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BACKGROUND A substantial number of melanoma patients develop local or metastatic recurrence, and early detection of these is vital to maximise benefit from new therapies such as inhibitors of BRAF and MEK, or immune checkpoints. This study explored the use of novel DNA copy-number profiles in circulating cell-free DNA (cfDNA) as a potential biomarker of active disease and survival. PATIENTS AND METHODS Melanoma patients were recruited from oncology and dermatology clinics in Sheffield, UK, and cfDNA was isolated from stored blood plasma. Using low-coverage whole-genome sequencing, we created copy-number profiles from cfDNA from 83 melanoma patients, 44 of whom had active disease. We used scoring algorithms to summarize copy-number aberrations and investigated their utility in multivariable logistic and Cox regression analyses. RESULTS The copy-number aberration score (CNAS) was a good discriminator of active disease (odds ratio, 3.1; 95% CI, 1.5–6.2; P = 0.002), and CNAS above or below the 75th percentile remained a significant discriminator in multivariable analysis for active disease (P = 0.019, with area under ROC curve of 0.90). Additionally, mortality was higher in those with CNASs above the 75th percentile than in those with lower scores (HR, 3.4; 95% CI, 1.5–7.9; P = 0.005), adjusting for stage of disease, disease status (active or resected), BRAF status, and cfDNA concentration. CONCLUSIONS This study demonstrates the potential of a de novo approach utilizing copy-number profiling of cfDNA as a biomarker of active disease and survival in melanoma. Longitudinal analysis of copy-number profiles as an early marker of relapsed disease is warranted.

The implementation of bowel cancer screening in the UK requires the maintenance of high standards in colonoscopy. Part of this quality control requires the reliable documentation of complete colonoscopy that can be externally audited and assessed. It has been suggested that terminal ileal biopsy is the only definitive and reliable method of confirming caecal intubation, but it is not cost-effective and may now be contraindicated because of potential prion infection.To determine how reliable routine terminal ileal images were as an independent predictor of complete colonoscopy and whether their interpretation was aided with water insufflation or indigo-carmine dye-spraying. Method Forty-nine histologically confirmed terminal ileal images were obtained from a single endoscopist's database; 19 were conventional white-light images, 15 were taken with water insufflation and 15 were taken using chromoscopy enhancement. The images were transferred onto CD-ROM and sent as a questionnaire to 42 colonoscopists who were asked to identify the images as terminal ileum or not.Twenty questionnaires were returned resulting in a total of 980 responses. Overall, the accuracy of positive identification was 53.4%. Water insufflation and chromoscopy improved the accuracy to 68.3% and 63% respectively. Experience of (1000 colonoscopies) did not increase overall accuracy. Less experienced endoscopists had an increased accuracy rate with dye-spraying (76.7%vs 59.3%, P0.05) but experienced endoscopists had an increased accuracy rate with water insufflation (67.4%vs 63.3%, P.05).Currently, terminal ileal imaging is not a reliable mode of documenting complete colonoscopy. Using water insufflation or dye-spraying coupled with modifications in image acquisition technique may improve its reliability but these methods require further investigation before they can replace the use of caecal landmarks as completion parameters.

Background Conventional colonoscopy has a significant false-negative rate for intraepithelial neoplasia. Chromoendoscopy increases sensitivity but lacks specificity. The aim was to assess prospectively the clinical applicability and predictive power of the EC3870CIFK confocal laser endomicroscope (CLE) for the in vivo diagnosis of intraepithelial neoplasia during colonoscopy. Methods Lesions were identified using chromoscopy followed by CLE imaging and graded according to vascular and cellular changes. CLE imaging of circumscribed lesions and four segmental ‘normal’ colorectal quadrants was performed. Targeted biopsy specimens were then compared with histopathological results. Results Forty patients completed the protocol (22 men and 18 women; median age 62 (range 39–82) years). The median duration of ileal intubation and total procedure time were 12 (range 5–26) and 55 (range 28–92) min respectively. Chromoscopic colonoscopy revealed 162 lesions in 39 patients. CLE imaging was obtained on all 162 lesions. Some 5422 confocal images were compared with 802 targeted biopsy specimens. Intraepithelial neoplasia was predicted with an accuracy of 99·1 per cent (sensitivity 97·4 per cent and specificity 99·3 per cent) (P = 0·711). Conclusion Confocal laser endomicroscopy permits high-quality cellular, subsurface vascular and stromal imaging, enabling prediction of intraepithelial neoplasia with a high level of accuracy.

