Shared genetic basis and causality between schizophrenia and inflammatory bowel disease: evidence from a comprehensive genetic analysis.

BACKGROUND: The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders. RESULTS: SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07­1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06­1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04­1.18, p = 1.84 × 10−3). CONCLUSIONS: We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

The utility of EBUS-TBNA in the diagnosis of suspected intrathoracic recurrence after esophageal cancer surgery.

OBJECTIVES: Postoperative recurrences, especially anastomotic recurrence and regional lymph node recurrence were common in patients even with curative esophageal cancer surgery. Endobronchial ultrasound-guided transbronchial needle aspiration is an alternative to mediastinoscopy in patients with lung cancer and mediastinal lymphadenopathy. The aim of our study is to evaluate the utility of endobronchial ultrasound-guided transbronchial needle aspiration in postoperative patients suffered from esophageal malignancy. METHODS: All endobronchial ultrasound-guided transbronchial needle aspiration cases performed between August 2015 and December 2018 in our center were all retrospective reviewed. The patients with enlarged mediastinal lymph node and/or unknown intrathoracic mass after esophageal cancer surgery were enrolled. Final diagnoses were determined by the result of endobronchial ultrasound-guided transbronchial needle aspiration, second surgery and/or clinical follow-up for at least 6 months. RESULTS: Overall 29 patients were included in the analysis with 30 lesions sampled. No endobronchial ultrasound-guided transbronchial needle aspiration related complications were observed. In total, 22 of these (73.3%) had a diagnosis of tumor recurrence, whereas eight (26.7%) had a different diagnosis: two (6.7%) had a second primary malignancy and three (10.0%) had non-neoplastic diagnosis. Cases were false-negative in 3 (10.0%) out of 30 lesions. The overall sensitivity, negative predicted value and diagnostic accuracy were 88.9, 50.0 and 90.0%, respectively. CONCLUSIONS: Given its safety, low invasiveness, high sensitivity and diagnostic accuracy, endobronchial ultrasound-guided transbronchial needle aspiration could be considered for mediastinal lymphadenopathy and intrathoracic masses of unknown origin in patients after radical esophageal cancer resection, and its strategic role in the management of these patients was confirmed.

Efficacy of Endoscopic Ultrasonography for Determining Clinical T Category for Esophageal Squamous Cell Carcinoma: Data From 1434 Surgical Cases.

BACKGROUND: The efficacy of endoscopic ultrasonography (EUS) for determining T category is variable for esophageal squamous cell carcinoma (ESCC). We aimed to assess the efficacy of EUS in accurately identifying T category for ESCC based on the 8th AJCC Cancer Staging Manual. METHODS: A retrospective analysis was conducted using a prospectively collected ESCC database from January 2003 to December 2015, in which all patients underwent EUS examination followed by esophagectomy. The efficacy of EUS was evaluated by sensitivity, specificity, and accuracy compared with pathological T category as gold standard. Overall survival of different EUS-T (uT) categories was assessed. RESULTS: In total, 1434 patients were included, of whom 58.2% were correctly classified by EUS, with 17.9% being overstaged and 23.9% being understaged. The sensitivity and accuracy of EUS for Tis, T1a, T1b, T2, T3, and T4a categories were 15.8 and 98.8%, 16.3 and 95.7%, 33.1 and 89.3%, 56.8 and 65.0%, 65.8 and 70.0%, and 27.3 and 97.5%, respectively. The survival difference between uT1a and uT1b was not statistically significant (p = 0.90), nor was that between uT4a and uT4b (p = 0.34). However, when uT category was integrated as uTis, uT1, uT2, uT3, and uT4, overall survival was clearly distinguished between the categories (p < 0.01). CONCLUSIONS: EUS is in general feasible for classifying clinical T category for ESCC. However, EUS should be used with caution for discriminating between Tis, T1a, and T1b disease, as well as T4 disease.

Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma.

We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2) gemcitabine on Days 1 and 8 and 20 mg/m(2) cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2) DDP and 500 mg/m(2) 5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC-RT group were significantly higher than those observed in the Con-RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3-year OS, DFS and MFS rates between the Con-RT and the sPF-RT groups. The GC-RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC-RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.

