Clinical outcome of non-curative endoscopic submucosal dissection for early colorectal cancer.

OBJECTIVE: Endoscopic submucosal dissection (ESD) in a curative intent for submucosa-invasive early (T1) colorectal cancers (T1-CRCs) often leads to subsequent surgical resection in case of histologic parameters indicating higher risk of nodal involvement. In some cases, however, the expected benefit may be offset by the surgical risks, suggesting a more conservative approach. DESIGN: Retrospective analysis of consecutive patients with T1-CRC who underwent ESD at 13 centres ending inclusion in 2019 (n=3373). Cases with high risk of nodal involvement (non-curative ESD: G3, submucosal invasion>1000 µm, lymphovascular involvement, budding or incomplete resection/R1) were analysed if follow-up data (endoscopy/imaging) were available, regardless of the postendoscopic management (follow-up vs surgery) selected by the multidisciplinary teams in these institutions. Comorbidities were classified according to Charlson Comorbidity Index (CCI). Outcomes were disease recurrence, death and disease-related death rates in the two groups. Rate of residual disease (RD) at both the previous resection site and regional lymph nodes was assessed in the surgical cases as well as from follow-up in the follow-up group. RESULTS: Of 604 patients treated by colorectal ESD for submucosally invasive cancer, 207 non-curative resections (34.3%) were included (138 male; mean age 67.6±10.9 years); in 65.2% of cases, no complete resection was achieved (R1). Of the 207 cases, 60.9% (n=126; median CCI: 3; IQR: 2-4) underwent surgical treatment with RD in 19.8% (25/126), while 39.1% (n=81, median CCI: 5; IQR: 4-6) were followed up by endoscopy in all cases. Patients in the follow-up group had a higher overall mortality (HR=3.95) due to non-CRC causes (n=9, mean survival after ESD 23.7±13.7 months). During this follow-up time, tumour recurrence and disease-specific survival rates were not different between the groups (median follow-up 30 months; range: 6-105). CONCLUSION: Following ESD for a lesion at high risk of RD, follow-up only may be a reasonable choice in patients at high risk for surgery. Also, endoscopic resection quality should be improved. TRIAL REGISTRATION NUMBER: NCT03987828.

Incidence of microscopic residual adenoma after complete wide-field endoscopic resection of large colorectal lesions: evidence for a mechanism of recurrence.

BACKGROUND AND AIMS: EMR of large (≥2 cm) nonpedunculated colorectal polyps (LNPCPs) is associated with high rates of recurrent/residual adenoma, possibly because of microadenoma left at the margin of resection. Data supporting this mechanism are required. We aimed to determine the incidence of residual microadenoma at the defect margin and base after EMR. METHODS: We performed a retrospective observational study of patients undergoing EMR of large LNPCPs with the lateral defect margin further resected using the EndoRotor device (Interscope Medical, Inc, Worcester, Mass, USA) after confirming no visible residual adenomatous tissue. Aspects of the defect base were also resected in selected patients. Patients underwent surveillance at 3 to 6 months. RESULTS: Resection of the normal defect margin was performed in 41 patients and of aspects of the base in 21 patients. Mean lesion size was 43.0 mm (range, 20-130). Microscopic residual lesion was detected in the margin of apparently normal mucosa in 8 cases (19%). In 7 cases this was an adenoma, and in 1 case a serrated lesion was found at the margin of a resected tubular adenoma. Microscopic residual lesion was detected at the base in 5 of 21 cases. Residual/recurrent adenoma was detected in 2 patients. Neither had residual microadenoma at the lateral margin or base detected after the primary resection. CONCLUSIONS: Microscopic residual adenoma after wide-field EMR was detected in 19% of cases at the apparently normal defect margin and at the resection base in 5 of 21 cases. This study confirms the presence of residual microadenoma after resection of LNPCPs, providing evidence for the mechanism of recurrence.

Near-focus narrow-band imaging classification of villous atrophy in suspected celiac disease: development and international validation.

