Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms.

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

MiR-92a expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening.

OBJECTIVE: This study seeks to assess the efficacy of exfoliated colonocytes isolated from feces (ECIF) miR-92a as a clinical colorectal cancer diagnostic marker in a larger cohort. METHODS: Clinicopathologic data from colorectal cancer patients and health controls that underwent colonoscopy, as well as patients of other cancers diagnosed, were included. A total of 963 Chinese participants were enrolled, with 292 (27.4%) having colorectal cancer, 140 (14.5%) having other types of cancer, e.g., pancreatic, liver, oral, bile duct, esophagus, and stomach cancer, 171 (17.8%) having infection in the intestine, rectal, stomach, appendix, and gastrointestinal ulcer, and 360 (37.4%) of healthy controls. ECIF samples were gathered and miR-92a levels were detected using TaqMan probe-based miR-92a real-time quantitative PCR (RT-qPCR) kit developed by Shenzhen GeneBioHealth Co., Ltd. RESULTS: Through a series of experiments, we demonstrated that the Ep-LMB/Vi-LMB magnetic separation system is feasible, highly specific, and highly sensitive at a cutoff value of 1053 copies per 6 ng of ECIF RNA. ECIF miR-92a levels were significantly higher in colorectal cancer patients than in controls. Colorectal cancer detection sensitivity and specificity were 87.3% and 86.9% respectively. Furthermore, the performance of this miR-92a detection kit demonstrated that it is an effective tool for colorectal cancer, with a high sensitivity of 84.1%, even in early cancer stages (0, I, and II). Furthermore, tumor removal resulted in lower stool miR-92a levels (3.21±0.58 vs. 2.14±1.14, P < 0.0001, n = 65). CONCLUSION: Finally, the miR-92a RT-qPCR kit detects ECIF-increased miR-92a and could be used for colorectal cancer screening.

Targeted demethylation at ZNF154 promotor upregulates ZNF154 expression and inhibits the proliferation and migration of Esophageal Squamous Carcinoma cells.

Zinc finger protein 154 (ZNF154) is hypermethylated at the promoter in many epithelial-derived solid tumors. However, its methylation status and function in esophageal squamous carcinoma (ESCC) are poorly understood. We found that the ZNF154 promoter is hypermethylated in ESCC and portends poor prognosis. In addition, ZNF154 functions as a tumor suppressor gene (TSG) in ESCC, and is downregulated by promoter hypermethylation. We established a targeted demethylation strategy based on CRISPR/dCas9 technology and found that the hypermethylation of ZNF154 promoter repressed ZNF154 induction, which in turn promoted the proliferation and migration of ESCC cells in vitro and in vivo. Finally, high-throughput CUT&Tag analysis, GEPIA software and qPCR were used to revealed the role of ZNF154 as a transcription factor to upregulate the expression of ESCC-associated tumor suppressor genes. Taken together, hypermethylation of the ZNF154 promoter plays an important role in the development of ESCC, and epigenetic editing is a promising tool for inhibiting ESCC cells with aberrant DNA methylation.

Gastric lymphangioma: a case report and review of literature.

BACKGROUND: Gastric lymphangioma is one of the highly rare benign tumors characterized by multilocular or unilocular lymphatic spaces. Herein, we report a case of lymphangioma in the gastric antrum. CASE PRESENTATION: A 77-year-old male patient who had been experiencing epigastric discomfort for a year was presented to our hospital. A gastric subepithelial lesion was diagnosed by upper endoscopy and was entirely excised via diatal subtotal gastrectomy. Endoscopic ultrasonography revealed an echoless homogenous echo pattern in the third wall layer. A lymphangioma was diagnosed by pathologic investigation of the resected specimen. The PubMed, Embase and Web of Science databases were reviewed for literature in English while using the keywords of "gastric lymphangioma" or "lymphangioma of stomach" or "gastric lymphatic cyst" or "lymphatic cyst of stomach" and the results were discussed. CONCLUSION: Gastric lymphangioma is a rarely occurring submucosal tumor that should be considered when diagnosing subepithelial lesions in the stomach.

