NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1.

Deficiency of DNA repair pathways drives the development of colorectal cancer. However, the role of the base excision repair (BER) pathway in colorectal cancer initiation remains unclear. This study shows that Nei-like DNA glycosylase 1 (NEIL1) is highly expressed in colorectal cancer (CRC) tissues and associated with poorer clinical outcomes. Knocking out neil1 in mice markedly suppresses tumorigenesis and enhances infiltration of CD8+ T cells in intestinal tumors. Furthermore, NEIL1 directly forms a complex with SATB2/c-Myc to enhance the transcription of COL17A1 and subsequently promotes the production of immunosuppressive cytokines in CRC cells. A NEIL1 peptide suppresses intestinal tumorigenesis in ApcMin/+ mice, and targeting NEIL1 demonstrates a synergistic suppressive effect on tumor growth when combined with a nuclear factor κB (NF-κB) inhibitor. These results suggest that combined targeting of NEIL1 and NF-κB may represent a promising strategy for CRC therapy.

Endonasopharyngeal ultrasound and magnetic resonance imaging features of recurrent retropharyngeal nodes in nasopharyngeal carcinoma patients: A radiologic-histopathologic study.

BACKGROUND: The imaging criteria of malignant retropharyngeal lymph node (RLN) in nasopharyngeal cancer (NPC) have yet to be fully elucidated. This study aimed to establish predictive models based on ultrasound (US) and magnetic resonance (MR) characteristics for identifying malignant RLN in NPC patients after radiotherapy. METHODS: 81 post-radiotherapy NPC patients with abnormal enlargement of RLN underwent endonasopharyngeal ultrasound-guided fine-needle aspirations (EPUS-FNA) to access the nature of RLN. The following features were assessed on US and MR: size, margin, vascular signal, echogenicity, enhancement signal and accompany with suspicious cervical nodes or not. A multivariate analysis was performed to screen out high-risk imaging features for recurrent RLN (RRLN), and models for the diagnosis of RRLN was constructed and tested with internal verification. We evaluated the clinical usefulness of the models through comparison of C-index and decision curve analysis. RESULTS: High-risk features of RRLN were heterogeneous echo (p < 0.01), vascular signal (p < 0.01) on EPUS, heterogeneous enhancement (p < 0.01) and minimum axis diameter > 10 mm (p < 0.01) on MR. The models based on the US and MR features showed good discrimination (AUC of 0.76 in the US model, 0.74 in the MR model and 0.77 in the US + MR model) and good net benefit in the validation group. CONCLUSION: Prediction models based on the US and MR features show good diagnostic performance for RRLN after radiotherapy in NPC patients. The combination of EPUS and MR may be constructed to provide prompt and reliable guidance to manage RLN.

The Prognostic Value of Microvascular Density in Early Postoperative Recurrence and Metastasis of T1 Esophageal Squamous Cell Carcinoma.

OBJECTIVE: To identify the relation of microvascular density (MVD) to the early postoperative recurrence and metastasis of T1 esophageal squamous cell carcinoma, and to determine whether MVD could be a prognostic predictor of esophageal squamous cell carcinoma. METHODS: Patients with T1 esophageal squamous cell carcinoma were enrolled. Immunohistochemistry with primary antibody against CD-34 was performed to count MVD. ROC curve was plotted and appropriate cutoff value was determined to evaluate the potential power of MVD in predicting early recurrence and metastasis of T1 esophageal squamous cell carcinoma. Survival curves were drawn by the Kaplan-Meier method and significance were tested by the Mantel-Cox test. RESULTS: A total of 37 patients with T1 esophageal squamous cell carcinoma were enrolled. The MVD of T1 esophageal squamous cell carcinoma patients with early metastasis was significantly higher than that of T1 esophageal squamous cell carcinoma patients without early metastasis (65.83±4.39 vs. 42.26±2.34, p<0.001). MVD was available in distinguishing whether patients with early esophageal are prone to postoperative recurrence or metastasis (AUC=0.861; 95% CI 0.738-0.984, p<0.001), with 88.89% sensitivity and 68.42% specificity of MVD being obtained when the cut-off is 44.5. Kaplan-Meier survival curves showed that patients with a higher MVD had a lower survival (37.35 months) compared with those with low MVD (40.79 months) (p<0.05). CONCLUSIONS: MVD could be a promising indicator for early postoperative recurrence and metastasis of T1 esophageal squamous cell carcinoma and the prognosis of these patients.

