Detection of occult metastases in lung carcinomas: progress and implications for lung cancer staging.

The ability to detect occult regional and systemic metastases in patients with operable lung carcinoma could have a significant impact on the management of the disease. Here, we review the literature, including studies from our own laboratory, regarding the clinical significance of the presence of occult metastases in patients with lung cancer. The accumulated evidence strongly suggests that the detection of occult regional and systemic metastases is an important predictor of disease progression. The use of this method should be considered in the future design of lung cancer clinical trials, at the very least. The detection of occult metastases should have an impact on lung cancer management; to reflect this, we propose a change in the TNM staging system to indicate the presence or absence of occult regional (lymph node) and systemic (bone marrow) metastases. The proposed change is TNnMm, where n and m are occult nodal and bone marrow metastases status.

Advances in the pathologic staging of lung cancer: detection of regional and systemic occult metastases.

Approximately 78% of lung carcinomas would be potentially curable by surgery if they were detected early enough. Thus, the most important factor in predicting outcome and defining therapy is the stage of the disease. This chapter discusses the TNM (primary tumor/nodal involvement/distant metastasis) staging system for lung cancer as well as lymph node and bone marrow micrometastasis status.

Surgical treatment of non-small cell lung cancer in patients older than seventy years.

Surgical treatment of non-small cell lung cancer has been reported to be associated with increased mortality, especially when pneumonectomy has been employed. A 9-year review of 81 patients treated surgically, with a policy of avoiding pneumonectomy and using internal radiation and wedge excisions rather than lobectomy among patients with impaired reserve, resulted in an operative mortality of 4.9% compared with an overall mortality of 2.1%. Three of the four deaths were among patients older than 80 3/17 (17.6%) years so that mortality of patients 70 < age < 80 was not significantly different from overall mortality. Two of the four deaths were related to pulmonary emboli but there have been no such deaths since routine use of mini-heparin was initiated in 1990. Five-year survival was 42% overall, 65% for stage 1, and 24% for stages II-IIIB. We conclude that surgical treatment of patients 70 < age < 80 may be accomplished with similar mortality and survival as the overall population. Heparin prophylaxis may be especially important among patients older than 80 years.

Detection of occult bone marrow micrometastases in patients with operable lung carcinoma.

OBJECTIVES: A large proportion of patients with operable lung carcinoma (no evidence of systemic spread of tumor) develop metastatic disease after primary therapy. More sensitive and specific methods are needed to identify patients at highest risk for recurrence who may benefit most from adjuvant therapy, while sparing those patients who do not require such treatment. SUMMARY BACKGROUND DATA: Using epithelial-specific monoclonal antibodies, the authors have developed an immunocytochemical assay capable of detecting as few as 2 lung cancer cells in 1 million bone marrow cells. METHODS: The assay was used to test the bone marrow (from resected ribs) of 43 patients with primary non-small cell lung carcinoma who showed no clinical or pathologic evidence of systemic disease. RESULTS: Occult bone marrow micrometastases (BMMs) were detected in 40% of patients (17/43) with non-small cell lung cancer, including 29% (5/17) of patients with stage I or II disease and 46% of whom (12/26) had stage III disease. The median follow-up was 13.6 months. Patients with occult BMMs had significantly shorter times to disease recurrence compared with patients without BMMs (7.3 vs. > 35.1 months, p = 0.0009). Furthermore, for patients with stage I or II disease, the presence of occult BMMs was significantly associated with a higher rate of recurrence (p = 0.0004). CONCLUSIONS: The detection of occult BMMs identifies patients with operable non-small cell lung carcinoma who are at significantly increased risk for recurrence, independent of tumor stage, and may be useful in evaluating patients for adjuvant treatment protocols.

Early experience with videothoracoscopic hydrodissection pleurectomy in the treatment of malignant pleural effusion.

Parietal pleurectomy is our preferred procedure for management of malignant pleural effusion. However, the morbidity of a major thoracotomy has precluded all but highly selected patients from the conventional (open) procedure. Recently, we have been able to perform parietal pleurectomy by means of a video-assisted, thoracoscopic technique. We have retrospectively analyzed the results of this procedure performed on 11 patients between March 1993 and February 1995. These patients ranged in age from 40 to 87 years of age, with a mean age of 61.5 years. Primary tumors were non-small cell lung cancer (5), breast cancer (4), mesothelioma (1), and unknown (1). There was one operative mortality (9.1%). All were relieved of symptoms of pleural effusion. Median survival was 128 days. Early experience indicates we are accomplishing an operation equivalent to that formerly performed by "open" technique. If continued results are similar to our initial experience, we will be able to offer this superior palliation of malignant pleural effusion to a wider range of patients.

