Blood group type antigens in pancreatic intraductal papillary mucinous neoplasms

BACKGROUND: There are few data on blood group(BG) types and types of pancreatic cancers. The aims of this study were to study BG types and BG-antigens in pancreatic intraductal papillary mucinous neoplasms(IPMNs). METHODS: BG type and tumor BG-antigen(glycoprotein) expression(studied by immunohistochemistry on tissue microarrays) were analyzed with regard to characteristics of 101 surgically resected pancreatic IPMNs. RESULTS: Non-O BG type predicted invasive carcinoma independently from high serum CA19-9 and male gender. BG type A was observed more frequently in women than in men. Chronic pancreatitis was more frequently seen in patients with BG type B or AB. Aberrant tumor expression(with regard to BG type) of loss of A antigen expression type occurred in 15.0% of IPMNs and of loss of B antigen expression type in 62.5% of IPMNs. Intraneoplasm BG-antigen expression was not related to dysplasia grade or invasion. CONCLUSION: The results of the study suggest that in pancreatic IPMN, non-O BG type predicted invasive carcinoma, whereas for intratumor BG-antigen expression no specific patterns were detected with regard to the progression of glandular epithelial dysplasia or invasion.

Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

Serum IgG response to differentiated antigens of Helicobacter pylori

AIM To detect antibodies against Helicobacter pylori spiral and coccoid antigens in human sera. METHODS Blood samples were collected from 278 patients with gastric diseases. A 3 day old culture of H. pylori on chocolate blood agar was used to provide spiral form. ‘Synchronous’ coccoids were cultured in (BHY) (brain heart infusion supplemented with 10% horse serum and 0 4% yeast extract) medium in a chemostat. Antigens from spiral and coccoid form were prepared using acid glycine extraction. Enzyme linked immunosorbent assay (ELISA) was performed to detect serum IgG antibodies against spiral and coccoid forms of H. pylori . RESULTS Seroprevalence of H. pylori infection was higher in patients with gastric ulcer (79%) and gastric cancer (83%) than those with non ulcer dyspepsia (NUD) (44%) and other diseases (45%) ( P <0 05). IgG antibodies against spiral and coccoid antigens were detected in 50 7% (141/278) and 49 6% (138/278) , respectively. CONCLUSION The spiral and coccoid forms of H. pylori coexist in patients infected with the bacterium.

Relationship between expression of apoptosis-related antigens in hepatocelular carcinoma and in situ end labeling

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Trends and hotspots in gastrointestinal neoplasms risk assessment: A bibliometric analysis from 1984 to 2022

BACKGROUND Gastrointestinal neoplasm(GN)significantly impact the global cancer burden and mortality,necessitating early detection and treatment.Understanding the evolution and current state of research in this field is vital.AIM To conducts a comprehensive bibliometric analysis of publications from 1984 to 2022 to elucidate the trends and hotspots in the GN risk assessment research,focusing on key contributors,institutions,and thematic evolution.METHODS This study conducted a bibliometric analysis of data from the Web of Science Core Collection database using the"bibliometrix"R package,VOSviewer,and CiteSpace.The analysis focused on the distribution of publications,contributions by institutions and countries,and trends in keywords.The methods included data synthesis,network analysis,and visualization of international collaboration networks.RESULTS This analysis of 1371 articles on GN risk assessment revealed a notable evolution in terms of research focus and collaboration.It highlights the United States'critical role in advancing this field,with significant contributions from institutions such as Brigham and Women's Hospital and the National Cancer Institute.The last five years,substantial advancements have been made,representing nearly 45%of the examined literature.Publication rates have dramatically increased,from 20 articles in 2002 to 112 in 2022,reflecting intensified research efforts.This study underscores a growing trend toward interdisciplinary and international collaboration,with the Journal of Clinical Oncology standing out as a key publication outlet.This shift toward more comprehensive and collaborative research methods marks a significant step in addressing GN risks.CONCLUSION This study underscores advancements in GN risk assessment through genetic analyses and machine learning and reveals significant geographical disparities in research emphasis.This calls for enhanced global collaboration and integration of artificial intelligence to improve cancer prevention and treatment accuracy,ultimately enhancing worldwide patient care.

