Influence of early colorectal cancer component on the positive margins after endoscopic resection: a retrospective study.

BACKGROUND: Endoscopic treatment methods for early colorectal cancer (ECRC) mainly depend on the size and morphology. It is unclear whether different endoscopic resection methods could achieve curative resection for ECRC confined in the mucosa. The study was designed to compare the rate of positive vertical margin (VM) of ECRC with advanced adenomas (AAs) including adenoma > 1 cm, villous adenoma, high-grade intraepithelial neoplasia/dysplasia stratified by different endoscopic resection methods. METHODS: Rate of positive VM for 489 ECRCs including Intramucosal (pTis) and superficial submucosal invasion (pT1) carcinomas were compared with those of 753 AAs stratified by different endoscopic resection methods using Chi-squared test. Multivariate logistic model was performed to investigate the risk factors of positive VM for different endoscopic resection methods. RESULTS: The pTis ECRC exhibited a similar rate of positive VM as that of AAs for en bloc hot snare polypectomy (HSP, 0% Vs. 0.85%, P = 0.617), endoscopic mucosal resection (EMR, 0.81% vs. 0.25%, P = 0.375) and endoscopic submucosal dissection (ESD, 1.82% Vs. 1.02%, P = 0.659). The pTis carcinoma was not found to be a risk factor for positive VM by en bloc EMR (P = 0.349) or ESD (P = 0.368). The en bloc resection achieved for pT1a carcinomas exhibited similar to positive VM achieved through ESD (2.06% Vs. 1.02%, P = 1.000) for AAs. Nonetheless, EMR resulted in higher risk of positive VM (5.41% Vs. 0.25%, P < 0.001) for pT1a carcinomas as compared to AAs. The pT1a invasion was identified as a risk factor for positive VM in polyps with en bloc EMR (odds ratio = 23.90, P = 0.005) but not ESD (OR = 2.96, P = 0.396). CONCLUSION: Collectively, the pTis carcinoma was not found to be a risk factor for positive VM resected by en bloc HSP, EMR or ESD. Additionally, ESD may be preferred over EMR for pT1a carcinomas with lower rate of positive VM.

The role of early video capsule endoscopy in the diagnosis and prognosis of obscure gastrointestinal bleeding: A multi-center propensity score matching study.

BACKGROUND AND AIM: Video capsule endoscopy (VCE) is a first-line procedure for the diagnosis of obscure gastrointestinal bleeding (OGIB). The opinions on the timing for such diagnostic evaluation remain unclear. We aimed to explore the role of early VCE in OGIB patients. METHODS: A total of 997 patients that underwent VCE at Renji Hospital and Nagoya University from May 15, 2002, to December 28, 2016, were included in this study. We matched patients that underwent early VCE within 14 days of bleeding (early group, n = 678) to patients that did not (late group, n = 319) via 1:1 propensity score matching (PSM). We then compared VCE diagnostic rates and the prevalence of post-VCE rebleeding in patients with initial negative VCE findings within 1 year between these groups before and after PSM. RESULTS: Following PSM, early VCE was associated with a significantly higher rate of OGIB diagnosis (56.4% vs 45.5%, P = 0.001) and with a significantly lower incidence of rebleeding within 1 year following treatment (24.7% vs 36.7%, P = 0.041). In univariate and multivariate analyses, VCE timing (odds ratio 0.648; 95% confidence interval 0.496-0.847, P = 0.001 and odds ratio 0.666; 95% confidence interval 0.496-0.894, P = 0.007, respectively) was found to be linked with a higher rate of positive findings. CONCLUSION: Early VCE can improve the reliability of OGIB diagnosis while also reducing rates of post-VCE rebleeding. This suggests that timely and accurate diagnosis can help to improve OGIB patient treatment and prognosis.

Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation.

