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.

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.

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.

Endoscopic repair of bronchial dehiscence after lung transplantation.

We report a case of bronchial dehiscence after right single lung transplantation and describe a novel means of management: bronchoscopic closure of the defect with alpha-cyanoacrylate glue.

The role of positron emission tomography in evaluating mediastinal lymph node metastases in non-small-cell lung cancer.

Positron emission tomography (PET) is a modality that differentiates malignant from benign processes based upon metabolism rather than anatomy. A number of studies have confirmed improved accuracy of PET over computed tomography (CT), but until a few recent studies, most had failed to include satisfactory histologic confirmation. The objective of this study was to compare PET and CT to histologic staging of the mediastinum in patients with non-small-cell lung cancer (NSCLC). Histologic examination of mediastinal lymph nodes (MLNs) was performed on 40 patients with NSCLC at mediastinoscopy and/or at surgical resection. PET scans were interpreted by one of two nuclear medicine physicians, blinded to histology, using CT scans for anatomic localization. CT scans were independently evaluated for mediastinal lymphadenopathy. The overall accuracy, sensitivity, and specificity of PET were 78% (31 of 40), 67% (four of six), and 79% (27 of 34), respectively. The overall accuracy, sensitivity, and specificity of CT were 68% (27 of 40), 50% (three of six), and 71% (24 of 34), respectively. PET was superior to CT at correctly identifying mediastinal nodal metastases; however, both modalities were inferior to the gold standard of surgical staging. PET is more accurate than CT in staging the mediastinum of patients with NSCLC. PET failed to identify lymph node metastasis in 33% of patients with histologically proven MLN involvement, and false positives were present in 15%. At present, mediastinoscopy should remain the standard of care for preoperative mediastinal staging for NSCLC.

Occult lung cancer treatment.

Occult lung carcinomas are rare and provide a particular challenge for treatment. They are lesions not evident on routine chest roentgenogram and chest computed tomography. Surgical resection remains the gold standard for the treatment of occult lung primaries; however, for nonsurgical candidates, multiple promising treatment strategies are on the horizon.

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), Barrett's 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.

Laparoscopic repair of giant paraesophageal hernia: 100 consecutive cases.

OBJECTIVE: To summarize the authors' laparoscopic experience for paraesophageal hernia (PEH). SUMMARY BACKGROUND DATA: Laparoscopic antireflux surgery and repair of small hiatal hernias are now routinely performed. Repair of a giant PEH is more complex and requires conventional surgery in most centers. Giant PEH accounts for approximately 5% of all hiatal hernias. Medical management may be associated with a 50% progression of symptoms and a significant death rate. Conventional open surgery has a low death rate, but complications are significant and return to routine activities is delayed in this frequently elderly population. Recently, short-term outcome studies have reported that minimally invasive approaches to PEH may be associated with a lower complication rate, a shorter hospital stay, and faster recovery. METHODS: From July 1995 to February 2000, 100 patients (median age 68) underwent laparoscopic repair of a giant PEH. Follow-up included heartburn scores and quality of life measurements using the SF-12 physical component and mental component summary scores. RESULTS: There were 8 type II hernias, 85 type III, and 7 type IV. Sac removal, crural repair, and antireflux procedures were performed (72 Nissen, 27 Collis-Nissen). The 30-day death rate was zero; there was one surgery-related death at 5 months from a perioperative stroke. Intraoperative complications included pneumothorax, esophageal perforation, and gastric perforation. There were three conversions to open surgery. Major postoperative complications included stroke, myocardial infarction, pulmonary emboli, adult respiratory distress syndrome, and repeat operations (two for abscess and one each for hematoma, repair leak, and recurrent hernia). Median length of stay was 2 days. Median follow-up at 12 months revealed resumption of proton pump inhibitors in 10 patients and one repeat operation for recurrence. The mean heartburn score was 2.3 (0, best; 45, worst); the satisfaction score was 91%; physical and mental component summary scores were 49 and 54, respectively (normal, 50). CONCLUSION: This report represents the largest series to date of laparoscopic repair of giant PEH. In the authors' center with extensive experience in minimally invasive surgery, laparoscopic repair of giant PEH was successfully performed in 97% of patients, with a minimal complication rate, a 2-day length of stay, and good intermediate results.

Endoscopic photodynamic therapy for obstructing esophageal cancer: 77 cases over a 2-year period.

