Current trends in clinical genetics of colorectal cancer

Recent innovations in molecular biology and colorectal cancer (CRC) genetics have facilitated the understanding of the pathogenesis of sporadic and hereditary CRC syndromes. The development of technology has enabled data collection for a number of genetic factors, which lead to understanding of the molecular mechanisms underlying CRC. The incidence and the nature of CRC is a mixture of genetic and environmental factors. The current field of interest is to understand how molecular basis could shape predisposition for developing CRC, disease progression and response to chemotherapy. In this article, we summarize new and developing genetic markers, and assess their clinical value for inherited and sporadic CRC

Effective notification of important non-urgent radiology results : a qualitative study of challenges and potential solutions

Introduction: We report on the implementation of a Radiology Notification System (RNS), set up by the medical imaging department of a major Sydney teaching hospital in March 2010. This study aimed to investigate the views of the medical imaging department staff about: (i) the results follow-up problem encountered by the medical imaging department prior to the implementation of the RNS; (ii) what changes occurred following implementation of the RNS; and (iii) suggestions for improving the RNS. Methods: This is a cross-sectional qualitative study incorporating semi-structured interviews with 16 staff (15 radiologists and 1 clerk) after the implementation of the RNS. Interviews were conducted in August/September 2011. Results: The reasons behind the development of the RNS were related to: (i) major existing problems with the communication of results between the imaging department and hospital wards; (ii) cumbersome and inefficient paper-based notification systems; and (iii) the absence of standardised guidelines and procedures for radiology test notification and follow-up. The RNS managed to free up a significant proportion of radiologist time, resulting in greater efficiencies. Study participants also highlighted a number of areas for improvement, including the need for a 24-h service, feedback and acknowledgement of test results by clinicians and the standardisation of test management definitions and procedures. Conclusion: Test management systems can play an important part in enhancing safe and effective communications between wards and hospital departments. However, their uptake and sustainability will require the establishment of a multidisciplinary and hospital-wide collaboration that includes clinicians

Microsatellite instability affecting the T17 repeats in intron 8 of HSP110, as well as five mononucleotide repeats in patients with colorectal carcinoma

Aim: To investigate mononucleotide markers: BAT-25, BAT-26, NR-21, NR-22 and NR-24 in patients with colorectal cancer (CRC), and the status of HSP110T17, KRAS, BRAF and the MLH1 promoter mutations in microsatellite unstable CRC. Methods: Genetic assessments were performed on samples obtained following resection of CRC in 200 patients. Results: Allelic variations of HSP110T17 were found in all 18 patients with microsatellite instabilities (MSIs) in at least three markers (high-frequency MSI). By contrast, mutations of HSP110T17 were absent in all 20 patients with no MSI frequency. Eight out of 182 patients with low (instability in one marker) or no frequency MSI had allelic shifts due to polymorphisms of BAT-25 (1.5%), NR-21 (1.75%) and NR-24 (1.5%). BRAF mutations were associated with >5 bp shortening of HSP110T17. Conclusion: Patients with high-frequency MSI CRC had allelic variations of HSP110T17. BRAF mutations occur along with greater shortening in HSP110T17 during oncogenesis via the MSI pathway

Microsatellite instability & survival in patients with stage II/III colorectal carcinoma

Background & objectives: The two key aspects associated with the microsatellite instability (MSI) as genetic phenomenon in colorectal cancer (CRC) are better survival prognosis, and the varying response to 5-fluorouracil (5-FU)-based chemotherapy. This study was undertaken to measure the survival of surgically treated patients with stages II and III CRC based on the MSI status, the postoperative 5-FU treatment as well as clinical and histological data. Methods: A total of 125 consecutive patients with stages II and III (American Joint Committee on Cancer, AJCC staging) primary CRCs, were followed prospectively for a median time of 31 months (January 2006 to December 2009). All patients were assessed, operated and clinically followed. Tumour samples were obtained for cytopathological verification and MSI grading. Results: Of the 125 patients, 21 (20%) had high MSI (MSI-H), and 101 patients (80%) had MSI-L or MSS (low frequency MSI or stable MSI). Patients with MSS CRC were more likely to have recurrent disease (P=0.03; OR=3.2; CI 95% 1-10.2) compared to those with MSI-H CRC. Multi- and univariate Cox regression analysis failed to show a difference between MSI-H and MSS groups with respect to disease-free, disease-specific and overall survival. However, the disease-free survival was significantly lower in patients with MSI-H CRC treated by adjuvant 5-FU therapy (P=0.03). Interpretation & conclusions: MSI-H CRCs had a lower recurrence rate, but the prognosis was worse following adjuvant 5-FU therapy

A comparison between radiation therapists and medical specialists in the use of kilovoltage cone-beam computed tomography scans for potential lung cancer radiotherapy target verification and adaptation

Target volume matching using cone-beam computed tomography (CBCT) is the preferred treatment verification method for lung cancer in many centers. However, radiation therapists (RTs) are trained in bony matching and not soft tissue matching. The purpose of this study was to determine whether RTs were equivalent to radiation oncologists (ROs) and radiologists (RDs) in alignment of the treatment CBCT with the gross tumor volume (GTV) defined at planning and in delineating the GTV on the treatment CBCT, as may be necessary for adaptive radiotherapy. In this study, 10 RTs, 1 RO, and 1 RD performed a manual tumor alignment and correction of the planning GTV to a treatment CBCT to generate an isocenter correction distance for 15 patient data sets. Participants also contoured the GTV on the same data sets. The isocenter correction distance and the contoured GTVs from the RTs were compared with the RD and RO. The mean difference in isocenter correction distances was 0.40. cm between the RO and RD, 0.51. cm between the RTs, and RO and 0.42. cm between the RTs and RD. The 95% CIs were smaller than the equivalence limit of 0.5. cm, indicating that the RTs were equivalent to the RO and RD. For GTV delineation comparisons, the RTs were not found to be equivalent to the RD or RO. The alignment of the planning defined GTV and treatment CBCT using soft tissue matching by the RTs has been shown to be equivalent to those by the RO and RD. However, tumor delineation by the RTs on the treatment CBCT was not equivalent to that of the RO and RD. Thus, it may be appropriate for RTs to undertake soft tissue alignment based on CBCT; however, further investigation may be necessary before RTs undertake delineation for adaptive radiotherapy purposes