Table 2 - uploaded by Damien L Stella
Content may be subject to copyright.
Source publication
Lynch syndrome gene carriers have a 50-80% risk of colorectal cancer (CRC). Current guidelines recommend yearly colonoscopy, with associated procedure-related risks. Magnetic resonance colonography (MRC) was evaluated as a non-invasive alternative for CRC screening in this high-risk population. Adult Lynch syndrome gene carriers underwent both scre...
Citations
... This is particularly relevant given the large numbers of such scans performed each year and the possibility of using magnetic resonance imaging (MRI) as a non-IR alternative for surveillance in the future. Compared to CTC, the accuracy of MRI colonography is relatively low limiting its utility for adenoma screening [34]. ...
The aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treatment of rectal cancer in these patients. No data or longitudinal observational studies of the impact of radiation exposure on humans with Lynch syndrome were identified. Limited experimental studies utilizing cell lines and primary cells exposed to both low and high radiation doses have been carried out to help determine radio-sensitivity associated with DNA mismatch repair gene deficiency, the defining feature of Lynch syndrome. On balance, these studies suggest that mismatch repair deficient cells may be relatively radio-resistant (particularly for low dose rate exposures) with higher mutation rates, albeit no firm conclusions can be drawn. Mouse model studies, though, showed an increased risk of developing colorectal tumors in mismatch repair deficient mice exposed to radiation doses around 2 Gy. With appropriate ethical approval, further studies investigating radiation risks associated with CT imaging and radiotherapy relevant doses using cells/tissues derived from confirmed Lynch patients or genetically modified animal models are urgently required for future clinical guidance.
... This second phase resulted in seven studies being included for analysis. [18][19][20][21][22][23][24] One of these was only published as an abstract. 21 We decided to include this study as the results were described in sufficient detail and the methodology was provided upon request by the first author (by referring to two high-quality studies 25,26 ). ...
... Two prospective studies reported on the use of imaging techniques for surveillance: one evaluated magnetic resonance colonography (MRC), 22 the other computed tomographic colonography (CTC). 23 The procedures were performed after standard bowel preparation, with MRC/CTC undertaken prior to but on the same day as colonoscopy. ...
... MRC was evaluated in 30 individuals, using a 1.5 T MRI and intravenous contrast. 22 Three-dimensional T2-weighed images were acquired, which were interpreted by two independent radiologists using 2D and 3D modes. Eighty-three percent of scans were rated as adequate to good quality. ...
Background
Individuals with Lynch syndrome are at high risk for colorectal cancer (CRC). Regular colonoscopies have proven to decrease CRC incidence and mortality. However, colonoscopy is burdensome and interval CRCs still occur. Hence, an accurate, less‐invasive screening method that guides the timing of colonoscopy would be of important value.
Aim
To outline the performance of non‐endoscopic screening modalities for Lynch‐associated CRC and adenomas.
Methods
Systematic literature search in MEDLINE and EMBASE to identify studies investigating imaging techniques and biomarkers for detection of CRC and adenomas in Lynch syndrome. The QUADAS‐2 tool was used for the quality assessment of included studies.
Results
Seven of 1332 screened articles fulfilled the inclusion criteria. Two studies evaluated either CT colonography or MR colonography; both techniques were unable to detect CRC and (advanced) adenomas <10 mm. The other five studies evaluated plasma methylated‐SEPTIN9, faecal immunochemical test (FIT), faecal tumour DNA markers (BAT‐26, hMLH1, p53, D9S171, APC, D9S162, IFNA and DCC) and faecal microbiome as screening modalities. Sensitivity for CRC varied from 33% (BAT‐26) to 70% (methylated‐SEPTIN9) to 91% (hMLH1). High specificity (94–100%) for CRC and/or adenomas was observed for methylated‐SEPTIN9, FIT and BAT‐26. Desulfovibrio was enriched in the stool of patients having adenomas. However, all these studies were characterised by small populations, high/unclear risk of bias and/or low prevalence of adenomas.
Conclusions
Imaging techniques are unsuitable for colon surveillance in Lynch syndrome, whereas biomarkers are understudied. Having outlined biomarker research in Lynch‐associated and sporadic CRC/adenomas, we believe that these non‐invasive markers may hold potential (whether or not combined) for this population. As they could be of great value, (pre‐)clinical studies in this field should be prioritised.
... Thus, MRC has a significant role in screening for younger patients with genetically increased risks for colon cancer. 17 Most of the techniques like bowel preparation, distension of colon, and imaging of an individual in prone and supine are similar to those required for CTC. As routinely done for all other MR studies, even in MRC, patients must be screened for general contraindications to MRI including the presence of metallic implants, cardiac pacemaker, or severe claustrophobia. ...
Evolution of imaging technique in the past decade has played essential role in decreasing the incidence and mortality of colorectal cancers in the United States. Imaging significantly assists in the management of colorectal cancer, especially in screening, surveillance, diagnosis, staging, selection of treatment, and follow up.
Comprehensive knowledge of their application, strengths, and weaknesses is required by the radiologists to play a significant part on multidisciplinary teams in deciding how colorectal cancer patients should be managed. This article describes the pros and cons of the various imaging modalities in the management of colorectal cancer.
... Dies wurde auch für Adenome mit einer Größe von 5 mm durch Rijcken et al. verifiziert [29]. Auch wurden bereits Karzinome in einer Größe < 5 mm bei dieser Hochrisikogruppe beschrieben [30]. Das Auftreten von sessil serratierten Adenomen und selteneren traditionell serratierten Adenomen ist beim LS vergleichbar zur Allgemeinbevölkerung [31]. ...
