Chi-Ju Yeh

High expression of phosphorylated 4E-binding protein 1 is an adverse prognostic factor in esophageal squamous cell carcinoma

Cell signaling pathways play important roles in oncogenesis. Among a large number of signaling regulators in different pathways, 4E-binding protein 1 (4E-BP1) was found to be a key factor, which converges several oncogenic signals, phosphorylates the molecules, and drives the downstream proliferative signals. Recent studies showed that high expression of phosphorylated 4E-BP-1 (p-4E-BP1) is associated with poor prognosis, tumor progression, or nodal metastasis in different human cancers, but its prognostic significance in esophageal cancer remains undefined. In this study, we investigated the expression levels of p-4E-BP1 with two different phosphorylation sites Thr37/46 and Thr70 by immunohistochemistry and their prognostic significance in 78 cases of surgically resected esophageal squamous cell carcinoma (SCC) for the first time. We found no correlation of p-4E-BP1 expression with age, gender, preoperative concurrent chemoradiotherapy, tumor grade, pT classification, pN, pM, or pStage. Multivariate Cox regression analysis showed that high expression of p-4E-BP-1 Thr37/46 was an independent adverse prognostic factor, with a hazard ratio of 1.73 (95% confidence interval = 1.03–2.90) and a p value of 0.038. Stratifying the patients with other prognostic factors, we found that the effect of p-4E-BP1 Thr37/46 on survival was significant only in patients with relatively early stage disease (pT1/pT2, pN0, or pStage I/II; p = 0.0047, 0.012, and 0.011, respectively). Our data suggest that assessment of p-4E-BP1 expression could identify a subpopulation of earlier stage esophageal SCC patients with poor prognosis. These patients could be possible candidates for future studies on more aggressive treatment or target therapy.

Vascular endothelial growth factors and angiopoietins in presentations and prognosis of papillary thyroid carcinoma.

Angiogenesis from thyroid cancer cell plays the important roles in post‐surgical persistent, recurrent, and metastatic papillary thyroid cancer (PTC). This study is to investigate the expression of angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2), Tek/Tie‐2 receptor, and vascular endothelial growth factors (VEGF) in normal, benign thyroid tissues and different stage of PTC. We expect angiogenetic factors are important in the presentation of local‐regional neck or distant metastases in PTC.

Prognostic significance of high podoplanin expression after chemoradiotherapy in esophageal squamous cell carcinoma patients.

The correlation between high tumor podoplanin (PP) immunoreactivity and poor outcome in patients with non‐chemoradiotherapy(CRT) pretreated upper aerodigestive tract squamous cell carcinoma (SCC) has been reported recently. Little is known about the implication of PP expression after CRT. Therefore, we conducted this study.

High phosphorylated 4E-binding protein 1 expression after chemoradiotherapy is a predictor for locoregional recurrence and worse survival in esophageal squamous cell carcinoma patients.

As a well‐known pivotal factor of 4E‐binding protein 1 (4E‐BP1) in controlling cancer proliferation, high expression of its phosphorylated form (p‐4E‐BP1) has been reported to be associated with poor outcome in various human cancers without pretreated with chemoradiotherapy (CRT). However, no data is available regarding the implication of p‐4E‐BP1 expression after CRT. Therefore, we conducted this study.

Recurrence Risk Factors Analysis for Stage I Non-small Cell Lung Cancer.