BACKGROUND: Small bowel vascular malformation disease (SBVM) is the most common cause of obscure gastrointestinal bleeding (OGIB). Several studies suggested that EGFL6 was able to promote the growth of tumor endothelial cells by forming tumor vessels. To date, it remains unclear how EGFL6 promotes pathological angiogenesis in SBVM and whether EGFL6 is a target of thalidomide. METHODS: We took advantage of SBVM plasma and tissue samples and compared the expression of EGFL6 between SBVM patients and healthy people via ELISA and Immunohistochemistry. We elucidated the underlying function of EGFL6 in SBVM in vitro and by generating a zebrafish model that overexpresses EGFL6, The cycloheximide (CHX)-chase experiment and CoIP assays were conducted to demonstrate that thalidomide can promote the degradation of EGFL6 by targeting CRBN. RESULTS: The analysis of SBVM plasma and tissue samples revealed that EGFL6 was overexpressed in the patients compared to healthy people. Using in vitro and in vivo assays, we demonstrated that an EMT pathway triggered by the EGFL6/PAX6 axis is involved in the pathogenesis of SBVM. Furthermore, through in vitro and in vivo assays, we elucidated that thalidomide can function as anti-angiogenesis medicine through the regulation of EGFL6 in a proteasome-dependent manner. Finally, we found that CRBN can mediate the effect of thalidomide on EGFL6 expression and that the CRBN protein interacts with EGFL6 via a Lon N-terminal peptide. CONCLUSION: Our findings revealed a key role for EGFL6 in SBVM pathogenesis and provided a mechanism explaining why thalidomide can cure small bowel bleeding resulting from SBVM.

Inverse Association of Age with Risk of Lymph Node Metastasis in Superficial Colorectal Cancer: A Large Population-Based Study.

BACKGROUND: Superficial colorectal cancer (SCRC) is defined as colorectal cancer (CRC) confined to the mucosa or submucosa. Endoscopic resection (ER) is widely used to resect differentiated SCRC from patients without lymph node metastasis (LNM). However, it is unclear whether ER is suitable for use with patients with differentiated early-onset SCRC because early-onset CRC is more aggressive. Therefore, we aimed to investigate the association between age of CRC onset and LNM. MATERIALS AND METHODS: We retrieved data for patients with surgically resected differentiated-type SCRCs from the Surveillance, Epidemiology, and End Results (SEER) database. Rate of LNM was compared among patients aged 18-39, 40-49, 50-59, 60-69, and ≥70 years. The association between age and LNM was further examined using multivariate logistic regression. RESULTS: We retrieved 34,506 records of differentiated SCRCs from the SEER database, including 667 patients aged 18-39 years, 2,385 aged 40-49, 8,075 aged 50-59 years, 9,577 aged 60-69 years, and 13,802 aged ≥70 years. Rates of LNM were 15.74%, 14.13%, 10.67%, 8.07%, and 6.76% for patients aged 18-39, 40-49, 50-59, 60-69, and ≥70 years, respectively. We found an inverse correlation between age at diagnosis and risk of LNM from the univariate analysis (p < .001). Compared with patients aged 18-39, the odds ratios with 95% confidence interval (CI) for patients aged 40-49, 50-59, 60-69, and ≥70 years were 0.90 (0.71-1.15, p = .376), 0.69 (0.56-0.87, p = .001), 0.54 (0.43-0.68, p < .001), and 0.47 (0.38-0.60, p < .001), respectively. CONCLUSION: In differentiated SCRCs, younger age at diagnosis was associated with higher risk of LNM. IMPLICATIONS FOR PRACTICE: Endoscopic resection (ER) is widely used to resect differentiated superficial colorectal cancer (SCRC) without lymph node metastasis (LNM). However, no study has ever investigated risk of LNM of early-onset SCRC compared with average onset SCRC to explore whether ER is suitable for early-onset SCRC. To the authors' knowledge, this population-based study is the first study to find inverse correlation between age at diagnosis and risk of LNM in differentiated SCRCs. This finding indicates that ER may not be suitable for young patients with differentiated SCRC. Because the 30-day operative mortality after surgery is higher but the risk of LNM is lower in older patients compared with younger patients, ER for differentiated SCRCs may be advantageous over surgery for older patients.

