Comparison of adenoma miss rate and adenoma detection rate between conventional colonoscopy and colonoscopy with second generation distal attachment cuff: a multicenter, randomized, back-to-back trial.

BACKGROUND AND AIMS: Endocuff VisionTM has been designed to enhance mucosal visualization thereby improving detection of (pre-)malignant colorectal lesions. This multicenter, international, back-to-back, randomized colonoscopy trial compared adenoma detection rate (ADR) and adenoma miss rate (AMR) between Endocuff Vision-assisted colonoscopy (EVC) and conventional colonoscopy (CC). METHODS: Patients aged 40-75 years referred for non-immunochemical fecal occult blood test-based screening, surveillance, or diagnostic colonoscopy were included at ten hospitals and randomized into four groups: Group 1; 2xCC, Group 2; CC followed by EVC, Group 3; EVC followed CC and Group 4; 2xEVC. Primary outcomes included ADR and AMR. RESULTS: A total of 717 patients were randomized of which 661 patients (92.2%) had one and 646 (90.1%) patients had two completed back-to-back colonoscopies. EVC did not significantly improve ADR compared to CC (41.1% [95%-CI;36.1-46.3] versus 35.5% [95%-CI;30.7-40.6], respectively, P=0.125), but EVC did reduced AMR by 11.7% (29.6% [95%-CI;23.6-36.5] versus 17.9% [95%-CI;12.5-23.5], respectively, P=0.049). AMR of 2xCC compared to 2xEVC was also not significantly different (25.9% [95%-CI;19.3-33.9] versus 18.8% [95%-CI;13.9-24.8], respectively, P=0.172). Only 3.7% of the polyps missed during the first procedures had advanced pathologic features. Factors affecting risk of missing adenomas were age (P=0.002), Boston Bowel Preparation Scale (P=0.008) and region where colonoscopy was performed (P<0.001). CONCLUSIONS: Our trial shows that EVC reduces the risk of missing adenomas but does not lead to a significant improved ADR. Remarkably, 25% of adenomas are still missed during conventional colonoscopies, which is not different from miss rates reported 25 years ago; reassuringly, advanced features were only found in 3.7% of these missed lesions. TRAIL REGISTRATION NUMBER: NCT03418948.

AI-doscopist: a real-time deep-learning-based algorithm for localising polyps in colonoscopy videos with edge computing devices.

We have designed a deep-learning model, an "Artificial Intelligent Endoscopist (a.k.a. AI-doscopist)", to localise colonic neoplasia during colonoscopy. This study aims to evaluate the agreement between endoscopists and AI-doscopist for colorectal neoplasm localisation. AI-doscopist was pre-trained by 1.2 million non-medical images and fine-tuned by 291,090 colonoscopy and non-medical images. The colonoscopy images were obtained from six databases, where the colonoscopy images were classified into 13 categories and the polyps' locations were marked image-by-image by the smallest bounding boxes. Seven categories of non-medical images, which were believed to share some common features with colorectal polyps, were downloaded from an online search engine. Written informed consent were obtained from 144 patients who underwent colonoscopy and their full colonoscopy videos were prospectively recorded for evaluation. A total of 128 suspicious lesions were resected or biopsied for histological confirmation. When evaluated image-by-image on the 144 full colonoscopies, the specificity of AI-doscopist was 93.3%. AI-doscopist were able to localise 124 out of 128 polyps (polyp-based sensitivity = 96.9%). Furthermore, after reviewing the suspected regions highlighted by AI-doscopist in a 102-patient cohort, an endoscopist has high confidence in recognizing four missed polyps in three patients who were not diagnosed with any lesion during their original colonoscopies. In summary, AI-doscopist can localise 96.9% of the polyps resected by the endoscopists. If AI-doscopist were to be used in real-time, it can potentially assist endoscopists in detecting one more patient with polyp in every 20-33 colonoscopies.

Receptor tyrosine kinase fusions act as a significant alternative driver of the serrated pathway in colorectal cancer development.

