Colorectal cancer

摘要： Adult stem cells are necessary for self-renewal tissues and regeneration after damage.Especially in the intestine,which self-renews every few days,they play a key role in tissue homeostasis.Therefore,complex regulatory mechanisms are needed to prevent hyperproliferation,which can lead in the worst case to carcinogenesis or under-activation of stem cells,which can result in dysfunctional epithelial.One main regulatory signaling pathway is the Wnt/β-catenin signaling pathway.It is a highly conserved pathway,withβ-catenin,a transcription factor,as target protein.Translocation ofβ-catenin from cytoplasm to nucleus activates the transcription of numerous genes involved in regulating stem cell pluripotency,proliferation,cell differentiation and regulation of cell death.This review presents a brief overview of the Wnt/β-catenin signaling pathway,the regulatory mechanism of this pathway and its role in intestinal homeostasis.Additionally,this review highlights the molecular mechanisms and the histomorphological features of Wnt hyperactivation.Furthermore,the central role of the Wnt signaling pathway in intestinal carcinogenesis as well as its clinical relevance in colorectal carcinoma are discussed.

摘要： BACKGROUND Connective tissue growth factor(CTGF)is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling,inflammatory processes and fibrosis in various illnesses including cancer.AIM To investigate the role of CTGF in colorectal cancer(CRC)progression and to compare the CTGF expression with different clinicopathological parameters.METHODS Real-time polymerase chain reaction,immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16.RESULTS CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens.The higher protein expression levels showed a significant association with smoking,staging,tumor grade,invasion depth,necrosis of tumor tissue,and both lymphovascular and perineural invasion.As per the cox regression model and classification tree analysis,tumor-nodemetastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients.Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival.CONCLUSION Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients.These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.

摘要： BACKGROUND Colon cancer is one the most common forms of cancer in both sexes.Due to important progress in the field of early detection and effective treatment,colon and rectal cancer survivors currently account for 10%of cancer survivors worldwide.However,the effects of anti-cancer treatments,especially oxaliplatinbased chemotherapy,on the quality of life(QoL)have been less evaluated.Although the incidence of severe chemotherapy-induced neuropathy(CIPN)in clinical studies is below 20%,data from real-world studies is scarce,and CIPN is probably under-reported due to patient selection and the patients’fear that reporting side-effects might lead to treatment cessation.AIM To determine the impact of CIPN on QoL in colorectal cancer patients with a recent history of oxaliplatin-based chemotherapy.METHODS We performed a prospective cross-sectional study in two major Romanian oncology tertiary hospitals—the Regional Institute of Oncology Ia?i(Iasi,Romania)and the Fundeni Clinical Oncology Institute(Bucharest,Romania).All consecutive patients with colon or rectal cancer,undergoing Oxaliplatin-based chemotherapy that consented to enroll in the study,were assessed by means of two questionnaires—the EORTC QQ-CR29(quality of life in colon and rectal cancer patients)and the QLQ-CIPN20(assessment of neuropathy).Several demographical,social,clinical and treatment data were also collected.Statistical analysis was performed by means of SPSS v20.The student t test was used to assess the relationship between the QLQ-CIPN20 and QLQ-CR29 results.Kaplan Meyer-curves were used to report 3-year progression-free survival(PFS)in patients that discontinued chemotherapy vs those that completed the recommended course.RESULTS Of the 267 patients that fulfilled the inclusion criteria in the pre-specified time frame,101(37.8%)agreed to participate in the clinical study.At the time of the enrolment in the study,over 50%of the patients had recently interrupted their oxaliplatin-based chemotherapy,most often due to neuropathy.Almost 85%of the responders reported having tingling or numbness in their fingers or hands,symptoms that were associated with pain in over 20%of the cases.When comparing the scores in the two questionnaires,a statistically significant relationship(P<0.001)was found between the presence of neuropathic symptoms and a decreased quality of life.This correlation was consistent when the patients were stratified by sex,disease stage,comorbidities and the presence of stoma or treatment type,suggesting that neuropathy in itself may be a reason for a decreased quality of life.At the 3 year final assessment,median recurrence-free survival in stageⅢpatients was 26.88 mo.When stratified by completion of chemotherapy,median recurrence freesurvival of stageⅢpatients that completed chemotherapy was 28.27 mo vs 24.33 mo in patients that discontinued chemotherapy due to toxicity,a difference that did not reach statistical significance.CONCLUSION CIPN significantly impacts QoL in colorectal cancer patients.CIPN is also the most frequent reason for treatment discontinuation.Physicians should actively assess for CIPN in order to prevent chronic neuropathy.

