Hui-Ping Liu

Comparison of IHC, FISH and RT-PCR methods for detection of ALK rearrangements in 312 non-small cell lung cancer patients in Taiwan.

Background Recently Echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK) fusion gene has become an important biomarker for ALK tyrosine kinase inhibitor (crizotinib) treatment in NSCLC. However, the best detection method and the significance of EML4-ALK variant types remain uncertain. Methods Reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence in Situ hybridization (FISH) and Immunohistochemical (IHC) stain were performed on tumor tissues of 312 NSCLC patients for detection of ALK rearrangements. Mutation analyses for EGFR and KRAS genes were also performed. Results Thirteen of the 312 patients (4.17%) had ALK rearrangements detected by RT-PCR. If RT-PCR data was used as the gold standard, FISH tests had a low sensitivity (58.33%), but very good specificity (99.32%). IHC stain had better sensitivity (91.67%) than FISH, but lower specificity (79.52%), when the cut off was IHC2+. All of the 8 patients with high abundance of EML4-ALK positive cells in tumor tissues (assessed by the signal intensities of the RT-PCR product), were also have high expression of ALK protein (IHC3+), and positive for FISH, except one failed in FISH. Variants 3a+3b (4/5, 80%) of EML4-ALK fusion gene were more common to have high abundance of EML4-ALK positive cells in tumor tissues than variant 1 (1/3, 33.3%). Meta-analysis of the published data of 2273 NSCLC patients revealed that variant 3 (23/44, 52.3%) was the most common type in Chinese population, while variant 1 (28/37, 75.7%) was most common in Caucasian. Conclusions Among the three detection methods, RT-PCR could detect not only the presence of EML4-ALK fusion gene and their variant types, but also the abundance of EML4-ALK positive cells in NSCLC tumor tissues. The latter two factors might affect the treatment response to anti-ALK inhibitor. Including RT-PCR as a diagnostic test for ALK inhibitor treatment in the prospective clinical trials is recommended.

Thoracoscopic Removal of Intrathoracic Neurogenic Tumors: A Combined Chinese Experience

ObjectiveTo review the surgical and clinical results of minimally invasive resection of intrathoracic neurogenic tumors using a video-assisted thoracoscopic technique. Summary Background DataThoracoscopy has emerged as a possible means for diagnosing and managing various intrathoracic disorders. Benign intrathoracic tumors often are ideal lesions for resection using a video-assisted technique. The authors report on their combined experience with the thoracoscopic resection of 143 intrathoracic neurogenic tumors. MethodsBetween March 1992 and February 1999, 143 patients with intrathoracic neurogenic tumors were diagnosed and underwent resection using video-assisted thoracoscopic techniques in three teaching centers. Case selection, surgical technique, and clinical results were reviewed. ResultsThe average age of the patients was 40.8 years; 57.3% were male. Thirty-eight patients (27%) had symptoms attributable to the masses. Seventy-two masses were neurofibromas, 33 were neurilemmomas, 7 were paragangliomas, and 31 were ganglioneuromas. All but seven tumors were located in the posterior mediastinum. The masses were on average 3.5 cm in greatest diameter. The mean surgical time was 40 minutes, and the average hospital stay was 4.1 days. There were no major postoperative complications or recurrences to date. Nine patients reported paresthesias over the chest wall during a mean follow-up of 29 months. ConclusionsResection of intrathoracic neurogenic tumors using a thoracoscopic technique based on standard surgical indications would seem to be appropriate. Most of these masses are benign and readily removed. For dumbbell tumors, a combined thoracic and neurosurgical approach is mandatory.

Thoracoscopic Surgery for Spontaneous Pneumothorax

Abstract. Spontaneous pneumothorax in apparently healthy individuals is a relatively common occurrence. The management of patients with spontaneous pneumothorax remains controversial. With the advances in thoracoscopic techniques and instrumentation, video-assisted thoracic surgery (VATS) is now accepted by many as the procedure of choice for surgical treatment of spontaneous pneumothorax. We report our combined experience with 757 patients who suffered from recurrent or persistent spontaneous pneumothorax treated by VATS over a 5-year period. Surgical indications included persistent air leak (n= 165), recurrence (n= 325), radiologically demonstrated huge bulla (n= 12), spontaneous hemopneumothorax (n= 13), incomplete expansion of the lung (n= 212), and bilateral involvement (n= 30). Several surgical procedures were undertaken, based on the thoracoscopic findings: endoscopic stapled bullectomy (n= 312), argon beam coagulation (n= 6), endoscopic suturing (n= 52), and endoloop ligation (n= 352). In 49 cases, mechanical or chemical pleurodesis was the only procedure performed. There were no mortalities or intraoperative hazards. Complications consisted of wound infections (n= 16), localized empyema (n= 2), chest wall bleeding (n= 1), and persistent air leaks (bulla type III) (n= 31). The median duration of the operation was 55 minutes (15–160 minutes), and the average postoperative hospital stay was 4.5 days (range 0–27 days). There were 16 recurrences (2.1%), after a mean follow-up of 30 months (range 1–60 months). Seven patients had recurrence from 9 to 17 months after stapled bullectomy. All the remaining patients had recurrence after failed pleurodesis. On the basis of our results, we conclude that video-assisted thoracoscopic management allows effective, safe performance of standard surgical procedures, avoiding a formal thoracotomy incision. We consider thoracoscopy the treatment of choice for patients with pneumothorax requiring surgical therapy.

