screened,and 242 potential targets were identified for treatment of CRC,including 18 core targets.Five core key targets closely related to CRC,identified through signaling pathway analysis,were protein kinase B1(AKT1),mitogen-activated protein kinase 3(MAPK3),proto-oncogene FOS,tumor protein p53(TP53),and proto-oncogene MYC.The GO functional enrichment analysis results mainly involved various biological processes related to cellular stress responses.The KEGG signaling pathway enrichment analysis results showed that potential targets were highly enriched in the cancer pathway;further analysis on CRC core targets via KEGG signaling pathway revealed involvement primarily in pathways related to endocrine resistance,apoptosis,and epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)resistance.The molecular docking results showed that the active components of Huangqin Tang,including quercetin,kaempferol,baicalein,7-methoxy-2-methyl isoflavone,and naringenin,were stably docked with AKT1,MAPK3,FOS,TP53,and MYC,and quercetin exhibited the best binding with AKT1.Conclusion:The active components of Huangqin Tang can treat CRC through multi-target and multi-pathway.The core ligand quercetin and AKT1 may exert the therapeutic effect in CRC by regulating the phosphatidylinositol 3-kinase(PI3K)/AKT and mammalian target of rapamycin(mTOR)signaling pathways to influence the cell proliferation,differentiation,and apoptosis processes.

Correlation of tumor budding with KRAS,NRAS,BRAF gene mutation and MSI status in colorectal adenocarcinoma and their clinical significance / 临床与实验病理学杂志

Purpose To explore the clinicopathological re-lationship between tumor budding and KRAS,NRAS,BRAF gene mutations and MSI status in colorectal adenocarcinoma and their clinical significance.Methods The clinical data of 237 cases of colorectal adenocarcinoma were collected to interpret tumor budding.RT-PCR was used to detect the gene mutations of KRAS,NRAS,BRAF in 229 cases and to analyze the corre-lation between tumor budding and gene mutations.MSI was de-tected by PCR and its relationship with tumor budding was ana-lyzed.Results Of the 237 patients,147 showed low-to medi-um-grade tumor budding and 90 showed high-grade tumor bud-ding.Tumor budding was associated with tumor size,vascular involvement,perineural invasion,tumor differentiation,lymph node metastasis,tumor nodule formation,tumor recurrence and TNM staging(P＜0.05),while it was not associated with age,sex and location.Single factor logistic regression analysis showed that tumor budding was associated with the risk of lymph node metastasis(P＜0.05),while multivariate logistic regres-sion analysis showed that tumor budding was an independent pre-dictor of lymph node metastasis in colorectal adenocarcinoma(P＜0.05).Of the 229 cases,the mutation rate of KRAS,NRAS and BRAF was 42.4％,2.6％and 3.1％,respectively.A-mong KRAS,NRAS and BRAF mutation cases,the proportion of high-grade tumor budding was 56.7％,33.3％and 14.3％,respectively.Tumor budding was associated with mutations in the Kras 12 and Kras 13 codons,as well as KRAS total muta-tions(P＜0.05).However,tumor budding had no relationship with NRAS and BRAF.In the high-grade budding tumors,KRAS mutations were mainly KRAS codons 12 and 13.Among the cases with KRAS mutation,the disease-free survival time and total survival time of the cases with high-grade tumor bud-ding were significantly shorter(P＜0.05).Of the 237 patients,the rate of MSI-H was 6.8％and only 2 out of 16 MSI-H pa-tients had high-grade tumor budding.There was a negative cor-relation between tumor budding and MSI status(r=-0.143,P＜0.05).Conclusion Tumor budding is related to the muta-tions in the Kras 12 and Kras 13 codons,as well as total KRAS mutations and MSI status.Tumor budding is also related to the prognosis of patients with colorectal adenocarcinoma,which can provide a reference for their outcome judgment.