Chemoradiation in advanced nonsmall cell lung cancer.

PURPOSE: Resectability, local control, and survival were evaluated in advanced stage nonsmall cell lung cancer treated with simultaneous chemoradiation therapy delivered in an accelerated, interrupted twice-a-day schedule. METHODS AND MATERIALS: Forty-seven consecutive patients with Stage IIIA or IIIB nonsmall cell lung cancer, consenting to participation in the study, received cisplatin, 30 mg/m2 for 3 days, etoposid, 80 mg/m2 for 3 days, and 5-fluorouracil, 900 mg/m2 for 4 days. Radiation therapy consisted of 2 Gy given twice a day for 5 days. Two weeks rest was planned between cycles. Patients were evaluated for resectability after the second cycle. Any patient with unresectable tumor received a third cycle of treatment. RESULTS: Forty-seven patients were evaluable for acute toxicity: eighteen (38%) required an extended rest period for esophagitis or low blood count; 3 (6%) had sepsis, of whom 1 (2%) expired. Three patients (6%) had multiple blood transfusions for low hemoglobin. Median follow-up is 23.6 months, with a range of 10-49 months. Nine patients (19%) failed locally; 15 (32%) had local and distant failure; 7 (15%) failed only at distant sites. Twelve patients (25.5%) are alive with no evidence of disease; 4 patients were lost to follow-up with disease. The 2-year actuarial survival is 49%, and the 4-year is 28.2%. CONCLUSION: Simultaneous chemoradiation is well tolerated with acceptable toxicity. The overall 2- and 4-year actuarial survival is somewhat better than that reported in the literature. Resectability in Stage IIIB patients was not increased with this regimen nor was any surgical specimen free of cancer. The 47% distant failure rate is not different from those reported by others.

Aortoesophageal fistula after reconstruction of the thoracic spine.

Aortoesophageal fistula is a rare complication after neurosurgical repair of the thoracic spine. We report an instance of a lethal aortoesophageal fistula caused by a pseudoaneurysm that developed after long contact between the prosthetic material from a spinal reconstruction procedure and the thoracic aorta. Pathologic examination showed that the mesh formed the roof of the pseudoaneurysm and was the most probable cause of the lesion.

Pneumonectomy.

Success in pneumonectomy, or any pulmonary surgery, depended upon learning the principles of positive pressure ventilation with endotracheal intubation, management of the pleural space, and confirming the advantage of anatomic dissection in individual ligation of hilar structures. The earliest successful pneumonectomies were performed for suppurative disease, but eventually became the procedure of choice for treatment of lung cancer until it became known that lobectomies would result in the same cure rate but with a decreased complication rate. At the present time, pneumonectomy is reserved for patients whose cancers require complete pneumonectomy for cure and for selected suppurative problems. Accepted techniques for conventional, intrapericardial and extrapleural pneumonectomies are described along with indications for the particular procedures.

Complications of transhiatal esophagectomy.

A total of 23 papers published between 1981 and 1992, reporting a total of 1,353 patients, were reviewed for intraoperative and postoperative complications of transhiatal esophagectomy. Intraoperative complications included massive bleeding, tracheal injuries, cardiac arrhythmias, and incidental splenectomies. Even though the chest was not opened, the commonest postoperative complications were pulmonary. Leakage from the cervical anastomosis was seen in as many as 15% of all patients, but almost all resolved spontaneously. Postoperative benign strictures were seen in almost as many patients. Hoarseness due to recurrent laryngeal nerve injury, symptomatic gastro-esophageal reflux, chylothorax, Horner's syndrome, subphrenic abscess, hiatal hernia, and biliary cutaneous fistula were some of the other postoperative complications. An overview of these complications is presented, along with suggested methods of avoiding them and their treatment. The overall mortality for the 1,353 patients was 7.17%.

Management of malignant pleural effusions with pleuroperitoneal shunting.