[Effects of arbuscular mycorrhizal fungi inoculation on non-structural carbohydrate contents and C:N:P stoichiometry of Heptacodium miconioides under drought stress]. / å¹²æ—±èƒè¿«ä¸‹æŽ¥ç§ä¸›æžèŒæ ¹çœŸèŒå¯¹ä¸ƒå­èŠ±éžç»“æž„æ€§ç¢³æ°´åŒ–åˆç‰©ç§¯ç´¯åŠC、N、P化学计量特征的影响.

A pot experiment was conducted to investigate the effects of drought stress and arbuscular mycorrhizal fungi (AMF) inoculation on C:N:P stoichiometry and non-structural carbohydrate (NSC) contents in two-year-old Heptacodium miconioides seedlings. There were four treatments, including control (CK), drought stress (D), AMF inoculation (AMF), and combined drought stress and AMF inoculation (D+AMF). The results showed that drought stress significantly reduced AMF colonization rate, whereas plant height and leaf number of inoculated treatment were significantly higher than the non-inoculated treatment. Inoculation with AMF significantly increased soluble sugar and NSC content in root and leaf, as well as starch content in stem and leaf. The inoculation significantly decreased the stem and leaf soluble sugar to starch ratio under drought stress. Drought stress caused a significant increase in C content in roots and leaves, and a significant decrease in P content in stems. Compared with no inoculation drought stress, P content in roots, stems, leaves, and C content in leaves of mycorrhizal seedlings were significantly increased by inoculation under drought stress, whereas root C and N content and stem C content were significantly reduced. Under drought stress, AMF inoculation significantly decreased C:N, C:P, and N:P ratios in roots and stems, and N:P ratios in leaves of H. miconioides. P content in roots and leaves were significantly positively correlated with soluble sugar and NSC content. Stem P content was significantly positively correlated with starch and NSC content. N:P ratios in each organ was significantly negatively correlated with NSC content. In all, inoculation with AMF can improve the drought tolerance of H. miconioides seedling by increasing soluble sugar content in roots and leaves and the soluble sugar/starch ratio in roots, improving starch content in above-ground organs, promoting the P absorption, and reducing N:P ratios in each organ. Therefore, AMF colonization could improve the survival rate of H. miconioides seedling in dry environments.

Study of preoperative diagnostic modalities in Chinese patients with superficial esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic ultrasonography (EUS) and magnifying endoscopy (ME) reliably determine indications for endoscopic resection in patients with superficial esophageal squamous cell carcinoma (SESCC). ME is widely accepted for predicting the invasion depth of superficial esophageal cancer with satisfying accuracy. However, the addition of EUS is controversial. AIM: To evaluate the diagnostic efficiency of ME vs EUS for invasion depth prediction and investigate the influencing factors in patients with SESCC to determine the best diagnostic model in China. METHODS: We retrospectively analyzed patients with suspected SESCC who completed both ME and EUS and then underwent endoscopic or surgical resection at Sun Yat-Sen University Cancer Center between January 2018 and December 2021. We evaluated and compared the diagnostic efficiency of EUS and ME according to histological results, and investigated the influencing factors. RESULTS: We included 152 lesions from 144 patients in this study. The diagnostic accuracies of ME and EUS in differentiating invasion depth were not significantly different (73.0% and 66.4%, P = 0.24); both demonstrated moderate consistency with the pathological results (ME: kappa = 0.58, 95% confidence interval [CI]: 0.48-0.68, P < 0.01; EUS: kappa = 0.46, 95%CI: 0.34-0.57, P < 0.01). ME was significantly more accurate in the diagnosis of high-grade intraepithelial (HGIN) or carcinoma in situ (odds ratio [OR] = 3.62, 95%CI: 1.43-9.16, P = 0.007) subgroups. Using a miniature probe rather than conventional EUS can improve the accuracy of lesion depth determination (82.3% vs 49.3%, P < 0.01). Less than a quarter of circumferential occupation and application of a miniature probe were independent risk factors for the accuracy of tumor invasion depth as assessed by EUS (< 1/4 circumferential occupation: OR = 3.07, 95%CI: 1.04-9.10; application of a miniature probe: OR = 5.28, 95%CI: 2.41-11.59, P < 0.01). Of the 41 lesions (41/152, 27.0%) that were misdiagnosed by ME, 24 were corrected by EUS (24/41, 58.5%). CONCLUSION: Preoperative diagnosis of SESCC should be conducted endoscopically using white light and magnification. In China, EUS can be added after obtaining patient consent. Use of a high-frequency miniature probe or miniature probe combined with conventional EUS is preferable.