Evolución de la mortalidad por cáncer colorrectal en Chile: un estudio de 25 años (1997-2022) / Colorectal cancer mortality evolution in Chile: a 25 years study (1997-2022)

El cáncer colorrectal (CCR) es un problema de salud prevalente y significativo a nivel mundial, especialmente en países desarrollados. Este estudio tuvo como objetivo evaluar la tasa de mortalidad por CCR en Chile en los últimos 25 años. Se llevó a cabo un estudio descriptivo ecológico utilizando datos públicos de mortalidad desde 1997 hasta 2022, que incluyeron un total de 50.944 defunciones. Los resultados revelaron que el cáncer de colon representó la mayoría de los casos (72,15%) donde el colon sigmoide fue el sitio más afectado. La tasa de mortalidad promedio fue de 11,19 por cada 100.000 habitantes, mostrando un aumento significativo a lo largo del tiempo. El análisis por edad indicó una mayor carga de mortalidad en individuos de 75 a 90 años. Se observó disparidades de género, con predominio de muertes femeninas hasta el año 2019. El análisis de la tasa ajustada por región reveló diferencias no significativas en las tasas de mortalidad, siendo Valparaíso y Magallanes y Antártica Chilena las regiones con tasas más altas para el cáncer de colon y el cáncer de recto, respectivamente. Estos hallazgos contribuyen a nuestra comprensión de la epidemiología del CCR en Chile y enfatizan la necesidad de intervenciones específicas en prevención primaria y screening para reducir la mortalidad por esta enfermedad.

Colorectal cancer (CRC) is a prevalent and significant health problem worldwide, especially in developed countries. The aim of this study was to evaluate the CRC mortality rate in Chile in the last 25 years. An ecological descriptive study was carried out using public mortality data from 1997 to 2022, which included a total of 50,944 deaths. The results revealed that colon cancer represented the majority of cases (72.15%) where the sigmoid colon was the most affected site. The average mortality rate was 11.19 per 100,000 individuals, showing a significant increase over time. The analysis by age showed a greater burden of mortality in individuals from 75 to 90 years. Gender disparities were observed, with a predominance of female deaths until 2019. The analysis of the rate configured by region revealed non-significant differences in mortality rates, with Valparaíso and Magallanes and Antártica Chilena being the regions with the highest rates for colon and rectal cancer, respectively. These findings contribute to our understanding of the epidemiology of CRC in Chile and emphasize the need for specific interventions in primary prevention and screening to reduce mortality from this disease.

Grandes e pequenas lesões colorretais são efetivamente tratadas pela técnica de mucosectomia / Small as well as large colorectal lesions are effectively managed by endoscopic mucosal resection technique

ABSTRACT Background Endoscopic mucosal resection (EMR) is an easy-to-use treatment option for superficial colorectal lesions, including lesions ≥20 mm. Objective To evaluate the effectiveness of EMR. Methods We evaluated 430 lesions removed by EMR in 404 patients. The lesions were analyzed according to their morphology, size, location, and histology. Lesions <20 mm were resected en bloc, whereas lesions ≥20 mm were removed by piecemeal EMR (p-EMR). Adverse events and recurrence were assessed. Results Regarding morphology, 145 (33.7%) were depressed lesions, 157 (36.5%) were polypoid lesions and 128 (29.8%) were laterally spreading lesions, with 361 (84%) lesions <20 mm and 69 (16%) ≥20 mm. Regarding histology, 413 (96%) lesions were classified as neoplastic lesions. Overall, 14 (3.3%) adverse reactions occurred, most commonly in lesions removed by p-EMR (P<0.001) and associated with advanced histology (P=0.008). Recurrence occurred in 14 (5.2%) cases, more commonly in lesions removed by p-EMR (P<0.001). Conclusion EMR is an effective technique for the treatment of superficial colorectal lesions, even of large lesions.

RESUMO Contexto Ressecção endoscópica da mucosa (REM) é uma opção fácil para o tratamento das lesões superficiais do cólon e reto, inclusive para as lesões ≥20 mm de diâmetro. Objetivo Avaliar a efetividade da REM. Métodos Este estudo prospectivo observacional avaliou 430 lesões ressecadas por REM em 404 pacientes. As lesões foram analisadas de acordo com a morfologia, tamanho, localização e histologia. Lesões <20 mm foram removidas em bloco, enquanto lesões ≥20 mm foram ressecadas em piecemeal REM (p-REM). Eventos adversos e recorrência foram avaliados. Resultados Quanto à morfologia, 145 (33,7%) eram lesões deprimidas, 157 (36,5%) eram lesões polipoides e 128 (29,8%) eram lesões que se espalham lateralmente, com 361 (84%) lesões <20 mm e 69 (16%) ≥20 mm. Em relação à histologia, 413 (96%) foram classificadas como lesões neoplásicas. Globalmente tivemos 14 (3,3%) de reações adversas, mais presente nas lesões ≥20 mm removidas por p-REM (P<0,001) e associadas com histologia avançada (P=0,008). A recorrência ocorreu em 14 (5,2%) casos, sendo mais observada em lesões removidas por p-REM (P<0,001). Conclusão REM é uma técnica efetiva para o tratamento das lesões colorretais superficiais, até mesmo para as grandes lesões.

