Yin-Kai Chao

Salvage surgery after failed chemoradiotherapy in squamous cell carcinoma of the esophagus.

AIMS To investigate the survival benefit and preoperative risk factors for hospital mortality of salvage surgery in esophageal cancer patients who had locoregional residual/recurrent tumor after definitive chemoradiotherapy. METHODS We retrospectively reviewed the esophageal cancer patients who presented at our hospital from 1997 to 2004. Forty-seven patients who had squamous cell cancer and developed locoregional recurrent/persistent disease after primary definitive chemoradiotherapy were elected. Twenty-seven of them received salvage esophagectomy (group 1) and the other 20 underwent non-operative treatment only (group 2). In order to assess the surgery-related mobility and mortality in group 1, 191 patients who received neoadjuvant chemoradiotherapy followed by operation during the same time period were also enrolled (group 3). RESULTS The 5-year overall survival of group 1 patients was 25.4%. In contrast, all of the patients in the group 2 died within 16.7 months. The difference was statistically significant (p=0.0029). In comparison with group 3, group 1 patients had significantly more surgery-related complications and hospital mortality. In univariate analysis for preoperative risk factors, a low albumin or hemoglobulin level was associated with high hospital mortality in group 1 (p=0.004 and 0.003, respectively). After multivariate analysis, only the low albumin level remained borderline significance. As for disease specific survival after salvage surgery, R0 resection was the only independent prognosticator (p=0.049). CONCLUSION Salvage surgery provides survival benefit in esophageal cancer patients with locoregional persistent or recurrent disease after primary definitive chemoradiotherapy. Preoperative albumin and hemoglobulin levels are associated with hospital mortality and may aid in selecting suitable patient for salvage surgery.

Management of lung metastases from colorectal cancer: video-assisted thoracoscopic surgery versus thoracotomy--a case-matched study.

OBJECTIVES The benefits of video-assisted thoracoscopic surgery (VATS) for performing pulmonary metastasectomy are considered controversial. This case-matched study aimed to compare long-term outcomes after surgical resection of pulmonary metastases from colorectal cancer using different approaches (VATS vs. thoracotomy). METHODS Between 1997 and 2008, 143 patients with colorectal cancer who had received their first pulmonary metastasectomy were selected. Fifty-three patients underwent a surgical procedure that utilized a thoracotomy approach (Group 1), and 90 patients underwent a surgical procedure that used a VATS-based approach (Group 2). After being matched for tumor number, diameter (measured by computed tomography), and surgical procedure (wedge resection or lobectomy), 35 pairs of patients were finally enrolled. Study endpoints included tumor recurrence and survival. RESULTS There was no hospital mortality in both groups. Within the mean follow-up period of 50 months, 47.1% patients developed a recurrence (52% at the pulmonary level and 48% at systemic level), and 52.9% of the patients were alive at the time of analysis. There was no difference between Groups 1 and 2 in terms of overall recurrences (54 vs. 40%, p = 0.23), all pulmonary recurrences (25.7 vs. 22.9%, p = 0.78), and same side lung recurrences (14.3 vs. 20%, p = 0.75). The 5-year overall survival (OS) after lung resection was 43 and 51% in Groups 1 and 2, respectively (p = 0.21). CONCLUSIONS Our case-matched study showed that survival outcome of pulmonary metastasectomy using VATS is not inferior to that of open thoracotomy in selected cases.

Pretreatment T3-4 Stage is an Adverse Prognostic Factor in Patients with Esophageal Squamous Cell Carcinoma Who Achieve Pathological Complete Response Following Preoperative Chemoradiotherapy

Background:Preoperative chemoradiotherapy (CRT) followed by esophagectomy is becoming one of the standard treatment strategies for esophageal cancer. Pathologic complete response (pCR) after CRT is the best predictor of survival in squamous cell carcinoma (SCC) of the esophagus. Although no adjuvant treatment is recommended for individuals who achieve pCR, approximately 30% of these patients develop recurrence. Herein we sought to retrospectively investigate the independent predictors of tumor recurrence in this patient group. Methods:Between 1995 and 2004, we investigated seventy patients (69 males and 1 female; mean age: 56.1 years) with esophageal SCC who achieved pCR following preoperative chemoradiotherapy. Study end points included tumor recurrence, disease-specific survival (DSS), and disease-free survival (DFS). Univariate and multivariate analyses were used to identify risk factors for the study end points. Results:Mean follow-up time for patients who survived was 65.8 months. At the time of analysis, 18 patients (25.7%) died of the disease and 22 patients (31.4%) developed recurrence. Multivariate analysis showed that pretherapy T3-4 disease was the most important adverse factor for tumor recurrence (P = 0.007), DFS (P = 0.005), and DSS (P = 0.026). The 5-year DFS was 45% for patients with clinical T3-4 disease and 85% for those with clinical T1-2 disease (P = 0.02). Conclusions:We have shown that up to 31.4% of patients with esophageal SCC who achieve pCR develop tumor recurrence thereafter. Pretherapy T3-4 disease was a strong and independent adverse risk factor for 5-year tumor recurrence, DSS and DFS. High-risk patients with T3-4 disease should be followed with a strict surveillance protocol.

Treatment of esophageal perforation in a referral center in taiwan.