Serrated polyps are a clinically and molecularly heterogeneous group of lesions that can contribute to the development of colorectal cancers (CRCs). However, the molecular mechanism underlying the development of serrated lesions is still not well understood. Here, we combined multiple approaches to analyze the genetic alterations in 86 colorectal adenomas (including 35 sessile serrated lesions, 15 traditional adenomas, and 36 conventional adenomatous polyps). We also investigated the in vitro and in vivo oncogenic properties of a novel variant of the NCOA4-RET fusion gene. Molecular profiling revealed that sessile serrated lesions and traditional serrated adenomas have distinct clinicopathological and molecular features. Moreover, we identified receptor tyrosine kinase translocations exclusively in sessile serrated lesions (17%), and the observation was validated in a separate cohort of 34 sessile serrated lesions (15%). The kinase fusions as well as the BRAF and KRAS mutations were mutually exclusive to each other. Ectopic expression of a novel variant of the NCOA4-RET fusion gene promoted cell proliferation in vitro and in vivo, and the proliferation was significantly suppressed by RET kinase inhibitors. All of these underscored the importance of mitogen-activated protein kinase (MAPK) pathway activation in the serrated pathway of colorectal tumorigenesis. In addition, we demonstrated that the kinase fusion may occur early in the precursor lesion and subsequent loss of TP53 may drives the transformation to carcinoma during serrated tumorigenesis. In conclusion, we identified kinase fusions as a significant alternative driver of the serrated pathway in colorectal cancer development, and detecting their presence may serve as a biomarker for the diagnosis of sessile serrated lesions. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Localisation of Colorectal Polyps by Convolutional Neural Network Features Learnt from White Light and Narrow Band Endoscopic Images of Multiple Databases.

Algorithms for localising colorectal polyps have been studied extensively; however, they were often trained and tested using the same database. In this study, we present a new application of a unified and real-time object detector based on You-Only-Look-Once (YOLO) convolutional neural network (CNN) for localizing polyps with bounding boxes in endoscopic images. The model was first pre-trained with non-medical images and then fine-tuned with colonoscopic images from three different databases, including an image set we collected from 106 patients using narrow-band (NB) imaging endoscopy. YOLO was tested on 196 white light (WL) images of an independent public database. YOLO achieved a precision of 79.3% and sensitivity of 68.3% with time efficiency of 0.06 sec/frame in the localization task when trained by augmented images from multiple WL databases. In conclusion, YOLO has great potential to be used to assist endoscopists in localising colorectal polyps during endoscopy. CNN features of WL and NB endoscopic images are different and should be considered separately. A large-scale database that covers different scenarios, imaging modalities and scales is lacking but crucial in order to bring this research into reality.

Translation and validation of the traditional Chinese version of the faecal incontinence quality of life scale.

PURPOSE: Psychometric evaluation with tools such as the faecal incontinence quality of life scale is an essential component of clinical assessment. Currently, there is no translated Traditional Chinese version of the scale. A validated translated version may help to improve the quality of healthcare received in countries with Chinese minorities (0.5, 1.2 and 4.0% of the UK, USA and Australian population, respectively) as well as local population of Hong Kong. The purpose of this study is to validate the Traditional Chinese version of the faecal incontinence quality of life scale (FIQL). METHODS: The FIQL questionnaire was translated into Traditional Chinese Language followed by linguistic validation. It was then tested on 55 patients with faecal incontinence and 93 controls in the colorectal outpatients clinic. Faecal incontinence severity index was also used for the assessment of disease severity. RESULTS: Internal consistency was good/excellent for all scales (Cronbach's alpha >0.70, between 0.71 and 0.93). The intra-class correlation indicated a high stability over time with coefficients ranging between 0.78 and 0.90. Test and retest of all four scales found no significant differences of mean scores between baseline and retest. The mean faecal incontinence quality of life scale scores of all four domains improved significantly after treatment of 10 patients whose faecal incontinence severity index scores decreased by 50 % of their pre-treatment scores, hence indicating good sensitivity. CONCLUSIONS: This study demonstrates the linguistic and psychometric validity of the traditional Chinese version of the faecal incontinence quality of life scale.

Characterization of rare transforming KRAS mutations in sporadic colorectal cancer.