AbstractLung cancer is the leading cause of cancer-related death worldwide. Even early-stage patients might encounter disease recurrence with relative high risk. Effective postoperative therapy is based on an accurate assessment of treatment failure after surgery. The aim of this study is to construct a disease-free survival (DFS) prediction model and stratify patients into different risk score groups.A total of 356 pathological stage I patients (7th American Joint Committee on Cancer) who underwent lung resection from January 2005 through June 2011 were retrospectively reviewed. Of these patients, 63 patients were eliminated for this study. A total of 293 p-stage I patients were included for further univariate and multivariate analysis. Clinical, surgical, and pathological factors associated with high risk of recurrence were analyzed, including age, gender, smoking status, additional primary malignancy (APM), operation method, histology, visceral pleural invasion, angiolymphatic invasion, tumor necrosis, and tumor size.Of the 293 p-stage I non-small cell lung cancer (NSCLC) patients examined, 143 were female and 150 were male, with a mean age of 62.8-years old (range: 25–83-years old). The 5-year DFS and overall survival rates after surgery were 58.9% and 75.3%, respectively. On multivariate analysis, current smoker (hazards ratio [HR]: 1.63), APM (HR: 1.86), tumor size (HR: 1.54, 2.03), nonanatomic resections (HR: 1.81), adenocarcinoma histology (HR: 2.07), visceral pleural invasion (HR: 1.54), and angiolymphatic invasion (HR: 1.53) were found to be associated with a higher risk of tumor recurrence. The final model showed a fair discrimination ability (C-statistic = 0.68). According to the difference risk group, we found patients with intermediate or higher risk group had a higher distal relapse tendency as compared with low risk group (P = 0.016, odds ratio: 3.31, 95% confidence interval: 1.21–9.03).Greater than 30% of disease recurrences occurred after surgery for stage I NSCLC patients. That is why we try to establish an effective DFS predicting model based on clinical, pathological, and surgical covariates. However, our initial results still need to be validated and refined into greater population for better application in clinical use.

Feasibility of transumbilical surgical lung biopsy and pericardial window creation.

Background. To date there are no practical platforms for performing natural orifice transluminal endoscopic surgery in the thoracic cavity. This study evaluates the feasibility of transumbilical thoracosopy for lung biopsy and pericardial window creation. Methods. Eleven dogs (6 in the nonsurvival group and 5 in the survival group) were used for this study. A homemade metallic tube was advanced into the abdominal cavity via a 12-mm umbilical incision. The metallic tube was advanced into the thoracic cavity through a subxyphoid diaphragmatic incision under video guidance. Access to the thoracic cavity was achieved by a flexible bronchoscope via the metallic tube. Surgical lung biopsy and pericardial window creation were performed using an electrocautery loop and needle knife. The animals were euthanized 20 minutes after the surgery was complete (nonsurvival group) or 14 days postsurgery (survival group) for necropsy evaluation. Results. Eight pericardial window creations and 21 of 22 preplanned lung biopsies were completed in a median time of 72.18 minutes (range 50-105 minutes). One dog in the nonsurvival group died after tension pneumothorax due to postprocedure massive air leaks. In the survival group, the postoperative period was uneventful in all 5 dogs. Autopsies revealed no signs of vital organ injury and complete healing of the diaphragmatic incision occurred in all animals. Conclusions. The study demonstrated that transumbilical thoracoscopic surgical lung biopsy and pericardial window creation is feasible. The safety and efficacy of the transumbilical approach need to be verified by a more detailed survival study.

Acute leukaemia in chronic hepatitis B patients with lamivudine therapy

Extensive clinical data have shown that lamivudine is an effective and safe drug for patients with chronic hepatitis B virus infection. No significant serious side effect has been reported.

Correlation Between Tumor Regression Grade and Clinicopathological Parameters in Patients With Squamous Cell Carcinoma of the Esophagus Who Received Neoadjuvant Chemoradiotherapy.