PurposeThe high mortality associated with esophageal perforation can be reduced by aggressive surgery and good critical care. We report our experience of treating esophageal perforation in a clinic in Taiwan.MethodsThe subjects were 28 patients who underwent surgery for a benign esophageal perforation.ResultsThe esophageal perforation was iatrogenic in 11 patients, spontaneous in 8, and caused by foreign body injury in 9. Most (22/28) of the patients were seen longer than 24 h after perforation, and 77% had empyema preoperatively. The perforation was located in the cervical area in 5 patients and in the thoracic esophagus in 23. We performed primary repair in 24 patients, esophagectomy in 3, and drainage in 1. Leakage occurred after primary repair in ten (41%) patients, resulting in one death, and two patients died of other diseases. Postoperative leakage prolonged the hospital stay but had no impact on mortality. Overall survival was 90%. Univariate analysis revealed that age, timing of treatment, and cause and location of the perforation influenced outcome, but multivariate analysis failed to identify a predictor of mortality.ConclusionsEarly diagnosis and intervention are crucial to prevent morbidity and mortality in patients with esophageal perforation. Primary repair is feasible even if the diagnosis is delayed.

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.

Original ResearchPulmonary ProceduresBiodegradable Cisplatin-Eluting Tracheal Stent for Malignant Airway Obstruction: In Vivo and In Vitro Studies

BACKGROUND Self-expandable metallic stents (SEMSs) are effective in the palliation of malignant airway obstruction. Tumor ingrowth, however, frequently occurs because of a shortage of effective local therapy. Additionally, SEMSs are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems. METHODS Biodegradable stents made of polycaprolactone were fabricated by a laboratory-made, microinjection molding machine. In vitro mechanical strength of the stents was compared with the strength of Ultraflex SEMSs. Polylactide-polyglycolide copolymer and cisplatin were coated onto the surfaces of the stents. Elution method and high-performance liquid chromatography (HPLC) analysis were used to examine the in vitro cisplatin release characteristics. In vivo, the stents were surgically implanted into the cervical trachea of 15 New Zealand white rabbits. Bronchoscopic examination was performed weekly (1 to approximately 5 weeks) before killing. Cisplatin concentrations in trachea, lung, and blood were analyzed by HPLC. Histologic examination was also performed. RESULTS The biodegradable stent exhibited mechanical strength comparable to the strength of Ultraflex SEMSs and provided a steady release of cisplatin for >4 weeks in vitro. The in vivo study showed sustained cisplatin levels in rabbit trachea for >5 weeks with a minimum drug level in blood. Histologic examination showed an intact ciliated epithelium and marked leukocyte infiltration in the submucosa of the stented area. CONCLUSIONS Our study demonstrated that the biodegradable stents provided physical properties comparable to the properties of SEMSs and a sustained release of cisplatin for >5 weeks, which showed great potential in the treatment of malignant airway obstruction.

Feasibility of Endoscopic Transoral Thoracic Surgical Lung Biopsy and Pericardial Window Creation

BACKGROUND The thoracic cavity approach for natural orifice transluminal endoscopic surgery (NOTES) is technically challenging. The aim of this study was to evaluate the feasibility of a transoral endoscopic technique for a surgical lung biopsy and pericardial window creation METHODS Under general anesthesia, a 12 mm incision was made over the vestibulum oris region. Under video guidance, a homemade metallic tube was introduced through the incision, extending along the pre-tracheal space to the substernal space with blunt dissection technique, and used as the entrance into the thoracic cavity. A surgical lung biopsy and a pericardial window creation were performed in 12 canines, using the transoral NOTES technique. RESULTS The transoral endoscopic surgical lung biopsy and pericardial window creation were successfully completed in 11 of the 12 canines. Intraoperative bleeding and death from an injury to the pulmonary hilum developed in one animal during the electrosurgical excision of lung tissue. CONCLUSIONS Transoral surgical lung biopsy and pericardial window creation in canine models is technically feasible and can be used as a novel experimental platform for studies of NOTES for intra-thoracic surgery.

Predictors of pathological complete response to neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma.

BackgroundsIn this study, we evaluated the factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC).MethodsPre-nCRT parameters in ESCC patients treated between 1999 and 2006 were analyzed to identify predictors of pCR. All patients received 5-fluorouracil/cisplatin-based chemotherapy and external beam radiation followed by scheduled esophagectomy. Variables were analyzed using univariate and multivariate analyses with pCR as the dependent variable. Estimated pCR rate was calculated with a regression model.ResultsFifty-nine (20.9%) of 282 patients achieved pCR. Univariate analysis identified four patient factors (age, smoking status, drinking history and hypertension), one pre-nCRT parameter (tumor length) as significant predictors of pCR (all P <0.05). On multivariate analysis, tumor length ≤3 cm (favorable, odds ratio (OR): 4.85, P = 0.001), patient age >55 years (favorable, OR: 1.95, P = 0.035), and being a non-smoker (favorable, OR: 3.6, P = 0.003) were independent predictors of pCR. The estimated pCR rates based on a logistic regression including those three predictors were 71%, 35 to approximately 58%, 19 to approximately 38%, and 12% for patients with 3, 2, 1 and 0 predictors, respectively.ConclusionAge, smoking habit and tumor length were important pCR predictors. These factors may be used to predict outcomes for ESCC patients receiving nCRT, to develop risk-adapted treatment strategies, and to select patients who could participate in trials on new therapies.

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.

Risk factors in surgical management of thoracic empyema in elderly patients.

Background:  Although elderly patients with thoracic disease were considered to be poor candidates for thoracotomy before, recent advances in preoperative and postoperative care as well as surgical techniques have improved outcomes of thoracotomies in this patient group. The aim of this study was to investigate surgical risk factors and results in elderly patients (aged ≥70 years) with thoracic empyema.