Oncogenic PAX6 elicits CDK4/6 inhibitor resistance by epigenetically inactivating the LATS2-Hippo signaling pathway.

Intrinsic resistance to CDK4/6 inhibitors hinders their clinical utility in cancer treatment. Furthermore, the predictive markers of CDK4/6 inhibitors in gastric cancer (GC) remain incompletely described. Here, we found that PAX6 expression was negatively correlated with the response to palbociclib in vitro and in vivo in GC. We observed that the PAX6 expression level was negatively correlated with the overall survival of GC patients and further showed that PAX6 can promote GC cell proliferation and the cell cycle. The cell cycle is regulated by the interaction of cyclins with their partner serine/threonine cyclin-dependent kinases (CDKs), and the G1/S-phase transition is the main target of CDK4/6 inhibitors. Therefore, we tested whether PAX6 expression was correlated with the GC response to palbociclib. We found that PAX6 hypermethylates the promoter of LATS2 and inactivates the Hippo pathway, which upregulates cyclin D1 (CCND1) expression. This results in a suppressed response to palbociclib in GC. Furthermore, we found that the induction of the Hippo signaling pathway or treatment with a DNA methylation inhibitor could overcome PAX6-induced palbociclib resistance in GC. These findings uncover a tumor promoter function of PAX6 in GC and establish overexpressed PAX6 as a mechanism of resistance to palbociclib.

High Diagnostic Accuracy and Safety of Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Malignant Lymph Nodes: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is increasingly being used for diagnosing lymphadenopathy. We aim to systematically review the accuracy of EUS-FNA in differentiating benign and malignant mediastinal and abdominal lymph nodes (LNs). METHODS: A comprehensive literature search was performed on multiple electronic databases through February 2020. A random or fixed effect model generated the pooled sensitivity, specificity, likelihood ratio (LR), and diagnostic odds ratio (DOR) of EUS-FNA. Subgroup analyses and meta-regression were used to explore sources of heterogeneity. RESULTS: Twenty-six studies involving 2753 patients with 2833 LNs were included. In the differential diagnosis of benign and malignant LNs, EUS-FNA had a pooled sensitivity, specificity, positive LR, and negative LR of 87% (95% confidence interval [CI] 86-90%), 100% (95% CI 99-100%), 68.98 (95% CI 42.10-113.02), and 0.14 (95% CI 0.11-0.17), respectively. The pooled rate of adverse events associated with EUS-FNA was 1.57% (95% CI 1.06-2.24%). The summary receiver operating characteristic (SROC) yielded an area under the curve (AUC) of 0.9912. EUS-FNA performed in mediastinal LNs gained a sensitivity of 85% (95% CI 81-88%), while in abdominal LNs, it reached 87% (95% CI 82-91%). The sensitivity of the subgroup with rapid on-site evaluation (ROSE) was 91% (95% CI 89-93%), while non-ROSE was 85% (95% CI 82-87%). CONCLUSIONS: EUS-FNA is a sensitive, highly specific, and safe method for distinguishing benign and malignant mediastinal or abdominal LNs. However, the sensitivity of EUS-FNA still varies significantly among different centers.

The relation between Helicobacter pylori immunoglobulin G seropositivity and leukocyte telomere length in US adults from NHANES 1999-2000.