BACKGROUND: Photodynamic therapy (PDT) is an alternative treatment option for the palliation of obstructive esophageal cancer. We report our experience with PDT for patients presenting with inoperable, obstructing, or bleeding esophageal cancer. METHODS: Seventy-seven patients with inoperable, obstructing esophageal cancer were treated with PDT from November 1996 to July 1998. Photofrin (1.5-2.0 mg/kg) was administered, followed by endoscopic light treatment (630 nm red dye laser) at 48 h. Dysphagia score (1 for no dysphagia to 5 for complete obstruction), dysphagia-free interval, and patient survival were assessed. RESULTS: Seventy-seven patients underwent 125 PDT courses. The mean dysphagia score at 4 weeks after PDT in 90.8% of the patients improved from 3.2 +/- 0.7 to 1.9 +/- 0.8 (p < 0.05). PDT adequately controlled bleeding in all six patients who had bleeding. The most common complications after the 125 PDT courses were esophageal stricture (4.8%), Candida esophagitis (3.2%), symptomatic pleural effusion (3.2%), and sunburn (10.0%). Twenty-nine patients (38%) required more than one PDT course, and seven patients required placement of an expandable metal stent for recurrent dysphagia. The mean dysphagia-free interval was 80.3 +/- 58.2 days. The median survival was 5.9 months. CONCLUSIONS: Photodynamic therapy is a safe and effective treatment for the palliation of obstructing and bleeding esophagus cancer.

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.

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

BACKGROUND: Second 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 System to identify second lung primaries in patients who have had a previous curative resection of a non-small-cell lung cancer. METHODS: Patients 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. RESULTS: A 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. CONCLUSIONS: Use 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.

Evaluation of distant metastases in esophageal cancer: 100 consecutive positron emission tomography scans.

BACKGROUND: Pilot studies suggest positron emission tomography (PET) scanning may be superior to conventional imaging in staging esophageal cancer, especially in the detection of radiographically occult distant metastases. This report summarizes our experience with PET in staging esophageal cancer. METHODS: One hundred consecutive PET scans in 91 patients with esophageal cancer referred for surgery were prospectively collected (1995 to 1998) and compared with computerized tomography (CT) and bone scan. PET images were acquired after injection of 18F-fluorodeoxyglucose and evaluated for abnormal uptake. Minimally invasive surgical staging (MIS) and/or clinical correlation were used to confirm or refute imaging results. RESULTS: MIS or clinical correlation confirmed 70 distant metastases in 39 cases. PET detected 51 metastases in 27 of 39 cases (69% sensitivity, 93.4% specificity, 84% accuracy) compared with CT, which detected 26 metastases in 18 of 39 cases (46.1% sensitivity, 73.8% specificity, 63% accuracy) (p < 0.01). CONCLUSIONS: PET was more accurate than CT in detecting distant metastases, but was only 69% sensitive compared with minimally invasive staging.

Photodynamic therapy for treatment of malignant dysphagia.

Photodynamic therapy (PDT) was recently approved by the Food and Drug Administration for palliating obstructing esophageal cancer. This report reviews our initial experience using PDT to treat malignant dysphagia. Patients with inoperable, obstructing esophageal cancer were considered for PDT. Photofrin was injected 48 hours before endoscopic laser activation. Dysphagia score was assessed. Thirty patients underwent 53 PDT courses. Improvement in dysphagia occurred in 83%. Mean dysphagia score decreased from 2.8 to 1.8 (p < 0.05). Complications included esophageal stricture (9.4%), candida esophagitis (5.7%), symptomatic pleural effusion (5.7%), contained esophageal perforation (1.9%), aspiration pneumonia (1.9%), and sunburn (13.2%). Seventeen patients (57%) required more than one PDT treatment, and in 10 an expandable metal stent was used as an adjunct. The 30-day mortality rate was 7%. PDT is effective in palliating patients with malignant dysphagia. The ideal patient for PDT has an obstructing, primarily endoluminal esophageal tumor with minimal extrinsic compression.

Fluorescence bronchoscopic surveillance in patients with a history of non-small cell lung cancer.

Background Second lung primaries occur at a rate of 2% per patient per year after curative resection for non-small cell lung carcinoma (NSCLC). The aim of this study was to evaluate the role of fluorescence bronchoscopy using the Xillix((R)) LIFE-Lung Fluorescent Endoscopy System(TM) (LIFE-Lung system) in the surveillance of patients for second NSCLC primaries after resection or curative photodynamic therapy (PDT).Methods NSCLC patients who were disease-free following resection or endobronchial PDT were identified and recruited to participate in a LIFE bronchoscopy surveillance program. All suspicious areas were biopsied; areas of apparent normal mucosa served as negative controls. Biopsy specimens were reviewed by a single pulmonary pathologist.Results Thirty-six patients underwent 53 surveillance LIFE bronchoscopies and 6/112 biopsies revealed intraepithelial neoplasia (IEN) or invasive carcinoma in 6/36 (17%) of patients. The overall relative sensitivity of LIFE versus conventional bronchoscopy was 165% with a negative predictive value of 0.96, for the post-resection subset of patients these values increased to 200% and 0.97, respectively.Conclusions Surveillance LIFE bronchoscopy identified intraepithelial or invasive lesions in 17% of patients previously thought to be disease-free. These data support future multicenter trials on fluorescence bronchoscopic surveillance of NSCLC patients after curative surgical resection or PDT.

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.