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The treatment of choice for leiomyoma, the most common benign esophageal tumor, is thoracoscopic enucleation. One of the most difficult aspects of thoracoscopic enucleation is the precise localization of small tumors (=1.5 cm) and tumors without external protrusion. No simple, feasible solutions to this problem are available. We developed a novel methylene blue staining technique to localize small esophageal leiomyomas and evaluated the feasibility of our technique. Between January 2013 and July 2014, eight patients with small esophageal leiomyomas (=1.5 cm) underwent thoracoscopic enucleation in Tongji Hospital. Preoperative endoscopic ultrasonography was performed in all patients. The leiomyomas were located in the middle (n = 5) and lower (n = 3) thirds of the esophagus. We preoperatively injected 0.5-1.0mLmethylene blue in the submucosa adjacent to the tumors under standard gastroscope guidance. The entire staining process took about 10 minutes. Staining was successful in all patients. The unstained tumor was exposed after the blue-stained mediastinal pleura, and overlying muscle were incised longitudinally. All procedures were successfully completed without conversion to open surgery. No abnormalities were detected in the esophageal mucosa. The median operating time was 60minutes (range, 40-90 minutes). Postoperative histopathology confirmed leiomyoma in all patients. The median postoperative hospital stay was 6 days (range, 5-7 days). No major complications, such as esophageal leakage or esophageal diverticulum, occurred. Endoscopic methylene blue staining is safe and feasible for localizing small esophageal leiomyomas during thoracoscopic enucleation. This method will enable precise and easy enucleation. [ABSTRACT FROM AUTHOR]

The effectiveness of neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) for esophageal cancer patients is well established. However, neoadjuvant therapy may induce severe adverse effects that could increase postoperative morbidity. The current study evaluated the impacts of nCT and nCRT on postoperative cardiopulmonary complications in patient with esophageal cancer. We conducted a prospective study in esophageal cancer patients who received nCT (n = 126) or nCRT (n = 141) prior to surgery. Surgery was performed in all these patients following nCT or nCRT treatment. More patients occurred pneumonia in the nCRT-treated group compared with the nCT group (P < 0.01). The E-velocity (early diastolic filling velocity) decreased significantly (P = 0.026), while the N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly increased (P < 0.01) in patients of the nCRT group compared with patients from the nCT group. Furthermore, a multivariate analysis revealed that nCRT was correlated with the incidence of pneumonia and NT-proBNP level significantly. The nCRT caused more cardiopulmonary toxicity than nCT. The strategies are needed to prevent the postoperative cardiopulmonary complications especially in patients with nCRT treatment. [ABSTRACT FROM AUTHOR]

The treatment of choice for leiomyoma, the most common benign esophageal tumor, is thoracoscopic enucleation. One of the most difficult aspects of thoracoscopic enucleation is the precise localization of small tumors (≤1.5 cm) and tumors without external protrusion. No simple, feasible solutions to this problem are available. We developed a novel methylene blue staining technique to localize small esophageal leiomyomas and evaluated the feasibility of our technique. Between January 2013 and July 2014, eight patients with small esophageal leiomyomas (≤1.5 cm) underwent thoracoscopic enucleation in Tongji Hospital. Preoperative endoscopic ultrasonography was performed in all patients. The leiomyomas were located in the middle ( n = 5) and lower ( n = 3) thirds of the esophagus. We preoperatively injected 0.5-1.0 mL methylene blue in the submucosa adjacent to the tumors under standard gastroscope guidance. The entire staining process took about 10 minutes. Staining was successful in all patients. The unstained tumor was exposed after the blue-stained mediastinal pleura, and overlying muscle were incised longitudinally. All procedures were successfully completed without conversion to open surgery. No abnormalities were detected in the esophageal mucosa. The median operating time was 60 minutes (range, 40-90 minutes). Postoperative histopathology confirmed leiomyoma in all patients. The median postoperative hospital stay was 6 days (range, 5-7 days). No major complications, such as esophageal leakage or esophageal diverticulum, occurred. Endoscopic methylene blue staining is safe and feasible for localizing small esophageal leiomyomas during thoracoscopic enucleation. This method will enable precise and easy enucleation. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is a common malignant cancer threatening people's health. There are no universally accepted parameters for its early diagnosis. The aim of this study was to observe the expression of human leukocyte antigen class I (HLA-I) on peripheral blood mononuclear cells (PBMCs) of EC patients and in individuals of high-incidence area of EC so as to evaluate the feasibility of using this parameter as a potential non-invasive biomarker for the early diagnosis of EC. The present study enrolled 58 pathological confirmed EC patients, 46 patients with benign esophageal disease, and 65 healthy volunteers. Expression levels of HLA-I protein and mRNA on PBMCs were determined by flow cytometry and quantitative reverse transcriptase polymerase chain reaction, respectively. Then, 181 volunteers from Lijiadian, a village with high morbidity of EC, and 153 age- and gender-matched health volunteers were involved in this study to observe HLA-I expressions in individuals of high-incidence area of EC. Compared with benign esophageal disease and health volunteers, the expressions of HLA-I protein and mRNA on PBMCs of EC patients are significantly decreased, especially in patients with stage III and IV EC, but was not influenced by patient's age and gender. Furthermore, individuals of high-incidence area of EC also show downregulated HLA-I protein, but not mRNA, expression on PBMCs. Altogether, HLA-I expression on PBMCs of EC patients and individuals from high-incidence area of EC is downregulated, and this parameter might be used as a potential predictor of EC. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the accuracy of preoperative ultrasonography ( US) in depicting the structure of esophageal atresia with distal fistula ( EA-DF) and to determine its role in planning the surgical strategy by digitally measuring the interpouch distance ( ID). Thirty-six neonates (20 males and 16 females) born with EA-DF were included in this study. After obtaining chest radiographs of the neonates with a coiled nasogastric tube in the upper esophageal pouch, longitudinal esophageal high-frequency US was performed. The esophageal structures were displayed, and the IDs measured on US images were compared with the surgical findings. With the use of US, the structure of EA-DF was accurately depicted, and the ID detected by US correlated well with the surgical findings. Statistical analysis demonstrated no significant difference in the ID as assessed by US and surgery ( R = 0.99, P < 0.001).). US findings were crucial for planning the surgical strategy in 9 (25.0%) patients. Preoperative US could provide more accurate information on the structure of EA-DF and play a crucial role in planning the surgical strategy. [ABSTRACT FROM AUTHOR]