BACKGROUND: Helicobacter pylori (H pylori) immunoglobulin G (IgG) seropositivity is prevalent but its relation with leukocyte telomere length (LTL), a cellular aging biomarker, is unclear. METHODS: Among 3,472 participants from the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000, LTL was measured with the quantitative polymerase chain reaction. H pylori IgG was measured by enzyme-linked immunosorbent assays and defined as seropositivity with an immune status ratio score > 0.9. We used linear regression models to examine the relation of H pylori IgG seropositivity with continuous LTL and logistic regression for the relation with short LTL (<10th percentile of the population distribution) adjusting for potential confounders. We stratified the analyses by a priori selected variables. RESULTS: Population prevalence of H pylori IgG seropositivity was 31.5% in the overall population with higher prevalence found in those with older age, other races than non-Hispanic whites, lower education, and being born out of the United States. Continuous LTL was non-significantly shorter in those with H Pylori IgG seropositivity versus seronegativity (mean difference = -40.3 bp, 95% CI: -112.4, 31.9). This difference was not significant after adjusting for potential confounders nor stratifying by potential effect modifiers. H Pylori IgG seropositivity was significantly associated with short LTL among the elderly (55-75 years, adjusted OR: 3.06, 95% CI: 1.17, 7.99), but not in the overall population (OR: 1.28, 95% CI: 0.81-2.02). CONCLUSION: H Pylori IgG seropositivity was not associated with continuous LTL in the general population but may be associated with an excessively short LTL in the elderly.

Prognostic efficacy of preoperative mGPS, SIS and LCS in patients with gastric cancer.

BACKGROUND: Systemic inflammation and interactions with host-tumor are currently identified as a hallmark of cancer. The purpose of this study was to assess the prognostic value of preoperative modified Glasgow Prognostic Score (mGPS), systemic inflammation score (SIS) and "lymphocyte C-reactive protein score" (LCS) in gastric cancer (GC) patients. METHODS: 358 GC patients were enrolled in this retrospective study. Kaplan-Meier method, multivariate Cox regression analysis, time-dependent receiver operating characteristics analysis (ROC), concordance index (C-index), and Akaike information criterion (AIC) were applied for assessments of the prognostic values. RESULTS: Preoperative increased mGPS, SIS and LCS were all significantly linked with unfavorable overall survival using the Kaplan-Meier method (P < 0.001). Multivariate analysis proved that SIS was the only independent indicator among these three scoring systems. At the 4th-month point postoperatively, the time-dependent ROC curves of SIS and LCS crossed the curve of mGPS and were consistently superior to that of mGPS thereafter. The model incorporating SIS had higher C-index and smaller AIC than did the model without SIS or the models with mGPS or LCS. CONCLUSION: Preoperative SIS exceeded both the mGPS and LCS and was the most clinically promising and feasible prognostic scoring system for GC patients.

Submucosal Saline Injection Followed by Endoscopic Ultrasound versus Endoscopic Ultrasound Only for Distinguishing between T1a and T1b Esophageal Cancer.

PURPOSE: To examine whether submucosal saline injection (SSI) can improve traditional endoscopic ultrasound (EUS) accuracy in distinguishing between T1a and T1b stage esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: Patients with T1N0M0 stage ESCC (n = 180) ages 18 to 85 years were enrolled between February 14, 2012 to June 4, 2018 at Sun Yat-sen University Cancer Center (Guangdong, China). They were randomly assigned (1:1) to receive either EUS examination after 3-5 mL SSI or EUS only examination. All the patients were referred to thoracic surgeons to receive endoscopic resection (ER) or esophagectomy 5 to 10 days after EUS examination. Standard EUS criteria were used to preoperatively stage the ESCC cases, and surgical pathology reports after referral were used to postoperatively stage the cases. The primary endpoint was the diagnostic accuracy of T1b staging [defined as the sum of the true positive (T1b) and true negative (T1a) cases divided by the total number of cases]. RESULTS: Among the per-protocol population, the SSI+EUS group (n = 81) was superior to the EUS-only group (n = 85) in terms of the diagnostic accuracy for T1b staging [93.8% (95% confidence interval (CI), 88.6-99.1) vs. 65.9% (95% CI, 55.8-76.0); P < 0.001]. The positive predictive value of SSI+EUS for diagnosing T1b ESCC reached 90.9% (95% CI, 81.1-100), which was significantly superior to that of EUS only [0.576 (0.450-0.702), P = 0.001]. CONCLUSIONS: SSI significantly improves the diagnostic accuracy of EUS in distinguishing between T1a and T1b ESCC, which might help avoid unnecessary esophagectomy and diagnostic ER.