Relationship between postoperative delirium and preoperative modified frailty index in elderly patients undergoing colorectal cancer surgery / 中华麻醉学杂志

Objective:To evaluate the relationship between postoperative delirium and preoperative modified frailty index (mFI) score in elderly patients undergoing colorectal cancer surgery.Methods:The medical records of elderly patients of either sex, aged 65-90 yr, with primary tumor, without radiotherapy and chemotherapy before operation, with the expected operating time ≥ 2 h, undergoing colorectal cancer surgery under general anesthesia, were collected.The patients′ preoperative frailty was assessed using mFI scale.Primary outcome was the incidence of delirium within 7 days after operation, and delirium was assessed using Confusion Assessment Method.The preoperative baseline characteristics, BI score, mFI score and Mini-Mental State Examination were recorded; anesthesia-related information, surgery-related information, intraoperative adverse events, total volume of intraoperative fluid infused, blood loss, and urine output were recorded.The patients were divided into delirium group (D group) and non-delirium group (N group) according to whether delirium occurred or not, and logistic regression analysis was used to screen the risk factors for postoperative delirium in elderly patients with colorectal cancer.Results:A total of 370 patients were enrolled in this study, and the incidence of delirium was 10.8%.There were significant differences in age, ASA grading ratio, mFI score, anesthetic time and total volume of intraoperative fluid infused between group N and group D ( P<0.05). The results of multivariate logistic regression analysis showed that increased age and mFI were independent risk factors for the occurrence of postoperative delirium ( P<0.05). Conclusions:Increased mFI score and age are independent risk factors for postoperative delirium in elderly patients undergoing colorectal cancer.

Diagnostic efficacy of hypersensitivity quantitative fecal immunochemical test in colorectal cancer and advanced adenoma / 中华消化杂志

Objective:To evaluate the diagnostic efficiency of hypersensitivity quantitative fecal immunochemical test (hs-qFIT) in colorectal cancer (CRC) and advanced adenoma.Methods:From July to December 2020, consecutive patients aged 50 to 75 years who underwent colonoscopy in Qilu Hospital of Shandong University, and had the Asia-Pacific colorectal screening score of medium or high risk were enrolled. All patients were requested to complete two hs-qFIT before colonoscopy. The diagnostic efficacy of hs-qFIT for CRC and advanced adenoma were assessed. Receiver operating characteristic curve of hs-qFIT in CRC diagnosis was drawn and the area under the curve (AUC) was calculated.Results:A total of 811 patients including 20 (2.5%) cases of CRC, 47 (5.8%) cases of advanced adenoma, 206 (25.4%) cases of non-advanced adenoma, 219 (27.0%) cases of non-adenomatous polyp, 76 (9.4%) cases of other colorectal lesions and 243 (30.0%) cases of non-colorectal lesions were involved. When the fecal hemoglobin cut-off values were 10, 30, 50, 75 and 100 ng/mL, the positive rates of hs-qFIT detection were 17.9% (145/811), 10.9% (88/811), 8.3% (67/811), 7.4% (60/811) and 5.8% (47/811), respectively. When the cut-off value of fecal hemoglobin decreased from 100 ng/mL to 10 ng/mL, the sensitivity of hs-qFIT for CRC diagnosis increased from 90.0% to 100.0%, and the specificity decreased from 96.3% to 84.2%; and the sensitivity of hs-qFIT for the diagnosis of advanced adenoma increased from 19.1% to 66.0%, and the specificity decreased from 95.0% to 85.1%. The AUC of hs-qFIT for the diagnosis of CRC and advanced adenoma were 0.981 (95% confidence interval ( CI) 0.970 to 0.992) and 0.846 (95% CI 0.807 to 0.886), respectively. When the optimal cut-off values were taken, the sensitivity and specificity were 100.0% and 91.2% for the diagnosis of CRC, and 66.0% and 85.3% for the diagnosis of advanced adenoma, respectively. Conclusion:Hs-qFIT can help the early screening of CRC and advanced adenoma.