Low-dose and same day use of polyethylene glycol improves image of video capsule endoscopy: A multi-center randomized clinical trial.

BACKGROUND AND AIM: Clear visualization of the small bowel is a requirement for satisfactory video capsule endoscopy (VCE). The aim of this study was to identify the optimal dose and timing of polyethylene glycol (PEG) for small bowel preparation before VCE. METHODS: A total of 410 patients were enrolled in this prospective randomized trial. All patients fasted for 12 h and ingested 320 mg simethicone 30 min before swallowing the capsule. Patients were randomized into five groups: Group A (no PEG), Group B (1-L PEG, 12 h before VCE), Group C (2-L PEG, 12 h before VCE), Group D (1-L PEG, 4 h before VCE), and Group E (2-L PEG, 4 h before VCE). The primary endpoint was small bowel visualization quality (SBVQ), and the secondary endpoints were patient acceptability and diagnosis rate of VCE. RESULTS: Excellent SBVQ was achieved in 27 (32.5%) of Group A, 38 (46.3%) of Group B, 40 (48.2%) of Group C, 55 (66.3%) of Group D, and 43 (54.4%) of Group E. The percentage of excellent SBVQ in Group D was significantly more than in Group A (66.3% vs 32.5%, P < 0.001), and diagnostic rate in the distal segment was higher (28.9% vs 10.8%, P = 0.0035). Patient acceptance of 1-L PEG was better than of 2-L PEG (P < 0.005). CONCLUSION: Small bowel cleansing with 1-L PEG given 4 h before VCE was the optimal preparation for visualization of the bowel and patient acceptance (ClinicalTrials.gov, ID: NCT02486536).

EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/ß-catenin pathway.

Epidermal growth factor-like protein 6 (EGFL6) serves as an exocrine protein promoting proliferation and migration during carcinogenesis in ovarian cancer. However, its function and mechanisms in colorectal cancer (CRC) have not been completely explored. To investigate the role of EGFL6 in CRC cell growth, in vitro CCK8, colony formation assays, flow cytometric analysis of the cell cycle and apoptosis, and an in vivo tumor xenograft model were utilized. Additionally, Western blotting and luciferase reporter assays were used to investigate the underlying mechanisms of EGFL6 function on the WNT/ß-catenin signaling pathway. Immunohistochemical staining showed that EGFL6 is overexpressed in CRCs and this overexpression was highly correlated with advanced T classification, N classification, distant metastasis, and poor survival. Knocking down EGFL6 in CRC cell lines induced the inhibition of cell growth, cell cycle arrest at the G0/G1 phase, and apoptosis. Further, knockdown of EGFL6 blocked WNT/ß-catenin signaling as measured by Western blotting and luciferase reporter assay. Results also showed that recombinant EGFL6 (rEGFL6) induced ß-catenin in a concentration- and time-dependent manner. Further experiments showed that administration of rEGFL6 to cell cultures with EGFL6 knocked down or treated with the WNT/ß-catenin inhibitor ICG-001 increased ß-catenin and its downstream protein CyclinD1. The CCK8 assay showed that EGFL6 promoted CRC cell growth partly by the promotion of TCF7L2 expression. These findings suggest that EGFL6 plays a crucial role in the progression of CRC by regulation of the WNT/ß-catenin signaling pathway.

Use of Advanced Modalities Does Not Guarantee Early Detection of Small-Bowel Crohn's Disease in the Absence of Complications.