Real-time artificial intelligence for detection of upper gastrointestinal cancer by endoscopy: a multicentre, case-control, diagnostic study.

BACKGROUND: Upper gastrointestinal cancers (including oesophageal cancer and gastric cancer) are the most common cancers worldwide. Artificial intelligence platforms using deep learning algorithms have made remarkable progress in medical imaging but their application in upper gastrointestinal cancers has been limited. We aimed to develop and validate the Gastrointestinal Artificial Intelligence Diagnostic System (GRAIDS) for the diagnosis of upper gastrointestinal cancers through analysis of imaging data from clinical endoscopies. METHODS: This multicentre, case-control, diagnostic study was done in six hospitals of different tiers (ie, municipal, provincial, and national) in China. The images of consecutive participants, aged 18 years or older, who had not had a previous endoscopy were retrieved from all participating hospitals. All patients with upper gastrointestinal cancer lesions (including oesophageal cancer and gastric cancer) that were histologically proven malignancies were eligible for this study. Only images with standard white light were deemed eligible. The images from Sun Yat-sen University Cancer Center were randomly assigned (8:1:1) to the training and intrinsic verification datasets for developing GRAIDS, and the internal validation dataset for evaluating the performance of GRAIDS. Its diagnostic performance was evaluated using an internal and prospective validation set from Sun Yat-sen University Cancer Center (a national hospital) and additional external validation sets from five primary care hospitals. The performance of GRAIDS was also compared with endoscopists with three degrees of expertise: expert, competent, and trainee. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of GRAIDS and endoscopists for the identification of cancerous lesions were evaluated by calculating the 95% CIs using the Clopper-Pearson method. FINDINGS: 1 036 496 endoscopy images from 84 424 individuals were used to develop and test GRAIDS. The diagnostic accuracy in identifying upper gastrointestinal cancers was 0·955 (95% CI 0·952-0·957) in the internal validation set, 0·927 (0·925-0·929) in the prospective set, and ranged from 0·915 (0·913-0·917) to 0·977 (0·977-0·978) in the five external validation sets. GRAIDS achieved diagnostic sensitivity similar to that of the expert endoscopist (0·942 [95% CI 0·924-0·957] vs 0·945 [0·927-0·959]; p=0·692) and superior sensitivity compared with competent (0·858 [0·832-0·880], p<0·0001) and trainee (0·722 [0·691-0·752], p<0·0001) endoscopists. The positive predictive value was 0·814 (95% CI 0·788-0·838) for GRAIDS, 0·932 (0·913-0·948) for the expert endoscopist, 0·974 (0·960-0·984) for the competent endoscopist, and 0·824 (0·795-0·850) for the trainee endoscopist. The negative predictive value was 0·978 (95% CI 0·971-0·984) for GRAIDS, 0·980 (0·974-0·985) for the expert endoscopist, 0·951 (0·942-0·959) for the competent endoscopist, and 0·904 (0·893-0·916) for the trainee endoscopist. INTERPRETATION: GRAIDS achieved high diagnostic accuracy in detecting upper gastrointestinal cancers, with sensitivity similar to that of expert endoscopists and was superior to that of non-expert endoscopists. This system could assist community-based hospitals in improving their effectiveness in upper gastrointestinal cancer diagnoses. FUNDING: The National Key R&D Program of China, the Natural Science Foundation of Guangdong Province, the Science and Technology Program of Guangdong, the Science and Technology Program of Guangzhou, and the Fundamental Research Funds for the Central Universities.

Decreased Pituitary Height and Stunted Linear Growth After Radiotherapy in Survivors of Childhood Nasopharyngeal Carcinoma Cases.