Association between body composition measured by bioelectrical impedance analysis and platelet-to-lymphocyte ratio in colorectal cancer

PURPOSE: This study investigated the relationship between body composition and platelet-to-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC).METHODS: This retrospective study included 110 patients who underwent anthropometric measurement by bioelectrical impedance analysis before surgical treatment for CRC between May 2015 and June 2018.RESULTS: According to PLR, 45 patients (40.9%) had low PLR (PLR<150), and 65 patients (59.1%) had high PLR (PLR≥150). Serum hemoglobin (P<0.001) and albumin levels (P=0.021) were significantly lower in high PLR group. Tumor mass diameter was significantly larger in high PLR group (P=0.048) and the proportion of poorly differentiated or mucinous tumors was significantly higher in high PLR group (P=0.037). All indices related to fat (body fat mass, percent body fat, body fat mass of trunk, visceral fat area, fat mass index, measured fat thickness of abdomen) and two indices related to muscle (arm muscle circumference, measured muscle circumference of abdomen) were significantly lower in high PLR group (P<0.05). According to subgroup analysis based on the sex, all indices significantly differed between PLR groups; however, in females no index was significantly different between PLR groups.CONCLUSION: Body composition indices including fat and muscle indices measured by InBody 770 were related to PLR in CRC, especially in male patients. These results suggest that low muscle and fat indices may be related to poor prognosis of CRC.

Application of urinary 5- aminolevulinic acid detection in screening and identification of colorectal cancer and adenomatous polyps / 中国医师进修杂志

Objective To study the application of urinary 5-aminolevulinic acid (5-ALA) detection in screening and identification of colorectal cancer and adenomatous polyps. Methods The clinical data of 500 high-risk patients(including 22 cases with colorectal cancer, 134 cases with adenomatous polyps, and 344 cases with other patients) at the First Affiliated Hospital of Hebei North University from January 2018 to October 2018 were collected. High performance liquid chromatography (HPLC) was used to detect urinary 5-ALA and fecal occult blood test was used to detect faeces. Sensitivity and specificity of two methods was compared. At the same time, urine samples of 431 cases (including 22 cases with colorectal cancer, 134 cases with adenomatous polyps and 275 cases with colorectal normal mucosa)were collected, and the difference of the content of urinary 5-ALA among three groups was compared. Results The sensitivity of urinary 5-ALA for the colorectal cancer screening was 74.9% , and the specificity was 72.5% . The sensitivity of urinary 5-ALA for the adenomatous polyps screening was 70.1% , and the specificity was75.0% . The sensitivity of fecal occult blood test for the colorectal cancer screening was 63.6% , and the specificity was 62.1% . The sensitivity of fecal occult blood test for the adenomatous polyps screening was 42.3%, and the specificity was 62.5%. The content of urinary 5-ALA of the colorectal cancer group [(9.35 ± 0.46) μmol/g] was significantly higher than that of the adenomatous polyps group [(7.24 ± 0.64) μmol/g] (P<0.05) and normal colorectal mucosa group [(3.12 ± 0.24) μmol/g] (P<0.05), and the content of urinary 5-ALA of the adenomatous polyps group was significantly higher than that of colorectal normal mucosa group (P<0.05). Conclusions For screening of colorectal cancer and adenomatous polyps, the content of urinary 5-ALA by HPLC is better than fecal occult blood test, and this approach can do great help to identify colorectal cancer, adenomatous polyps and normal colorectal mucosa.

Application of urinary 5-aminolevulinic acid detection in screening and identification of colorectal cancer and adenomatous polyps / 中国医师进修杂志

Objective@#To study the application of urinary 5-aminolevulinic acid (5-ALA)detection in screening and identification of colorectal cancer and adenomatous polyps.@*Methods@#The clinical data of 500 high-risk patients(including 22 cases with colorectal cancer, 134 cases with adenomatous polyps, and 344 cases with other patients) at the First Affiliated Hospital of Hebei North University from January 2018 to October 2018 were collected. High performance liquid chromatography(HPLC) was used to detect urinary 5-ALA and fecal occult blood test was used to detect faeces. Sensitivity and specificity of two methods was compared. At the same time, urine samples of 431 cases(including 22 cases with colorectal cancer, 134 cases with adenomatous polyps and 275 cases with colorectal normal mucosa)were collected, and the difference of the content of urinary 5-ALA among three groups was compared.@*Results@#The sensitivity of urinary 5-ALA for the colorectal cancer screening was74.9%, and the specificity was 72.5%. The sensitivity of urinary 5-ALA for the adenomatous polyps screening was 70.1%, and the specificity was75.0%. The sensitivity of fecal occult blood test for the colorectal cancer screening was 63.6%, and the specificity was 62.1%. The sensitivity of fecal occult blood test for the adenomatous polyps screening was 42.3%, and the specificity was 62.5%. The content of urinary 5-ALA of the colorectal cancer group [(9.35 ± 0.46) μmol/g] was significantly higher than that of the adenomatous polyps group [(7.24 ± 0.64) μmol/g] (P < 0.05) and normal colorectal mucosa group [(3.12 ± 0.24) μmol/g] (P < 0.05), and the content of urinary 5-ALA of the adenomatous polyps group was significantly higher than that of colorectal normal mucosa group (P < 0.05).@*Conclusions@#For screening of colorectal cancer and adenomatous polyps, the content of urinary 5-ALA by HPLC is better than fecal occult blood test, and this approach can do great help to identify colorectal cancer, adenomatous polyps and normal colorectal mucosa.