Clinicopathological features and survival analysis of gastroenteropancreatic neuroendocrine neoplasms: a retrospective study in a single center of China

Objective： To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms（GEP-NENs） in a Chinese population.Methods： We investigated 154 consecutive patients（88 males, 66 females; median age 56 years, age range 9-86 years） diagnosed with GEP-NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved.Results： The pancreas was the most common site of involvement（63/154, 40.9%）. Tumor size varied from 0.3 to 16.0 cm（median, 1.2 cm）. The patients were followed up for a median period of 22 months（range, 1-157 months）. The estimated 3- and 5-year overall survival（OS） rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome.Conclusions： Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.

Analysis of Significant Genes and Pathways in Esophageal Cancer Based on Gene Expression Omnibus Database

Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes,and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis,protein-protein interaction(PPI)network,and survival analysis based on the Gene Expression Omnibus(GEO)database.Methods By screening with highly expressed genes,we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites.Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis,PPI network,and survival analysis.Several software and platforms including Prism 8,R language,Cytoscape,DAVID,STRING,and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma(ESCC)tissue.Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer.Four genes including ALDH3A1,C2,SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer.Keratinization may greatly impact the pathogenesis of esophageal cancer.Genes ALDH3A1,C2,SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.

Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation

Donor human leukocyte antigen(HLA)-specific antibodies(DSA) play an important role in solid organ transplantation. Preexisting IgG isotype DSA are considered a risk factor for antibody mediated rejection, graft failure or graft loss. The post-transplant development of DSA depends on multiple factors including immunogenicity of mismatched antigens, HLA class Ⅱ typing of the recipient, cytokine gene polymorphisms, and cellular immunoregulatory mechanisms. De novo developed antibodies require special attention because not all DSA have equal clinical significance. Therefore, it is important for transplant clinicians and transplant immunologists to accurately characterize DSA. In this review, the contemporary immunological techniques for detection and characterization of anti-HLA antibodies and their pitfalls are described.

Identification of distant co-evolving residues in antigen 85C from Mycobacterium tuberculosis using statistical coupling analysis of the esterase family proteins

A fundamental goal in cellular signaling is to understand allosteric communication, the process by which sig-nals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Statistical coupling analysis （SCA） is a statistical technique that uses evolutionary data of a protein family to measure correlation between distant functional sites and suggests allosteric communication. In proteins, very distant and small interactions between collections of amino acids provide the communication which can be important for signaling process. In this paper, we present the SCA of protein alignment of the esterase family （pfam ID： PF00756） containing the sequence of antigen 85C secreted by Mycobacterium tuberculosis to identify a subset of interacting residues. Clustering analysis of the pairwise correlation highlighted seven important residue positions in the esterase family alignments. These resi-dues were then mapped on the crystal structure of antigen 85C （PDB ID： 1DQZ）. The mapping revealed corre-lation between 3 distant residues （Asp38, Leu123 and Met125） and suggests allosteric communication between them. This information can be used for a new drug against this fatal disease.

Meta analysis of safety and effectiveness of anastomosis of esophagus and jejunum overlap in total laparoscopic total gastrectomy

Objective:To systematically evaluate and compare the safety and effectiveness of esophagojejunostomy and traditional esophagojejunostomy in total laparoscopic total gastrectomy in the treatment of gastric cancer,providing evidence-based medical evidence for clinical practice.Methods:PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang and VIP databases were searched by computer,and the retrieval time was up to December 2021.Relevant literatures were obtained,and eligible studies were gradually screened and included.Cochrane ROB bias risk assessment tool and NOS scale were used to evaluate the quality of the articles,and required data were extracted from high-quality literatures.Finally,meta-analysis was performed using Review Manager 5.3 software.Results:Eleven studies were finally included,including 1398 patients,including 566 patients receiving overlap anastomosis and 832 patients receiving traditional anastomosis.The results show that overlap anastomosis and traditional anastomosis had the advantages of operation time(MD=0.63,95%CI=7.22,8.48,P=0.88),postoperative first exhaust time(MD=-0.13,95%CI=0.43,0.18,P=0.42),postoperative first feeding time(MD=0.02,95%CI=0.33,0.37,P=0.91),anastomotic leakage(OR=1.38,95%CI=0.73,2.63,P=0.32),and postoperative hospital stay(MD=-0.16,95%CI=0.82,0.51,P=0.64)had no significant differences(all P>0.05).Compared with traditional anastomosis,overlap anastomosis had longer anastomosis time(MD=5.60,95%CI=0.59,10.62,P=0.03),higher incidence of anastomotic bleeding(OR=2.48,95%CI=1.08,5.69,P=0.03),less intraoperative bleeding(MD=-6.42,MD=-6.42,OR=2.48,95%CI=1.08,P=0.03).95%CI=10.28,-2.56,P=0.001)and anastomotic stenosis(OR=0.17,95%CI=0.06,0.46,P=0.0006).Conclusion:Overlap esophagojejunostomy is a safe,effective and prognostic surgical method,and is expected to become the standard esophagojejunostomy in total laparoscopic total gastrectomy.