BACKGROUND AND AIMS: There are no agreed-on endoscopic signs for the diagnosis of villous atrophy (VA) in celiac disease (CD), necessitating biopsy sampling for diagnosis. Here we evaluated the role of near-focus narrow-band imaging (NF-NBI) for the assessment of villous architecture in suspected CD with the development and further validation of a novel NF-NBI classification. METHODS: Patients with a clinical indication for duodenal biopsy sampling were prospectively recruited. Six paired NF white-light endoscopy (NF-WLE) and NF-NBI images with matched duodenal biopsy sampling including the bulb were obtained from each patient. Histopathology grading used the Marsh-Oberhuber classification. A modified Delphi process was performed on 498 images and video recordings by 3 endoscopists to define NF-NBI classifiers, resulting in a 3-descriptor classification: villous shape, vascularity, and crypt phenotype. Thirteen blinded endoscopists (5 expert, 8 nonexpert) then undertook a short training module on the proposed classification and evaluated paired NF-WLE-NF-NBI images. RESULTS: One hundred consecutive patients were enrolled (97 completed the study; 66 women; mean age, 51.2 ± 17.3 years). Thirteen endoscopists evaluated 50 paired NF-WLE and NF-NBI images each (24 biopsy-proven VAs). Interobserver agreement among all validators for the diagnosis of villous morphology using the NF-NBI classification was substantial (κ = .71) and moderate (κ = .46) with NF-WLE. Substantial agreement was observed between all 3 NF-NBI classification descriptors and histology (weighted κ = 0.72-.75) compared with NF-WLE to histology (κ = .34). A higher degree of confidence using NF-NBI was observed when assessing the duodenal bulb. CONCLUSIONS: We developed and validated a novel NF-NBI classification to reliably diagnose VA in suspected CD. There was utility for expert and nonexpert endoscopists alike, using readily available equipment and requiring minimal training. (Clinical trial registration number: NCT04349904.).

Impedance planimetry values for predicting clinical response following peroral endoscopic myotomy.

BACKGROUND: There is growing interest in developing impedance planimetry as a tool to enhance the clinical outcomes for endoscopic and surgical management of achalasia. The primary aim of this study was to determine whether impedance planimetry measurements can predict clinical response and reflux following peroral endoscopic myotomy (POEM). METHODS: A multicenter cohort study of patients with achalasia undergoing POEM was established from prospective databases and retrospective chart reviews. Patients who underwent impedance planimetry before and after POEM were included. Clinical response was defined as an Eckardt score of ≤ 3. Tenfold cross-validated area under curve (AUC) values were established for the different impedance planimetry measurements associated with clinical response and reflux development. RESULTS: Of the 290 patients included, 91.7 % (266/290) had a clinical response and 39.4 % (108/274) developed reflux following POEM. The most predictive impedance planimetry measurements for a clinical response were: percent change in cross-sectional area (%ΔCSA) and percent change in distensibility index (%ΔDI), with AUCs of 0.75 and 0.73, respectively. Optimal cutoff values for %ΔCSA and %ΔDI to determine a clinical response were a change of 360 % and 272 %, respectively. Impedance planimetry values were much poorer at predicting post-POEM reflux, with AUCs ranging from 0.40 to 0.62. CONCLUSION: Percent change in CSA and distensibility index were the most predictive measures of a clinical response, with a moderate predictive ability. Impedance planimetry values for predicting reflux following POEM showed weak predictive capacity.

Multimodal Endoscopic Assessment Guides Treatment Decisions for Rectal Early Neoplastic Tumors.