Factors associated with adherence to colonoscopy among individuals who were positive in the preliminary screening for colorectal neoplasms.

OBJECTIVES: This study aimed to investigate the potential factors associated with adherence to colonoscopy among participants who were preliminarily screened positive in a community-based colorectal cancer screening program in China. METHODS: This study analyzed data from 1219 out of 6971 community residents who were identified as positive cases by the well-validated high-risk factor questionnaire (HRFQ) or fecal immunochemical test (FIT) in the preliminary screening stage for colorectal neoplasms. Patients showing adherence to colonoscopy were defined as those who received positive results in a preliminary screening for colorectal neoplasms and later received a colonoscopy examination as required. The associations of social-demographic factors, lifestyle behaviors, history of diabetes, body mass index (BMI), and risk factors in the HRFQ with adherence to colonoscopy were evaluated using logistic regression models. RESULTS: Among 1219 participants who preliminarily screened positive, the top five risk factors reported by the participants were chronic constipation (25.9%), hematochezia (23.5%), family history of CRC in first-degree relatives (22.1%), chronic diarrhea (21.8%), and history of polyps (16.6%). Around 14.2% of participants who preliminarily screened positive reported three or more risk factors, and the proportion was 26.2% among participants who were positive according to both HRFQ and FIT. Among all participants who were preliminarily screened positive, the multivariable results showed that those who were married (OR = 1.58, 95% CI: 1.12, 2.25, p = 0.01), had chronic diarrhea (OR = 1.34, 95% CI: 1.00, 1.78, p = 0.047), and had a positive FIT (OR = 1.60, 95% CI: 1.21, 2.10, p < 0.001 for patients who were negative according to HRFQ but positive according to FIT; OR = 2.12, 95% CI: 1.33, 2.78, p = 0.002 for patients who were positive for both HRFQ and FIT) were more likely to adhere to colonoscopy, while participants with a history of cancer (OR: 0.50, 95% CI: 0.31, 0.79, p = 0.003) were less likely to adhere to colonoscopy. The results among participants who were tested positive according to only HRFQ were similar to those among all participants who were tested positive according to HRFQ or FIT. However, among participants who were tested positive according to only FIT, we only found that those who were married (OR = 2.52, 95% CI: 1.08, 5.90, p = 0.033) had a higher odds of adhering to colonoscopy, while those with a history of diabetes (OR = 0.35, 95% CI: 0.13, 0.96, p = 0.042) were less likely to adhere to colonoscopy. CONCLUSION: Our findings provide evidence supporting the development of tailored interventional strategies that aim to improve adherence to colonoscopy for individuals with a high risk of colorectal neoplasms. Both barriers and facilitators associated with adherence to colonoscopy should be considered in supportive systems and health policies. However, further well-designed prospective studies are warranted to confirm our findings.

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.

Clinical outcomes of cap-assisted endoscopic resection for small rectal subepithelial tumors.

OBJECTIVE: To assess the effectiveness and safety of cap-assisted endoscopic resection and the usefulness of endoscopic ultrasonography (EUS) for managing small rectal subepithelial tumors (SETs). PATIENTS AND METHODS: Patients with small rectal SETs≤10mm in diameter were enrolled in this study at our hospital from October 2014 to December 2017. First, EUS was performed to evaluate the lesions. Then, cap-assisted endoscopic resection was performed by suctioning the SET into a transparent cap, ligating with a metal snare and then resecting the tumor. The wound was closed using endoclips if necessary. RESULTS: Forty patients were enrolled in the study. EUS showed lesions originating from muscularis mucosa or submucosa with an average diameter of 5.4×3.1mm. The en bloc resection rate was 85.0% obtained by cap-assisted endoscopic resection, with a mean total procedure time of 17.6min. No immediate perforation happened. Immediate bleeding occurred in five patients; all cases were managed successfully by endoscopy. No delayed bleeding was observed. Pathology examination showed that 70.0% of the lesions were neuroendocrine tumors (G1). One case of recurrence was seen in follow-up; it was managed successfully by endoscopic submucosal dissection. There was no tumor recurrence in a median follow-up period of 41 months in the remaining 39 patients. CONCLUSIONS: Most small rectal SETs arising from the muscularis mucosa or submucosa are neuroendocrine tumors and require proper treatment. Cap-assisted endoscopic resection is simple, effective and safe for resecting such lesions, and EUS is useful for case screening.

