A computer-aided diagnosis system using white-light endoscopy for the prediction of conventional adenoma with high grade dysplasia.

OBJECTIVES: We developed a computer-aided diagnosis system called ECRCCAD using standard white-light endoscopy (WLE) for predicting conventional adenomas with high-grade dysplasia (HGD) to optimise the patients' management decisions during colonoscopy. METHODS: Pretraining model was used to fine-tune the model parameters by transfer learning. 2,397 images of HGD and 2,487 low-grade dysplasia (LGD) images were randomly assigned (8:1:1) to the training, optimising, and internal validation dataset. The prospective validation dataset is the frames accessed from colonoscope videoes. One independent rural hospital provided an external validation dataset. Histopathological diagnosis was used as the standard criterion. The capability of the ECRCCAD to distinguish HGD was assessed and compared with two expert endoscopists. RESULTS: The accuracy, sensitivity and specificity for diagnosis of HGD in the internal validation set were 90.5%, 93.2%, 87.9%, respectively. While 88.2%, 85.4%, 89.8%, respectively, for the external validation set. For the prospective validation set, ECRCCAD achieved an AUC of 93.5% in diagnosing HGD. The performance of ECRCCAD in diagnosing HGD was better than that of the expert endoscopist in the external validation set (88.2% vs. 71.5%, P < 0.0001). CONCLUSION: ECRCCAD had good diagnostic capability for HGD and enabled a more convenient and accurate diagnosis using WLE.

Clinical Impact of X-Ray Repair Cross-Complementary 1 (XRCC1) and the Immune Environment in Colorectal Adenoma-Carcinoma Pathway Progression.

PURPOSE: Colorectal cancer (CRC) can develop via a hypermutagenic pathway characterized by frequent somatic DNA base-pair mutations. Alternatively, the immunogenicity of tumor cells themselves may influence the anticancer activity of the immune effector cells. Impaired DNA repair mechanisms drive mutagenicity, which then increase the neoantigen load and immunogenicity. However, no studies have analyzed immune checkpoint protein expression, particularly programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), in adenoma-carcinoma progression and its relationship with the emergence of other DNA repair gene mutation. MATERIALS AND METHODS: We investigated mutations of 10 genes involved in DNA repair function: XRCC1, TP53, MLH1, MSH, KRAS, GSTP, UMP, MTHF, DPYD, and ABCC2. We performed sequencing to determine mutations and immunohistochemistry of immune checkpoints in clinical samples and determined changes in XRCC1 expression during progression through the adenoma-carcinoma pathway. We further investigated the prognostic associations of gene XRCC1 according to the expression, mutational profile, and immune profile using The Cancer Genome Atlas-colon adenocarcinoma (TCGA-COAD) dataset. RESULTS: From clinical samples, XRCC1 mutation demonstrated the strongest association with adenomas with a mutation frequency of 56.2% in adenomas and 34% in CRCs (p =0.016). XRCC1 was abnormally expressed and altered by mutations contributing to adenoma carcinogenesis. High expression of XRCC1, CD4, FOXP3, and PD-1/PD-L1 showed an overall upward trend with increased lesion severity (all p < 0.01). PD-1/PD-L1 expression and CD4+ intraepithelial lymphocytes (IELs) correlated with cytological dysplasia progression, specifically in patients with wild-type XRCC1 (all p < 0.01), whereas FOXP3 expression was independently associated with adenoma-carcinoma progression. From TCGA-COAD analysis, XRCC1 expression was associated with patients survival, tumor-infiltrating lymphocytes and immune marker expression. CONCLUSION: Increased IEL density and PD-1/PD-L1 expression correlate with cytological dysplasia progression and specifically with the XRCC1 mutation status in CRC. Our findings support a stepwise dysplasia-carcinoma sequence of adenoma carcinogenesis and an XRCC1 hypermutated phenotypic mechanism of lesions.

[Analysis of risk factors for anastomotic infectious complications following bowel resection for Crohn disease].