BACKGROUND: There is a trend toward organ conservation in the management of rectal tumors. However, there is no consensus on standardized investigations to guide treatment. OBJECTIVE: We report the value of multimodal endoscopic assessment (white light, magnification chromoendoscopy and narrow band imaging, selected colonoscopic ultrasound) for rectal early neoplastic tumors to inform treatment decisions. DESIGN: This was a retrospective study. SETTING: The study was conducted in a tertiary referral unit for interventional endoscopy and early colorectal cancer. PATIENTS: A total of 296 patients referred with rectal early neoplastic tumors were assessed using standardized multimodal endoscopic assessment and classified according to risk of harboring invasive cancer. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values of multimodal endoscopic assessment, and previous biopsy to predict invasive cancer were calculated and treatment outcomes reported. RESULTS: After multimodal endoscopic assessment, lesions were classified as invasive cancer, at least deep submucosal invasion (n = 65); invasive cancer, superficial submucosal invasion or high risk of covert cancer (n = 119); or low risk of covert cancer (n = 112). Sensitivity, specificity, positive predictive values, and negative predictive values of multimodal endoscopic assessment for diagnosing invasive cancer, deep submucosal invasion, were 77%, 98%, 93%, and 93%. The combined classification of all lesions with invasive cancer or high risk of covert cancer had a negative predictive value of 96% for invasive cancer on final histopathology. Sensitivity of previous biopsy was 37%. A total of 47 patients underwent radical surgery and 33 transanal endoscopic microsurgery. No patients without invasive cancer were subjected to radical surgery; 222 patients initially underwent endoscopic resection. Of the 203 without deep submucosal invasion, 95% avoided surgery and were free from recurrence at last follow-up. LIMITATIONS: This was a retrospective study from a tertiary referral unit. CONCLUSIONS: Standardized multimodal endoscopic assessment guides rational treatment decisions for rectal tumors resulting in organ-conserving treatment for all patients without deep submucosal invasive cancer. See Video Abstract at http://links.lww.com/DCR/B133. LA EVALUACIÓN ENDOSCÓPICA MULTIMODAL COMO GUÍA DE DECISIONES EN EL TRATAMIENTO DE TUMORES RECTALES NEOPLÁSICOS PRECOCES: La tendencia actual es la preservación del órgano en el manejo de los tumores de rectao. Sin embargo, no hay consenso sobre las investigaciones estandar para guiar dicho tratamiento.Presentamos los valores de la evaluación endoscópica multimodal (luz blanca, cromoendoscopia de aumento, imagen de banda estrecha y ecografía colonoscópica seleccionada) para tumores rectales neoplásicos tempranos y así notificar las decisiones sobre el tratamiento.Estudio retrospectivo.El estudio se realizó en una unidad de referencia terciaria para endoscopia intervencionista y cáncer colorrectal temprano.Se evaluaron 296 pacientes referidos con tumores neoplásicos precoces de recto mediante una evaluación endoscópica multimodal estandarizada y se clasificaron de acuerdo al riesgo de albergar un cáncer invasivo.Se calcularon la sensibilidad, la especificidad, los valores predictivos positivos y negativos de la evaluación endoscópica multimodal y la biopsia previa para predecir el cáncer invasivo y se notificaron los resultados para el tratamiento.Después de la evaluación endoscópica multimodal, las lesiones se clasificaron como: cáncer invasive (al menos invasión submucosa profunda n = 65); cáncer invasive (invasión submucosa superficial o alto riesgo de cáncer encubierto n = 119) y finalmente aquellos de bajo riesgo de cáncer encubierto (n = 112). La sensibilidad, la especificidad, los valores predictivos positivos y negativos de la evaluación endoscópica multimodal para el diagnóstico de cáncer invasivo, la invasión submucosa profunda fueron 77%, 98%, 93% y 93% respectivamente. La clasificación combinada de todas las lesiones con cáncer invasivo o de alto riesgo de cáncer encubierto tuvo un VPN del 96% para el cáncer invasivo en la histopatología final. La sensibilidad fué de 37% en todas las biopsias previas. 47 pacientes fueron sometidos a cirugía radical, 33 por microcirugía endoscópica transanal. Ningún paciente sin cáncer invasivo fue sometido a cirugía radical. Inicialmente, 222 pacientes fueron sometidos a resección endoscópica. De los 203 sin invasión submucosa profunda, el 95% evitó la cirugía y no tuvieron recurrencia en el último seguimiento.Estudio retrospectivo de una unidad de referencia terciaria.La evaluación endoscópica multimodal estandarizada guía las decisiones racionales de tratamiento para los tumores rectales que resultan en un tratamiento conservador de órganos para todos los pacientes sin cáncer invasivo submucoso profundo. Consulte Video Resumen en http://links.lww.com/DCR/B133.

The future of endoscopy: Advances in endoscopic image innovations.