KRAS mutational status has been shown to be a predictive biomarker of resistance to anti-EGFR monoclonal antibody (mAb) therapy in patients with metastatic colorectal cancer. We report the spectrum of KRAS mutation in 1506 patients with colorectal cancer and the identification and characterization of rare insertion mutations within the functional domain of KRAS. KRAS mutations are found in 44.5% (670/1506) of the patients. Two cases are found to harbor double mutations involving both codons 12 and 13. The frequencies of KRAS mutations at its codons 12, 13, 61, and 146 are 75.1%, 19.3%, 2.5%, and 2.7%, respectively. The most abundant mutation of codon 12 is G12D, followed by G12V and G12C while G13D is the predominant mutation in codon 13. Mutations in other codons are rare. The KRAS mutation rate is significantly higher in women (48%, 296/617) than in men (42.1%, 374/889, P = 0.023). Tumors on the right colon have a higher frequency of KRAS mutations than those on the left (57.3% vs. 40.4%, P<0.0001). Two in-frame insertion mutations affect the phosphate-binding loop (codon 10-16) of KRAS are identified. One of them has never been reported before. Compared with wild-type protein, the insertion variants enhance the cellular accumulation of active RAS (RAS-GTP) and constitutively activate the downstream signaling pathway. NIH3T3 cells transfected with the insertion variants show enhanced anchorage-independent growth and in vivo tumorigenicity. Potentially these mutations contribute to primary resistance to anti-EGFR mAb therapy but the clinical implication requires further validation.

Long-term oncologic outcomes of laparoscopic versus open surgery for rectal cancer: a pooled analysis of 3 randomized controlled trials.

OBJECTIVE: To compare long-term oncologic outcomes between laparoscopic and open surgery for rectal cancer and to identify independent predictors of survival. BACKGROUND: Few randomized trials comparing laparoscopic and open surgery for rectal cancer have reported long-term survival data. METHODS: Data from the 3 randomized controlled trials comparing curative laparoscopic (n=136) and open surgery (n=142) for upper, mid, and low rectal cancer conducted at the Prince of Wales Hospital, Hong Kong, between September 1993 and August 2007 were pooled together for this analysis. Survival and disease status were updated to February 2012. Survival was calculated using the Kaplan-Meier method, and independent predictors of survival were determined using the Cox regression analysis. RESULTS: The demographic data of the 2 groups were comparable. The median follow-up time of living patients was 124.5 months in the laparoscopic group and 136.6 months in the open group. At 10 years, there were no significant differences in locoregional recurrence (5.5% vs. 9.3%; P=0.296), cancer-specific survival (82.5% vs. 77.6%; P=0.443), and overall survival (63.0% vs. 61.1%; P=0.505) between the laparoscopic and open groups. There was a trend toward lower recurrence rate at 10 years in the laparoscopic group than in the open group among patients with stage III cancer (P=0.078). The Cox regression analysis showed that stage III cancer, lymphovascular permeation, and blood transfusion, but not the operative approach, were independent predictors of poorer cancer-specific survival. CONCLUSIONS: This pooled analysis with a follow-up of more than 10 years confirms the long-term oncologic safety of laparoscopic surgery for rectal cancer.

Laparoscopic-assisted versus open total mesorectal excision with anal sphincter preservation for mid and low rectal cancer: a prospective, randomized trial.

BACKGROUND: This single-center, prospective, randomized trial was designed to compare the short-term clinical outcome between laparoscopic-assisted versus open total mesorectal excision (TME) with anal sphincter preservation (ASP) in patients with mid and low rectal cancer. Long-term morbidity and survival data also were recorded and compared between the two groups. METHODS: Between August 2001 and August 2007, 80 patients with mid and low rectal cancer were randomized to receive either laparoscopic-assisted (40 patients) or open (40 patients) TME with ASP. The median follow-up time for all patients was 75.7 (range 16.9-115.7) months for the laparoscopic-assisted group and 76.1 (range 4.7-126.6) months for the open group. The primary endpoint of the study was short-term clinical outcome. Secondary endpoints included long-term morbidity rate and survival. Data were analyzed by intention-to-treat principle. RESULTS: The demographic data of the two groups were comparable. Postoperative recovery was better after laparoscopic surgery, with less analgesic requirement (P < 0.001), earlier mobilization (P = 0.001), lower short-term morbidity rate (P = 0.043), and a trend towards shorter hospital stay (P = 0.071). The cumulative long-term morbidity rate also was lower in the laparoscopic-assisted group (P = 0.019). The oncologic clearance in terms of macroscopic quality of the TME specimen, circumferential resection margin involvement, and number of lymph nodes removed was similar between both groups. After curative resection, the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 85.9 and 91.3 %, respectively (P = 0.912). The respective probabilities of being disease-free were 83.3 and 74.5 % (P = 0.114). CONCLUSIONS: Laparoscopic-assisted TME with ASP improves postoperative recovery, reduces short-term and long-term morbidity rates, and seemingly does not jeopardize survival compared with open surgery for mid and low rectal cancer ( http://ClinicalTrials.gov Identifier: NCT00485316).