Identification of cancer stem cell characteristics in liver hepatocellular carcinoma by WGCNA analysis of transcriptome stemness index.

Cancer stem cells (CSCs) are characterized by self-renewal and -differential potential as compared to common cancer cells and play an important role in the development and therapeutic resistance of liver hepatocellular carcinoma (LIHC). However, the specific pathogenesis of LIHC stem cells is still unclear, and the genes involved in the stemness of LIHC stem cells are currently unknown. In this study, we investigated novel biomarkers associated with LIHC and explored the expression characteristics of stem cell-related genes in LIHC. We found that mRNA expression-based stemness index (mRNAsi) was significantly overexpressed in liver cancer tissues. Further, mRNAsi expression in LIHC increased with the tumor pathological grade, with grade 4 tumors harboring the greatest stem cell features. Upon establishing mRNAsi scores based on mRNA expression of every gene, we found an association with poor overall survival in LIHC. Moreover, modules of interest were determined based on weighted gene co-expression network analysis (WGCNA) inclusion criteria, and three significant modules (red, green, and brown) and 21 key genes (DCN, ECM1, HAND2, PTGIS, SFRP1, SRPX, COLEC10, GRP182, ADAMTS7, CD200, CDH11, COL8A1, FAP, LZTS1, MAP1B, NAV1, NOTCH3, OLFML2A, PRR16, TMEM119, and VCAN) were identified. Functional analysis of these 21 genes demonstrated their enrichment in pathways involved in angiogenesis, negative regulation of DNA-binding transcription factor activity, apoptosis, and autophagy. Causal relationship with proteins indicated that the Wnt, Notch, and Hypoxia pathways are closely related to LIHC tumorigenesis. To our knowledge, this is the first report of a novel CSC biomarker, mRNAsi, to predict the prognosis of LIHC. Further, we identified 21 key genes through mRNA expression network analysis, which could be potential therapeutic targets to inhibit the stemness of cancer cells in LIHC.

Mir-124 Attenuates STAT3-Mediated TH17 Differentiation in Colitis-Driven Colon Cancer.

BACKGROUND: Inflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the miR-124 acts as a safeguard to inhibit the pro-inflammatory production and reparative regeneration. METHODS: The expression levels of miR-124 and IL-17, IFN-γ were detected by qRT-PCR. TH17 or TH1 cells were detected by flow cytometer, respectively. The binding of STAT3 to the promoter region of IL-17 gene was analyzed by Chip assay. miR-124 binding to the 3'UTR of STAT3 gene was detected by reported plasmid construction and luciferase assay. Furthermore, DSS-induced colitis mice model and T cell transfer model were used to confirm the function of miR-124 in vivo. The related gene expression was analyzed by ELISA and western blot experiments. RESULTS: The results indicated that miR-124 decrease promotes colon tumorigenesis after Citrobacter rodentium infection and AOM/DSS induced colon cancer murine model. In molecular mechanism, miR-124 targets STAT3 to inhibit TH17 cell polarization and keep TH17 polarization in colonic microenvironment. CONCLUSIONS: Our study strengthened the important role of miR-124 in the regulation of adaptive immune responses and blocking the development of colitis-related cancer.