This is a case report of a patient who underwent Oxaliplatin based neo-adjuvant chemotherapy for colorectal liver metastases, and subsequently developed sinusoidal obstruction, which was detected by Primavist enhanced MRI scan.

Advances in imaging technology and engineering have now permitted functional integration of a confocal endomicroscope into the distal tip of a conventional video colonoscope enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. For the first time, the endoscopist is now able to resolve the surface and subsurface mucosa at cellular resolution in vivo and in real time. A new era in endoscopic imaging has therefore begun - histoendoscopy. In addition to providing a high-accuracy in vivo optical biopsy tool for the differentiation between benign hyperplasia, intra-epithelial neoplasia and carcinoma in sporadic cohorts, endomicroscopy with targeted biopsies has now been shown to increase the yield of intra-epithelial neoplasia complicating ulcerative colitis. Furthermore, recent data examining endomicroscopic molecular ex vivo imaging using anti-CD44v6 antibody has identified aberrant crypt foci based on their surface molecular expression. Receptor overexpression in vivo in humans may, in the near future, be exploited for the diagnosis of inflammation, neoplasia and in predicting targeted molecular therapy. Endomicroscopy will be key to this immuno-imaging interface. Within the present review, we discuss the current clinical evidence in support of confocal endomicroscopy and explore the new diagnostic possibilities for this technology.

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Background: Resection of an adenoma-like mass (ALM) in chronic ulcerative colitis (CUC) complicated by mucosal fibrosis has historically not been technically feasible. Endoscopic submucosal dissection techniques may now provide a therapeutic tool enabling the division of submucosal fibrotic scarring, hence enabling endoluminal resection for the first time in this select patient group. The aim was prospective evaluation of endoscopic submucosal dissection-assisted (ESD) resection of flat, sessile, and lateral spreading tumors in CUC complicated by submucosal desmoplasis. Clinical endpoints were postresection recurrence rates, R0 resection status, and complications. Methods: ESD-assisted endoscopic mucosal resection (EMR) using the Olympus KD-630L insulation-tipped knife was performed on selected lesions. Results: Sixty-nine patients met inclusion criteria, of which 2 were excluded due to follow-up default. En bloc resection was performed in 52/67 (78%) cases with 15/67 (7%) requiring a piecemeal approach. R0 resection was achieved in 49/52 (94%) of lesions undergoing en bloc resection (perforation rate 2/67 [3%]). Bleeding complications occurred in 7/67 (10%) of cases. No metachronous circumscribed intraepithelial neoplastic lesions or cancer was detected at follow-up. At a median of 18 months follow-up, overall cure rates for the ESD-assisted EMR cohort was 66/67 (98%). Conclusions: We have shown for the first time that endoscopic resection of ALM even in the presence of complicating mucosal fibrosis is technically achievable using a combined ESD-assisted EMR technique. In an appropriately selected cohort, this technique may provide a technically feasible and clinically acceptable therapy where otherwise colectomy would be required. (Inflamm Bowel Dis 2008)

Objective A prospective technical feasibility study of cap assisted ESD for ‘curative intent’ in patients with residual or local neoplastic recurrence following EMR. Primary end points were second stage R0 resection rate, safety and recurrence. Method Salvage ESD was performed using the Olympus GIF-XQ240 gastroscope and KD-630L insulation tipped knife. Thirty-day mortality, re-admission rates, complications and histological resection status were collected prospectively up to 9 months following index resection. Results Thirty patients met eligibility criteria. Index R0 resection was achieved in 25/30 (83%) lesions. One patient underwent surgical excision with a second receiving a curative second stage dissection. Ninety-six per cent (29/30) patients were discharged within 24 h of the procedure with a 0% 30-day mortality and re-admission rate. Bleeding occurred in 5/30 (16%) treated successfully with endoluminal haemostasis. There were no perforations. Overall ‘cure’ rates at short-term follow-up [median 6/12 (range; 3–18)] was 96%. Conclusion This novel application of ESD for first line ‘salvage’ therapy in treating residual or locally recurrent neoplastic disease may be a safe, minimally invasive and cost effective alternative to direct surgical resection in a select patient cohort.