BACKGROUND This study investigated the approach for detection of small-bowel (SB) Crohn's disease (CD) in the absence of complications at diagnosis using advanced modalities. MATERIAL AND METHODS Patients diagnosed with CD in Renji Hospital from 2005 to 2014 were divided into 2 groups by year of diagnosis: 2005 to 2009 and 2010 to 2014. The modalities used and the clinical characteristics of patients were retrospectively examined. RESULTS Advanced modalities did not detect higher rate of non-stricturing/non-penetrating disease in 2010 to 2014 than older modalities in 2005 to 2009. Further analysis showed that a stricturing complication was significantly more common in patients with SB CD than in those who had CD with SB and colonic involvement, and the duration from symptom onset to lesion detection was significantly longer in patients with SB CD than in those who had CD with SB and colonic involvement. Fewer patients with SB CD underwent SB capsule endoscopy compared to the other advanced modalities. Abdominal pain (74.4%) was the most common presentation, and 94.0% patients with SB CD presented gastrointestinal bleeding and anemia. CONCLUSIONS Early detection of SB CD without complications remains difficult even if advanced modalities are introduced. Our hypothesis is that the fecal occult blood test and routine blood test should be administered to patients with abdominal pain or gastrointestinal manifestations. Once the patients are found to have GI bleeding or anemia, they would be further examined according to the guideline and SBCE would be used in the early stage of SB CD.

Pseudopod-associated protein KIF20B promotes Gli1-induced epithelial-mesenchymal transition modulated by pseudopodial actin dynamic in human colorectal cancer.

Kinesin family member 20B (KIF20B) has been reported to have an oncogenic role in bladder and hepatocellular cancer cells, but its role in colorectal cancer (CRC) progression remains unclear. In this study, we assessed the mRNA and protein levels of KIF20B in CRC tissues using qRT-PCR and immunohistochemistry, respectively. KIF20B was overexpressed in CRC tissues and was associated with cancer invasion and metastasis. Mechanistically, KIF20B overexpression promoted the epithelial-mesenchymal transition (EMT) process mediated by glioma-associated oncogene 1 (Gli1) as well as CRC cell migration and invasion. Interestingly, KIF20B was localized in pseudopod protrusions of CRC cells and influenced the formation of cell protrusions, especially the EMT-related invadopodia. Moreover, intracellular actin dynamic participated in the modulation of the Gli1-mediated EMT and EMT-related cell pseudopod protrusion formation induced by KIF20B. We identified a role for KIF20B in CRC progression and revealed a correlation between KIF20B expression in CRC tissues and patient prognosis. The underlying mechanism was associated with the Gli1-mediated EMT and EMT-related cell protrusion formation modulated by intracellular actin dynamic. Thus, KIF20B may be a potential biomarker and promising treatment target for CRC.

Narrow-band imaging in the diagnosis of deep submucosal colorectal cancers: a systematic review and meta-analysis.

Background and aims Magnifying endoscopy with narrow-band imaging (M-NBI) has been widely used in the differential diagnosis of deep submucosal colorectal cancers (dSMCs) from superficial submucosal cancers (sSMCs) and intramucosal neoplasms. We aimed to pool the diagnostic efficacy of M-NBI and compare it with that of magnifying chromoendoscopy (M-CE) in diagnosing colorectal dSMC. Methods PubMed, EMBASE, and the Cochrane Library were searched to identify eligible studies. Meeting abstracts were also searched. A bivariate mixed-effects binary regression model was used in the meta-analysis to calculate the pooled diagnostic efficacy of M-NBI and compare it with that of M-CE in the diagnosis of dSMC. Subgroup analyses and meta-regression were conducted to explore sources of heterogeneity. Results We included 17 studies: 14 full texts and 3 meeting abstracts. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) with 95 % confidence intervals (CIs) in diagnosing dSMC were 74 % (66 % - 81 %; I2 = 84.6 %), 98 % (94 % - 99 %; I2 = 94.4 %), and 0.91 (0.88 - 0.93), respectively, for M-NBI. The pooled sensitivity, specificity and AUC (95 %CI) were 84 % (76 % - 89 %; I2 = 76.9 %), 97 % (94 % - 99 %; I2 = 90.2 %), and 0.97 (0.95 - 0.98), respectively, for M-CE. M-NBI had lower sensitivity (P < 0.01) than M-CE with similar specificity (P = 0.32). Subgroup analyses and meta-regression indicated that endoscopic diagnostic criteria, study type, endoscope type, risk of index test bias, and histopathological diagnostic criteria might be the sources of heterogeneity. Conclusions M-NBI and M-CE had comparable specificities in diagnosing dSMC, but the sensitivity of M-NBI was slightly lower than that of M-CE.