Cleavage and polyadenylation specific factor 4 promotes colon cancer progression by transcriptionally activating hTERT.

CPSF4 was identified as a crucial tumorigenic factor in lung cancer development. However, its precise function and the underlying molecular mechanisms in colon cancer progression remain completely unknown. Here, we demonstrate CPSF4 was highly expressed in human colon cancer cells and tissues. Its knockdown inhibited colorectal cancer progression in vitro, including cell proliferation, migration, invasion and stemness maintenance. In contrast, the ectopic overexpression of CPSF4 had the opposite effects in vitro and in vivo. Further mechanistic studies demonstrated that CPSF4 facilitated colorectal tumorigenesis and development partially through transcriptionally regulating hTERT expression by cooperating with NF-kB1 and co-anchoring at hTERT promoter -321 to -234 fragment. In addition, clinical samples analysis indicated that CPSF4 expression was positively correlated with hTERT, and the simultaneously high expression of CPSF4 and hTERT predicted poor patient outcome. Overall, our findings established CPSF4 as a pro-tumorigenic factor in colorectal cancer progression, and suggested that targeting CPSF4-hTERT axis may represent a promising therapeutic strategy in colon cancer treatment.

Comparison of microwave ablation and radiofrequency ablation for hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Microwave ablation (MWA) has several advantages over radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of MWA with those of RFA for HCC from the perspectives of percutaneous and laparoscopic approaches. METHODS: PubMed/MEDLINE, Embase, the Cochrane library, and China Biology Medicine databases were searched. Studies comparing the efficacy and safety of MWA with those of RFA in patients with HCC were considered eligible. Complete ablation (CA), local recurrence (LR), disease-free survival (DFS), overall survival (OS), and the major complication rate were compared between MWA and RFA. RESULTS: Four randomized controlled trials and 10 cohort studies were included. For percutaneous ablation, no significant difference was found between MWA and RFA regarding CA, LR, DFS, OS, and the major complication rate. A subgroup analysis of tumors measuring ≥3 cm revealed no difference in CA and LR for percutaneous ablation. For laparoscopic ablation, a significantly lower LR rate and a non-significant trend toward a higher major complication rate were observed for the MWA group (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.16-4.02, p = .01 for LR; OR 0.21, 95% CI 0.04-1.03, p = .05 for major complication rate). CA, DFS, and OS were similar between the two groups. CONCLUSIONS: Percutaneous (P)-MWA had similar therapeutic effects compared with P-RFA for HCC. Patients undergoing laparoscopic MWA had a lower LR rate; however, their major complication rate appeared to be higher. The superiority of MWA over RFA remains unclear and needs to be confirmed by high-quality evidence.

An early report of a screening program for colorectal cancer in Guangzhou, China.

BACKGROUND: We launched a screening program for colorectal cancer (CRC) in Yuexiu District, Guangzhou, China, in 2014. Here we aimed to report the early results of the program and evaluate the benefits of a screening questionnaire. METHODS: Residents aged between 50 and 74 were eligible for the screening. A questionnaire and two consecutive fecal immunological tests (FITs) were used as primary screening methods. Subjects who were positive for any of the two tests were referred for further examination with colonoscopy. Neoplasms were removed either colonoscopically or by colectomy. Atypical adenoma and CRC were defined as advanced neoplasms. RESULTS: A total of 6,971 residents in Dadong Street, Yuexiu District were screened with a questionnaire, and among them, 5,343 underwent at least one FIT. Four thousand and two hundred eleven (60.4%) were female, and 2,760 (39.6%) were male, with a median age of 62.0 years. Questionnaire and FITs identified 1,219 candidates for further examination with colonoscopy, among whom only 647 (53.1%) comply. As of this writing, 623 colonoscopy results were obtained, among which 270 (43.3%) had positive findings. The adenoma detection rate (ADR) was 43.3% (270/623). The ADR was 43.3% (270/623). Of the 270 patients, 10 (3.07%) had CRC, 81 (30.0%) had advanced adenoma, 178 had low-grade adenoma or other benign polyps, one had carcinoid. Except for three advanced CRC, all neoplasms detected were benign or in an early stage. CONCLUSIONS: Our screening program help identified patients with colonic neoplasms at an early stage, precluding them from developing into the malignant disease. The addition of the questionnaire significantly increased the sensitivity of primary screening, while also decreasing the specificity. Long-term results should evaluate the social and economic benefits of this program.