The status analysis of diagnosis and treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China: a report of 1 003 cases in 16 domestic medical centers / 中华外科杂志

Objective@#To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China.@*Methods@#Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ2 test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method.@*Results@#Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ2=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection.@*Conclusions@#It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.

Application of D2-40/CD34-CK cocktail antibodies for colorectal cancer with insufficient lymph node harvest / 临床与实验病理学杂志

Purpose To investigate the value of application of D2-40/CD34-CK cocktail antibodies by double immunohistochemical staining for assessment of lymphovascular invasion (LVI) and to determine its prognostic significance in colorectal cancer with insufficient lymph node harvest. Methods Specimens from 133 cases of colorectal cancer with less than 12 lymph nodes were selected. HE staining and double immunohistochemical staining of the cocktail antibodies were performed to compare the difference of the two methods in screening for LVI. The The relationship between LVI confirmed by cocktail antibody immunohistochemical staining and clinicopathological characteristics and overall survival (OS) of patients was analyzed. Results (1) The detection rates of cocktail antibody double immunohistochemical staining and HE staining for LVI were 42.9％ (57/133) and 21.8％ (29/133) with statistically significant difference (P < 0.001). (2) The presence of LVI confirmed by double staining was significantly associated with Dukes staging, depth of invasion, clinical stages, lymph node metastasis and tumor budding (P < 0.05). (3) The presence of LVI, the location and extent of LVI, and the number of tumor cells in thrombus ≥5.5 for cases with LVI ≤2 clusters, were significantly associated with OS (P < 0.05). Conclusion D2-40/CD34-CK cocktail antibodies double staining is superior to routine HE staining in assessing LVI. LVI is intimately associated with tumor stage, lymph nodes metastasis and tumor budding, and it is an independent prognostic factor for CRC patients. It should be a supplementary examination for these patients with insufficient lymph node harvest.

Expression of Fascin-1 and β-catenin protein in colorectal adenocarcinoma and its relevance with K-ras gene mutations / 临床与实验病理学杂志

Purpose To examine the expression of Fascin-1 and β-catenin protein and K-ras gene mutation in colorectal adenocarcinoma, and to explore their role in progression of colorectal neoplasm and their relevance. Methods Fascin-1 and β-catenin were analyzed by use of immunohistochemistry En Vision two-step. K-ras gene mutation was detected by ARMS method.Relationship between overexpression of Fascin-1, the nuclear expression of β-catenin, and the mutations of K-ras gene and clinicopathologic parameters was analyzed, the correlation between them was also analyzed. Results In 112 colorectal adenocarcinoma samples, the overexpression rate of Fascin-1 protein was 27.7％ (31/112), significantly higher than non-neoplastic mucosa (P < 0.01). The high nuclear expression rate of β-catenin was 29.5％ (33/112) in adenocarcinoma and non-neoplastic mucosa respectively with a significant difference between two groups (P < 0.01). High expression rate of Fascin-1 protein and β-catenin were correlated significantly with lymph node metastasis (P = 0.022, P = 0.027), and TNM staging (P =0.042, P = 0.019) in colorectal adenocarcinoma. The overexpression of Fascin-1 protein was correlated with tumor location (P = 0.004). The mutation rate of K-ras gene was 34.8％ (39/112), which showed no correlation with age, gender, tumor size, grade of differentiation, lymph node metastasis and TNM staging (P> 0.05). There was a correlation between the overexpressison of Fascin-1 protein, the nuclear expression of β-catenin and the mutation of K-ras gene (rs= 0.252, rs= 0.258, P < 0.05). The overexpression of Fascin-1 protein positively correlated with the nuclear expression of β-catenin (rs= 0.213, P < 0.05). Conclusion Fascin-1 protein and β-catenin protein are involved in invasion and metastasis of colorectal cancer and are associated with K-ras gene mutation. K-ras may promote the overexpression of Fascin-1 by virtue of nuclear expression ofβ-catenin, which provided a new research direction on the treatment of K-ras gene mutated colorectal adenocarcinoma.