Spatial autocorrelation analysis of 13 leading malignant neoplasms in Taiwan: a comparison between the 1995-1998 and 2005-2008 periods

Spatial autocorrelation methodologies, including Global Moran’s I and Local Indicators of Spatial Association statistic (LISA), were used to describe and map spatial clusters of 13 leading malignant neoplasms in Taiwan. A logistic regression fit model was also used to identify similar characteristics over time. Two time periods (1995-1998 and 2005-2008) were compared in an attempt to formulate common spatio-temporal risks. Spatial cluster patterns were identified using local spatial autocorrelation analysis. We found a significant spatio-temporal variation between the leading malignant neoplasms and well-documented spatial risk factors. For instance, in Taiwan, cancer of the oral cavity in males was found to be clustered in locations in central Taiwan, with distinct differences between the two time periods. Stomach cancer morbidity clustered in aboriginal townships, where the prevalence of Helicobacter pylori is high and even quite marked differences between the two time periods were found. A method which combines LISA statistics and logistic regression is an effective tool for the detection of space-time patterns with discontinuous data. Spatio-temporal mapping comparison helps to clarify issues such as the spatial aspects of both two time periods for leading malignant neoplasms. This helps planners to assess spatio-temporal risk factors, and to ascertain what would be the most advantageous types of health care policies for the planning and implementation of health care services. These issues can greatly affect the performance and effectiveness of health care services and also provide a clear outline for helping us to better understand the results in depth.

Clinical characteristics and prognostic analysis of gastroenteropancreatic neuroendocrine neoplasm(GEP-NEN)

Objective： The aim of the study was to analyze the clinicopathologic characteristics of gastroenteropancreatic neuroendocrine neoplasm （GEP-NEN） and to explore the prognostic factors for patients and differences of immunohisto- chemical markers between neuroendocrine tumor （NET） and neuroendocrine carcinoma （NEC）. Methods： Retrospective reviews were conducted for the charts of 119 patients with GEP-NEN at the Affiliated Hospital of Qingdao University （China） from August 2003 to December 2013. Kaplan-Meier method was used to do the overall survivals analysis for the patients at different levels of predictive factors. Meanwhile, Cox proportional hazard model was used to select independent risk factors of surJival. Analysis of variance was used to compare the expression of immunohistochemical markers among different patho- logical grades. Results：Among 119 patients, pancreas （45/119, 37.82%） and rectum （33/119, 27.73%） were mostly involved. The onset age of GEP-NEN in female group was younger than that of the male group. There were 13 deaths （10.92%） during 18.9 （0.1-133.4） months follow-up period. Multivariate analysis indicated that neural invasion, gender and pathological grades of NET and NEC were independent risk factors. In neuroendocrine neoplasm （NEN）, Syn expression in G2 was higher than G1 and G3, while CgA showed no significant difference. All markers showed no significant differences between NET and NEC. Conclusion： GEP-NEN may occur at multiple sites of digestive system and lack specific clinical manifestations. Syn expression detected for the prognosis of G1, G2 and G3 tumors have clinical significance. Neural invasion, sex and patho- logical grades were independent prognostic factors for GEP-NEN patients. No significant difference was found in different pathological grades of NET and NEC.

Impact of human leukocyte antigen mismatching on outcomes of liver transplantation:A meta-analysis

AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies.METHODS:Articles in PubMed/MEDLINE,EMBASE and the Cochrane database from January 1970 to June 2009,including non-English literature identified in these databases,were searched.Only studies comparing HLA or sub-phenotype matching with mismatching were extracted.The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed.A meta-analysis was performed when at least 3 studies provided data.RESULTS:Sixteen studies met the inclusion criteria.A lower number of HLA mismatches(0-2 vs 3-6) did reduce the incidence of acute rejection(relative risk:0.77,P = 0.03).The degree of HLA mismatching(0-2 vs 3-6) had no significant effect on 1-year [hazard ratio(HR):1.04,P = 0.68] and 5-year(HR:1.09,P = 0.38) graft survival.In sub-phenotype analysis,the degree of HLA-A,B and DR mismatching(0 vs 1-2) had no significant effect on 1-year and 5-year graft survival,either.The HRs and P-values were 0.95,0.71(HLA-A,1-year);1.06,0.60(HLA-A,5-year);0.77,0.16(HLA-B,1-year);1.07,0.56(HLA-DR,1-year);1.18,0.23(HLADR,5-year),respectively.CONCLUSION:The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes.To obtain a short recovery time and minimize rejection post transplantation,HLA matching studies should be considered before the operation.