To examine the morphological changes of the pituitary glands and linear growth of childhood nasopharyngeal carcinoma (NPC) cases who accepted radiotherapy. A total of 90 children (i.e., age less than 18 years) who were diagnosed as NPC at Sun Yat-sen University Cancer Center from January 2009 to January 2016 were identified by reviewing medical records. Two radiologists reviewed and measured the pre-radiation, post-radiation, and the latest available pituitary gland heights independently. Patients' current height information was collected by telephone interviews. We compared the pituitary height differences using paired t-tests and estimated the pituitary height trajectories within each sex by mixed regression models. Height-for-age Z-score was calculated for each patient using the WHO growth reference data for 5-19 years as reference. Most of the included participants were of male sex (75.6%) and over half were diagnosed at stage IV (58.4%). Among the 90 included participants, 89 had one repeated measurement of the pituitary height and 79 had two repeated measurements of the pituitary height. Seventy six of the 89 childhood NPC participants had reduced pituitary heights after radiation and accounted for 85.4% of the whole population. The means of the pituitary heights before and after radiotherapy were 6.4 ± 1.3 mm and 5.6 ± 1.2 mm (P < 0.001), respectively. The mean of height-for-age Z-score for childhood NPC cases was significantly below zero (-0.54, 95% CI = -0.74, -0.34). We concluded that childhood NPC cases had decreased pituitary heights and stunted linear growth after radiotherapy.

HOXC10 promotes gastric cancer cell invasion and migration via regulation of the NF-κB pathway.

Homeobox gene C10 (HOXC10), known to regulate cell differentiation and proliferation, is upregulated in gastric cancer (GC). The mechanism underlying HOXC10 involvement in GC metastasis is unclear. Herein, we found that HOXC10 is overexpressed in GC relative to normal controls. In the 73 GC patients tissue microarrays (TMA) tested, HOXC10 expression was closely related with tumor-node-metastasis (TNM) stage, lymph node metastasis, and distant metastasis. HOXC10 overexpression tended to associate with low 5-year cumulative survival. Cox regression analysis identified HOXC10 as an independent prognostic factor for poor patient survival. HOXC10 promoted GC cell invasion and migration, regulated the expression of activated ATM and markers of NF-κB signaling. HOXC10 may promote invasion and migration of GC by regulating ATM/NF-κB signaling pathway. HOXC10 should be explored as a clinical marker of GC prognosis.

Ultrasound-guided fine needle aspiration of retropharyngeal lymph nodes after radiotherapy for nasopharyngeal carcinoma: a novel technique for accurate diagnosis.

BACKGROUND: Enlarged retropharyngeal lymph nodes (RLNs) are very common in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. The most suitable treatment option for enlarged RLNs depends on the pathological results. However, RLN sampling is difficult and imminent in the clinic setting. We recently developed a novel minimally invasive technique termed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for sampling RLN tissues sufficient for pathological or cytological diagnosis. METHODS: We enrolled 30 post-radiotherapy patients with NPC with suspected RLN metastasis detected via magnetic resonance imaging (MRI). The EUS probe was introduced into the nasopharynx via the nostrils, and EUS was then used to scan the retropharyngeal space and locate the RLN in the anterior carotid sheath. EUS-FNA was subsequently performed. The safety and efficacy of using EUS-FNA to sample the RLN tissues were assessed. RESULTS: Strips of tissue were successfully sampled from all patients using EUS-FNA. Of the 30 patients, 23 were confirmed to have cancer cells in the biopsied tissues via pathology or cytology examinations with 1 EUS-FNA biopsy session. The seven cases without confirmed cancer cells were subsequently reanalyzed by using another EUS-FNA biopsy session, and two more cases were confirmed possessing cancer cells. The other five patients without confirmed cancer cells were closely followed with MRI every month for 3 months. After follow-up for 3 months, three patients were still considered cancer-free due to the presence of RLNs with stable or shrinking diameters. The rest two patients who showed progressive disease underwent a third EUS-FNA biopsy procedure and were further confirmed to be cancer cell-positive. In the whole cohort reported here, the EUS-FNA procedure was not associated with any severe complications. CONCLUSION: EUS-FNA is a safe and effective diagnostic approach for sampling tissues from the RLNs in patients with suspected recurrent NPC.