... Für die entsprechende Dokumentation und Terminologie der endoskopischen Befunde verweisen wir auf das Konsensusprojekt der Deutschen Gesellschaft für Gastroenterologie, Verdauungsund Stoffwechselerkrankungen (DGVS) [36]. Es besteht keine Indikation zur virtuellen Koloskopie mittels Computertomografie (CT) oder Magnetresonanztomografie (MRT) [30,37]. ...
... Mutations in this gene were earlier reported in individuals with hereditary non-polyposis colon cancer (HNPCC) and endometrial cancer. In earlier reports, mutations in MSH6 were found to be associated with some cancers such as hereditary prostate cancer [35] and colorectal cancer [36]. ...
The susceptibility of an individual to oral cancer is mediated by genetic factors and carcinogen-exposure behaviors such as betel quid chewing, tobacco use, and alcohol consumption. This pilot study was aimed to identify the genetic alteration in 100 bp upstream and downstream flanking regions in addition to the exonic regions of 169 cancer-associated genes by using Next Generation sequencing with aim to elucidate the molecular pathogenesis of tobacco- and betel quid-associated oral cancer of Northeast India. To understand the role of chemical compounds present in tobacco and betel quid associated with the progression of oral cancer, single nucleotide polymorphisms (SNPs) and insertion and deletion (Indels) found in this study were analyzed for their association with chemical compounds found in tobacco and betel quid using Comparative Toxogenomic Database. Genes (AR, BRCA1, IL8, and TP53) with novel SNP were found to be associated with arecoline which is the major component of areca nut. Genes (BARD1, BRCA2, CCND2, IGF1R, MSH6, and RASSF1) with novel deletion and genes (APC, BRMS1, CDK2AP1, CDKN2B, GAS1, IGF1R, and RB1) with novel insertion were found to be associated with aflatoxin B1 which is produced by fermented areca nut. Genes (ADH6, APC, AR, BARD1, BRMS1, CDKN1A, E2F1, FGFR4, FLNC, HRAS, IGF1R, IL12B, IL8, NBL1, STAT5B, and TP53) with novel SNP were found to be associated with aflatoxin B1. Genes (ATM, BRCA1, CDKN1A, EGFR, IL8, and TP53) with novel SNP were found to be associated with tobacco specific nitrosamines.
Robotic colonoscopes could potentially provide a comfortable, less painful and safer alternative to standard colonoscopy. Recent exciting developments in this field are pushing the boundaries to what is possible in the future. This article provides a comprehensive review of the current work in robotic colonoscopes including self-propelled, steerable and disposable endoscopes that could be alternatives to standard colonoscopy. We discuss the advantages and disadvantages of these systems currently in development and highlight the technical readiness of each system to help the reader understand where and when such systems may be available for routine clinical use and get an idea of where and in which situation they can best be deployed.
Introduction:
Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome and accounts for ~3 % of all CRCs. This autosomal dominant disorder is caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM). One in 300 individuals of the general population are considered to be mutation carriers (300 000 individuals/Germany). Mutation carriers are at a high CRC risk of 15-46 % till the age of 75 years. LS also includes a variety of extracolonic malignancies such as endometrial, small bowel, gastric, urothelial, and other cancers.
Methods:
The German Consortium for Familial Intestinal Cancer consists of 14 university centers in Germany. The aim of the consortium is to develop and evaluate surveillance programs and to further translate the results in clinical care. We have revisited and updated the clinical management guidelines for LS patients in Germany.
Results:
A surveillance colonoscopy should be performed every 12-24 months starting at the age of 25 years. At diagnosis of first colorectal cancer, an oncological resection is advised, an extended resection (colectomy with ileorectal anastomosis) has to be discussed with the patient. The lifetime risk for gastric cancer is 0.2-13 %. Gastric cancers detected during surveillance have a lower tumor stage compared to symptom-driven detection. The lifetime risk for small bowel cancer is 4-8 %. About half of small bowel cancer is located in the duodenum and occurs before the age of 35 years in 10 % of all cases. Accordingly, patients are advised to undergo an esophagogastroduodenoscopy every 12-36 months starting by the age of 25 years.
Conclusion:
LS colonic and extracolonic clinical management, surveillance and therapy are complex and several aspects remain unclear. In the future, surveillance and clinical management need to be more tailored to gene and gender. Future prospective trials are needed.
Magnetic resonance colonography with its high tissue contrast and without the use of ionizing radiation was designed as a minimally invasive screening tool for colorectal cancer and its precursors. Nonetheless, heterogeneous data on diagnostic performance and patient burden have hindered its use in screening. This article provides an overview on the status and potential of magnetic resonance colonography in the setting of detection and screening of colorectal cancer and its precursors.
Colorectal cancer is the second most common cause of cancer-related death in Europe and the United States, and a major cause of mortality. Early detection of colorectal cancer and its precursors reduces mortality and morbidity, and a minimally invasive screening tool is essential for high patient acceptance and participation. To achieve this goal, computed tomographic colonography and magnetic resonance (MR) colonography have been introduced. A wide variety of methods of bowel preparation, colon distension, and imaging exists for MR colonography. This article presents an up-to-date overview of the status of MR colonography in screening for colorectal cancer, and its diagnosis.