The latest state of the art technological innovations have led to a palpable progression in endoscopic imaging and may facilitate standardisation of practice. One of the most rapidly evolving modalities is artificial intelligence with recent studies providing real-time diagnoses and encouraging results in the first randomised trials to conventional endoscopic imaging. Advances in functional hypoxia imaging offer novel opportunities to be used to detect neoplasia and the assessment of colitis. Three-dimensional volumetric imaging provides spatial information and has shown promise in the increased detection of small polyps. Studies to date of self-propelling colonoscopes demonstrate an increased caecal intubation rate and possibly offer patients a more comfortable procedure. Further development in robotic technology has introduced ex vivo automated locomotor upper gastrointestinal and small bowel capsule devices. Eye-tracking has the potential to revolutionise endoscopic training through the identification of differences in experts and non-expert endoscopist as trainable parameters. In this review, we discuss the latest innovations of all these technologies and provide perspective into the exciting future of diagnostic luminal endoscopy.

Outcomes from an international multicenter registry of patients with acute gastrointestinal bleeding undergoing endoscopic treatment with Hemospray.

BACKGROUND AND AIM: Acute gastrointestinal bleeding carries poor outcomes unless prompt endoscopic hemostasis is achieved. Mortality in these patients remains significant. Hemospray is a novel intervention that creates a mechanical barrier over bleeding sites. We report the largest dataset of patient outcomes after treatment with Hemospray from an international multicenter registry. PATIENTS AND METHODS: Prospective data (Jan 2016-May 2018) from 12 centers across Europe were collected. Immediate hemostasis was defined as endoscopic cessation of bleeding within 5 min after application of Hemospray. Rebleeding was defined as subsequent drop in hemoglobin, hematemesis, persistent melena with hemodynamic compromise post-therapy. RESULTS: Three hundred and fourteen cases were recruited worldwide (231 males, 83 females). Median pretreatment Blatchford score was 11 (IQR: 8-14) and median complete Rockall score (RS) was 7 (IQR: 6-8) for all patients. Peptic ulcer disease (PUD) was the most common pathology (167/314 = 53%) and Forrest Ib the most common bleed type in PUD (100/167 = 60%). 281 patients (89.5%) achieved immediate hemostasis after successful endoscopic therapy with Hemospray. Rebleeding occurred in 29 (10.3%) of the 281 patients who achieved immediate hemostasis. Seven-day and 30-day all-cause mortality were 11.5% (36/314) and 20.1% (63/314), respectively (lower than the predicted rates as per the RS). Similar hemostasis rates were noted in the Hemospray monotherapy (92.4%), combination therapy (88.7%) and rescue therapy (85.5%) groups. CONCLUSIONS: These data show high rates of immediate hemostasis overall and in all subgroups. Rebleeding and mortality rates were in keeping/lower than predicted rates.

Risk factors for early and late adenoma recurrence after advanced colorectal endoscopic resection at an expert Western center.

BACKGROUND AND AIMS: Few large Western series examine risk factors for recurrence after endoscopic resection (ER) of large (≥20 mm) colorectal laterally spreading tumors. Recurrence beyond initial surveillance is seldom reported, and differences between residual/recurrent adenoma and late recurrence are not scrutinized. We report the incidence of recurrence at successive surveillance intervals, identify risk factors for recurrent/residual adenoma and late recurrence, and describe the outcomes of ER of recurrent adenomas. METHODS: Recurrence was calculated for successive surveillance periods after colorectal ER. Multiple logistic regression was used to identify independent risk factors for recurrent/residual adenoma and late recurrence (≥12 months). RESULTS: Six hundred twenty colorectal ERs were performed, and 456 eligible patients (98%) had completed 3- to 6-month surveillance. Residual/recurrent adenoma (3-6 months) was detected in 8.3%, at 12 months in 6.1%, between 24 and 36 months in 6.4%, and after 36 months in 13.5%. Independent risk factors for residual/recurrent adenoma were piecemeal resection (odds ratio [OR], 13.0; P = .01), adjunctive argon plasma coagulation (OR, 2.4; P = .01), and lesion occupying ≥75% of the luminal circumference (OR, 5.6; P < .001) and for late recurrence were lesion size >60 mm (OR, 6.3; P < .001) and piecemeal resection (OR, 4.4; P = .04). Of 66 patients with recurrence, 5 required surgery, 8 left the treatment pathway, 20 are still receiving ER or surveillance, and 33 had ER with normal subsequent surveillance. CONCLUSIONS: Recurrence occurs at successive periods of surveillance after ER even beyond 3 years. Aside from piecemeal resection, risk factors for residual/recurrent adenoma and late recurrence are different. Recurrence can be challenging to treat, but surgery is rarely required.