Exploration of Racial Differences in Reproductive Factors for Breast Cancer among Women aged 55-74.

Background Reproductive factors have been well-documented risk factors for breast cancer. Few studies have examined whether the associations between reproductive factors and breast cancer differed across races/ethnicities. Methods We analyzed a sub-sample (70, 734) of the Prostate, Lung, Colorectal, and Ovarian (PLCO) dataset. Participants with valid baseline questionnaire and without breast cancer at enrollment were included into analysis. We stratified the participants into subgroups based on their races/ethnicities then estimated the effects of the reproductive factors on breast cancer within each group using Cox-proportion regression models. Results Oral contraceptive use (HR=1.09, 95% confidence interval or CI=1.01, 1.18), advanced age at natural menopause (HR=1.25, 95% CI=1.06, 1.49) were associated with increased risk of breast cancer in non-Hispanic Caucasians group only. Long term use of menopausal hormone therapy (more than five years) was associated with increased risk of breast cancer in both of the non-Hispanic Caucasian (HR=1.44, 95% CI=1.31, 1.59) group and the non-Hispanic Asian/Pacific Islander (HR=1.98, 95% CI=1.23, 3.20) group, but not in other race/ethnic groups. Hispanics who tried to become pregnant for a year or more had increased risk of breast cancer (HR=2.60, 95% CI=1.05, 6.46) than their counterparts without difficulty in getting pregnancy. In addition, surgery induced menopause was found to be a protective factor for breast cancer in non-Hispanic Caucasian (HR=0.88, 95% CI=0.79, 0.98) group only. Conclusions We concluded that different races/ethnicities had different breast cancer related reproductive risk factors. Non-Hispanic Caucasians had the most breast cancer related reproductive risk factors, while the minorities had none or few breast cancer related reproductive risk factors and among these few factors only 1 was also risk factor for non-Hispanic Caucasians.

Virtual Laparoscopic Training System Based on VCH Model.

Laparoscopy has been widely used to perform abdominal surgeries, as it is advantageous in that the patients experience lower post-surgical trauma, shorter convalescence, and less pain as compared to traditional surgery. Laparoscopic surgeries require precision; therefore, it is imperative to train surgeons to reduce the risk of operation. Laparoscopic simulators offer a highly realistic surgical environment by using virtual reality technology, and it can improve the training efficiency of laparoscopic surgery. This paper presents a virtual Laparoscopic surgery system. The proposed system utilizes the Visible Chinese Human (VCH) to construct the virtual models and simulates real-time deformation with both improved special mass-spring model and morph target animation. Meanwhile, an external device that integrates two five-degrees-of-freedom (5-DOF) manipulators was designed and made to interact with the virtual system. In addition, the proposed system provides a modular tool based on Unity3D to define the functions and features of instruments and organs, which could help users to build surgical training scenarios quickly. The proposed virtual laparoscopic training system offers two kinds of training mode, skills training and surgery training. In the skills training mode, the surgeons are mainly trained for basic operations, such as laparoscopic camera, needle, grasp, electric coagulation, and suturing. In the surgery-training mode, the surgeons can practice cholecystectomy and removal of hepatic cysts by guided or non-guided teaching.

Evaluation of preoperative staging for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is known for its rapid progression and poor outcomes. China has the highest incidence and mortality in the world. Diagnoses made at early stages and accurate staging are associated with better outcomes, all of which can play a significant role in the selection of treatment protocols. ESCC is staged according to the widely accepted TNM system. Common imaging modalities used in staging ESCC before treatment include endoscopy, computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI). Endoscopic ultrasound is useful for staging tumor depth and nodal status. Narrow band imaging is valuable for early stage disease assessment. CT and PET provide additional valuable information regarding node and metastasis staging. The ability of MRI to delineate ESCC is continuously being improved and adds information regarding locoregional status to routine examinations.

Endoscopic Ultrasound for Preoperative Esophageal Squamous Cell Carcinoma: a Meta-Analysis.