This study looks at toxicity and survival data when chemoradiation ( CRT) is delivered using intensity-modulated radiation therapy ( IMRT) after induction chemotherapy. Forty-one patients with esophageal adenocarcinoma treated with IMRT from March 2007 to May 2009 at Memorial Sloan- Kettering Cancer Center were analyzed. All patients received induction chemotherapy prior to CRT. Thirty-nine percent ( n = 16) of patients underwent surgical resection less than 4 months after completing CRT. Patients were predominantly male (78%), with a median age of 68 years (range 32-85 years). The majority of acute treatment-related toxicity was hematologic or gastrointestinal, with 17% of patients having grade 3+ hematologic toxicity and 12% of patients having grade 3+ gastrointestinal toxicity. Only two patients developed grade 2-3 pneumonitis (5%) and 5 patients experienced post-operative pulmonary complications (29%). Eight patients (20%) required a treatment break. With a median follow up of 41 months for surviving patients, 2-year overall survival was 61%, and the cumulative incidences of local failure ( LF) and distant metastases were 40% and 51%, respectively. This rate of LF was reduced to 13% in patients who underwent surgical resection. Surgery and younger age were significant predictors of decreased time to LF on univariate analysis. Induction chemotherapy followed by CRT using IMRT in the treatment of esophageal cancer is well tolerated and is not associated with an elevated risk of postoperative pulmonary complications. The use of IMRT may allow for integration of more intensified systemic therapy or radiation dose escalation for esophageal adenocarcinoma, ultimately improving outcomes for patients with this aggressive disease. [ABSTRACT FROM AUTHOR]

Interferon ( IFN)-β has efficient antitumor effect both in vitro and in vivo, but its clinical implication is limited by short half-life and systemic toxicities. Gene therapy could be the choice to avoid the defects. Adenovirus vector containing human IFN-β gene was transfected into esophageal squamous cell carcinoma KYSE150 cells. Expression of human (h) IFN-β was detected by reverse transcription polymerase chain reaction and immunocytochemistry in KYSE150 cells. Cell growth and clonogenic assays, and flow cytometry were used to observe the antiproliferation effect and apoptosis on tumor cells, respectively. Reverse transcription polymerase chain reaction and immunocytochemistry showed obvious h IFN-β expression in KYSE150 cells after transfection and the tumor cell proliferation was obviously inhibited through cell proliferation and clonogenic assays. Flow cytometry analysis showed 27.3% cell apoptosis in adenovirus vector containing human IFN-β gene transfection group compared with 1.12% in empty vector control group. These findings indicate that h IFN-β gene mediated by recombinant adenovirus may have antitumor activity against human esophageal carcinoma cell by inducing apoptosis in vitro. [ABSTRACT FROM AUTHOR]

The mammalian cyclin-dependent kinase subunit ( Cks) family has two members, Cks1 and Cks2. Overexpression of Cks1 and Cks2 has been reported to be associated with high aggressiveness and poor prognosis in several malignancies, including prostate and hepatocellular carcinomas. However, whether Cks1 and Cks2 are overexpressed in esophageal carcinoma remains uncharacterized. To investigate whether overexpression of the Cks family is clinically relevant in esophageal carcinoma, and whether expression patterns of Cks1 and Cks2 can serve as biomarkers for esophageal carcinoma. Real-time quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot analyses were applied to detect the expression of Cks1 and Cks2 at the mRNA and protein levels, respectively. The associations between Cks1 or Cks2 expressions and clinical features and p27kip1 expressions in esophageal carcinoma were analyzed. Comparing with the adjacent noncancerous tissues, esophageal carcinoma exhibited elevated expression of Cks1 in 58% cases at the mRNA level and 54% cases at the protein level, and elevated expression of Cks2 in 65% cases at the mRNA level and 61% cases at the protein level, respectively. The expressions of both Cks1 and Cks2 were negatively associated with the p27kip1 protein level in the tumor tissues. Furthermore, overexpression of Cks1 and Cks2 in esophageal carcinoma was closely associated with poor pathological features of esophageal carcinoma, including higher histologic grade of tumor, regional lymph nodes invasion, and neoplastic embolus. Overexpression of Cks1 and Cks2 is associated with the aggressive tumor behaviors of esophageal carcinoma. Further efforts are needed to determine whether overexpression of Cks1 and Cks2 can serve as novel biomarkers for esophageal carcinoma. [ABSTRACT FROM AUTHOR]

