Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission.

BACKGROUND AND AIMS: Outcomes of cessation of anti-TNF therapy for Crohn's disease (CD) in clinical and/or endoscopic remission in routine clinical practice is uncertain. This study aimed to evaluate clinical outcomes and factors associated with relapse in CD patients following formal disease assessment and elective anti-TNF withdrawal. METHODS: Prospective observational study of CD patients in whom anti-TNF therapy was stopped electively after ≥12months and follow-up of ≥6months. Investigations at assessment prior to cessation included ≥1 of clinical assessment, endoscopic and/or imaging. Relapse was defined as recurrent symptoms of CD requiring medical or surgical therapy. RESULTS: Eighty-six patients received anti-TNF for a median duration of 23 (12-80) months for severe active luminal (70%), fistulating perianal (25.5%) and other fistulating disease (4.5%). Relapse rates at 90,180 and 365days were 4.7%, 18.6% and 36%, respectively. If anti-TNF dose escalation occurred 6months prior to withdrawal, 88% (7/8) relapsed. Based on multivariate analysis, risk factors for relapse include ileocolonic disease at diagnosis and previous anti-TNF therapy. An elevated faecal calprotectin (FC) is likely to predict relapse (p=0.02), with a PPV of 66.7% at >50µg/g. Of 36 patients who relapsed, 31 were retreated with anti-TNF, with an overall recapture rate of 93%. CONCLUSION: Relapse rates at 1year following elective withdrawal of anti-TNF are 36%, with high retreatment response rate. Predictors of relapse include ileocolonic involvement, previous anti-TNF therapy and raised FC. Endoscopic/radiologic assessment prior to cessation of therapy does not appear to predict those at lower risk of relapse.

Nuclear targeting of dystroglycan promotes the expression of androgen regulated transcription factors in prostate cancer.

Dystroglycan is frequently lost in adenocarcinoma, but the mechanisms and consequences are poorly understood. We report an analysis of ß-dystroglycan in prostate cancer in human tissue samples and in LNCaP cells in vitro. There is progressive loss of ß-dystroglycan immunoreactivity from basal and lateral surfaces of prostate epithelia which correlates significantly with increasing Gleason grade. In about half of matched bone metastases there is significant dystroglycan re-expression. In tumour tissue and in LNCaP cells there is also a tyrosine phosphorylation-dependent translocation of ß-dystroglycan to the nucleus. Analysis of gene expression data by microarray, reveals that nuclear targeting of ß-dystroglycan in LNCaP cells alters the transcription of relatively few genes, the most unregulated being the transcription factor ETV1. These data suggest that proteolysis, tyrosine phosphorylation and translocation of dystroglycan to the nucleus resulting in altered gene transcription could be important mechanisms in the progression of prostate cancer.

Dystroglycan function is a novel determinant of tumor growth and behavior in prostate cancer.

BACKGROUND: Dystroglycan is a ubiquitously expressed cell adhesion molecule frequently found to be altered or reduced in adenocarcinomas, however the mechanisms or consequences of dystroglycan loss have not been studied extensively. METHODS: We examined the consequence of overexpression or RNAi depletion of dystroglycan on properties of in vitro growth migration and invasion of LNCaP, PC3, and DU145 prostate cancer cell lines. RESULTS: Using LNCaP cells we observed cell density-dependent changes in ß-dystroglycan with the appearance of several lower molecular weight species ranging in size from 43 to 26 kDa. The bands of 31 and 26 kDa were attributed to proteolysis, whereas bands between 43 and 38 kDa were a consequence of mis-glycosylation. The localization of ß-dystroglycan in LNCaP colonies in culture also varied, cells with a mesenchymal appearance at the periphery of the colony had more pronounced membrane localization of dystroglycan. Whereas some cells demonstrated nuclear dystroglycan. Increased dystroglycan levels were inhibitory to growth in soft agar but promoted Matrigel invasion, whereas reduced dystroglycan levels promoted growth in soft agar but inhibited invasion. Similar results were also obtained for PC3 and DU145 cells. CONCLUSIONS: This study suggests that changes in ß-dystroglycan distribution within the cell and/or the loss of dystroglycan during tumorigenesis, through a combination of proteolysis and altered glycosylation, leads to an increased ability to grow in an anchorage independent manner, however dystroglycan may need to be re-expressed for cell invasion and metastasis to occur.