Development and validation of a scoring system for advanced colorectal neoplasm in young Korean subjects less than age 50 years

BACKGROUND/AIMS: Colorectal cancer incidence among patients aged ≤50 years is increasing. This study aimed to develop and validate an advanced colorectal neoplasm (ACRN) screening model for young adults aged <50 years in Korea. METHODS: This retrospective cross-sectional study included 59,575 consecutive asymptomatic Koreans who underwent screening colonoscopy between 2003 and 2012 at a single comprehensive health care center. Young Adult Colorectal Screening (YCS) score was developed as an optimized risk stratification model for ACRN using multivariate analysis and was internally validated. The predictive power and diagnostic performance of YCS score was compared with those of Asia-Pacific Colorectal Screening (APCS) and Korean Colorectal Screening (KCS) scores. RESULTS: 41,702 and 17,873 subjects were randomly allocated into the derivation and validation cohorts, respectively, by examination year. ACRN prevalence was 0.9% in both cohorts. YCS score comprised sex, age, alcohol, smoking, obesity, glucose metabolism abnormality, and family history of CRC, with score ranges of 0 to 10. In the validation cohort, ACRN prevalence was 0.6% in the low-risk tier (score, 0–4), 1.5% in the moderate-risk tier (score, 5–7), and 3.4% in the high-risk tier (score, 8–10). ACRN risk increased 2.5-fold (95% confidence interval [CI], 1.8–3.4) in the moderate-risk tier and 5.8-fold (95% CI, 3.4–9.8) in the high-risk tier compared with the low-risk tier. YCS score identified better balanced accuracy (53.9%) than APCS (51.5%) and KCS (50.7%) scores and had relatively good discriminative power (area under the curve=0.660). CONCLUSIONS: YCS score based on clinical and laboratory risk factors was clinically effective and beneficial for predicting ACRN risk and targeting screening colonoscopy in adults aged <50 years.

Screening for Lung Cancer Using Low-dose Chest Computed Tomography in Korean Long-term Colorectal Cancer Survivors

BACKGROUND: The National Lung Screening Trial (NLST) and NELSON trial showed that low-dose chest computed tomography (LDCT) screening significantly reduced the mortality form lung cancer. Although cancer survivors are known to have high risk for second malignant neoplasm (SMN), the usefulness of LDCT screening for lung cancer in cancer survivors is not clear. METHODS: Between August 2016 and August 2017, 633 long-term colorectal cancer (CRC) survivors visited the survivorship clinic in Cancer Prevention Center, Yonsei Cancer Center, Seoul, Republic of Korea. We surveyed the smoking status and recommended LDCT screening to ever-smoking CRC survivors aged 55–80 years. The participants were classified into three risk groups: risk group 1 (RG1) who met the NLST criteria (Age 55–74 years, ≥ 30 pack-years of smoking, smoking cessation < 15 years); risk group 2 (RG2) who would not meet the NLST criteria but were at increased 6-year risk of lung cancer (PLCOM2012 ≥ 0.0151); risk group 3 (RG3) who did not meet any of the criteria above. RESULTS: Among 176 ever-smoking CRC survivors, 173 (98.3%) were male, 32 (18.2%) were current-smoker, and median age was 66 years (range, 55–79 years). We found 38 positive findings (non-calcified nodule ≥ 4 mm), 8 clinically significant findings, 66 minor abnormalities, and 64 negative findings on LDCT. Positive findings were identified in 15 of 79 (19.0%) of RG1, in 9 of 36 (25%) of RG2, and in 14 of 61 (23.0%) of RG3. Second primary lung cancers were found in 2 patients of RG2, and in 1 patient of RG3. SMN was most frequently found in RG2 (11 of 36 patients, 30.6%), compared with RG1 (12.7%) or RG3 (9.8%) (P = 0.016). CONCLUSIONS: LDCT screening for lung cancer in Korean CRC survivors is feasible. Well-designed clinical trial for defining high risk patients for lung cancer among CRC survivors is needed.