Erratum: Phosphodiesterase-5 inhibition suppresses colonic inflammation-induced tumorigenesis via blocking the recruitment of MDSC.

[This corrects the article on p. 41 in vol. 7, PMID: 28123846.].

Via mucosa incision EUS-guided sampling for the diagnosis of conventional endoscopic biopsy-negative gastric wall thickening.

Abnormal thickened lesions of the gastric wall are usually covered with normal mucosa. Conventional endoscopic biopsies often do not yield sufficient positive histological results for clinical treatment. To increase the rate of diagnosis of conventional endoscopic biopsy-negative gastric wall thickening, we used an endoscopic submucosal dissection (ESD)-like sampling method under endoscopic ultrasound (EUS) guidance to obtain tissue of gastric wall-thickening lesions. Between 2012 and 2016, patients with gastric wall thickening (as identified by computed tomography (CT), EUS or other imaging methods that showed no positive findings in repeating conventional endoscopic biopsy) underwent via mucosa incision EUS-guided sampling. Final diagnosis was determined after surgical or biopsy pathology. A total of 10 patients with gastric wall thickening were included in this study. Eight cases received definite results, whereas in two cases the biopsy results were ambiguous and in these two patients poorly differentiated adenocarcinoma was determined by postoperative pathology. The results of the cases presented in this study demonstrated that via mucosa incision EUS-guided sampling provided a complementary option for the diagnosis of conventional endoscopic biopsy-negative gastric wall thickening.

Effects of omeprazole in improving concurrent chemoradiotherapy efficacy in rectal cancer.

AIM: To explore the effects of omeprazole on chemoradiotherapy efficacy and tumor recurrence in rectal cancer. METHODS: The medical data of 125 rectal cancer patients who received the same neoadjuvant chemoradiotherapy (CRT) followed by surgery were retrospectively collected. Patients who received omeprazole (OME) orally at a dose of 20 mg at least once daily for six days and/or intravenously at 40 mg a day were recognized as eligible OME users (EOU). Otherwise, patients were regarded as non-eligible OME users (non-EOU). Moreover, a preferred OME dose cut-off of 200 mg on tumor recurrence was obtained by receiver operating characteristic (ROC) curves. Patients were divided into two groups: the effective OME group (EOG, OME ≥ 200 mg) and the non-effective OME group (non-EOG, OME < 200 mg). RESULTS: The good response rate of CRT efficacy (50.8%) in EOU was significantly increased compared with non-EOU (30.6%) (P = 0.02). The recurrence rate in the EOG was 10.3%, which was significantly lower compared with 31.3% in non-EOG (P = 0.025). The good response rate of CRT efficacy in EOG was 55.2%, which was obviously higher compared with 36.5% in non-EOG, with a significant difference (P = 0.072). Multivariate Cox analysis demonstrated that OME (non-EOG and EOG) was an independent and significant impact factor for DFS (P = 0.048, HR = 0.30, 95%CI: 0.09-0.99). CONCLUSION: When applied as an adjuvant drug in cancer treatment for relieving common side effects of chemotherapy, omeprazole has a synergetic effect in improving CRT efficacy and decreasing rectal cancer recurrence.

Phosphodiesterase-5 inhibition suppresses colonic inflammation-induced tumorigenesis via blocking the recruitment of MDSC.