PREDICT Plus: development and validation of a prognostic model for early breast cancer that includes HER2.

BACKGROUND: Predict (www.predict.nhs.uk) is an online, breast cancer prognostication and treatment benefit tool. The aim of this study was to incorporate the prognostic effect of HER2 status in a new version (Predict+), and to compare its performance with the original Predict and Adjuvant!. METHODS: The prognostic effect of HER2 status was based on an analysis of data from 10 179 breast cancer patients from 14 studies in the Breast Cancer Association Consortium. The hazard ratio estimates were incorporated into Predict. The validation study was based on 1653 patients with early-stage invasive breast cancer identified from the British Columbia Breast Cancer Outcomes Unit. Predicted overall survival (OS) and breast cancer-specific survival (BCSS) for Predict+, Predict and Adjuvant! were compared with observed outcomes. RESULTS: All three models performed well for both OS and BCSS. Both Predict models provided better BCSS estimates than Adjuvant!. In the subset of patients with HER2-positive tumours, Predict+ performed substantially better than the other two models for both OS and BCSS. CONCLUSION: Predict+ is the first clinical breast cancer prognostication tool that includes tumour HER2 status. Use of the model might lead to more accurate absolute treatment benefit predictions for individual patients.

Angiogenesis, vascular endothelial growth factor and its receptors in human surgical wounds.

BACKGROUND: Angiogenesis plays an essential role in tissue repair. Vascular endothelial growth factor (VEGF) mediates angiogenesis through receptor kinases VEGF-R1 and VEGF-R2, and co-receptors, neuropilins Np1 and Np2. This study examined the spatial and temporal expression of these factors in relation to angiogenesis in surgical wounds. METHODS: Scar biopsies were obtained from patients between 3 days and 2 years after surgery. Normal skin control biopsies were taken during surgery. Microvessel density (MVD) was quantified using a Chalkley grid. VEGF, VEGF-R1, VEGF-R2, Np1 and Np2 endothelial expression was determined by immunohistochemistry, and correlated with MVD and scar age. RESULTS: Cumulative MVD was significantly greater in scars than controls (P = 0.011), and was related to scar age (P = 0.007). Expression of VEGF, VEGF-R2, Np1 and Np2 was increased significantly in all scars and correlated with MVD. In contrast, scar VEGF-R1 expression was decreased, and correlated with increased VEGF and VEGF-R2. CONCLUSION: Levels of VEGF, VEGF-R2, Np1 and Np2 are increased, whereas VEGF-R1 expression is decreased in angiogenesis, suggesting a role for VEGF-receptor complexes in early wound healing. This altered protein expression and increased presence of vessels is prolonged, suggesting that structural remodelling continues for at least 2 years after surgery.

Angiogenesis is associated with the onset of hyperplasia in human ductal breast disease.

BACKGROUND: The precise timing of the angiogenic switch and the role of angiogenesis in the development of breast malignancy is currently unknown. METHODS: Therefore, the expression of CD31 (pan endothelial cells (ECs)), endoglin (actively proliferating ECs), hypoxia-inducible factor-1 (HIF-1alpha), vascular endothelial growth factor-A (VEGF) and tissue factor (TF) were quantified in 140 surgical specimens comprising normal human breast, benign and pre-malignant hyperplastic tissue, in situ and invasive breast cancer specimens. RESULTS: Significant increases in angiogenesis (microvessel density) were observed between normal and benign hyperplastic breast tissue (P<0.005), and between in situ and invasive carcinomas (P<0.0005). In addition, significant increases in proliferating ECs were observed in benign hyperplastic breast compared with normal breast (P<0.05) cancers and in invasive compared with in situ cancers (P<0.005). Hypoxia-inducible factor-1alpha, VEGF and TF expression were significantly associated with increases in both angiogenesis and proliferating ECs (P<0.05). Moreover, HIF-1alpha was expressed by 60-75% of the hyperplastic lesions, and a significant association was observed between VEGF and TF in ECs (P<0.005) and invasive tumour cells (P<0.01). CONCLUSIONS: These findings are the first to suggest that the angiogenic switch, associated with increases in HIF-1alpha, VEGF and TF expression, occurs at the onset of hyperplasia in the mammary duct, although the greatest increase in angiogenesis occurs with the development of invasion.

