Colorectal cancer(CRC)is the second most common cancer in Europe and its incidence is steadily increasing.This trend could be reversed through timely secondary prevention(screening).In the last twenty years,CRC screen...Colorectal cancer(CRC)is the second most common cancer in Europe and its incidence is steadily increasing.This trend could be reversed through timely secondary prevention(screening).In the last twenty years,CRC screening programs across Europe have experienced considerable improvements(fecal occult blood testing;transition from opportunistic to population based program settings).The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality rates.Each year,approximately 8000 people are diagnosed with CRC and some 4000 die from this malignancy.Twenty years ago,the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in 2000.Originally,this program was based on the guaiac fecal occult blood test(FOBT)offered by general practitioners,followed by colonoscopy in cases of FOBT positivity.The program has continuously evolved,namely with the implementation of immunochemical FOBTs and screening colonoscopy,as well as the involvement of gynecologists.Since the establishment of the Czech CRC Screening Registry in 2006,2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening program.The overall program expanded to cover 25.0%of the target population by 2011.However,stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation,which is currently being prepared.展开更多
BACKGROUND One of the most notable applications for circulating tumor DNA(ctDNA)detection in peripheral blood of patients with metastatic colorectal cancer(mCRC)is a long-term postoperative follow-up.Sometimes referre...BACKGROUND One of the most notable applications for circulating tumor DNA(ctDNA)detection in peripheral blood of patients with metastatic colorectal cancer(mCRC)is a long-term postoperative follow-up.Sometimes referred to as a“liquid(re)biopsy”it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals(months or even weeks).The presence of the disease and the actual extent of the tumor burden(tumor mass)within the patient’s body can be monitored.This is of particular importance,especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence.AIM To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer.METHODSA total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers.Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling.In addition to the baseline ctDNA testing prior to surgery,a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals.The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient.RESULTS Among the monitored patients,the R0(curative)resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures(26/28,93%).In the remaining cases of R0 surgeries that displayed ctDNA,both patients were diagnosed with a recurrence of the disease after 6 months.In 7 patients who underwent an R1 resection,4 ctDNA positivities(4/7,57%)were detected after surgery and associated with the confirmation of early disease recurrence(after 3 to 7 months).All 15 patients(15/15,100%)undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period.In 22 cases of recurrence,ctDNA positivity was detected 22 times(22/22,100%)compared to 16 positives(16/22,73%)by imaging methods and 15 cases(15/22,68%)of elevated tumor markers.CONCLUSION ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.展开更多
AIM: To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine cli...AIM: To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine clinical practice. METHODS: A prospective 3-year study has resulted in the acquisition of samples from 159 large adenomas and 138 carcinomas along with associated clinical parameters including localization, grade and histological type for adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed using multiplex ligation-dependent probe amplification technique for the evaluation of Cp G-islandmethylator phenotype(CIMP), PCR fragment analysis for detection of microsatellite instability and denaturing capillary electrophoresis for sensitive detection of somatic mutations in KRAS, BRAF, TP53 and APC genes.RESULTS: Molecular types according to previously introduced Jass classification have been evaluated for large adenomas and early and late carcinomas. An increase in CIMP+ type, eventually accompanied with KRAS mutations, was notable between large adenomas and early carcinomas. As expected, the longitudinal observations revealed a correlation of the CIMP+/BRAF + type with proximal location. CONCLUSION: Prospective molecular classification of tissue specimens is feasible in routine endoscopy practice. Increased frequency of some molecular types corresponds to the developmental stages of colorectal tumors. As expected, a clear distinction is notable for tumors located in proximal colon supposedly arising from the serrated(methylation) pathway.展开更多
基金Supported by The Intern Grant Agency of the Czech Ministry of Health(IGA),No.NT 13673-4
文摘Colorectal cancer(CRC)is the second most common cancer in Europe and its incidence is steadily increasing.This trend could be reversed through timely secondary prevention(screening).In the last twenty years,CRC screening programs across Europe have experienced considerable improvements(fecal occult blood testing;transition from opportunistic to population based program settings).The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality rates.Each year,approximately 8000 people are diagnosed with CRC and some 4000 die from this malignancy.Twenty years ago,the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in 2000.Originally,this program was based on the guaiac fecal occult blood test(FOBT)offered by general practitioners,followed by colonoscopy in cases of FOBT positivity.The program has continuously evolved,namely with the implementation of immunochemical FOBTs and screening colonoscopy,as well as the involvement of gynecologists.Since the establishment of the Czech CRC Screening Registry in 2006,2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening program.The overall program expanded to cover 25.0%of the target population by 2011.However,stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation,which is currently being prepared.
基金Supported by the Ministry of Health of the Czech Republic,No.15-27939A
文摘BACKGROUND One of the most notable applications for circulating tumor DNA(ctDNA)detection in peripheral blood of patients with metastatic colorectal cancer(mCRC)is a long-term postoperative follow-up.Sometimes referred to as a“liquid(re)biopsy”it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals(months or even weeks).The presence of the disease and the actual extent of the tumor burden(tumor mass)within the patient’s body can be monitored.This is of particular importance,especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence.AIM To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer.METHODSA total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers.Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling.In addition to the baseline ctDNA testing prior to surgery,a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals.The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient.RESULTS Among the monitored patients,the R0(curative)resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures(26/28,93%).In the remaining cases of R0 surgeries that displayed ctDNA,both patients were diagnosed with a recurrence of the disease after 6 months.In 7 patients who underwent an R1 resection,4 ctDNA positivities(4/7,57%)were detected after surgery and associated with the confirmation of early disease recurrence(after 3 to 7 months).All 15 patients(15/15,100%)undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period.In 22 cases of recurrence,ctDNA positivity was detected 22 times(22/22,100%)compared to 16 positives(16/22,73%)by imaging methods and 15 cases(15/22,68%)of elevated tumor markers.CONCLUSION ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.
基金Supported by Internal Grant Agency of the Czech Ministry of Health,No.NT 14383
文摘AIM: To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine clinical practice. METHODS: A prospective 3-year study has resulted in the acquisition of samples from 159 large adenomas and 138 carcinomas along with associated clinical parameters including localization, grade and histological type for adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed using multiplex ligation-dependent probe amplification technique for the evaluation of Cp G-islandmethylator phenotype(CIMP), PCR fragment analysis for detection of microsatellite instability and denaturing capillary electrophoresis for sensitive detection of somatic mutations in KRAS, BRAF, TP53 and APC genes.RESULTS: Molecular types according to previously introduced Jass classification have been evaluated for large adenomas and early and late carcinomas. An increase in CIMP+ type, eventually accompanied with KRAS mutations, was notable between large adenomas and early carcinomas. As expected, the longitudinal observations revealed a correlation of the CIMP+/BRAF + type with proximal location. CONCLUSION: Prospective molecular classification of tissue specimens is feasible in routine endoscopy practice. Increased frequency of some molecular types corresponds to the developmental stages of colorectal tumors. As expected, a clear distinction is notable for tumors located in proximal colon supposedly arising from the serrated(methylation) pathway.