Chemotherapy for Patients with Colorectal Cancer - When and How? / 대한소화기암학회지

It is important to choose the appropriate treatment option for patients with colorectal cancer (CRC), because it could affect the prognosis of patients. Chemotherapy is effective in prolonging survival and time to progression in patients with advanced CRC. Adjuvant chemotherapy have been reported to reduce the recurrence rate of colorectal cancer by 30% in patients with stage 3 or high risk of stage 2 CRC. Although palliative chemotherapy does not offer long-term benefits, as life expectancy remains below 12 months in most of those receiving treatment, recent developments in the treatment including target agents and immunotherapy have improved the median overall survival time in patients with metastatic CRC by up to 30 months. Chemotherapy for patients with CRC is classified into neoadjuvant, adjuvant, and palliative therapy according to the status of patients. In this review, I summarized the chemotherapy for patients with CRC, which applying in clinical practice.

Application of intestinal CT texture analysis and nonlinear discriminant analysis in differential diagnosis of colorectal cancer and ulcerative colitis / 上海交通大学学报（医学版）

Objective • To evaluate the value of texture analysis in the discrimination of colorectal cancer (CRC) and ulcerative colitis (UC). Methods • The CT images of 61 CRC patients, 62 UC patients and 42 control objects were retrospectively analyzed. All the patients were pathologically proved and performed triphasic contrast-enhanced CT scan: non-enhanced phase (NP), the arterial phase (AP) and the enteric phase (EP). The region of interest was drawn along the abnormal bowel wall's edge in each scan phase and texture features were generated by MaZda software. Based on 3 texture feature selection methods, the optimal subsets were generated and analyzed by 6 texture feature classification methods. The results were shown by misclassification rate (MCR). To compare the performance of texture-based classification and human visual classification, two radiologists with more than 10 years of gastrointestinal disease diagnostic experience analyzed the data. Results • The texture analysis based average MCR of differentiation between CRC and UC was (28.42±6.89)%, (28.19±4.07)%, (19.10±3.58)% in NP, AP, EP respectively. Compared with other texture feature classification methods, nonlinear discriminant analysis (NDA) was more accurate. In EP, NDA achieved an excellent classification result (MCR=12.61%). The average MCR between CRC and normally dilated bowel wall (NOR) was (13.33±7.21)%, (15.49±5.47)%, (6.74±3.02)%, while the average MCR between UC and NOR was (19.26±4.68)%, (20.04±6.63)%, (16.74±6.36)% in NP, AP and EP respectively. For visual classification between CRC and UC, the average MCR was (40.48±3.21)%, (35.71±1.60)%, (26.43±1.15)% in NP, AP, EP respectively. But the MCR of texture classification was lower than that of human vision classification, and computer texture classification had higher differential diagnosis rate. Conclusion • The CT-based texture analysis could be a feasible supplementary method to differentiate CRC from UC. NDA is more accurate than other classification methods, especially in EP.

Clinicopathologic characteristics and survival rate in patients with synchronous or metachronous double primary colorectal and gastric cancer

PURPOSE: Double primary colorectal cancer (CRC) and gastric cancer (GC) represent the most common multiple primary malignant tumors (MPMT) in Korea. The recognition and screening of hidden malignancies other than the primary cancer are critical. This study aimed to investigate the clinicopathologic characteristics and survival rates in patients with synchronous or metachronous double primary CRC and GC.METHODS: Between January 1994 and May 2018, 11,050 patients were diagnosed with CRC (n=5,454) or GC (n=5,596) at Gil Medical Center. MPMT and metastatic malignant tumors were excluded from this study. A total of 103 patients with double primary CRC and GC were divided into two groups: the synchronous group (n=40) and the metachronous group (n=63). The incidence, clinicopathologic characteristics, and survival rate of the two groups were analyzed.RESULTS: The incidence of synchronous and metachronous double primary CRC and GC was 0.93%. Double primary CRC and GC commonly occurred in male patients aged over 60 years with low comorbidities and minimal previous cancer history. There were significant differences between the synchronous and metachronous groups in terms of age, morbidity, and overall survival. Metachronous group patients were 6 years younger on average (P=0.009), had low comorbidities (P=0.008), and showed a higher 5-year overall survival rate (94.8% and 61.3%, P < 0.001) in contrast to synchronous group.CONCLUSION: When primary cancer (CRC or GC) is detected, it is important to be aware of the possibility of the second primary cancer (GC or CRC) development at that time or during follow-up to achieve early detection and better prognosis.