Expression of beta-dystroglycan is reduced or absent in many human carcinomas.

AIMS: Dystroglycan is an important structural and signalling protein that is expressed in most human cells. alpha-Dystroglycan has been investigated and found to be reduced in human cancers, but there is only one published study on the expression of beta-dystroglycan in human cancer and that was only on small numbers of breast and prostatic cancers. The aim was to conduct a comprehensive immunohistochemical survey of the expression of beta-dystroglycan in normal human tissues and common cancers. METHODS AND RESULTS: Triplicate tissue microarrays of 681 samples of normal human tissues and common cancers were stained using an antibody directed against the cytoplasmic component of beta-dystroglycan. beta-Dystroglycan was strongly expressed at the intercellular junctions and basement membranes of all normal human epithelia. Expression of beta-dystroglycan was absent or markedly reduced in 100% of oesophageal adenocarcinomas, 97% of colonic cancers, 100% of transitional cell carcinomas of the urothelium and 94% of breast cancers. In the breast cancers, the only tumours that showed any retention of beta-dystroglycan expression were small low-grade oestrogen receptor-positive tumours. The only cancers that showed retention of beta-dystroglycan expression were cutaneous basal cell carcinomas. CONCLUSIONS: There is loss or marked reduction of beta-dystroglycan expression (by immunohistochemistry) in the vast majority of human cancers surveyed. Since beta-dystroglycan is postulated to have a tumour suppressor effect, this loss may have important functional significance.

Salvage endoscopic submucosal dissection for residual or local recurrent intraepithelial neoplasia in the colorectum: a prospective analysis.

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.

In vivo real-time confocal laser scanning endomicroscopic colonoscopy for the detection and characterization of colorectal neoplasia.

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.

EMR using dextrose solution versus sodium hyaluronate for colorectal Paris type I and 0-II lesions: a randomized endoscopist-blinded study.

BACKGROUND AND AIMS: Loss of mucosal 'lift' prior to submucosal dissection or endoscopic mucosal resection (EMR) increases the risk of complications. We conducted a randomized controlled trial comparing dextrose solution with sodium hyaluronic acid (SHA) for the EN BLOC resection of Paris type I/0-II and lateral spreading lesions of the colorectum. PATIENTS AND METHODS: Patients with Paris type I/0-II or lateral spreading tumor lesions of < 30 mm were randomized in a 1 : 1 ratio to undergo EMR using either dextrose solution or SHA. The primary study outcome was complete resection. Secondary outcomes were endoscopic complications (i. e. perforation or bleeding) and polyp recurrence rates. RESULTS: A total of 174 patients were randomized. R0 resection was achieved in 59 of the 82 lesions (72 %) in the dextrose group and 56 of the 81 lesions (69 %) in the SHA group ( P > 0.1), with no significant difference in median lesion diameter ( P > 0.1). The median number of post resection surveillance colonoscopies was 3 (range 2 - 7) in the dextrose group and 4 (range 2 - 6) in the SHA group ( P = NS). The median post index EMR resection follow-up period was 20 months (range 4 - 26) in the DS group and 18 months (range 3 - 22) in the SHA group ( P = NS). Recurrence rates were 1/82 (1.21 %) in the dextrose group and 1/81 (1.23 %) in the SHA group ( P = NS). CONCLUSIONS: EMR using dextrose solution is as effective as SHA in terms of resection completion, recurrence rates, and complications.