Accuracy of Magnetically Controlled Capsule Endoscopy, Compared With Conventional Gastroscopy, in Detection of Gastric Diseases.

BACKGROUND & AIMS: Diseases of the stomach, including gastric cancer and peptic ulcer, are the most common digestive diseases. It is impossible to visualize the entire stomach with the passive capsule currently used in practice because of the large size of the gastric cavity. A magnetically controlled capsule endoscopy (MCE) system has been designed to explore the stomach. We performed a prospective study to compare the accuracy of detection of gastric focal lesions by MCE vs conventional gastroscopy (the standard method). METHODS: We performed a multicenter blinded study comparing MCE with conventional gastroscopy in 350 patients (mean age, 46.6 y), with upper abdominal complaints scheduled to undergo gastroscopy at a tertiary center in China from August 2014 through December 2014. All patients underwent MCE, followed by conventional gastroscopy 2 hours later, without sedation. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of detection of gastric focal lesions by MCE, using gastroscopy as the standard. RESULTS: MCE detected gastric focal lesions in the whole stomach with 90.4% sensitivity (95% confidence interval [CI], 84.7%-96.1%), 94.7% specificity (95% CI, 91.9%-97.5%), a positive predictive value of 87.9% (95% CI, 81.7%-94.0%), a negative predictive value of 95.9% (95% CI, 93.4%-98.4%), and 93.4% accuracy (95% CI, 90.83%-96.02%). MCE detected focal lesions in the upper stomach (cardia, fundus, and body) with 90.2% sensitivity (95% CI, 82.0%-98.4%) and 96.7% specificity (95% CI, 94.4%-98.9%). MCE detected focal lesions in the lower stomach (angulus, antrum, and pylorus) with 90.6% sensitivity (95% CI, 82.7%-98.4%) and 97.9% specificity (95% CI, 96.1%-99.7%). MCE detected 1 advanced gastric carcinoma, 2 malignant lymphomas, and 1 early stage gastric tumor. MCE did not miss any lesions of significance (including tumors or large ulcers). Among the 350 patients, 5 reported 9 adverse events (1.4%) and 335 preferred MCE over gastroscopy (95.7%). CONCLUSIONS: MCE detects focal lesions in the upper and lower stomach with comparable accuracy with conventional gastroscopy. MCE is preferred by almost all patients, compared with gastroscopy, and can be used to screen gastric diseases without sedation. Clinicaltrials.gov number: NCT02219529.

Carbon dioxide insufflation improves the intubation depth and total enteroscopy rate in single-balloon enteroscopy: a randomised, controlled, double-blind trial.

OBJECTIVE: The total enteroscopy rate of single-balloon enteroscopy (SBE) using air insufflation is not satisfactory, and whether carbon dioxide (CO2) insufflation increases the total enteroscopy rate of SBE is unknown. This randomised controlled trial aimed to determine whether CO2 insufflation facilitates the intubation depth and total enteroscopy rate of SBE. DESIGN: A total of 214 eligible patients referred for SBE were randomised to receive either air or CO2 insufflation, and included in the intention-to-test (ITT) analysis. In addition, 199 patients in whom enteroscopy was completed were included in the per-protocol (PP) analysis. Both the patients and endoscopists were blinded, and the intubation depth and total enteroscopy rate were defined as the primary outcomes. RESULTS: The CO2 group showed a superiority of intubation in the ITT analysis (oral route: 323.8±64.2 vs 238.3±68.6 cm; anal route: 261.6±74.2 vs 174.7±62.1 cm, both p<0.001), and the total enteroscopy rate (34.9% vs 17.6%, p=0.006). Similar results were obtained in a PP analysis for both outcomes. In addition, in the PP analysis, the addition of circumference after the procedure was less in the CO2 group (0.8±0.6 vs 3.3±1.8 cm, p=0.005) for the oral route. No serious complications were reported. The overall percentage of procedures with significant pathological findings was 52.8%; the rates were 58.5% and 47.2% (p=0.100, ITT analysis) in the CO2 and air groups, respectively. CONCLUSIONS: CO2 insufflation improves the intubation depth and total enteroscopy rate in SBE with a good safety profile and acceptability compared with that of air, and thus is recommended for clinical utilisation. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov identifier: NCT01758900.