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.

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.

Complications of high intensity focused ultrasound in patients with recurrent and metastatic abdominal tumors.

AIM: To analyze the local and systemic complications of high intensity focused ultrasound (HIFU) for patients with recurrent and metastatic abdominal tumors. METHODS: From Aug 2001 to Aug 2004, 17 patients with recurrent and metastatic abdominal tumors were enrolled in this study. Real-time sonography was taken, and vital signs, liver and kidney function, skin burns, local reactions, and systemic effects were observed and recorded before, during, and after HIFU. CT and MRI were also taken before and after HIFU. RESULTS: All 17 patients had skin burns and pain in the treatment region; the next common complication was neurapraxia of the stomach and intestines to variable degrees. The other local and systemic complications were relatively rare. Severe complications were present in two patients; one developed a superior mesenteric artery infarction resulting in necrosis of the entire small intestines, and the other one suffered from a perforation in terminal ileum due to HIFU treatment. CONCLUSION: Although HIFU is a one of noninvasive treatments for the recurrent and metastatic abdominal tumors, there are still some common and severe complications which need serious consideration.

Relationship Between PD-L1 Expression and CD8+ T-cell Immune Responses in Hepatocellular Carcinoma.

As PD-1/PD-L1 immune checkpoint inhibitors exhibited promising clinical outcomes in various types of solid tumors, PD-1/PD-L1 blockades have been explored for the treatment of hepatocellular carcinoma (HCC). However, the association of PD-L1 with antitumor immunoregulation is not clearly defined in HCC. Here, we evaluated the characteristics of PD-L1 expression, CD8 T-cell infiltration and their relationship in HCC. A total of 411 resected tumor specimens from HCC patients were immunostained for PD-L1 and CD8. Only 78 (19%) cases showed ≥5% membranous PD-L1 expression on tumor cells, although a significantly positive correlation was found between PD-L1 expression and CD8 T-cell densities. Moreover, patients with higher tumor PD-L1 expression also showed a higher hepatitis B virus load, which was also related to increased CD8 infiltration. Survival analysis suggested that both tumor and stroma PD-L1 status did not significantly affect overall survival or recurrence-free survival in patients. Although high CD8 T-cell density was overall associated with better overall survival and recurrence-free survival, its favorable prognostic value was eliminated by high tumor PD-L1 expression. Further flow cytometric and enzyme-linked immunosorbent assay (ELISA) results from the coculture of HCC cell lines with specific CD8 cytotoxic T lymphocytes (CTLs) demonstrated that CD8 CTLs remarkably upregulated PD-L1 expression on tumor cell lines by HLA class-I specificity, and the overexpression of tumor PD-L1 impaired interferon-γ secretion by CD8 CTLs in a negative feedback regulation mechanism. In conclusion, our findings reveal an interaction between PD-L1 expression and CD8 T-cell immunity in HCC, although PD-L1 is not a prognostic factor for the patients.

Concurrent chemoradiotherapy combined with enteral nutrition support: a radical treatment strategy for esophageal squamous cell carcinoma patients with malignant fistulae.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) significantly increases the survival rate of esophageal squamous cell carcinoma (ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long-term survival. METHODS: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat-sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were retrospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening (NRS) before, during, and after treatment. Twenty-two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT. RESULTS: With a median follow-up of 18 months (range, 3-39 months), patients' 1-year overall survival (OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score (P = 0.003), increase in NRS score (P = 0.024), fistula closure (P = 0.011), and response to treatment (P < 0.001) were significantly associated with OS. Multivariate analysis showed that tumor response (P = 0.044) and increase in NRS score (P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients (20.0%), grade 3 neutropenia was observed in 11 patients (27.5%), and grade 3 cough was observed in 13 patients (32.5%); 2 patients (5.0%) died of massive bleeding during treatment. CONCLUSIONS: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T-category ESCC who undergo CCRT.

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).

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.

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.

