Tracey L. Weigel

Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy

BACKGROUND The risks of complications in patients undergoing thoracotomy after neoadjuvant therapy for nonsmall cell lung cancer remain controversial. We reviewed our experience to define it further. METHODS All patients undergoing thoracotomy after induction chemotherapy from 1993 through 1999 were reviewed. Univariate and multivariate methods for logistic regression model were used to identify predictors of adverse events. RESULTS Induction chemotherapy included mitomycin, vinblastine, and cisplatin (179 patients), carboplatin and paclitaxel (152 patients), and other combinations (139 patients). Eighty-five patients (18%) received preoperative radiation. Operations were pneumonectomy (97 patients), lobectomy (297 patients), lesser resection (18 patients), and exploration only (58 patients). Total mortality was 7 of 297 (2.4%) and 11 of 97 (11.3%) for all lobectomies and pneumonectomies, respectively, but mortality was 11 of 46 (23.9%) for right pneumonectomy. Complications developed in 179 patients (38%). By multiple regression analysis, right pneumonectomy (p = 0.02), blood loss (p = 0.01), and forced expiratory volume in one second (percent predicted) (p = 0.01) predicted complications. No factor emerged to explain this high right pneumonectomy mortality rate. CONCLUSIONS Pulmonary resection after neoadjuvant therapy is associated with acceptable overall morbidity and mortality. However, right pneumonectomy is associated with a significantly increased risk and should be performed only in selected patients.

Minimally invasive esophagectomy.

BACKGROUND Open esophagectomy can be associated with significant morbidity and delay return to routine activities. Minimally invasive surgery may lower the morbidity of esophagectomy but only a few small series have been published. METHODS From August 1996 to September 1999, 77 patients underwent minimally invasive esophagectomy. Initially, esophagectomy was approached totally laparoscopically or with mini-thoracotomy; thoracoscopy subsequently replaced thoracotomy. RESULTS Indications included esophageal carcinoma (n = 54), Barretts high-grade dysplasia or carcinoma in situ (n = 17), and benign miscellaneous (n = 6). There were 50 men and 27 women with an average age of 66 years (range 30 to 94 years). Median operative time was 7.5 hours (4.5 hours with > 20 case experience). Median intensive care unit stay was 1 day (range 0 to 60 days); median length of stay was 7 days (range 4 to 73 days) with no operative or hospital mortalities. There were four nonemergent conversions to open esophagectomy; major and minor complication rates were 27% and 55%, respectively. CONCLUSIONS Minimally invasive esophagectomy is technically feasible and safe in our center, which has extensive minimally invasive and open esophageal experience. Open surgery should remain the standard until future studies conclusively demonstrate advantages of minimally invasive approaches.

Results of expandable metal stents for malignant esophageal obstruction in 100 patients: short-term and long-term follow-up

BACKGROUND Expandable metal stents palliate malignant dysphagia in most cases, but early complications and outcomes in long-term survivors have not been well described. This report summarizes our experience with expandable metal stents for malignant dysphagia. METHODS Over a 48-month period, 127 stents were placed in 100 patients with dysphagia from esophageal cancer (93%) or lung cancer. Most had undergone prior treatment. Dysphagia scores, duration of palliation, complications, and reintervention were evaluated. RESULTS Immediate improvement in dysphagia was observed in 85% of patients with no procedure-related deaths. Dysphagia score decreased from 3.3 before stent to 2.3 (p < 0.005). Average interval to reintervention was 80 days. In 40 patients surviving more than 120 days, 31 (78%) required reintervention. Major complications occurred in 3 patients receiving poststent chemoradiation (tracheoesophageal fistula, T1 vertebral body abscess, mediastinal abscess). Other complications included unsatisfactory deployment requiring immediate removal (3 patients), migration (11 patients), pain requiring removal (2 patients), food impaction (10 patients), and tumor ingrowth (37 patients). CONCLUSIONS Expandable metal stents offer excellent short-term palliation of malignant dysphagia. In long-term survivors, recurrent dysphagia requiring reintervention is common. In a small subset of patients receiving chemoradiation after stent placement, major complications were observed.

Detection of micrometastases in histologically negative lymph nodes in esophageal cancer

BACKGROUND New molecular techniques may identify micrometastases in histologically negative lymph nodes and have an impact on the staging of esophageal cancer. We investigated the role of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay to identify micrometastases in esophageal cancer. METHODS The RT-PCR assay to detect carcinoembryonic antigen (CEA) messenger ribonucleic acid (mRNA) was performed on lymph nodes from patients with esophageal cancer and benign esophageal disorders. The presence of CEA mRNA in lymph nodes was considered evidence of metastases. RESULTS Histopathologic study revealed metastases in 50 (41%) of 123 lymph nodes from 30 patients with esophageal cancer. All histologically positive lymph nodes contained CEA mRNA by RT-PCR. Of 73 histologically negative lymph nodes, 36 (49%) contained CEA mRNA, a significant increase compared with the histopathologic diagnosis (p < 0.001). Lymph nodes in patients with benign disease contained no CEA mRNA. In 10 patients, histologic stage was NO. Five of them were also negative by RT-PCR, and all are alive with only one recurrence. In the remaining 5 patients, RT-PCR was positive for occult lymph node metastases; 2 have died of disease, and 1 is alive with recurrent disease. CONCLUSIONS In patients with esophageal cancer, RT-PCR detects more lymph node metastases than does histopathology. Initial follow-up suggests a positive RT-PCR with negative histologic findings may have poor prognostic implications. Further studies will be needed to confirm any clinical implications.

Minimally invasive surgical staging for esophageal cancer

AbstractBackground: The incidence of esophageal adenocarcinoma is increasing in the United States, and the 5-year survival rate is dismal. Preliminary data suggest that conventional imaging is inaccurate in staging esophageal cancer and could limit accurate assessment of new treatments. The objective of this study was to compare minimally invasive surgical staging (MIS) with conventional imaging for staging esophageal cancer. Methods: Patients with potentially resectable esophageal cancer were eligible. Staging by conventional methods used computed tomography (CT) scan of the chest and abdomen, and endoscopic ultrasound (EUS), whereas MIS used laparoscopy and videothoracoscopy. Conventional staging results were compared to those from MIS. Results: In 53 patients, the following stages were assigned by CT scan and EUS: carcinoma in situ (CIS; n=1), I (n=1), II (n=23), III (n=20), IV (n=8). In 17 patients (32.1%), MIS demonstrated inaccuracies in the conventional imaging, reassigning a lower stage in 10 patients and a more advanced stage in 7 patients. Conclusions: In 32.1% of patients with esophageal cancer, MIS changed the stage originally assigned by CT scan and EUS. Therefore, MIS should be applied to evaluate the accuracy of new noninvasive imaging methods and to assess new therapies for esophageal cancer.

Postoperative fluorescence bronchoscopic surveillance in non–small cell lung cancer patients

BACKGROUND Second lung primaries occur at a rate of 1% to 3% per patient-year after complete resections for non-small cell lung carcinoma (NSCLC). Fluorescence bronchoscopy appears to be a sensitive tool for surveillance of the tracheobronchial tree for early neoplasias. METHODS Patients who were disease-free after complete resection of a NSCLC were entered into a fluorescence bronchoscopy surveillance program. All suspicious lesions were biopsied along with two areas of normal mucosa to serve as negative controls. RESULTS A total of 73 fluorescence bronchoscopies were performed after conventional bronchoscopy in 51 patients at a median of 13 months postresection. The majority (46 of 51) of patients had stage I or II NSCLC, whereas 10% (5 of 51) had stage IIIA. Three intraepithelial neoplasias and one invasive carcinoma were identified in 3 of 51 patients (6%), all current or former smokers. Of the four lesions identified, three were in the 20 patients with prior squamous cell carcinomas. No intraepithelial neoplasias were identified by white-light bronchoscopy, whereas two of three were detected by fluorescence examination. The one invasive cancer detected was apparent on both white-light and fluorescence bronchoscopic examinations. CONCLUSIONS Surveillance with fluorescence bronchoscopy identified lesions in 6% of postoperative NSCLC patients thought to be disease-free. Patients with prior squamous cell carcinomas appear to be a population that may warrant future prospective study of postoperative fluorescence bronchoscopic surveillance.

Fluorescence bronchoscopic surveillance after curative surgical resection for non-small-cell lung cancer.

BackgroundSecond lung primaries occur at a rate of up to 3% per patient-year after curative resection for non-small-cell lung carcinoma. Postresection patients are often poor candidates for further curative surgery because of their diminished pulmonary reserve. The aim of this study was to evaluate the role of fluorescence bronchoscopy by using the Xillix® LIFE-Lung Fluorescence Endoscopy SystemTM to identify second lung primaries in patients who have had a previous curative resection of a non-small-cell lung cancer.MethodsPatients who had no evidence of disease status after resection of a non-small-cell lung cancer were identified from a prospectively collected data base and entered onto a fluorescence bronchoscopy surveillance protocol. All suspicious areas, as well as several areas of apparently normal mucosa, were sampled for biopsy. A single pathologist reviewed all biopsy specimens, with 10% of biopsies re-reviewed, for quality control, by a second pulmonary pathologist.ResultsA total of 31 surveillance fluorescence bronchoscopies were performed on 25 patients after conventional bronchoscopy. Four intraepithelial neoplasias or invasive carcinomas were identified in 3 (12%) of 25 patients screened. The addition of the LIFE examination to conventional bronchoscopy increased the sensitivity of screening from 25.0% to 75.0%, which yielded a relative sensitivity of 300% with a negative predictive value of .97.ConclusionsUse of postresection surveillance with fluorescence bronchoscopy identified intraepithelial or invasive lesions in 12% of non-small-cell lung cancer patients, and the system was three times more sensitive than conventional bronchoscopy to identify these early mucosal lesions. Fluorescence bronchoscopic surveillance of this high-risk, postresection population will help better define the true rate of occurrence and the natural history of second primaries and may assist in monitoring their response to newer, noninvasive treatment methods, such as photodynamic therapy or chemopreventive agents, in future trials.

Paclitaxel-induced apoptosis in non-small cell lung cancer cell lines is associated with increased caspase-3 activity.

OBJECTIVE Our objective was to determine whether paclitaxel-induced apoptosis in human lung cancer cells is Fas dependent. METHODS Human lung cancer cell lines were evaluated for morphologic evidence of apoptosis, DNA fragmentation (TUNEL positivity), and caspase-3 activation after paclitaxel treatment. Human lung adenocarcinoma, squamous cell carcinoma, undifferentiated lung carcinoma, and bronchoalveolar carcinoma cell lines were each cultured in 10 micromol/L paclitaxel. RESULTS After 24 hours of culture in paclitaxel, a 22% to 69% increase in the number of apoptotic cells was evident by means of methylene blue-azure A-eosin staining with characteristic blebbing and nuclear condensation. TUNEL assay also confirmed an increase of 19.9% to 73.0% of cells with nuclear fragmentation. Caspase-3 activity, assayed by Z-DEVD cleavage, increased from 20% to 215% (P <.05). ZB4, an antagonistic anti-Fas antibody, did not block paclitaxel induction of caspase-3 activity (155.8 vs 165.8 U, not significant). Apoptotic morphologic changes were inhibited in cells cultured in the presence of paclitaxel and Ac-DEVD-CHO, a caspase-3 inhibitor. CONCLUSIONS Paclitaxel induces apoptosis in lung cancer cell lines, as assessed by a consistent increase in caspase-3 activity, DNA laddering, and characteristic morphologic changes. Paclitaxel-induced apoptosis in human lung cancer cells is associated with caspase-3 activation but is not Fas dependent.

Transgastric laparoscopic resection of a giant esophageal lipoma.

We present an unusual case of a giant, pedunculated esophageal lipoma originating in the mid-esophagus ball-valving through the gastroesophageal junction resulting in intermittent obstruction and hemorrhage. Endoscopic ultrasonography revealed a 1 cm in diameter vessel in the stalk of the polyp, and endoscopic resection was not performed. Transgastric laparoscopic resection with endoscopic guidance was successfully performed using 2 balloon-tipped laparoscopic trocars inserted laparoscopically into the gastric lumen through separate gastrotomies. Intraoperative esophagoscopy confirmed proper port placement and the exact location of the mass. Under direct visualization, a Snowden-Pencer grasper was used to pull the polyp down into the stomach and an Endo-GIA blue articulating stapler was used to transect its stalk. The polyp was retrieved via an endopouch placed through the intragastric laparoscopic port. We conclude that transgastric laparoscopy should be considered for the resection of a variety of pedunculated esophageal lesions when the use of standard endoscopic techniques is not possible.

Microinvasive transaxillary thoracoscopic sympathectomy: technical note.

OBJECTIVE To describe a two-port transaxillary thoracoscopic approach for thoracic sympathectomy that maximizes working space, improves manipulative ability, and enhances visualization of the surgical field. METHODS Positioning of the patients was optimized to displace the scapula posteriorly, widen the avenue of approach to the sympathetic ganglia, and create a more direct route to the target. The semi-Fowler position permitted the lung apex to fall away from mediastinal structures, obviating a separate retraction port. A 30-degree endoscope allowed an unobstructed view of surgical progress, and anatomic relationships were manipulated in a temporal sequence to facilitate dissection. RESULTS Microinvasive transaxillary sympathectomy was performed successfully in 13 patients, all of whom had a good outcome without complications. CONCLUSION The modifications implemented increase the speed and safety of thoracoscopic sympathectomy while minimizing complications.