AbstractThe aim of this study was 2-fold: first, to assess the prognostic significance on overall survival (OS) of the 3-point tumor regression grade (TRG) in patients with esophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy (nCRT); second, to investigate the associations of TRG with the clinicopathological characteristics of the study patients.A total of 357 ESCC patients were retrospectively enrolled. The 3-point TRG was determined by assessing the percentage of viable residual tumor cells (VRTC) in the resected specimens as follows: TRG 1, 0% VRTC; TRG 2, 1% to 50% VRTC; and TRG 3, >50% VRTC.A TRG of 1, 2, and 3 was found in 32.2%, 38.9%, and 28.9% of the specimens, respectively. High TRG values were significantly associated with advanced pretreatment clinical stage, longer tumor length, and higher posttreatment tumor depth of invasion (yT), the presence of lymph node metastases (LNM), and lymphovascular invasion. We observed a stepwise decrease in 5-year OS rates with increasing TRG, as follows: 51% for patients with a TRG of 1, 28% for patients with a TRG of 2, and 22% for patients with a TRG of 3 (P < 0.001). TRG and LNM were independent predictors of OS in multivariate analysis. Notably, the prognostic impact of TRG on OS was greater in patients without LNM (P < 0.001) and ypT3 disease (P = 0.021).TRG is independently associated with OS in ESCC patients treated with nCRT. The interrelationships between TRG, LNM, and depth of tumor invasion may improve the prognostic stratification in esophageal cancer.

Feasibility and safety of endoscopic transumbilical thoracic surgical lung biopsy: a survival study in a canine model

BACKGROUND Transumbilical laparoscopy allows the patient to undergo various surgical procedures associated with abdominal disease. The aim of this study was to evaluate the feasibility and safety of transumbilical thoracic exploration and surgical lung biopsy in a canine survival model. METHODS We performed the procedure in 12 dogs weighting 7.1-9.1 kg. The thoracic cavity was accessed using a metal tube inserted via umbilical and diaphragmatic incisions. After transumbilical thoracoscopy, we resected the predetermined lung lobe with an electrocautery loop. We carried out daily clinical examinations, including determination of respiratory rate and rectal temperature. Laboratory parameters (white blood cell count) and inflammatory parameters, including serum interleukin-6 and C-reactive protein, were measured before surgery and at postoperative days 1, 3, 7, and 14. We performed necropsies 2 wk after surgery. RESULTS We successfully performed corrected surgical lung biopsies for the predetermined lung lobe in all animals, with a median time of 43.5 min (range, 32-65 min). We observed two perioperative complications: One dog had minor postoperative air leakage and one had hemodynamic collapse because of inadequate ventilation. These animals recovered well without signs of perioperative infection. Necropsies at 2 wk after surgery showed no evidence of mediastinitis or peritonitis. CONCLUSIONS Exposure of the thoracic cavity and surgical lung biopsy via a transumbilical incision is feasible in this canine model of survival. This procedure may have potential advantages over currently used transthoracic thoracoscopy techniques.

Feasibility of Transumbilical Lung Wedge Resection in a Canine Model

BACKGROUND Chronic wound discomfort and intercostal neuralgia are well-known postoperative complications of video-assisted thoracoscopic surgery (VATS). To explore the possibility of a surgical platform that would cause less postoperative discomfort and avoid these complications, this study evaluated the feasibility of transumbilical lung wedge resection in a canine model. MATERIALS AND METHODS Twelve dogs (4 in the nonsurvival group and 8 in the survival group) were used in this study. Transumbilical thoracoscopy was performed using a homemade metallic tube via umbilical and diaphragmatic incisions with the animal in a supine position. After thoracic exploration, wedge resection was performed on the lung using an endoscopic stapling device placed through the transumbilical and transdiaphragmatic incisions under direct bronchoscopic guidance. The animals were sacrificed 30 minutes after the procedure (nonsurvival group) or 14 days postsurgery (survival group) for necropsy and histological evaluations. RESULTS Eleven preplanned lung wedge resections were completed in a median time of 101 minutes (range, 65-175 minutes) with one exception due to inadequate stapling in the early phase of the experiment. There was one death directly related to postoperative massive airleaks and sepsis in the survival group. The other 7 animals had an uneventful postoperative period. Necropsies at 2 weeks after surgery confirmed successful lung resections and revealed no evidence of vital organ injury. Two animals exhibited complete healing of the diaphragmatic incision. Liver herniation was identified in 1 of 5 animals with partial wound healing. CONCLUSIONS This preliminary animal study demonstrates that large lung wedge resection can be performed with mechanical staplers via a single transumbilical incision. Future studies will investigate the cardiopulmonary and immunologic effects of transumbilical VATS compared with conventional VATS.