Ownership and uses of human tissue: what are the opinions of surgical in-patients?

AIMS: To investigate whether patient opinion about the uses of tissue removed at therapeutic operations has changed since the adverse publicity surrounding the Alder Hey and Bristol Royal Infirmary Inquiries, and to see whether it aligns with the Human Tissue Act 2004. METHODS: A questionnaire was given to 220 postoperative patients in a teaching hospital during an 11 week period. Aggregated responses to each question were ranked in frequency order. Unweighted centroid linkage hierarchical clustering analysis was performed with dendrogram display for the main data on tissue usage. RESULTS: 203 completed questionnaires were collected (compliance rate 92.3%). 96.3% of patients indicated that they would not object to their tissue being used in research, significantly higher than in the 1996 study (89.1%) with no overlap of the 95% CIs. 29.1% of patients believed that the hospital had ownership of tissue once it has been removed during surgery, 23.2% believed they had ownership, 19.7% believed that the pathology laboratory had ownership, and 15.3% believed that nobody had ownership rights in the case of tissue samples. CONCLUSIONS: This new survey indicates that despite a turbulent decade for those involved in human tissue retention in the UK, public support for a wide range of human tissue based activities, especially biomedical research, has not diminished and that patient opinion aligns well with the Human Tissue Act 2004.

Confocal chromoscopic endomicroscopy is superior to chromoscopy alone for the detection and characterisation of intraepithelial neoplasia in chronic ulcerative colitis.

BACKGROUND: The diagnosis of intraepithelial neoplasia is pivotal for ongoing clinical management decisions in ulcerative colitis. Previous studies have compared the diagnostic yield of endomicroscopy with conventional "white light" endoscopy and hence the overall objective increase of endomicroscopy targeted biopsies as compared to chromoscopy guided alone is not apparent. AIMS: We performed a prospective randomised controlled study to compare the diagnostic yield of intraepithelial neoplasia and cancer in patients undergoing ulcerative colitis screening using chromoscopy assisted endomicroscopy (group A) versus pan-colonic chromoscopy assisted colonoscopy (group B). METHODS: Patients were randomised in a 1:1 ratio to undergo screening colonoscopy using either chromoscopic endomicroscopy or chromoscopy alone with targeted biopsies. Circumscribed lesions were characterised using endomicroscopy and chromoscopy with pit pattern analysis. Targeted biopsies in addition to conventional 10 cm quadrantic biopsies were taken. Primary outcome addressed the number of intraepithelial neoplasias detected in each group. RESULTS: Endomicroscopy targeted biopsies significantly increased the yield of intraepithelial neoplasia as compared to pan-chromoscopy and biopsy alone (p<0.001) and also increased the yield of high-grade dysplastic lesions (p<0.001). Endomicroscopy targeted biopsies increased the diagnostic yield of intraepithelial neoplasia as compared to chromoscopy guided biopsies alone by 2.5-fold. CONCLUSIONS: This is the first randomised controlled study to show the true clinical benefit of endomicroscopy for the in vivo detection and characterisation of intraepithelial neoplasia in chronic ulcerative colitis surveillance colonoscopy. Endomicroscopy with targeted biopsy may potentially be the "gold standard" for the detection of intraepithelial neoplasia in ulcerative colitis.

BMP-6 over-expression in prostate cancer is associated with increased Id-1 protein and a more invasive phenotype.