SUMMARY Circulating tumor cells (CTCs) have been associated with clinical outcome in various malignancies. The aim of this study was to examine CTC status in the peripheral blood of patients with esophageal squamous cell carcinoma (ESCC) before and after radiotherapy, and to evaluate its clinical significance. A total of 72 ESCC patients treated with radical radiotherapy were enrolled in this study. The nested reverse-transcriptase polymerase chain reaction was used to detect the three representative markers of CTCs, namely carcinoembryonic antigen, cytokeratin 19, and survivin. The results showed that CTC(+), a status with positive expression of at least one of these three markers, in patients with ESCC pre- and post-radiotherapy were 54.2% (39/72) and 38.9% (28/72), respectively ( P= 0.059). Furthermore, CTC (+) in patients pre- or post-radiotherapy was both correlated with lymph metastasis and adverse 2-year progression-free survival. It was also found that changes in CTC status after radiotherapy could reflect patients' response to radiotherapy. The response rates in cases with CTC status pre-radiotherapy(+)/post-radiotherapy(+), pre-radiotherapy(−)/post-radiotherapy(+), pre-radiotherapy(−)/post-radiotherapy(−), pre-radiotherapy(+)/post-radiotherapy(−) were 58.3% (21/36), 0% (0/3), 73.7% (14/19), and 85.7% (12/14), respectively. In a multivariate analysis of Cox proportional hazard model, only CTC (+) post-radiotherapy was an independent unfavorable prognostic factor for ESCC apart from subsequent chemotherapy and patients' Karnofsky performance status scores. In conclusion, positive detection of CTCs in patients with ESCC after radiotherapy may be a promising biomarker for radiation efficiency and prognosis assessment in ESCC. [ABSTRACT FROM AUTHOR]

The optimized concurrent chemoradiotherapy has not been established for patients with advanced esophageal squamous cell carcinoma (SCC). The aim of the present study was to evaluate the safety and efficacy of concurrent chemotherapy and selective lymph node (SLN) late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) for the patients with thoracic SC C. Twelve patients with T3-4N0-1M0-1a thoracic esophageal SCC were included. The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks. The concurrent chemotherapy protocol was as following: cisplatin 10 mg/m on days 1-5 and 22-26, pemetrexed in escalating doses, from the base level of 500 mg/m once every 21 days. The primary objectives were to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLTs). Secondary end point included determination of preliminary radiographic response rates. As a result, three patients were enrolled in dose level 1 with pemetrexed 500 mg/m and nine patients in dose level 0 with 400 mg/m, respectively. At dose level 1, DLTs occurred in two of three patients. However, only two of nine patients in Level 0 developed DLTs. The complete response and partial response were observed in eight and four patients, respectively. Furthermore, no patient experienced cancer progression with a median follow-up of 9 months. In conclusion, the concurrent SLN LCAF IMRT and chemotherapy is feasible. The MTD of pemetrexed in this regimen was 500 mg/m and RD was 400 mg/m. Although toxicities were common, the protocol was safe, well tolerated, and achieved an encouraging outcome. [ABSTRACT FROM AUTHOR]

Forkhead box protein 3 (FOXP3) has been studyed as a biomarker in many human malignancies recently. But in esophageal squamous cell carcinoma (ESCC) the studies are limited. In this study, expression of FOXP3 in ESCC tissue was evaluated in relation to the clinical data. Detection of FOXP3 mRNA was made by using quantitative real-time PCR while protein expression was assessed by immunocytochemistry (n = 112). The results were correlated to the clinical data including age, gender, carcinoma size, carcinoma differentiation, lymphatic invasion and pathological stage. A significantly higher FOXP3 expression in tumors was confirmed than in normal-appearing mucosa. The FOXP3 mRNA and protein expressions were higher in advanced stages (stage II B and III) than in early stages (stage I and stage II A). A significantly higher FOXP3 expression in tumors with lymph node metastasis was also confirmed than in those without lymph node metastasis. No significant correlation was found in age, gender, carcinoma size, or carcinoma differentiation. These results suggest that expression of FOXP3 was higher in ESCC tissue and was closely correlated to lymphatic invasion and pathological stage. It may imply that FOXP3 might play an important role in esophageal carcinoma progression. [ABSTRACT FROM AUTHOR]