Outcomes of endoscopic resection of large colorectal lesions subjected to prior failed resection or substantial manipulation.

PURPOSE: Injudicious attempts at resection and extensive sampling of large colorectal adenomas prior to referral for endoscopic resection (ER) are common. This has deleterious effects, but little is known about the outcomes following ER. We retrospectively analysed the outcomes of ER of large adenomas previously subjected to substantial manipulation. METHOD: ER of large (≥ 2 cm) colorectal adenomas were grouped according to level of manipulation: prior attempted resection, heavy manipulation (≥ six biopsies or tattoo under lesion) or minimal manipulation (< six biopsies). Outcomes were compared between groups. Independent predictors of outcomes were identified using multiple logistic regression. RESULTS: Five hundred forty-two lesions (mean size 53.7 mm) were included. Two hundred sixty-five (49%) had been subjected to prior attempted resection or heavy manipulation, 151 (28%) to minimal manipulation, and 126 (23%) were not previously manipulated. ESD techniques were used more frequently than EMR after substantial manipulation. There were no differences in initial success of ER (99%, 98%, 98%, p = 0.71). Prior attempted resection was independently associated with recurrence (OR 2.2, 95% CI 1.1-4.5, p = 0.03) and negatively associated with en bloc resection (OR 0.29, 95% CI 0.1-0.7, p = 0.004). Regardless of level of prior manipulation, there were no differences in sustained endoscopic cure with > 95% of patients overall free from recurrence and avoiding surgery at last follow-up. CONCLUSION: There is a substantial burden of injudicious lesion manipulation before referral, which makes recurrence more likely and en bloc resection less likely. However, with appropriate expertise, sustained successful endoscopic treatment is achievable for the vast majority of patients treated in a specialist unit.

Endoscopic resection of colorectal circumferential and near-circumferential laterally spreading lesions: outcomes and risk of stenosis.

PURPOSE: Almost any colorectal superficial neoplastic lesion can be treated by endoscopic resection (ER) but very little is known about outcomes of ER leaving circumferential or near-circumferential mucosal defects. We report the outcomes of ER leaving ≥ 75% circumferential mucosal defects performed in a western expert centre. METHODS: Five hundred eighty-seven ERs of large colorectal lesions ≥ 20 mm were grouped according to the extent of the mucosal defect and comparisons made between those with < 75% and ≥ 75% defects. Independent predictors of stenosis were identified. RESULTS: Forty-seven patients had ER leaving ≥ 75% circumference defect, most located at or distal to the rectosigmoid, with ≥ 90% defects in 5 and 100% in 11. There were no significant colonic muscle injuries in patients with ≥ 75% defect and no differences in post-procedure bleeding (OR 1.6, 95% CI 0.2-13.7, p = 0.64) between patients with ≥ 75% and < 75% defects. Stenosis developed in 9 patients. ≥ 90% circumference defect was the only independent risk factor for stenosis (OR 286, p < 0.001). Three of 4 patients with asymptomatic stenosis had successful expectant management. The remainder were treated with dilatation. Recurrence was more likely in those with ≥ 75% defect (OR 7.9, 95% CI 3.8-16.4, p < 0.001) but was managed with further ER in all but 2 cases. CONCLUSION: ER of colorectal lesions resulting in defects ≥ 75% of the luminal circumference is challenging but safe and effective when performed in an expert centre. The only independent predictor of stenosis is ≥ 90% circumference defect but some patients improve with expectant management; therefore, pre-emptive intervention may not be warranted.

Safe and Effective Endoscopic Resection of Massive Colorectal Adenomas ≥8 cm in a Tertiary Referral Center.