Bone morphogenetic protein-6 (BMP-6) has been strongly implicated in prostate cancer development and bone metastasis. Our previous data showed that BMP-6 mRNA was absent in patients with benign prostatic hyperplasia, but evident in primary tumours with established secondary skeletal metastases. To examine the role of BMP-6 in prostate cancer progression, we have developed a BMP-6-regulatable, doxycycline-inducible gene expression system. BMP-6 induction by doxycycline addition led to increased levels of BMP-6 RNA and protein, associated with nuclear translocation of SMADs and activation of the downstream target gene Id-1. BMP-6 protein did not enhance the proliferation rate of PC3M cells but did significantly increase the rate of migration and invasion in both PC3M and DU145 cells. Increased metalloproteinase (MMP-1 and MMP-9) mRNA levels were also observed following BMP-6 induction. Luciferase reporter assays confirmed BMP-6-mediated activation of MMP-1 and MMP-9 promoters, indicating direct transcriptional activation of MMPs by BMP-6. BMP-6 stimulation also led to an increase in phosphorylation levels of MAPK proteins. We next examined the effects of BMP-6 on the downstream gene Id-1 in a cohort of prostate cancer patients. A tissue microarray (TMA) was constructed and samples stained for BMP-6 and Id-1 expression. We observed a significant increase in the intensity of staining of epithelial BMP-6 in the cancer cases compared to the benign cases (Mann-Whitney U test, p < 0.0005) and in the intensity of staining of epithelial Id-1 in the cancer cases compared to the benign cases (Mann-Whitney U test, p = 0.015). We further observed a significant positive correlation between epithelial staining for Id-1 and BMP-6 (p = 0.001) across all samples for both benign and cancer cases. These data demonstrate that BMP-6 promotes migration and invasion of prostate cancer cells, potentially through activation of Id-1 and MMP activation.

The Polycomb Group protein EZH2 regulates actin polymerization in human prostate cancer cells.

BACKGROUND: The Polycomb Group protein EZH2 is implicated in prostate cancer progression. EZH2 promotes prostate cancer cell proliferation and invasiveness. We describe a link between EZH2 function and actin polymerization in prostate cancer cells. METHODS: Nuclear and cytoplasmic EZH2 expression in benign and malignant prostate tissue samples was assessed. An association between EZH2 function and actin polymerization in prostate cancer cells was investigated using siRNA-mediated knock-down of EZH2. Effects of EZH2 knock-down on actin polymerization dynamics were analyzed biochemically using immunoblot analysis of cell lysate fractions, and morphologically using immunocytochemistry. RESULTS: Cytoplasmic EZH2 is expressed at low levels in benign prostate epithelial cells and over-expressed in prostate cancer cells. Cytoplasmic EZH2 expression levels correlate with nuclear EZH2 expression in prostate cancer samples. Knock-down of EZH2 in PC3 prostate cancer cells increases the amount of F-actin polymerization, cell size, and formation of actin-rich filaments. CONCLUSIONS: Cytoplasmic EZH2 is over-expressed in prostate cancer cells. EZH2 function promotes a reduction in the pool of insoluble F-actin in invasive prostate cancer cells. EZH2 may regulate actin polymerization dynamics and thereby promote prostate cancer cell motility and invasiveness.

In vivo confocal laser scanning chromo-endomicroscopy of colorectal neoplasia: changing the technological paradigm.

Recently, miniaturization of a novel confocal laser endomicroscope (Optiscan Pty, Notting Hill, Victoria, Australia) has permitted functional integration into the distal tip of a conventional video colonoscope (Pentax EC3870K; Pentax, Tokyo, Japan) enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. Using endomicroscopy and intravenous sodium fluorescein as a contrast agent, 'virtual histology' can be created, which allows visualization of both the surface epithelium, and some of the lamina propria (down to a quarter of a millimetre), including the microvasculature. Confocal endomicroscopy may have major implications in the future of colonoscopy as uniquely it allows in vivo diagnosis of colonic intraepithelial neoplasia and carcinoma enabling 'smart' biopsy targeting and hence potentially influencing 'on table' management decisions. Initial pilot data have now shown that confocal imaging in vivo using the newly developed EC3870K has high overall accuracy for the immediate diagnosis of intraepithelial neoplasia and carcinoma in sporadic screened cohorts, but also has a role in the detection of intraepithelial neoplasia detection in chronic ulcerative colitis cancer screening when used in conjunction with methylene blue chromoscopy. We discuss the current evidence in support of confocal endomicroscopy in the colorectum and explore the new diagnostic possibilities for this technology.

Patchy villous atrophy in adult patients with suspected gluten-sensitive enteropathy: is a multiple duodenal biopsy strategy appropriate?