Hypoxia and low-glucose environments co-induced HGDILnc1 promote glycolysis and angiogenesis.

Small bowel vascular malformation disease (SBVM) commonly causes obscure gastrointestinal bleeding (OGIB). However, the pathogenetic mechanism and the role of lncRNAs in SBVM remain largely unknown. Here, we found that hypoxia and low-glucose environments co-augment angiogenesis and existed in SBVM. Mechanistically, hypoxia and low-glucose environments supported angiogenesis via activation of hypoxia and glucose deprivation-induced lncRNA (HGDILnc1) transcription by increasing binding of the NeuroD1 transcription factor to the HGDILnc1 promoter. Raised HGDILnc1 acted as a suppressor of α-Enolase 1 (ENO1) small ubiquitin-like modifier modification (SUMOylation)-triggered ubiquitination, and an activator of transcription of Aldolase C (ALDOC) via upregulation of Histone H2B lysine 16 acetylation (H2BK16ac) level in the promoter of ALDOC, and consequently promoting glycolysis and angiogenesis. Moreover, HGDILnc1 was clinically positively correlated with Neurogenic differentiation 1 (NeuroD1), ENO1, and ALDOC in SBVM tissues, and could function as a biomarker for SBVM diagnosis and therapy. These findings suggest that hypoxia and low-glucose environments were present in SBVM tissues, and co-augmented angiogenesis. Hypoxia and low-glucose environments co-induced HGDILnc1, which is higher expressed in SBVM tissue compared with normal tissue, could promoted glycolysis and angiogenesis.

Multi-step validation of a deep learning-based system with visual explanations for optical diagnosis of polyps with advanced features.

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.

Assessment of capsule endoscopy scoring index, clinical disease activity, and C-reactive protein in small bowel Crohn's disease.

BACKGROUND AND STUDY AIMS: Small bowel Crohn's disease (SBCD) patients are frequently assessed by capsule endoscopy (CE), which enables direct visualization of small bowel mucosal abnormalities; however, the correlations between CE scoring index (CESI), C-reactive protein (CRP), and disease activity indices remain undefined. We aimed to determine correlations between the CESI, clinical disease activity indices, and CRP in SBCD patients. PATIENTS AND METHODS: A prospective study was conducted between October 2008 and February 2011 on 58 established SBCD patients and suspected patients who received a definitive SBCD diagnosis during study. Patients underwent complete CE and were scored according to the CESI and Harvey-Bradshaw index (HBI). Statistical correlation among CESI, HBI, and CRP was assessed. RESULTS: Weak, but significant, correlations were found between CESI and HBI (r = 0.4, P < 0.01). The correlation between CESI and CRP was moderate (r = 0.58, P < 0.01). The median CRP value was significantly higher in patients with moderate to severe CESI compared with the mild group (22.60 ± 16.79 mg/L vs 11.88 ± 8.39 mg/L, P < 0.01). Changes between baseline and follow-up CESI failed to correlate with the delta-HBI or delta-CRP (both, P > 0.05). CONCLUSIONS: In this cohort of SBCD patients, clinical disease activity index was not reliable predictors of mucosal inflammation. CRP, however, might be a useful inflammatory marker for evaluating the moderate to severe CE activity in SBCD patients. Furthermore, therapy-induced clinical and biological improvement was not associated with repair of SBCD mucosal lesions.

Evaluation of narrow-band imaging in the diagnosis of colorectal lesions: is a learning curve involved?