The combined detection of carcinoembryonic antigen,carcinogenic antigen 125,and carcinogenic antigen 19-9 in colorectal cancer patients

BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)surgery.The predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is unclear.AIM To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of CRC.METHODS The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January 2023.Serum CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis.In addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic accuracy.RESULTS The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group.Specifically,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL respectively.and 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL respectively.In addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(P<0.05).ROC curve analysis results showed that the areas under the ROC curves of CEA,CA125 and CA19-9 were 0.607,0.692 and 0.586.CONCLUSION These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the Colon: A Case Report

Here we report a rare case of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). A 51-year-old lady with no known family history of malignancies developed this rare type of malignancy without any active gastrointestinal symptoms. However, during a routine health check, physicians noticed a raised Carcinoembryonic Antigen (CEA) level and the patient subsequently was referred to the surgical department for further management. A colonoscopy and CECT abdomen were done and she was electively admitted for a left hemicolectomy operation for a splenic flexure tumour. The histopathological report revealed the tumour is a case of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) [moderately differentiated adenocarcinoma and neuroendocrine tumour grade 3]. TNM (8th edition, 2016): pT3, pN2 (20/21), pMX. Both resection margins were clear from malignant cells. Colorectal MiNENs, constitute a rare group of gastrointestinal tumours composed of both neuroendocrine and non-neuroendocrine components. Given their non-diagnostic macroscopic features, specific histological features and lack of disease awareness which are responsible for the underestimated incidence and conflicting data. In this case, a multidisciplinary team approach is important in managing patients with this malignancy to achieve the best outcome.

Down-regulation of human leukocyte antigens class I on peripheral T lymphocytes and NK cells from subjects in region of high-incidence gastrointestinal tumor

Background Many types of human tumors can suppress the immune system to enhance their survival. Loss or down-regulation of human leukocyte antigens （HLA） class I on tumors is considered to be a major mechanism of tumor immune escape. Our previous studies found that HLA class I on peripheral-blood mononuclear cells was significantly lower in gastric cancer patients. The present study made an analysis of HLA class I expression on peripheral-blood T lymphocytes and NK cells from subjects of Lijiadian village, a village with high-incidence gastrointestinal tumor. Methods A total of 181 villagers from Lijiadian village and 153 normal controls from the Department of Health Examination Center were enrolled in this study. Using a multi-tumor markers detection system, these villagers were divided into two groups： high-risk group （tumor markers positive group） and low-risk group （tumor markers negative group）. The percentage of T lymphocytes and NK cells and levels of HLA class I on their surface were determined in these subjects by flow cytometry. Results Percentages of T lymphocytes and NK cells in peripheral-blood mononuclear cells did not vary with age. The expression level of HLA class I on peripheral T lymphocytes and NK cells was not affected by age or gender, but was significantly down-regulated in Lijiadian villagers （P 〈0.05）, with the low-risk group, there was a significant reduction of cells （P 〈0.05） in the high-risk group. especially on the surface of NK cells （P 〈0.01）. Compared HLA class I on peripheral T lymphocytes （P 〈0.05） and NK Conclusions HLA class I on peripheral T lymphocytes and NK cells may be involved in tumorigenesis and development of gastrointestinal tumor, and understanding their changes in expression may provide new insights into the mechanism of tumor immunity.