BACKGROUND AND STUDY AIMS: The current internationally accepted gold standard for diagnosing celiac disease is a small-bowel biopsy demonstrating villous atrophy. However, it has been suggested that the diagnosis might not be considered as confirmed if the villous atrophy is patchy. Our aim was to assess whether there is an optimal duodenal biopsy strategy for detecting villous atrophy in adult patients with suspected gluten-sensitive enteropathy. PATIENTS AND METHODS: Patients who had positive endomysial or tissue transglutaminase antibodies were prospectively recruited. Nine biopsies were taken from the duodenum: one from the duodenal bulb, four from the proximal duodenum, and four from the distal duodenum. Each biopsy was graded according to the Marsh criteria. All possible biopsy regimes were evaluated for their ability to detect the presence and severity of villous atrophy. RESULTS: A total of 56 patients were recruited (23 men [41 %], 33 women [59 %]; mean age 47, range 16 - 85): 53/56 patients had villous atrophy present in at least one biopsy; 10/53 patients had biopsy specimens that showed "patchy" villous atrophy. In all 53 patients with villous atrophy this was detected by taking a minimum of three biopsies (sensitivity 100 %, 95 % confidence interval [CI] 93.2 % - 100 %). However, this strategy always incorporated a duodenal bulb biopsy. The most severe degree of villous atrophy in all 56 patients was only detected by using a five-biopsy regime (sensitivity 100 %, 95 % CI 93.6 % - 100 %). CONCLUSIONS: In this study we observed that villous atrophy in adult patients with suspected gluten-sensitive enteropathy (antibody-positive) is patchy. For this reason we would suggest a minimum of three biopsies, incorporating a duodenal bulb biopsy, to ensure that villous atrophy is detected. However, a five-biopsy regime is required for recognition of the most severe lesion.

Achieving R0 resection in the colorectum using endoscopic submucosal dissection.

BACKGROUND: Endoscopic mucosal resection is established for the removal of non-invasive colorectal tumours smaller than 20 mm but is unsatisfactory for larger lesions. Endoscopic submucosal dissection (ESD) enables en bloc resection of lesions larger than 20 mm. A UK-based prospective feasibility study of ESD for colorectal tumours was undertaken; primary endpoints were R0 resection, safety and recurrence. METHODS: Patients with Paris 0-II adenomas or laterally spreading tumours (LSTs) greater than 20 mm in diameter were enrolled between November 2004 and August 2006. Lesions were assessed by chromoscopy and high-frequency ultrasonography. Dysplasia, resection status, 30-day complication rates and recurrence after ESD were recorded. RESULTS: ESD was performed in 42 of 56 identified patients; en bloc resection was possible in 33. Fourteen Paris 0-II lesions and 28 LSTs were identified; 40 were dysplastic adenomas and two adenocarcinomas. R0 resection was achieved in 31 patients (74 per cent). The 30-day mortality rate was 0 per cent. Perforation occurred in one patient and uncomplicated bleeding in five. The 6-month cure rate was 81 per cent (34 of 42 patients). CONCLUSION: High cure rates are achievable using ESD for Paris 0-II adenomas and LSTs greater than 20 mm in diameter, with R0 resection possible in most patients. ESD is feasible throughout the colorectum with no increase in complication rates. It should be considered for selected Tim/T1 N0 colorectal lesions.

High-magnification chromoscopic colonoscopy in ulcerative colitis: a valid tool for in vivo optical biopsy and assessment of disease extent.