OBJECTIVE: To investigate the risk factors for anastomotic infectious complications after bowel resection in patients with Crohn disease. METHODS: Clinical data of 124 patients with Crohn disease undergoing bowel resection between January 1990 and October 2012 were analyzed retrospectively. The risk factors were identified by χ(2) test and Logistic regression. RESULTS: Fourteen patients (12.3%, 14/114) developed anastomotic infectious complications in the postoperative period, including anastomotic leak (n=7), intra-abdominal abscess (n=6), and enterocutaneous fistula (n=1). Crohn disease activity index (CDAI)>150 (OR=2.185, 95%CI:1.098-6.256, P=0.040), steroid usage (OR=2.674, 95%CI:1.118-8.786, P=0.027), and the presence of preoperative abscess/fistula (OR=3.447, 95%CI:1.254-10.462, P=0.014) were identified as independent risk factors of anastomotic infectious complications. In the absence of these 3 risk factors, the rate of anastomotic infectious complication was 5.7% (3/53), which increased to 11.4% (4/35) when one risk factor was present, 21.1% (4/19) when two risk factors were present, and 42.9% (3/7) when all the 3 risk factors were present. CONCLUSIONS: CDAI>150, steroid usage and preoperative abscess/fistula are associated with higher rates of anastomotic infectious complications following bowel resection for Crohn disease. A prudent management should be carried out if risk factors can not be eliminated preoperatively.

[Diagnostic value of Crohn disease activity indices in assessing postoperative recurrence].

OBJECTIVE: To evaluate the diagnostic value of Crohn disease activity indices (CDAI) in assessing symptomatic recurrence following ileocolic resection for Crohn disease. METHODS: A total of 85 patients who underwent ileocolic resection between March 2003 and March 2010 were included. Clinical and endoscopic evaluation were performed within 12 months after operation. Endoscopic appearance was assessed using Rutgeers score and endoscopic recurrence was defined as endoscopic score ≥i2. Symptomatic recurrence was defined by the composite of symptom severity warranting medical therapy and endoscopic recurrence. The receiver operator characteristic (ROC) curve was used to explore the utility of CDAI in determining the presence or absence of symptomatic disease. RESULTS: Nineteen patients had symptomatic recurrence within 12 months postoperatively. The mean CDAI of patients with symptomatic recurrence was 205±93, significantly higher than those with sustained remission(97±44, P<0.01). The area under the ROC curve for symptomatic recurrence and CDAI was 0.786. Symptomatic recurrence was best predicted by a CDAI cutoff of 150 and the sensitivity, specificity, and accuracy was 73.7%, 81.8% and 80.0% respectively. When a combined endoscopic and CDAI was applied, the specificity and accuracy was markedly improved to 95.5% and 90.6%. In comparison to CDAI alone, the combined use of CDAI and endoscopic evaluation had a higher level of agreement on symptomatic recurrence(Kappa value, 0.718 vs. 0.462). CONCLUSIONS: CDAI is effective to predict symptomatic recurrence. A combination of CDAI and endoscopic evaluation can further improve the accuracy of assessing symptomatic recurrence.

[Value of quantitative examination via contrast-enhanced ultrasonography in evaluating the activity of Crohn disease at endoscopy].

OBJECTIVE: To evaluate the predictive value of quantitative examination via contrast-enhanced ultrasonography on the activity of Crohn disease at endoscopy. METHODS: A total of 59 cases with Crohn disease in People's Hospital of Lishui City between January 2009 and December 2010 were collected prospectively and underwent both colonoscopy and contrast-enhanced ultrasonography. According to the Simple Endoscopic Score, Crohn disease was divided into inactive and active disease by colonoscopy. To assess the vascularization of the involved bowel loop in a region expected to be seen at colonoscopy, the contrast agent uptake was measured by using quantitative analysis. Measurement of contrast enhancement was assessed as the percentage of increase in wall brightness in regions of interest (ROI). The receiver operating characteristic curve was used to evaluate the value of contrast agent uptake in predicting the severity determined at endoscopy. RESULTS: Colonoscopy showed active lesions in 45 cases and inactive lesions in 14 cases, in whom the percentages of increase of brightness were (90±32)% and (41±29)% respectively. At a threshold value of 45% for the percentage of increase of brightness, sensitivity, specificity and accuracy of predicting the severity at endoscopy were 95.6%, 78.6% and 91.5%, the Youden index was 0.74, and area under curve was 0.846. CONCLUSIONS: Quantitative measurement of bowel enhancement by using contrast-enhanced ultrasonography can discriminate between active and inactive Crohn disease at endoscopy. Contrast-enhanced ultrasonography may be a useful technique to monitor the activity of Crohn disease.