Phosphodiesterase 5 (PDE-5) is a major isoform of cGMP phosphodiesterase in diverse tissues and plays a critical role in regulating intracellular cGMP concentrations. However, the distribution and expression of PDE-5 in colitis-related colon cancer was still unclear, not even the function and mechanism. Western blotting and ELISA were performed to detect colonic PDE-5 expression in AOM/DSS-induced tumorigenesis model. Sildenafil, a specific PDE-5 inhibitor, was used to treat AOM/DSS-induced and AOM-induced colonic tumorigenesis model and DSS-induced colitis model. The leukocyte infiltration in colonic tissue was examined by flow cytometry and immunofluorescence staining. Further matrigel-based invasion assay was employed to determine the effects of Sildenafil on myeloid-derived suppressor cell (MDSC) in vitro. We first demonstrated the upregulation of colonic PDE-5 expression and the prevention role of PDE-5 inhibition in AOM/DSS-induced tumorigenesis model. More importantly, PDE-5 inhibitor Sildenafil inhibited colonic tumorigenesis dependent on inflammation and suppressed DSS-induced colitis. Molecular mechanism investigation indicated that Sildenafil regulated inflammation microenvironment via directly inhibiting MDSC infiltration in colonic tissue. The study provides solid evidence for the use of PDE-5 inhibitor in preventing and treating colonic inflammation-related tumorigenesis.

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).

Application of Endobronchial Ultrasonography for the Preoperative Detecting Recurrent Laryngeal Nerve Lymph Node Metastasis of Esophageal Cancer.

BACKGROUND: The preoperative detection of recurrent laryngeal nerve lymph node (RLN LN) metastasis provides important information for the treatment of esophageal cancer. We investigated the possibility of applying endobronchial ultrasonography (EBUS) with conventional preoperative endoscopic ultrasonography (EUS) and computerized tomography (CT) examination to evaluate RLN LN metastasis in patients with esophageal cancer. METHODS: A total of 115 patients with advanced thoracic esophageal cancer underwent EBUS examinations. Patients also underwent EUS and CT imaging as reference diagnostic methods. Positron emission tomography /computed tomography (PET/CT) was also introduced in partial patients as reference method. The preoperative evaluation of RLN LN metastasis was compared with the surgical and pathological staging in 94 patients who underwent radical surgery. RESULTS: The sensitivities of the preoperative evaluations of RLN LN metastasis by EBUS, EUS and CT were 67.6%, 32.4% and 29.4%, respectively. The sensitivity of EBUS was significantly different from that of EUS or CT, especially in the detection of right RLN LNs. In addition, according to the extra data from reference method, PET/CT was not superior to EBUS or EUS in detecting RLN LN metastasis. Among all 115 patients, 21 patients who were diagnosed with tracheal invasions by EUS or EBUS avoided radical surgery. Another 94 patients who were diagnosed as negative for tracheobronchial tree invasion by EUS and EBUS had no positive findings in radical surgery. CONCLUSIONS: EBUS can enhance the preoperative sensitivity of the detection of RLN LN metastasis in cases of thoracic esophageal cancer and is a useful complementary examination to conventional preoperative EUS and CT, which can alert thoracic surgeons to the possibility of a greater range of preoperative lymph node dissection. EBUS may also indicate tracheal invasion in cases of esophageal stricture.

Methyl-methanesulfonate sensitivity 19 expression is associated with metastasis and chemoradiotherapy response in esophageal cancer.

AIM: To investigate the clinical significance of methyl-methanesulfonate sensitivity 19 (MMS19) expression in esophageal squamous cell carcinoma (ESCC). METHODS: Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls. MMS19 protein expression was measured by immunohistochemistry. Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin. Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed. RESULTS: The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens. High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclear expression of MMS19 was found in 35.0%. High cytoplasmic MMS19 expression was associated with regional lymph node metastases (OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases (OR = 13.1, 95%CI: 1.7-103.0; P = 0.002). Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy (OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively. Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC. CONCLUSION: The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC.