PubMed Health⌕ Search

Biomedical subjects

Thomas Ng

Publications and source records attributed to Thomas Ng.

15 recordsLinked to original sources

Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma.

PURPOSE: To determine the overall survival for patients with locally advanced, HER2 overexpressing, esophageal adenocarcinoma receiving trastuzumab, paclitaxel, cisplatin, and radiation on a Phase I-II study. METHODS AND MATERIALS: Patients with adenocarcinoma of the esophagus without distant organ metastases and 2+/3+ HER2 overexpression by immunohistochemistry (IHC) were eligible. All patients received cisplatin 25 mg/m2 and paclitaxel 50 mg/m2 weekly for 6 weeks with radiation therapy (RT) 50.4 Gy. Patients received trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg. RESULTS: Nineteen patients were entered: 7 (37%) had celiac adenopathy, and 7 (37%) had retroperitoneal, portal adenopathy, or scalene adenopathy. Fourteen of 19 patients (74%) had either 3+ HER2 expression by immunohistochemistry, or an increase in HER2 gene copy number by HER2 gene amplification or high polysomy by fluorescence in situ hybridization. The median survival of all patients was 24 months and the 2-year survival was 50%. CONCLUSIONS: Assessment of the effect of trastuzumab in the treatment of patients with esophageal adenocarcinoma overexpressing HER2 is limited by the small number of patients in this study. Overall survival, however, was similar to prior studies without an increase in toxicity. Evaluation of HER2 status should be performed in future trials for patients with adenocarcinoma of the esophagus that investigate therapies targeting the HER family.

Adenocarcinoma↗

Evolution to video-assisted thoracic surgery lobectomy after training: initial results of the first 30 patients.

BACKGROUND: In early-stage lung cancer, evidence is accumulating for the benefits of lobectomy by video-assisted thoracic surgery (VATS) over open lobectomy. Few thoracic training programs offer sufficient experience in this technically demanding procedure. This article describes the evolution of a new graduate's practice from open thoracotomy to VATS lobectomy. STUDY DESIGN: Our model involves a transition in technique from posterolateral thoracotomy to muscle-sparing thoracotomy and, ultimately, to VATS lobectomy. This approach was evaluated by examining outcomes of open thoracotomy patients before VATS lobectomy and outcomes of the initial 30 VATS patients. Data were collected prospectively. RESULTS: Before undertaking VATS lobectomy, 94 major pulmonary resections were performed by thoracotomy. Mortality was 1.2% for lobectomy and 0% for pneumonectomy. Use of the muscle-sparing thoracotomy increased from 17% of patients in the first half to 70% in the latter half of this group. For the first 30 VATS lobectomy patients, the mean operative time was 168 minutes. Median blood loss was 200 mL. Conversion rate to open thoracotomy was 13.3%. Mortality was 3.3% and morbidity was 26.7%. After short-term followup (mean followup 16 months), overall survival for stage I lung cancer was 96%. CONCLUSIONS: With our approach, new graduates of thoracic surgery programs can safely transition to VATS lobectomy. Gaining experience with the lateral muscle-sparing thoracotomy is an important step in the transition, as it offers similar operative exposure. Longterm disease-free and overall survival data are needed to evaluate our oncologic efficacy with this approach.

Adult↗

Multimodality treatment of esophageal cancer: a review of the current status and future directions.

Surgical resection will cure only 15% to 20% of patients with seemingly localized esophageal cancer. Multimodality therapy has the potential to increase the cure rate by improving locoregional control and preventing systemic relapse. Randomized trials demonstrate that chemoradiation followed by surgery decreases local relapse as compared with surgery alone; however, the effect on overall survival remains uncertain. The additional impact of surgery following chemoradiation also remains unclear, with two randomized trials demonstrating an improvement in locoregional control without a benefit in survival. Morbidity and mortality of trimodality therapy have limited potential gains. Incorporation of docetaxel, irinotecan, and oxaliplatin into chemotherapy regimens prior to chemoradiation or as adjuvant therapy may decrease systemic recurrence. New radiation sensitizers may improve locoregional control. Biologic agents, such as cetuximab, trastuzumab, erlotinib, and bevacizumab, may enhance chemoradiation and target systemic micrometastases. Advances in radiation oncology and surgery may decrease morbidity and mortality from trimodality therapy, improving patient outcome.

Antineoplastic Combined Chemotherapy Protocols↗

Management of empyema cavity with the vacuum-assisted closure device.

Management of empyema after pulmonary resection remains a challenging problem. Along with mandatory drainage of the thoracic cavity and investigations to rule out bronchopleural fistula, a reliable method of thoracic cavity closure is needed. The open thoracic window and Eloesser flap techniques rarely represent definitive therapy. Muscle flap and thoracoplasty procedures may provide well-vascularized tissue to close bronchopleural fistula and obliterate the empyema cavity, but they are quite complex and involve significant patient morbidity. We report a case of empyema without bronchopleural fistula after lobectomy in which the vacuum-assisted closure device was used to achieve complete wound healing after open drainage.

Drainage↗

Improved hepatic transduction, reduced systemic vector dissemination, and long-term transgene expression by delivering helper-dependent adenoviral vectors into the surgically isolated liver of nonhuman primates.

Helper-dependent adenoviral vectors (HDAds) are attractive vectors for liver-directed gene therapy because they can mediate sustained, high-level transgene expression without chronic toxicity. However, high vector doses are required to achieve efficient hepatic transduction by systemic delivery because of a nonlinear dose response. Unfortunately, such high doses result in systemic vector dissemination and dose-dependent acute toxicity with potentially severe and lethal consequences. We hypothesize that the threshold to efficient hepatic transduction may be circumvented by delivering the vector into the surgically isolated liver via the portal vein. Total hepatic isolation was achieved by occluding hepatic inflow from the portal vein and hepatic artery and by occluding hepatic venous outflow at the inferior vena cava. We demonstrate in nonhuman primates that this approach resulted in significantly higher efficiency hepatic transduction with reduced systemic vector dissemination compared with systemic intravascular delivery. This method of delivery was associated with transient acute toxicity, the severity of which was variable. Importantly, stable, high levels of transgene expression were obtained for at least 665 days for one baboon and for at least 560 days for two baboons with no evidence of long-term toxicity.

Adenoviruses, Human↗

Paclitaxel poliglumex (PPX-Xyotax) and concurrent radiation for esophageal and gastric cancer: a phase I study.

OBJECTIVES: To determine the maximal tolerated dose (MTD) and dose limiting toxicities of poly(l-glutamic acid)-paclitaxel (PPX) and concurrent radiation (PPX/RT) for patients with esophageal and gastric cancer. METHODS: Patients with esophageal or gastric cancer receiving chemoradiation for loco-regional, adjuvant, or palliative intent were eligible. The initial dose of PPX was 40 mg/m2/wk, for 6 weeks with 50.4 Gy radiation. Dose levels were increased in increments of 10 mg/m2/wk of PPX. RESULTS: Twenty-one patients were enrolled over 5 dose levels. Sixteen patients had esophageal cancer and 5 had gastric cancer. Twelve patients received PPX/RT as definitive loco-regional therapy, 4 patients had undergone resection and received adjuvant PPX/RT, and 5 patients had metastatic disease and received PPX/RT for palliation of dysphagia. Dose limiting toxicities of gastritis, esophagitis, neutropenia, and dehydration developed in 3 of 4 patients treated at the 80 mg/m2 dose level. Four of 12 patients (33%) with loco-regional disease had a complete clinical response. CONCLUSIONS: The maximally tolerated dose of PPX with concurrent radiotherapy is 70 mg/m2/wk for patients with esophageal and gastric cancer.

Adenocarcinoma↗

Deep anterior lamellar keratoplasty using the manual dissection technique of Melles: a histopathologic correlation.

PURPOSE: To report the histopathologic findings in the host tissue of 2 human keratoconic corneas undergoing maximum-depth anterior lamellar keratoplasty (MDALK) using the manual dissection technique described by Melles. METHODS: Corneal buttons were examined from 2 patients with keratoconus who underwent MDALK using the manual dissection technique of Melles and converted to penetrating keratoplasty after rupture of the lamellar bed. Manual dissection was performed in 1 patient, and combined manual and viscoelastic dissection of Descemet membrane (DM) was performed in the other. RESULTS: Light microscopy of the corneal buttons showed a deep pre-Descemet dissection plane with minimal residual stroma. DM appeared to be thinned in both eyes and measured 3 to 8 microm in thickness. CONCLUSION: By using the manual dissection technique of Melles, LK can be performed exposing the smooth DM of the recipient bed. We confirmed exposure of DM in patient corneas, using this technique by light microscopy. There may be an increased risk of rupture of DM during surgery when this membrane is thinned, particularly in patients with keratoconus. This surgical technique allows conversion to penetrating keratoplasty after rupture of DM.

Adult↗

Radiofrequency ablation followed by conventional radiotherapy for medically inoperable stage I non-small cell lung cancer.

PURPOSES: The standard treatment of stage I non-small cell lung cancer (NSCLC) is surgical resection. Some patients are poor surgical candidates due to severe comorbid medical conditions. Radiotherapy alone has historically been used in this patient population with limited success. Radiofrequency ablation (RFA) is an image-guided, thermally mediated ablative technique recently applied to lung tumors. Combination therapy with both these treatments has not been previously performed. We report our experience with combined CT-guided RFA and conventional radiotherapy in 24 medically inoperable patients with a minimum of 2-year study follow-up in surviving patients. PATIENTS AND METHODS: Twenty-four consecutive, medically inoperable patients with biopsy-proven, stage I NSCLC were treated with CT-guided RFA followed by radiotherapy to a dose of 66 Gy. RFA was performed with a single or cluster cool-tip F electrode; 21 patients were staged before therapy using fluorodeoxyglucose-positron emission tomography. RESULTS: There were 14 women and 10 men (median age, 76 years; range, 58 to 85 years). The histologic subtypes were squamous cell (n = 13), adenocarcinoma (n = 5), and undifferentiated (n = 6). All patients received RFA followed by three-dimensional conformal radiotherapy. There were no treatment-related deaths or grade 3/4 toxicities. Pneumothorax requiring chest tubes developed in three patients (12.5%). At a mean follow-up period of 26.7 months (range, 6 to 65 months), 14 patients (58.3%) died, with cumulative survival rates of 50% and 39% at the end of 2 years and 5 years, respectively. Ten of the deaths were cancer related. Two patients had local recurrence (8.3%), while nine patients had systemic metastatic disease. Three patients died of respiratory failure with no evidence of active disease, and one patient died of a cerebrovascular accident at 18-month follow-up. Pleural effusions developed after treatment in six patients (25%), which proved to be malignant in one patient. CONCLUSION: RFA followed by conventional radiotherapy is feasible in this population of medically inoperable stage I NSCLC patients. Procedural complication rates are low, and no additional major toxicities were seen despite the addition of RFA. Local control and survival rates appear to be better than with radiotherapy alone.

Adult↗

Trastuzumab, paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus: a phase I study.

PURPOSE: To conduct a phase I study incorporating trastuzumab with paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus. METHODS AND MATERIALS: Patients with adenocarcinoma of the esophagus without distant organ metastases were eligible. All patients received cisplatin 25 mg/m2 and paclitaxel 50 mg/m2 weekly for 6 weeks with radiation 50.4 Gy. HER-2/neu-positive patients (2+/3+ by immunohistochemistry) received weekly trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg, respectively. HER-2/neu-negative patients received the same chemoradiation without trastuzumab as a control for toxicity. Dose-limiting toxicities were defined as grade 3 esophageal, cardiac, or pulmonary toxicity. RESULTS: Twelve of 36 screened patients (33%) overexpressed HER-2/neu by immunohistochemistry (seven 3+ and five 2+). Eight of 12 patients with HER-2/neu overexpression by IHC had an increase in the number of HER-2/neu genes, six from amplification of the HER-2/ neu gene and two were hypderdiploid for chromosome 17. Thirty patients were enrolled (12 HER-2/neu-positive and 18 HER-2/neu-negative controls). No increase in toxicity was seen with the addition of trastuzumab. One of 12 patients in the trastuzumab arm and 8 of 17 in the control arm had grade 3 esophagitis (p < or = .026). Mean left ventricular ejection fraction for the trastuzumab group was 57% before treatment and 56% after treatment. CONCLUSION: HER-2/neu is overexpressed in approximately one-third of esophageal adenocarcinomas. Trastuzumab can be added at full dose to cisplatin, paclitaxel, and radiation. Future studies of trastuzumab in esophageal adenocarcinoma are indicated.

Adenocarcinoma↗

Skull base chordoid meningioma: imaging features and pathology.

The clinical, imaging and pathological features of a skull base chordoid meningioma (CM) are described. The huge tumour resulted in obstructive hydrocephalus and partial erosion of the clivus such that a chordoma was suspected. The lesion's MRI findings were similar to those of a meningioma. Light microscopic, immunohistochemistry and ultrastructural features were diagnostic of CM. Chordoid meningioma is a rare subtype of meningioma and has a great tendency to recur should surgical resection be incomplete.

Choroid Neoplasms↗