BACKGROUND: The usefulness of endoscopy narrow-band imaging (NBI) in differentiating colorectal lesions has been demonstrated. However, the learning curve associated with this technique is a concern for endoscopists. METHODS: Prior to carrying out these colonoscopies, four endoscopists attended a training course designed to teach the principles of NBI and application of the Sano Capillary Pattern (CP) classification criteria. Following a pre-test, endoscopists used NBI with magnification and CP analysis for real-time colonoscopy exams to predict lesion histology. Three sets of 15 lesions were imaged. These three sets included both lesions requiring endoscopic treatment (e.g. target lesions) and lesions that were not, or could not be, treated by endoscopy (e.g. non-target lesions). The diagnostic accuracy of each endoscopist for each set of lesions was evaluated to assess the learning curve associated with the application of NBI. RESULTS: Overall accuracy, sensitivity, and specificity for differentiating neoplastic and non-neoplastic lesions were 95.4%, 98.0%, and 92.0%, respectively. For target lesions versus non-target lesions, the diagnostic accuracy associated with the second set of lesions was better than that achieved with the first set of lesions (78.3% vs 96.7% (P = 0.02) and 70.0% vs 96.7% ( P < 0.01), respectively in each case). In contrast, the difference in diagnostic accuracy between the second and third sets of lesions was not significant. CONCLUSION: NBI with magnification is a useful tool for the diagnosis of colorectal lesions. Moreover, following a short training program and with minimal clinic practice, less experienced endoscopists were able to become competent in the method.

Derivation and validation of a prediction rule for estimating advanced colorectal neoplasm risk in average-risk Chinese.

No prediction rule is currently available for advanced colorectal neoplasms, defined as invasive cancer, an adenoma of 10 mm or more, a villous adenoma, or an adenoma with high-grade dysplasia, in average-risk Chinese. In this study between 2006 and 2008, a total of 7,541 average-risk Chinese persons aged 40 years or older who had complete colonoscopy were included. The derivation and validation cohorts consisted of 5,229 and 2,312 persons, respectively. A prediction rule was developed from a logistic regression model and then internally and externally validated. The prediction rule comprised 8 variables (age, sex, smoking, diabetes mellitus, green vegetables, pickled food, fried food, and white meat), with scores ranging from 0 to 14. Among the participants with low-risk (≤3) or high-risk (>3) scores in the validation cohort, the risks of advanced neoplasms were 2.6% and 10.0% (P < 0.001), respectively. If colonoscopy was used only for persons with high risk, 80.3% of persons with advanced neoplasms would be detected while the number of colonoscopies would be reduced by 49.2%. The prediction rule had good discrimination (area under the receiver operating characteristic curve = 0.74, 95% confidence interval: 0.70, 0.78) and calibration (P = 0.77) and, thus, provides accurate risk stratification for advanced neoplasms in average-risk Chinese.

Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation.

BACKGROUND & AIMS: Patients with recurrent bleeding from gastrointestinal vascular malformations are a challenge to treat. We investigated the long-term efficacy and safety of thalidomide for refractory bleeding from gastrointestinal vascular malformations in an open-label, randomized study. METHODS: Eligible patients were randomly assigned to groups that were given either 100 mg thalidomide (n = 28) or 400 mg iron (n = 27, controls), daily for 4 months; patients were followed for at least 1 year (mean, 39 months). Bleeding was defined by a positive result from an immunoassay fecal occult blood test. The primary end point was the effective response rate, defined as the proportion of patients in whom bleeding episodes had decreased by ≥ 50% in the first year of the follow-up period. The secondary end points included the rates of cessation of bleeding, blood transfusion, overall hospitalization, and hospitalization for bleeding. We also quantified yearly bleeding episodes, bleeding duration, levels of hemoglobin, and yearly requirements for transfusions of red cells, numbers of hospitalizations for bleeding, and hospital stays. Plasma levels of vascular endothelial growth factor were measured in the group given thalidomide. RESULTS: Rates of response in the thalidomide and control groups were 71.4% and 3.7%, respectively (P < .001). All secondary end points differed significantly different between groups; thalidomide was more effective. No severe adverse effects were observed, although minor side effects were common among patients in the thalidomide group. Levels of vascular endothelial growth factor were significantly reduced by thalidomide (P < .001). CONCLUSIONS: Thalidomide is an effective and relatively safe treatment for patients with refractory bleeding from gastrointestinal vascular malformations. Mechanisms of thalidomide activity might involve vascular endothelial growth factor.