BACKGROUND: Endoscopic resection of large colorectal lesions is well reported and is the first line of treatment for all noninvasive colorectal neoplasms in many centers, but little is known about the outcomes of endoscopic resection of truly massive colorectal lesions ≥8 cm. OBJECTIVE: We report on the outcomes of endoscopic resection for massive (≥8 cm) colorectal adenomas and compare the outcomes with resection of large (2.0-7.9 cm) lesions. DESIGN: This was a retrospective study. SETTINGS: The study was conducted in a tertiary referral unit for interventional endoscopy. PATIENTS: A total of 435 endoscopic resections of large colorectal polyps (≥2 cm) were included, of which 96 were ≥8 cm. MAIN OUTCOME MEASURES: Outcomes included initial successful resection, complications, recurrence, surgery, and hospital admission. RESULTS: Endoscopic resection was successful for 91 of 96 massive lesions (≥8 cm). Mean size was 10.1 cm (range, 8-16 cm). A total of 75% had previous attempts at resection or heavy manipulation before referral. Thirty two were resected using endoscopic submucosal dissection or hybrid endoscopic submucosal dissection and the rest using piecemeal endoscopic mucosal resection. No patients required surgery for a perforation. Five patients had postprocedural bleeding. There were 25 recurrences: 2 were treated with transanal endoscopic microsurgery, 2 with right hemicolectomy, and the rest with endoscopic resection. Compared with patients with large lesions, more patients with massive adenomas had complications (19.8% versus 3.3%), required admission (39.6% versus 11.0%), developed recurrence (30.8% versus 9.9%), or required surgery for recurrence (5.0% versus 0.8%). LIMITATIONS: This was a retrospective study. CONCLUSIONS: Endoscopic resection of massive colorectal adenomas ≥8 cm is achievable with few significant complications, and the majority of patients avoid surgery. Systematic assessment is required to appropriately select patients for endoscopic resection, which should be performed in specialist units. See Video Abstract at http://links.lww.com/DCR/A653.

Using Endoscopic Submucosal Dissection as a Routine Component of the Standard Treatment Strategy for Large and Complex Colorectal Lesions in a Western Tertiary Referral Unit.

BACKGROUND: Colorectal endoscopic submucosal dissection results in high rates of en bloc resection, few recurrences, and accurate diagnosis, and it is useful in lesions with significant fibrosis. However, endoscopic submucosal dissection has not been widely adopted by Western endoscopists and the published experience from Western centers is very limited. OBJECTIVES: This study aims to report the outcomes from a UK tertiary center using colorectal endoscopic submucosal dissection as part of a standard lesion specific treatment approach. DESIGN: This was a retrospective study. SETTING: The study was conducted in a tertiary referral unit for interventional endoscopy in the United Kingdom. PATIENTS: A total of 116 colorectal lesions were resected using endoscopic submucosal dissection or hybrid endoscopic submucosal dissection in 107 patients. MAIN OUTCOME MEASURES: Outcomes included complications, recurrence, requirement for surgery, en bloc and R0 resection. RESULTS: One hundred sixteen lesions (mean size 58.8mm) were resected using endoscopic submucosal dissection (n = 58) and hybrid endoscopic submucosal dissection (n = 58). Eighty-two (70.7%) had failed attempts at resection (n = 58) or extensive sampling before referral. Twelve contained invasive adenocarcinoma; endoscopic resection was curative in 6. Only 2 of 6 patients with noncurative endoscopic resection agreed to surgery, and none had lymph node metastases. Six of 7 perforations were successfully treated with endoscopic clips. Where endoscopic submucosal dissection was used alone, en bloc resection was achieved in 93% and R0 resection was achieved in 91%. Two patients experienced recurrence; both were managed with endoscopic resection. LIMITATIONS: This was a retrospective study. Procedures were planned as endoscopic submucosal dissection, but some may have been converted to hybrid endoscopic submucosal dissection and not recorded. CONCLUSION: Colorectal endoscopic submucosal dissection can be used in a Western center as part of a standard lesion-specific approach to deliver effective organ-conserving treatment to patients with large challenging lesions. Lesion assessment in Western practice should be improved to reduce the incidence of prior heavy manipulation and to guide appropriate referral. See Video Abstract at http://links.lww.com/DCR/A601.

Early change in faecal calprotectin predicts primary non-response to anti-TNFα therapy in Crohn's disease.