摘要： The detection of dysplasia in patients with inflammatory bowel disease(IBD)continues to be important given the increased risk of colorectal cancer in this population.Therefore,in 2017,we performed a review and update of the recommendations for the management and follow-up of patients with IBD based on the clinical practice guidelines of various scientific societies.The present manuscript focuses on new aspects of the detection,follow-up,and management of dysplasia according to the latest studies and recommendations.While chromoendoscopy with targeted biopsy continues to be the technique of choice for the screening and detection of dysplasia in IBD,the associated difficulties mean that it is now being compared with other techniques(virtual chromoendoscopy),which yield similar results with less technical difficulties.Furthermore,the emergence of new endoscopy techniques that are still being researched but seem promising(e.g.,confocal laser endomicroscopy and full-spectrum endoscopy),together with the development of devices that improve endoscopic visualization(e.g.,Endocuff Vision),lead us to believe that these approaches can revolutionize the screening and follow-up of dysplasia in patients with IBD.Nevertheless,further studies are warranted to define the optimal follow-up strategy in this patient population.

摘要： BACKGROUND Peritoneal metastasis from colorectal cancer(CRC)carries a poor prognosis in most studies.The majority of those studies used either a single-agent or doublet chemotherapy regimen in the first-line setting.AIM To investigate the prognostic significance of peritoneal metastasis in a cohort of patients treated with triplet chemotherapy in the first-line setting.METHODS We retrospectively evaluated progression-free survival(PFS)and overall survival(OS)in 51 patients with metastatic CRC treated in a prospective clinical trial with capecitabine,oxaliplatin,irinotecan,and bevacizumab in the first-line setting according to the presence and absence of peritoneal metastasis.Furthermore,univariate and multivariate analyses for PFS and OS were performed to assess the prognostic significance of peritoneal metastasis at the multivariate level.RESULTS Fifty-one patients were treated with the above triplet therapy.Fifteen had peritoneal metastasis.The patient characteristics of both groups showed a significant difference in the sidedness of the primary tumor(left-sided primary tumor in 60%of the peritoneal group vs 86%in the nonperitoneal group,P=0.03)and the presence of liver metastasis(40%for the peritoneal group vs 75%for the nonperitoneal group,P=0.01).Univariate analysis for PFS showed a statistically significant difference for age less than 65 years(P=0.034),presence of liver metastasis(P=0.046),lung metastasis(P=0.011),and those who underwent metastasectomy(P=0.001).Only liver metastasis and metastasectomy were statistically significant for OS,with P values of 0.001 and 0.002,respectively.Multivariate analysis showed that age(less than 65 years)and metastasectomy were statistically significant for PFS,with P values of 0.002 and 0.001,respectively.On the other hand,the absence of liver metastasis and metastasectomy were statistically significant for OS,with P values of 0.003 and 0.005,respectively.CONCLUSION Peritoneal metastasis in patients with metastatic CRC treated with first-line triple chemotherapy does not carry prognostic significance at univariate and multivariate levels.Confirmatory larger studies are warranted.

摘要： BACKGROUND Hepatic resection has become the preferred treatment of choice for colorectal liver metastasis(CLM)patients.AIM To identify the prognostic factors and to formulate a new scoring system for management of CLM.METHODS Clinicopathologic and long-term survival data were analyzed to identify the significant predictors of survival by univariate and multivariate analyses with the Cox model.A clinical score was constructed based on the analysis results.RESULTS Three factors of worse overall survival were identified in the multivariate analysis.They were number of liver metastases≥5,size of the largest liver lesion≥4 cm,and the presence of nodal metastasis from the primary tumor.These three factors were chosen as criteria for a clinical risk score for overall survival.The clinical score highly correlated with median overall survival and 5-year survival(P=0.002).CONCLUSION Priority over surgical resection should be given to the lowest score groups,and alternative oncological treatment should be considered in patients with the highest score.