[The potential pathogenesis of gastrointestinal vascular malformation and the potential mechanism of thalidomide in the treatment of gastrointestinal vascular malformation].

OBJECTIVE: To study the pathogenesis of gastrointestinal vascular malformation (GIVM) and the potential mechanism of thalidomide in the treatment of gastrointestinal bleeding due to GIVM. METHODS: We collected the surgical intestinal specimens from 10 patients who suffered from massive hemorrhage of gastrointestinal tract owning to GIVM and the normal intestinal mucosa around the lesions, as well as normal intestinal mucosa from healthy subjects. Immunohistochemical (IHC) staining was carried out to investigate the differences of angiopoietin 2 (Ang2), Notch1 and delta like ligand 4 (Dll4) in the above three intestinal mucosa to find the relationship with the pathogenesis of GIVM. Human umbilical vein endothelial cells (HUVECs) were cultured with 0, 25, 50, 100 and 200 mg/L thalidomide for 24 or 48 hours to observe their mRNA and protein expressions of Ang2, Notch1, Dll4 by real-time PCR and Western blot. RESULTS: By IHC staining, more expressions of Ang2, Notch1 and Dll4 in the lesions were detected than those in the normal intestinal mucosa around the lesions and the normal intestinal mucosa in healthy people. The expressions of Ang2, Notch1 and Dll4 were significantly correlated (P = 0.016, r = 0.732), and the expressions of Notch1 and Dll4 were absolutely correlated (P = 0.000, r = 1.000). Real-time PCR and Western blot showed that thalidomide could down-regulate the expressions of them, which were in a concentration-dependent manner. CONCLUSION: Ang2, Notch1 and Dll4 may correlate with the pathogenesis of GIVM, while thalidomide can concentration-dependently down-regulate the expression of Ang2, Notch1 and Dll4, which may be one of the mechanism that thalidomide play a therapeutic role in GIVM.

Quadruple therapy with medications containing either rufloxacin or furazolidone as a rescue regimen in the treatment of Helicobacter pylori-infected dyspepsia patients: a randomized pilot study.

BACKGROUND: The eradication rates of first-line treatment for Helicobacter pylori infection are not satisfactory. Various regimens including quadruple therapies have been recommended as rescue therapies after the first H. pylori eradication attempt failed. AIMS: To compare the efficacy and safety between quadruple therapies with medications containing either rufloxacin or levofloxacin in the Chinese nonulcer dyspepsia patients infected with H. pylori. METHODS: One hundred and thirty-eight patients after an unsuccessful 10-day standard triple therapy were enrolled in this study. They were randomized to receive a 14-day quadruple therapy with pantoprazole, bismuth citrate, and furazolidone in combination with either rufloxacin (Group Ruf, n=70) or levofloxacin (Group Lev, n=68). The H. pylori eradication was evaluated by (13) C-urea breath test 4 and 12 weeks after therapy was completed. RESULTS: One hundred and twenty-seven patients (65 in Group Ruf and 62 in Group Lev) completed the study. The H. pylori eradication rates in Group Ruf were 81.4% for intention-to-treat (ITT) analysis and 87.7% for per-protocol (PP) analysis. The rates were statistically significantly higher than those in Group Lev (66.2% and 72.6%) (p<0.05). There were no severe adverse effects found in these two groups. CONCLUSIONS: Fourteen-day quadruple therapy with a combination of proton-pump inhibitor, bismuth citrate, furazolidone, and rufloxacin is considered an effective and safe rescue therapy for H. pylori eradication after failure of standard triple treatment.