Experience of the implementation and outcomes of universal testing for Lynch syndrome in the United Kingdom.

AIM: Colorectal cancer (CRC) is diagnosed in approximately 45 000 people annually in the UK, and it is estimated that Lynch syndrome (LS) accounts for 3.1% of these cases. In February 2017, National Institute for Health and Care Excellence (NICE guideline DG27 recommended universal testing of new cases of CRC for mismatch repair (MMR) status. The aim of this study was to implement universal testing for LS in CRC patients in a secondary care setting. METHOD: We prospectively collected data on consecutive newly diagnosed CRC patients at our centre from November 2016 to August 2018, including evidence of MMR status determined by immunohistochemistry. We recorded clinicopathological data including age at diagnosis, stage, tumour site, reported histological findings and MMR tumour status. Statistical analysis was performed using the chi-square test and the two-tailed t-test for binary and continuous variables, respectively. RESULTS: A cohort of 203 consecutive patients were diagnosed with CRC during this period. Universal MMR testing was performed for the 198 CRC patients in whom a diagnosis of adenocarcinoma was confirmed, with colonoscopic biopsy used as the source material in 68.6% of cases. Twenty-three CRCs (11.6%) were MMR deficient (dMMR). Most dMMR CRCs (21/23) were early stage tumours (Dukes A or B, P = 0.002). In 39 Dukes B CRCs in patients under 70 years of age, the result of MMR testing influenced decision-making about personalized treatment with 5-fluorouracil based chemotherapy. CONCLUSION: Our results demonstrate that universal testing of all new cases of CRC for features suggestive of LS is feasible and effective in the UK. Our data also indicate the importance of genetic testing and personalized oncological care.

A dedicated high-quality service for the management of patients with an inherited risk of colorectal cancer.

AIM: To demonstrate the quality improvement associated with the implementation of a specialist family history of bowel cancer service in secondary care. METHOD: The following outcomes were assessed: (1) adherence to the British Society of Gastroenterology (BSG) guidelines for colonoscopic surveillance of individuals with a family history of colorectal cancer (CRC); (2) adherence to the revised Bethesda criteria for the identification of CRC patients with suspected Lynch syndrome; (3) identification of inherited syndromes with increased CRC risk; and (4) colonoscopic adenoma detection rate. Data were collected for a 21-month period before and after the establishment of this service for all patients who underwent colonoscopic surveillance for a family history of CRC and all patients newly diagnosed with CRC. Analyses compared the number of colonoscopies performed that were not indicated by BSG guidelines, the average number of years early that patients were screened, the adenoma detection rate and the rate of tumour testing for mismatch repair genes before and after the implementation of the service. RESULTS: Following the establishment of the service there was a reduction in the number of colonoscopies not indicated by BSG guidelines (39.6% before and 5.8% after, P < 0.001, chi-square test) and surveillance colonoscopy took place at a more appropriate age (10.6 years too early before and 5.9 years early after, P = 0.01, t-test). There was an increased adenoma detection rate (17% before and 31.9% after, P < 0.01, chi-square test) and increased tumour MMR testing (3.4% before and 91.8% after, P < 0.01, chi-square test). CONCLUSION: The introduction of a family history of bowel cancer service results in improved patient care through improved adherence to guidelines for colonoscopic surveillance and increased cancer detection rates.

Endoscopic ultrasound guided fine needle aspiration for the diagnosis of pancreatic cystic neoplasms: a meta-analysis.

BACKGROUND AND OBJECTIVES: Mucinous cystic neoplasms and intraductal papillary mucinous tumours have greater malignant potential than serous cystic neoplasms. EUS alone is inadequate for characterising these lesions but the addition of FNA may significantly improve diagnostic accuracy. The performance of EUS-FNA is highly variable in published studies. AIM: To determine the diagnostic accuracy of EUS-FNA to differentiate mucinous versus non-mucinous cystic lesions with cyst fluid analysis for cytology and carcinoembryonic antigen (CEA) by performing a meta-analysis of published studies. METHODS: Relevant studies were identified via structured database search and included if they used a reference standard of definitive surgical histology or clinical follow-up of at least 6 months. Data from selected studies were pooled to give summary sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio and Receiver Operating Characteristic (ROC) curve. Pre-defined subgroup analysis was performed. RESULTS: Eighteen studies (published 2002-2011) were included, with a total of 1438 patients. For cytology, pooled sensitivity was 54(95%CI 49-59)% and specificity 93(90-95)%. The diagnostic odds ratio (DOR) was 13.3 (4.37-49.43), with I(2) of 77.1%. For CEA sensitivity was 63(59-67)% and specificity 88(83-91)%. The DOR was 10.76(6.29-18.41) with an I(2) of 25.4%. The diagnostic accuracy of EUS-FNA was enhanced in prospective studies and studies of <36 months duration. No impact of publication bias on our results was demonstrated. CONCLUSIONS: Fine-needle aspiration has moderate sensitivity but high specificity for mucinous lesions. EUS-FNA, when used in conjunction with cross sectional imaging, is a useful diagnostic tool for the correct identification of mucinous cysts.

Comparison and clinical application of frequency domain methods in analysis of neonatal heart rate time series.

The frequency content of the heart rate (HR) series contains information regarding the state of the autonomic nervous system. Of particular importance is respiratory sinus arrhythmia (RSA), the high-frequency fluctuation in HR attributable to respiration. The unevenly sampled nature of heart rate data, however, presents a problem for the discrete Fourier transform. Interpolation of the HR series allows even sampling, but filters high-frequency content. The Lomb periodogram (LP) is a regression-based method that addresses these issues. To evaluate the efficacy of the LP and Fourier techniques in detecting RSA, we compared the spectrum of intervals, the spectrum of HR samples, and the LP of simulated and clinical neonatal time series. We found the LP was superior to the spectrum of intervals and the spectrum of HR samples in analysis near the critical frequency of one half the average sampling rate. Applying the LP to clinical data, we found (1) evidence of stochastic resonance, an enhancement of periodicity with the addition of small amounts of noise, and (2) reduced power at all frequencies prior to clinical diagnosis of neonatal sepsis.