幽门螺杆菌感染与胃癌关系的Meta-analysis研究

目的:探讨幽门螺杆菌(Hp)感染胃粘膜与胃癌的关系。方法:根据资料一致性检验结果,采用随机效应模型(D-L法)对检索到的国内23篇有关流行病学研究文献进行了综合定量分析。结果:Hp感染与胃癌的发生有明显的联系(OR=2.72,95%CI:1.91-3.87);其中与胃非贲门部癌、腺癌的联系具有统计学意义,其合并OR(95%CI)依次为2.72(1.91-3.87)、3.94(2.41-6.42);与胃贲门部癌及非腺癌的联系无统计学意义(OR=1.38,95%CI:0.91-2.08)、(OR=1.55,95%CI:0.99-2.44)。结论:Hp感染与胃癌的发生有联系。文中对该综合分析结果及可能出现的偏倚进行了讨论。

Down-staging depth score to predict outcomes in locally advanced rectal cancer achieving ypl stage after neoadjuvant chemo-radiotherapy versus de novo stage pl cohort:A propensity score-matched analysis

Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determine whether the long-term outcome of yp T1–2N0 cases can be comparable to that of p T1–2N0 cohort that received definitive surgery for early disease.Method：From January 2008 to December 2013,449 consecutive patients with rectal cancer were treated and their outcome maintained in a database.Patients with LARC underwent total mesorectal excision（TME）surgery at4–8 weeks after completion of CRT,and those achieving stage yp I were identified as a group.As a comparison,stage p I group pertains to patients whose initially limited disease was not upstaged after TME surgery alone.After propensity score matching（PSM）,comparisons of local regional control（LC）,distant metastasis-free survival（DMFS）,disease-free survival（DFS）and overall survival（OS）were performed using Kaplan-Meier analysis and log-rank test between yp I and p I groups.Down-staging depth score（DDS）,a novel method of evaluating CRT response,was used for subset analysis.Results：Of the 449 patients,168 matched cases were generated for analysis.Five-year LC,DMFS,DFS and OS for stage p I vs.yp I groups were 96.7%vs.96.4%（P=0.796）,92.7%vs.73.6%（P=0.025）,91.2%vs.73.6%（P=0.080）and 93.1%vs.72.3%（P=0.040）,respectively.In the DDS-favorable subset of the yp I group,LC,DMFS,DFS and OS resulted in no significant differences in comparison with the p I group（P=0.384,0.368,0.277 and0.458,respectively）.Conclusions：LC was comparable in both groups;however,distant metastasis developed more frequently in down-staged LARC than de novo early stage cases,reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response.DDS can be an indicator to identify a subset of the yp I group whose longterm oncologic outcomes are as good as those of stage p I cohort.

CT Texture Analysis: A Potential Biomarker for Evaluating KRAS Mutational Status in Colorectal Cancer

Objective Texture analysis is deemed to reflect intratumor heterogeneity invisible to the naked eyes.The aim of this study was to evaluate the feasibility of assessing the KRAS mutational status in colorectal cancer(CRC)patients using CT texture analysis.Methods This retrospective study included 92 patients who had histopathologically confirmed CRC and underwent preoperative contrast-enhanced CT examinations.The patients were assigned into a training cohort(n=51)and a validation cohort(n=41).We placed the region of interest in the tumour regions on the selected axial images using software of lexRad to extract a series of quantitative parameters based on the spatial scaling factors(SSFs),including mean,standard deviation(SD),entropy,mean of positive pixels(MPP),skewness,and kurtosis.The texture parameters and clinical characteristics(age,gender,tumour location,histopathology;tumour size,1 N,M stages)were compared between the mutated and wild-type KRAS patient groups in training cohort and validation cohort.Before building the multiple feature classifier,we calculated the correlations of the features using Pearsons correlation coefficient,and if any two features were significantly correlated,the one with lower AUC was removed.Ultimately,only the most discriminative isolated features were combined to train a supporting vector machine(SVM)classifier.The receiver operating characteristic(ROC)curve was processed for evaluating the diagnostic efficiency of texture parameters in differentiating CRC patients with mutated KRAS from those with wild-type KRAS.Results None of the clinical characteristics were significant different between CRC patients with wild-type KRAS and mutated KRAS in both cohorts.For predicting the expression of mutated KRAS in CRC patients,the perfect model which combined skewness on SSF 5 by unenhanced CT,entropy on SSF 2,skewness and kurtosis on SSF 0,and kurtosis and mean on SSF 3 by enhanced CT,showed a desirable AUC of 0.951(95%CI:0.895-1,P<0.001),with a sensitivity of 88.9%and a specificity of 91.7%,when the cut-off value was 0.46 in the training cohort;while in the validation cohort,the AUC value was 0.995(95%CI:0.982-1,P<0.001),the sensitivity was 100%,and the specificity was 93.7%when the cut-off value was 0.28.Conclusion It is feasible to evaluate the KRAS mutational status in CRC using CT texture analysis.