BACKGROUND AND STUDY AIMS: Colonoscopy with mucosal biopsy is currently considered to be the "gold standard" investigation for the evaluation of disease activity and disease extent in ulcerative colitis. Conventional colonoscopic criteria are inadequate for assessing disease extent and for predicting clinical relapse, however. Histopathological markers of relapse, such as microscopic crypt abscess formation and mucin depletion cannot be identified using conventional endoscopy. The aim of this study was to evaluate the efficacy of high-magnification chromoscopic colonoscopy for the in vivo assessment of histopathological inflammation and disease extent using standardised endoscopic and histopathological criteria. PATIENTS AND METHODS: Total colonoscopy using the Olympus CF240Z magnifying colonoscope was performed prospectively in 325 consecutive patients with a known diagnosis of ulcerative colitis. A "biphasic" examination of all five colonic segments and the rectum was performed with conventional endoscopy followed by magnification imaging and biopsy. Disease activity was documented using Baron's classification, modified Saitoh criteria for magnification imaging, and Matts' histopathological grading. RESULTS: A total of 1800 images from 300 patients were analyzed (25 patients were excluded). The kappa coefficients of agreement between Saitoh's magnification criteria grades 1/2, 3/4, and 5/6 and Matts' histopathological grades 1/2, 3a/b, and 4/5 were 0.96, 0.62, and 0.51, respectively. Mild, moderate, and severe histopathological disease (Matts' grades 1/2, 3a - 4, and 5) were represented more accurately using Saitoh's criteria than by conventional Baron scores for all clinical parameters ( R = 0.976; P < 0.001). Magnification imaging was significantly better than conventional colonoscopy for predicting disease extent in vivo ( P < 0.0001). CONCLUSIONS: This is the largest prospective study and the only Western group to report on this application of magnification imaging. High-magnification imaging provides a sensitive and specific in vivo "virtual biopsy" in ulcerative colitis and so an instant biomarker for disease relapse, while accurately predicting disease extent. High-accuracy optical biopsy can limit the number of biopsies required, with significant cost savings for pathology services.

"Salvage" endoscopic mucosal resection in the colon using a retroflexion gastroscope dissection technique: a prospective analysis.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection and submucosal dissection can provide curative endoscopic therapy for Paris type I/II adenomas and node-negative early cancer. No studies have addressed the technical feasibility of retroflexion endoscopic dissection methods for luminal "salvage" therapy in patients considered unresectable using conventional forward-viewing resection. PATIENTS AND METHODS: Colonoscopy using an Olympus GIF-XQ240 gastroscope was carried out in 76 patients with Paris type I/II adenomas, early colorectal cancer (CRC), or laterally spreading tumors (LSTs) when the index endoscopist considered the lesion to be unresectable due to retrograde fold involvement. Endoscopic mucosal resection (EMR) and submucosal dissection were carried out using a complete retroflexion technique. Endoscopic and miniprobe 20-MHz or 12.5-MHz ultrasound follow-up data were collected prospectively up to 24 months after the index resection. RESULTS: Cecal intubation or cannulation to the neoterminal ileum was achieved in 76 (100 %) cases. Forty lesions (53 %) were classified in accordance with the Paris criteria as Is; 16 (21 %) as type II; 10 (13.5 %) as LST-G; and 10 (13.5 %) as LST-NG. Eight lesions (10 %) were excluded from EMR on the basis of endoscopic ultrasound criteria, with 68 of the 76 lesions (89 %) meeting the criteria for endoluminal resection. The median intubation time was 16 min (range 3-32 min). The median resection times were 98 min (range 30 - 242 min), 36 min (range 10-60 min), 172 min (range 20 - 240 min), and 60 min (range 10-116 min) for Paris Is, II, LST-G, and LST-NG lesions, respectively. LST-G morphology was associated with a high median submucosal injection volume in comparison with all other Paris types ( P < 0.05) and with a prolonged resection time ( P < 0.01). Sixty-one patients (94 %) completed the surveillance protocol. Higaki recurrence criteria were met in seven patients (11 %), with six undergoing successful adjunctive endoluminal resection. After 24 months of follow-up, the "cure" rate with endoscopic resection was 60 out of 61 (98 %). CONCLUSIONS: This is the first prospective study to address the safety and medium-term efficacy of retroflexion endoscopic resection in the colon. When appropriate exclusion criteria are applied, selected patients can receive curative resection using the retroflexion technique. "Salvage" endoluminal therapy may therefore be possible in such cases when surgical resection would otherwise have been required.