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.

Delayed pneumothorax complicating minor rib fracture after chest trauma

OBJECTIVE Pneumothorax (PTX) after trauma is a preventable cause of death. Drainage procedures such as chest tube insertion have been traditionally advocated to prevent fatal tension PTX. We evaluated the safety of close observation in patients with delayed PTX complicating rib fracture after minor chest trauma. MATERIALS AND METHODS Adult patients (>18 years) with a diagnosis of chest trauma and 3 or fewer fractured ribs were reviewed. Case patients were divided according to age, location and number of fractured ribs, mechanism of trauma, and initial pulmonary complication after thoracic trauma for comparative analysis. RESULTS There were 207 male (70.2%) and 88 female (29.8%) patients whose ages ranged from 18 to 93 years (median, 55 years). The mechanisms of trauma were a motor vehicle accident in 207 patients, falls in 66, pedestrian injury in 10, and assaults in 14. Ninety-five patients sustained 1 rib fracture, 95 had 2 rib fractures, and 105 suffered 3 rib fractures. Right-sided injury occurred in 164 cases, left-sided injury did in 127, and bilateral injury did in 4. The most frequent location of rib fractures was from the fourth rib to the ninth rib. The initial pulmonary complications after trauma were PTX in 16 patients, hemothorax in 43, pneumohemothorax in 14, lung contusion in 75, and isolated subcutaneous emphysema (SubcEmph) in 33. Thirty percent of the patients (n = 5/16) who presented with traumatic PTX were observed safely without drainage. Delayed PTX was recorded in 16 patients, occurring mostly during the first 2 days of their admission. Associated extrathoracic injury was recorded in 189 patients. The mean hospital stay of the patients was 7.66 days. Longer hospital stay was related to increasing number of fractured ribs, need for thoracic drainage, and the presence of associated extrathoracic injury. The mortality rate for the entire group was 2%. The presence of SubcEmph was the only risk factor associated with the development of delayed PTX. CONCLUSIONS Patients sustaining blunt chest trauma and minor rib fractures should be admitted for close observation when presenting with SubcEmph because of possible delayed presentation of PTX.

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.

Video-Assisted Coronary Artery Bypass Grafting During Hypothermic Fibrillatory Arrest

BACKGROUND Hypothermic fibrillatory arrest without aortic cross-clamping is a technique for quieting the heart during coronary artery bypass grafting. This report reviews the preliminary results with this technique in 4 patients having video-assisted coronary artery bypass grafting. METHODS Four male patients 28.5 to 64.5 years old (mean age, 45.4 years) underwent operation for unstable angina. With video-assisted techniques, coronary artery bypass grafting was performed through a left anterior minithoracotomy with femoral-femoral cardiopulmonary bypass without cross-clamping the aorta. The myocardium was protected by continuous coronary perfusion during hypothermic fibrillatory arrest. RESULTS A left internal thoracic artery graft was anastomosed to the left anterior descending coronary artery in each patient. The posterior descending branch of the right coronary artery was grafted with a pedicled right gastroepiploic artery in 1 patient. The duration of cardiopulmonary bypass was 72 to 127 minutes (mean duration, 92 +/- 21 minutes). The postoperative course of each patient was uneventful. Follow-up (range, 3.9 to 5.8 months; mean follow-up, 4.9 months) was complete for all patients. There were no late deaths. Coronary angiography showed patent grafts. All patients were in New York Heart Association functional class I or II (mean class, 1.25). CONCLUSIONS Hypothermic fibrillatory arrest is a simple and effective method of quieting the heart, thereby providing a motionless operative field for video-assisted coronary artery bypass grafting.

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.

AIRWAY STENTS IN MANAGEMENT OF TRACHEAL STENOSIS: HAVE WE IMPROVED?

Background:  Airway stenting is an alternative approach for relieving airway stenosis when lesions are inappropriate for single‐stage reconstruction. The aim of this study was to present our experience using airway stent in the management of patients with tracheal stenosis.