Malignant pleural effusions are often debilitating conditions for the patient with advanced carcinoma. Traditionally, treatment has been repeated thoracentesis or tube thoracostomy with instillation of sclerosing agents. However, this required the patient to be hospitalized and to have pain and inconveniences of the chest tubes. The drainage also had to be low enough for sclerotherapy to be effective. In 1982, the pleuroperitoneal shunt became a feasible alternative to sclerotherapy. We began using the Denver pleuroperitoneal shunt in July 1991. Twenty shunts were inserted into 19 patients during a two year period ending June 30, 1993. All patients but one were relieved of dyspnea. The mean duration of patency was 26 months and fewer than 25 percent of the shunts clotted before the death of the patient. Our favorable experience with the shunt has resulted in us recommending the Denver pleuroperitoneal shunt for treatment of recurrent malignant pleural effusions and selectively as primary treatment.

Surgical management of pulmonary metastases.

Pulmonary metastases, especially solitary ones, have been managed surgically over the past 50 years. Resection is recommended for multiple metastases in patients who are capable of tolerating the required procedure, in which all pulmonary metastases can be resected as long as the primary site and extrapulmonary metastases are controlled or controllable, unless there is better treatment offering the same chance of cure for superior palliation. Complete resectability is the most important prognostic indicator, but several authors have found that for some tumors the number of pulmonary nodules, disease-free interval, and tumor doubling time are also important.

Absorbable mesh in placement of temporary implants.

PURPOSE: To evaluate absorbable mesh for the suturing of afterloading catheters in patients with tumors involving the chest wall. METHODS AND MATERIALS: Patients underwent thoracotomy and resection of tumor; a layer of absorbable mesh was then sutured to the tumor bed. Nylon flexiguide afterloading catheters were sutured into the mesh at about 1.5 cm distance from each other. A second layer of mesh was then sutured on top of the catheters. The chest wall was closed. Orthogonal radiographs and CT scans of the area of implants were done to verify catheter position in each patient on day 1 and on the last day of implant. Computer dosimetry by digitization of dummy sources was performed on each set of radiographs. The same seed for both sets of films was chosen as the origin of digitization. All seed coordinates were compared directly to offset for any rotation of the patient during the two sets of films. The distances were calculated from all seed positions to the origin, then tabulated and compared. RESULTS: The distances agreed within a few millimeters (7-8 mm). The differences may be attributed to the patient's breathing and to the localization uncertainty. The resulting dose alteration was negligible. CONCLUSION: This technique appears to provide adequate anchorage of catheters with resulting constant seed position and dose distribution in areas of scant tissues or in surgical beds of considerable size.

Utility of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser for extensive pulmonary metastasectomy.

The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has been reported to have advantages in pulmonary resections including superior control of bleeding and air leak with relative sparing of pulmonary parenchyma. Extensive metastasectomies were performed in two patients with bilateral metastases who might have been excluded from surgery with other techniques. The patients were discharged within 8 days after uneventful postoperative courses. While this modality shows promise in permitting extensive metastasectomy, only long-term follow-up will demonstrate the ability to provide results comparable to those achieved with previous techniques.

High dose-rate endobronchial irradiation in malignant airway obstruction.

We evaluated the effectiveness of high dose rate (HDR) endobronchial irradiation for palliation of malignant airway obstruction. Between May 1989 and February 1992, 39 patients were treated in our department. Thirty-two patients (82 percent) had primary lung neoplasms and 7 (18 percent) had metastatic disease. Thirty-three patients (85 percent) had prior external irradiation (either alone or in combination with chemotherapy), and 9 patients (23 percent) received laser excision before treatment. Of the 39 patients, 14 (36 percent) presented with hemoptysis, 20 (51 percent) with cough, 15 (38.5 percent) had dyspnea, and 15 patients (38.5 percent) had pneumonia or atelectasis. There were 57 applications performed in the 39 patients. Patients with hemoptysis had 93 percent complete response (CR), 20 percent with cough had CR; 60 percent improved (partial response [PR]); no response was seen in 20 percent. Atelectasis and pneumonia resolved in 20 percent of patients. Eighteen patients (46 percent) underwent a second procedure and were evaluated for objective response; 34 percent had CR, 44 percent had PR, and 22 percent did not respond. There were two acute (one bronchospasm, one pneumothorax) and three late (two strictures, and one exsanguination) complications. In our experience, HDR was highly effective in the palliation of airway symptoms caused by malignant tumors, with acceptable toxicity.