OBJECTIVE: The early identification of primary non-response to anti-TNFα therapy facilitates the timely management of patients with Crohn's disease (CD). A recent, pilot study to detect prognostic markers of early response to anti-TNFα therapy identified the two genes coding for the calprotectin subunits (S100A8, S100A9) to be among the most highly expressed gene transcripts in non-responders. This study tests the hypothesis that measurements of faecal calprotectin (FCAL) pre- and post-anti-TNFα induction can predict primary non-response. METHODS: Retrospective study of 32 CD patients treated over a two-year period. Outcomes were assessed at 6 months based on clinical activity scores and the use of corticosteroids: (a) remission: Harvey-Bradshaw index (HBI) < 5, off corticosteroids >2 months; (b) response: drop in HBI >3, off corticosteroids; (c) non-response: ΔFCAL (and ΔCRP, respectively) was calculated as (FCAL post-induction - FCAL pre-induction) × 100/FCAL pre induction. RESULTS: At 6 months, 23 (72%) patients had responded (median (interquartile range) HBI: 4 (3-5), FCAL: 55 (27-146)), 17 (73%) of whom were in remission [HBI: 3 (2.5-4) and FCAL: 42 (16-115)]. There was a significant difference in the ΔFCAL from baseline to post-induction in the three groups (p < 0.0001). Comparing non-responders to combined response and remission groups, the AUC of ΔFCAL to predict outcome at 6 months was 0.97. Using ROC analysis, a Δ70% returned a sensitivity and specificity of 99% and 96%, respectively (likelihood ratio, LR= 23). ΔCRP did not predict 6 months outcomes. CONCLUSIONS: A drop in FCAL <70% after induction predicts primary non-response to anti-TNFα in CD.

High burden of polyp mischaracterisation in tertiary centre referrals for endoscopic resection may be alleviated by telestration.

Objective: Endoscopic resection (ER) often involves referral to tertiary centres with high volume practices. Lesions can be subject to prior manipulation and mischaracterisation of features required for accurate planning, leading to prolonged or cancelled procedures. As potential solutions, repeating diagnostic procedures is burdensome for services and patients, while even enriched written reports and still images provide insufficient information to plan ER. This project sought to determine the frequency and implications of polyp mischaracterisation and whether the use of telestration might prevent it. Design/method: A retrospective data analysis of ER referrals to four tertiary centres was conducted for the period July-December 2019. Prospective telestration with a novel digital platform was then performed between centres to achieve consensus on polyp features and ER planning. Results: 163 lesions (163 patients; mean age 67.9±12.2 y; F=62) referred from regional hospitals, were included. Lesion site was mismatched in 11 (6.7%). Size was not mentioned in the referral in 27/163 (16.6%) and incorrect in 81/136 (51.5%), more commonly underestimated by the referring centre (<0.0001), by a mean factor of 1.85±0.79. Incurred procedure time (in units of 20 min) was significantly greater than that allocated (p=0.0085). For 10 cases discussed prospectively, rapid consensus on lesion features was achieved, with agreement between experts on time required for ER. Conclusions: Polyp mischaracterisation is a frequent feature of ER referrals, but could be corrected by the use of telestration between centres. Our study involved expert-to-expert consensus, so extending to 'real-world' referring centres would offer additional learning for a digital pathway.

Rapid development of accurate artificial intelligence scoring for colitis disease activity using applied data science techniques.

Background and study aims Scoring endoscopic disease activity in colitis represents a complex task for artificial intelligence (AI), but is seen as a worthwhile goal for clinical and research use cases. To date, development attempts have relied on large datasets, achieving reasonable results when comparing normal to active inflammation, but not when generating subscores for the Mayo Endoscopic Score (MES) or ulcerative colitis endoscopic index of severity (UCEIS). Patients and methods Using a multi-task learning framework, with frame-by-frame analysis, we developed a machine-learning algorithm (MLA) for UCEIS trained on just 38,124 frames (73 patients with biopsy-proven ulcerative colitis). Scores generated by the MLA were compared to consensus scores from three independent human reviewers. Results Accuracy and agreement (kappa) were calculated for the following differentiation tasks: (1) normal mucosa vs active inflammation (UCEIS 0 vs ≥ 1; accuracy 0.90, κ = 0.90); (2) mild inflammation vs moderate-severe (UCEIS 0-3 vs ≥ 4; accuracy 0.98, κ = 0.96); (3) generating total UCEIS score (κ = 0.92). Agreement for UCEIS subdomains was also high (κ = 0.80, 0.83 and 0.88 for vascular pattern, bleeding and erosions respectively). Conclusions We have demonstrated that, using modified data science techniques and a relatively smaller datasets, it is possible to achieve high levels of accuracy and agreement with human reviewers (in some cases near-perfect), for AI in colitis scoring. Further work will focus on refining this technique, but we hope that it can be used in other tasks to facilitate faster development.