Analysis of clinical effect of high-intensity focused ultrasound on liver cancer.

AIM: To evaluate the clinical effect of high-intensity focused ultrasound (HIFU) in the treatment of patients with liver cancer. METHODS: HIFU treatment was performed in 100 patients with liver cancer under general anesthesia and by a targeted ultrasound. Evaluation of efficacy was made on the basis of clinical symptoms, liver function tests, AFP, MRI or CT before and after the treatment. RESULTS: After HIFU treatment, clinical symptoms were relieved in 86.6%(71/82) of patients. The ascites disappeared in 6 patients. ALT (95+/-44) U/L and AST (114+/-58) U/L before HIFU treatment were reduced to normal in 83.3%(30/36) and 72.9%(35/48) patients, respectively, after the treatment. AFP was lowered by more than 50% in 65.3%(32/49) patients. After HIFU treatment, MRI or CT findings indicated coagulation necrosis and blood supply reduction or disappearance of tumor in the target region. CONCLUSION: HIFU can efficiently treat the patients with liver cancer. It will offer a significant noninvasive therapy for local treatment of liver tumor.

[High intensity focused ultrasound for liver cancer].

OBJECTIVE: To evaluate the effect of high intensity focused ultrasound (HIFU) for liver cancer. METHODS: HIFU treatment was performed in 44 liver cancer patients under general anesthesia and ultrasound positioning. Before and after HIFU treatment, the clinical symptoms, liver functional tests, AFP and MRI were evaluated. RESULTS: After HIFU treatment, the remission rate of clinical symptoms was 87.5% (28/32), with the scanty ascites in 3 patients disappeared. ALT (79.73 +/- 12.31 U/L) and AST (103.47 +/- 24.55 U/L) before HIFU were reduced to normal in 84.6% (22/26) and 73.5% (25/34) patients. AFP in 64.3% (18/28) patients decreased > or = 50% of the original value. After HIFU, MRI showed coagulative necrosis and blood supply reduction or disappearance of tumor in the target region. CONCLUSION: HIFU treatment pocesses good effect on liver cancer, which will offer a considerable weight in noninvasive local treatment of hepatic tumor.

Extraesophageal saline during endoscopic submucosal dissection in a patient with early esophageal squamous cell carcinoma.

Saline submucosal injection (SSI) is an indispensable procedure before endoscopic submucosal dissection (ESD) in patients with early esophageal squamous cell carcinoma. Successful SSI should create a saline cushion in the submucosa rather than elsewhere. However, saline outside the esophagus was detected incidentally by endoscopic ultrasonography during ESD in a patient with early esophageal cancer. In this case, saline separated the esophageal adventitia from adjacent tissues, and there were no complications during or after ESD. This finding indicates that it is possible to use interventional extraesophageal saline injection to help differentiate advanced esophageal cancer of Stage T3 from Stage T4 by endoscopic ultrasonography.

Extraesophageal saline enhances endoscopic ultrasonography to differentiate esophagus and adjacent organs.

AIM: To distinguish between the esophagus and adjacent organs using extraesophageal saline injection (ESI) in a canine model. METHODS: ESI was performed through the esophagus under the guidance of linear-array endoscopic ultrasonography (EUS). Approximately 15 mL of methylene blue saline (0.5%) was then injected through each of the extraesophageal puncture points using a 22 G needle. Radial EUS examinations were conducted before and after ESI. EUS images of the trachea, tracheal bifurcation, arcus aortae and thoracic aorta were recorded. Vital signs were monitored during the ESI procedure and EUS examination. The dogs were then sacrificed for exploratory thoracotomy. RESULTS: No obvious fluctuation in vital signs or serious adverse events occurred during the ESI procedure. On EUS imaging, an apparent hypoechoic area outside the esophagus, which separated the esophagus and adjacent organs, was visualized. The adventitious of the esophagus and adjacent organs were easily distinguished. The findings of subsequent exploratory thoracotomy confirmed the EUS findings: obvious accumulation of a blue liquid in the extraesophageal tissues, as well as in the esophageal-thoracic aorta space, esophageal-arcus aortae space and esophageal-tracheal space. CONCLUSION: The esophagus and adjacent organs were successfully separated by ESI, and extraesophageal saline acted as an effective ultrasonic contrast agent.