Electroacupuncture reduces duration of postoperative ileus after laparoscopic surgery for colorectal cancer.

BACKGROUND & AIMS: We investigated the efficacy of electroacupuncture in reducing the duration of postoperative ileus and hospital stay after laparoscopic surgery for colorectal cancer. METHODS: We performed a prospective study of 165 patients undergoing elective laparoscopic surgery for colonic and upper rectal cancer, enrolled from October 2008 to October 2010. Patients were assigned randomly to groups that received electroacupuncture (n = 55) or sham acupuncture (n = 55), once daily from postoperative days 1-4, or no acupuncture (n = 55). The acupoints Zusanli, Sanyinjiao, Hegu, and Zhigou were used. The primary outcome was time to defecation. Secondary outcomes included postoperative analgesic requirement, time to ambulation, and length of hospital stay. RESULTS: Patients who received electroacupuncture had a shorter time to defecation than patients who received no acupuncture (85.9 ± 36.1 vs 122.1 ± 53.5 h; P < .001) and length of hospital stay (6.5 ± 2.2 vs 8.5 ± 4.8 days; P = .007). Patients who received electroacupuncture also had a shorter time to defecation than patients who received sham acupuncture (85.9 ± 36.1 vs 107.5 ± 46.2 h; P = .007). Electroacupuncture was more effective than no or sham acupuncture in reducing postoperative analgesic requirement and time to ambulation. In multiple linear regression analysis, an absence of complications and electroacupuncture were associated with a shorter duration of postoperative ileus and hospital stay after the surgery. CONCLUSIONS: In a clinical trial, electroacupuncture reduced the duration of postoperative ileus, time to ambulation, and postoperative analgesic requirement, compared with no or sham acupuncture, after laparoscopic surgery for colorectal cancer. ClinicalTrials.gov number, NCT00464425.

Laparoscopic colorectal fellowship training programme : a 6-year experience in a university colorectal unit.

BACKGROUND: The aim of this study was to evaluate a structured training programme for laparoscopic colorectal surgery in a university colorectal unit over a 6-year period. METHODS: Data on patients who underwent laparoscopic colectomy between November 2004 and October 2010 were analyzed. Operations were performed either by the consultant colorectal surgeons or colorectal fellows. The effectiveness and safety of our structured training programme were evaluated. RESULTS: During the study period, 813 patients (478 men) with a median age 69 years (range 22-93) underwent laparoscopic colectomy. A total of 370 cases (45.5 %) were performed by four colorectal fellows. Overall, 674 patients (82.9 %) were classified as ASA I or II. The conversion rate was 3.7 %. The conversion rate, intra-operative blood loss, number of lymph nodes retrieved and post-operative recovery were similar between the two groups. When comparing with consultant group, the patients operated by fellows were: (1) significantly older; (2) more were operated on as emergency cases; (3) had pathologically less advanced tumours; (4) less patients with low rectal cancers. There were two surgical mortalities in this series. The morbidities between the two groups were similar. At the end of 3 years of training, the fellows had performed more than 85 cases of laparoscopic colectomies. The level of supervision decreased with increased experience. Finally, experienced fellows were able to supervise more junior colleagues on laparoscopic colectomies. CONCLUSIONS: Our results confirmed a structured training programme for laparoscopic colectomy is safe and effective. Reasonable results were achieved even though a high volume of cases were performed by surgical fellows.