摘要： BACKGROUND Artificial intelligence in radiology has the potential to assist with the diagnosis,prognostication and therapeutic response prediction of various cancers.A few studies have reported that texture analysis can be helpful in predicting the response to chemotherapy for colorectal liver metastases,however,the results have varied.Necrotic metastases were not clearly excluded in these studies and in most studies the full range of texture analysis features were not evaluated.This study was designed to determine if the computed tomography(CT)texture analysis results of non-necrotic colorectal liver metastases differ from previous reports.A larger range of texture features were also evaluated to identify potential new biomarkers.AIM To identify potential new imaging biomarkers with CT texture analysis which can predict the response to first-line cytotoxic chemotherapy in non-necrotic colorectal liver metastases(CRLMs).METHODS Patients who presented with CRLMs from 2012 to 2020 were retrospectively selected on the institutional radiology information system of our private radiology practice.The inclusion criteria were non-necrotic CRLMs with a minimum size of 10 mm(diagnosed on archived 1.25 mm portal venous phase CT(FOLFOX,FOLFIRI,FOLFOXIRI,CAPE-OX,CAPE-IRI or capecitabine).The final study cohort consisted of 29 patients.The treatment response of the CRLMs was classified according to the RECIST 1.1 criteria.By means of CT texture analysis,various first and second order texture features were extracted from a single nonnecrotic target CRLM in each responding and non-responding patient.Associations between features and response to chemotherapy were assessed by logistic regression models.The prognostic accuracy of selected features was evaluated by using the area under the curve.RESULTS There were 15 responders(partial response)and 14 non-responders(7 stable and 7 with progressive disease).The responders presented with a higher number of CRLMs(P=0.05).In univariable analysis,eight texture features of the responding CRLMs were associated with treatment response,but due to strong correlations among some of the features,only two features,namely minimum histogram gradient intensity and long run low grey level emphasis,were included in the multiple analysis.The area under the receiver operating characteristic curve of the multiple model was 0.80(95%CI:0.64 to 0.96),with a sensitivity of 0.73(95%CI:0.48 to 0.89)and a specificity of 0.79(95%CI:0.52 to 0.92).CONCLUSION Eight first and second order texture features,but particularly minimum histogram gradient intensity and long run low grey level emphasis are significantly correlated with treatment response in non-necrotic CRLMs.

摘要： Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification.Methods: We retrospectively identified 161 consecutive patients with stage Ⅰ-Ⅲ CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction.Results: The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio(HR)=6.670;95% confidence interval(95% CI): 3.433-12.956;P<0.001), external validation cohort 1(HR=2.866;95% CI: 1.646-4.990;P<0.001) and external validation cohort 2(HR=3.342;95% CI: 1.289-8.663;P=0.002).Incorporating the EcoRad signature into the prediction model presented a higher prediction ability(P<0.001) with respect to the C-index(0.813, 95% CI: 0.804-0.822 in the training cohort;0.758, 95% CI: 0.751-0.765 in the external validation cohort 1;and 0.746, 95% CI: 0.722-0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis(TNM) system, as well as a better calibration,improved reclassification and superior clinical usefulness.Conclusions: This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage Ⅰ-Ⅲ CRC patients.

摘要： Background:A variety of therapy options are available for colorectal cancer,ranging from traditional medicine to complementary and alternative medicine.There is a growing body of evidence supporting the efficacy of complementary and alternative medicine.Therefore,the main aim of this study is to conduct a scoping evaluation of traditional and herbal medicine’s effectiveness as an additional therapy for colorectal cancer patients in clinical settings.Methods:A systematic search was conducted for all articles pertaining to clinical trials related to traditional herbal medicine(THM)with or without other treatments,such as chemotherapy,placebos,or other types of treatment,published from 2010 to November 13,2020,using four search engines,namely Medline,Web of Science,Cochrane Library,and Scopus.Results:The number of colorectal cancer patients in five trials ranged from 89 to 565 people.The THMs stated in these studies were catalpol(Rehmannia glutinosa extract),the traditional Japanese medicine Daikenchuto(mixture of herbal extracts)and Goshajinkigan,Chinese patent herbal medicine Aidi injection,and the traditional Chinese medicine Simo decoction.Positive results were reported in term of reduction of colorectal cancer tumour marker(by catalpol),improvement of gastrointestinal function following gastrointestinal surgery(by Daikenchuto and Simo decoction),better disease control rate and quality of life score(by combination of Aidi injection and chemotherapy),and a decrease in the incidence of oxaliplatin-induced peripheral neurotoxicity(Goshajinkigan).Conclusion:All studies demonstrated fewer adverse effects found in THM intervention groups,however,evidence pointing to THMs’favourable effects on colorectal cancer patients is still required.Therefore,researchers and clinicians are encouraged to perform more research in this area so that more evidence of THM’s efficacy and safety in clinical settings can be obtained.

摘要： Incidence of colorectal cancer(CRC)is on rise.While approximately 70%of all CRC cases are sporadic in nature,20%-25%have familial aggregation and only<5%is hereditary in origin.Identification of individuals with hereditary predilection for CRC is critical,as it has an impact on their overall surgical management including surgical timing,approach&technique and determines the role of prophylactic surgery and outcome.This review highlights the concept of hereditary CRC,provides insight into its molecular basis,possibility of its application into clinical practice and emphasizes the current treatment strategies with surgical management,based on the available international guidelines.