Analysis of community colorectal cancer screening in 50-74 years old people in Guangzhou,2015-2016 / 中华流行病学杂志

Objective To analyze the effect of colorectal cancer screening in the general population in Guangzhou,and provide evidence for the for development of colorectal cancer screening policy and strategy.Methods The data of colorectal cancer screening in Guangzhou during 2015-2016 were collected.The participation,the positive rate of fecal occult blood test,the detection rate of colonoscopy and screening effect of colonoscopy were evaluated.Results A total of 220 834 residents aged 50-74 years received the screening,and the positive rate of the screening was 16.77％ (37 040 cases).Colonoscopy was performed for 7 821 cases (21.12％).Colorectal lesions were found in 4 126 cases (52.76％),of which 614 (7.85％) and 73 (0.93％) and 230 (2.94％) were identified as advanced adenoma,severe dysplasia lesions and colorectal cancers,respectively.The detection rates of all colorectal lesions were higher in men than in women (all P＜0.01).The diagnostic rate of early lesion was 87.24％,and 99 early cancer cases were found,accounting for 46.26％ of the total cases.The overall screening detection rate of colorectal cancer was 104.15/100 000,higher than the incidence rate (81.18/100 000) in colorectal cancer surveillance (P＜0.001),but age group ＜70 years had higher detection rate,age group ≥70 years had higher incidence rate.Conclusions The colorectal cancer screening strategy in Guangzhou is effective in the detection of the population at high risk,increase the detection rate of colorectal lesions,early diagnosis rate of precancerous lesions and diagnosis rate of early colorectal cancer.The benefit in those aged ≤69 years was more obvious than that in those aged 70-74 years.It is necessary to improve the compliancy of colorectal cancer screening in population at high risk.

Analysis of community colorectal cancer screening in 50-74 years old people in Guangzhou, 2015-2016 / 中华流行病学杂志

Objective: To analyze the effect of colorectal cancer screening in the general population in Guangzhou, and provide evidence for the for development of colorectal cancer screening policy and strategy. Methods: The data of colorectal cancer screening in Guangzhou during 2015- 2016 were collected. The participation, the positive rate of fecal occult blood test, the detection rate of colonoscopy and screening effect of colonoscopy were evaluated. Results: A total of 220 834 residents aged 50-74 years received the screening, and the positive rate of the screening was 16.77% (37 040 cases). Colonoscopy was performed for 7 821 cases (21.12%). Colorectal lesions were found in 4 126 cases (52.76%), of which 614 (7.85%) and 73 (0.93%) and 230 (2.94%) were identified as advanced adenoma, severe dysplasia lesions and colorectal cancers, respectively. The detection rates of all colorectal lesions were higher in men than in women (all P<0.01). The diagnostic rate of early lesion was 87.24%, and 99 early cancer cases were found, accounting for 46.26% of the total cases. The overall screening detection rate of colorectal cancer was 104.15/100 000, higher than the incidence rate (81.18/100 000) in colorectal cancer surveillance (P<0.001), but age group <70 years had higher detection rate, age group ≥70 years had higher incidence rate. Conclusions: The colorectal cancer screening strategy in Guangzhou is effective in the detection of the population at high risk, increase the detection rate of colorectal lesions, early diagnosis rate of precancerous lesions and diagnosis rate of early colorectal cancer. The benefit in those aged ≤69 years was more obvious than that in those aged 70-74 years. It is necessary to improve the compliancy of colorectal cancer screening in population at high risk.

Serrated neoplasia pathway as an alternative route of colorectal cancer carcinogenesis

In the past two decades, besides conventional adenoma pathway, a subset of colonic lesions, including hyperplastic polyps, sessile serrated adenoma/polyps, and traditional serrated adenomas have been suggested as precancerous lesions via the alternative serrated neoplasia pathway. Major molecular alterations of sessile serrated neoplasia include BRAF mutation, high CpG island methylator phenotype, and escape of cellular senescence and progression via methylation of tumor suppressor genes or mismatch repair genes. With increasing information of the morphologic and molecular features of serrated lesions, one major challenge is how to reflect this knowledge in clinical practice, such as pathologic and endoscopic diagnosis, and guidelines for treatment and surveillance.