Faecal calprotectin is a surrogate marker of biliary inflammation in primary sclerosing cholangitis associated inflammatory bowel disease.

Objective: Faecal calprotectin (fCAL) is an established marker of intestinal inflammation in inflammatory bowel disease (IBD). Disproportionally high fCAL levels, for the severity of intestinal inflammation, have been previously observed in primary sclerosing cholangitis associated IBD (PSC-IBD). The aim of this study was to test the hypothesis that fCAL is a marker of biliary injury in PSC-IBD. Methods: We used two cohorts: (1) post hoc analysis of a colonoscopic surveillance study allowing correlation of fCAL to endoscopic severity as measured by the ulcerative colitis endoscopic index of severity (UCEIS) in PSC-IBD (n=20) and ulcerative colitis (UC, n=20) and (2) prospective recruitment of patients attending for endoscopic retrograde cholangiopancreatography allowed the correlation of fCAL to biliary calprotectin (n=8). Results: A strong correlation was seen between fCAL and UCEIS in UC (r=0.821, 95% CI (0.585 to 0.929), p<0.0001). In PSC-IBD, the correlation was weaker (r=0.596, 95% CI (0.195 to 0.8260), p=0.006). PSC-IBD patients with endoscopically quiescent colitis (UCEIS: 0-1) had higher fCAL than patients with UC (279 µg/g, IQR (68-601) vs 30 µg/g, IQR (14-107), p=0.015). This was associated with higher risk of biliary complications like need for antibiotics or instrumentation (HR 16.39, 95% CI (2.98 to 90.25)) rather than colitis flares (follow-up: 12 months). Calprotectin measured in faeces correlated positively with biliary calprotectin (r=0.898, p=0.0024). Conclusion: fCAL is a surrogate marker for biliary inflammation in PSC-IBD. Trial registration number: NCT02543021.

Real-Time Artificial Intelligence-Based Optical Diagnosis of Neoplastic Polyps during Colonoscopy.

BACKGROUND: Artificial intelligence using computer-aided diagnosis (CADx) in real time with images acquired during colonoscopy may help colonoscopists distinguish between neoplastic polyps requiring removal and nonneoplastic polyps not requiring removal. In this study, we tested whether CADx analyzed images helped in this decision-making process. METHODS: We performed a multicenter clinical study comparing a novel CADx-system that uses real-time ultra-magnifying polyp visualization during colonoscopy with standard visual inspection of small (≤5 mm in diameter) polyps in the sigmoid colon and the rectum for optical diagnosis of neoplastic histology. After committing to a diagnosis (i.e., neoplastic, uncertain, or nonneoplastic), all imaged polyps were removed. The primary end point was sensitivity for neoplastic polyps by CADx and visual inspection, compared with histopathology. Secondary end points were specificity and colonoscopist confidence level in unaided optical diagnosis. RESULTS: We assessed 1289 individuals for eligibility at colonoscopy centers in Norway, the United Kingdom, and Japan. We detected 892 eligible polyps in 518 patients and included them in analyses: 359 were neoplastic and 533 were nonneoplastic. Sensitivity for the diagnosis of neoplastic polyps with standard visual inspection was 88.4% (95% confidence interval [CI], 84.3 to 91.5) compared with 90.4% (95% CI, 86.8 to 93.1) with CADx (P=0.33). Specificity was 83.1% (95% CI, 79.2 to 86.4) with standard visual inspection and 85.9% (95% CI, 82.3 to 88.8) with CADx. The proportion of polyp assessment with high confidence was 74.2% (95% CI, 70.9 to 77.3) with standard visual inspection versus 92.6% (95% CI, 90.6 to 94.3) with CADx. CONCLUSIONS: Real-time polyp assessment with CADx did not significantly increase the diagnostic sensitivity of neoplastic polyps during a colonoscopy compared with optical evaluation without CADx. (Funded by the Research Council of Norway [Norges Forskningsråd], the Norwegian Cancer Society [Kreftforeningen], and the Japan Society for the Promotion of Science; UMIN number, UMIN000035213.)