BACKGROUND: Treatment options and prognosis of esophageal squamous cell carcinoma (ESCC) depend on the primary tumor depth (T-staging) and regional lymph node status (N-staging). Endoscopic ultrasound (EUS) has emerged as a useful staging tool, but studies regarding its benefits have been variable. The objective of this study was to evaluate the diagnostic accuracy of EUS for detecting preoperative ESCC. METHODS: We included in our meta-analysis studies involving EUS-based staging of preoperative ESCC compared with pathological staging. Using a random-effects model, we performed a meta-analysis of the accuracy of EUS by calculating pooled estimates of sensitivity, specificity and the diagnostic odds ratio. In addition, we created a summary receiver operating characteristic (SROC) curve. RESULTS: Forty-four studies (n = 2880) met the inclusion criteria. The pooled sensitivity and specificity of T1 were 77% (95%CI: 73 to 80) and 95% (95%CI: 94 to 96). Among the T1 patients, EUS had a pooled sensitivity in differentiating T1a and T1b of 84% (95%CI: 80 to 88) and 83% (95%CI: 80 to 86), and a specificity of 91% (95%CI: 88 to 94) and 89% (95%CI: 86 to 92). To stage T4, EUS had a pooled sensitivity of 84% (95%CI: 79 to 89) and a specificity of 96% (95%CI: 95 to 97). The overall accuracy of EUS for T-staging was 79% (95%CI: 77 to 80), and for N-staging, 71% (95%CI: 69 to 73). CONCLUSIONS: EUS has good diagnostic accuracy for staging ESCC, which has better performance in T1 sub-staging (T1a and T1b) and advanced disease (T4).

Macrophage migration inhibitory factor as a potential prognostic factor in gastric cancer.

AIM: To investigate macrophage migration inhibitory factor (MIF) expression and its clinical relevance in gastric cancer, and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS: Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry (IHC) semiquantitatively, and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Two pairs of siRNA targeting the MIF gene (MIF si-1 and MIF si-2) and one pair of scrambled siRNA as a negative control (NC) were designed and chemically synthesized. All siRNAs were transiently transfected in AGS cells with Oligofectamine(TM) to knock down the MIF expression, with the NC group and mock group (Oligofectamine(TM) alone) as controls. At 24, 48, and 72 h after transfection, MIF mRNA was analyzed by RT-PCR, and MIF and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot. The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium (MTT) assay and colony forming assay. RESULTS: The tissue microarray was informative for IHC staining, in which the MIF expression in gastric cancer tissues was higher than that in adjacent non-cancer normal tissues (P < 0.001), and high level of MIF was related to poor tumor differentiation, advanced T stage, advanced tumor stage, lymph node metastasis, and poor patient survival (P < 0.05 for all). After siRNA transfection, MIF mRNA was measured by real-time PCR, and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group, MIF expression was knocked down successfully in gastric cancer cells, and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection, and colonies formed were assayed by colony forming assay 10 d after transfection; all these showed significant changes in gastric cancer cells transfected with specific siRNA compared with the control siRNA and mock groups (P < 0.001 for all). CONCLUSION: MIF could be of prognostic value in gastric cancer and might be a potential target for small-molecule therapy.

A novel pathogenic germline mutation in the adenomatous polyposis coli gene in a Chinese family with familial adenomatous coli.

Familial adenomatous polyposis (FAP) is an autosomal dominant disease manifesting as colorectal cancer in middle-aged patients. Mutations of the adenomatous polyposis coli (APC) gene contribute to both FAP and sporadic or familial colorectal carcinogenesis. Here we describe the identification of the causative APC gene defects associated with FAP in a Chinese pedigree. All patients with FAP were diagnosed by their combination of clinical features, family history, colonoscopy, and pathology examinations. Blood samples were collected and genomic DNA was extracted. Mutation analysis of APC was conducted by targeted next-generation sequencing, long-range PCR and Sanger sequencing. A novel mutation in exon 14-15(c.1936-2148 del) and intron 14 of the APC gene was demonstrated in all FAP patients and was absent in unaffected family members. This novel deletion causing FAP in Chinese kindred expands the germline mutation spectrum of the APC gene in the Chinese population.