Surgical management of T3 and T4 lung cancer.

Locally advanced lung cancer (T(3) or T(4)) has a significantly worse prognosis than lower stage disease. However, this diagnosis is usually made radiologically, and experienced thoracic surgeons are familiar with the low radiologic to pathologic correlation in tumors that abut the great vessels, mediastinum, or chest wall. Commonly these tumors do not directly invade adjacent structures and are, in fact, T(1) or T(2) tumors that are resectable through standard techniques. Where there is no clearly evident invasion of unresectable structures, the patient should be given the benefit of the doubt and considered at a lower (resectable) stage until proven otherwise. The curability of T(3) tumors varies according to the involved site. A T(3)N(0) tumor involving the chest wall provides the most favorable prognosis among the resected T(3) lesions, with a 5-year survival of >50% in lymph node-negative patients if resection is complete. Palliative incomplete resections of T(4) disease, in which tumor has invaded mediastinal structures, have not shown any survival benefit and are associated with very high morbidity and mortality. However, patients with limited invasion of the carina, left atrium, superior vena cava, or pulmonary artery may be able to be completely resected despite their T(4) classification. Surgical resection remains an important part of the therapy for patients with locally advanced lung cancer. Modern techniques of chest wall resection and reconstruction and bronchoplastic procedures allow complete resection of locally advanced tumors with favorable 5-year survival rates and low morbidity and mortality.

Cyclooxygenase-2 inhibition decreases primary and metastatic tumor burden in a murine model of orthotopic lung adenocarcinoma.

OBJECTIVE: To assess cyclooxygenase-2 inhibition on primary tumor and mediastinal metastases in a murine model of orthotopic lung adenocarcinoma. METHODS: Human lung adenocarcinoma cells (CRL5908, female nonsmoker with cyclooxygenase-2 expression by Western blot) were implanted under direct visualization through the parietal pleura in the upper lobe of the left lung (2 x 10(6) cells/animal) of SCID mice. Mice were randomly assigned to 2 groups, either untreated (n = 62) or celecoxib-treated (n = 60). Celecoxib, a selective cyclooxygenase-2 antagonist, was solubilized in the animals' drink (25 mg/kg per day). Mice were arbitrarily killed at 1, 2, 3, and 4 weeks. A blinded observer assessed primary tumor volume and metastatic disease grossly and histologically. RESULTS: Gross metastatic lymph nodes were present at 3 weeks in none of 15 (0%) treated and 12 of 15 (80.0%) untreated animals (P <.0001). Mean primary tumor volumes at 3 weeks for treated mice were 7.9 +/- 10.0 mm(3) and for untreated mice were 533.1 +/- 453.6 mm(3) (mean +/- SD, P <.0001). Gross metastatic lymph nodes were present at 4 weeks in 3 of 15 (20%) treated and 17 of 17 (100%) untreated animals (P <.0001). Mean primary tumor volumes at 4 weeks for treated mice were 37.1 +/- 46.2 mm(3) and for untreated mice were 809.6 +/- 1226.4 mm(3) (mean +/- SD, P <.0001). Mean blood levels of celecoxib in treated mice were 236.8 +/- 34.2 ng/mL (mean +/- SD). CONCLUSIONS: Cyclooxygenase-2 inhibition results in decreased primary and metastatic tumor burden in a murine model using human lung adenocarcinoma. Cyclooxygenase-2 inhibition has the potential to decrease tumor progression and metastases in patients with lung adenocarcinoma.

Concomitant vascular procedures for malignancies with vascular invasion.

HYPOTHESIS: Contemporary reconstructive vascular techniques can be safely used to permit resection of tumors invading major vascular structures. DESIGN: Review of vascular surgery registry between January 1, 1987, and December 31, 2001. SETTING: An academic medical center and affiliated institutions. PATIENTS: Forty-nine patients (37 males and 12 females) aged 15 through 80 years (mean age, 55 years) who required concomitant vascular resection and reconstruction to allow complete tumor resection. MAIN OUTCOME MEASURES: Early (<30 days) morbidity and mortality, late (>30 days) vascular morbidity and mortality, primary patency of the vascular reconstruction, and tumor-free survival. RESULTS: Aortic resection with graft reconstruction was performed in 20 patients (41.7%) and inferior vena cava resection with reconstruction in 6 patients (12.5%). Five patients (10.4%) had both the aorta and inferior vena cava resected and reconstructed. Iliac, femoral, or popliteal reconstructions were performed in 15 patients (31.3%). Portal vein reconstruction was performed to permit resection of pancreatic neoplasms in 8 patients (16.7%). Resection and reconstruction of either a brachiocephalic vessel or superior vena cava was performed in 4 patients. Thirty-day mortality was 2.1%, as 1 patient died of a myocardial infarction following tumor resection with vascular reconstruction. Overall 30-day morbidity was 12.2%. Early vascular morbidity included bleeding from an arterial anastomosis and a compartment syndrome requiring fasciotomy. Primary patency of the vascular reconstructions at 24 months was 90% and tumor-free survival was 70%. Thirty-one patients (63%) were alive, without tumor recurrence and with a patent vascular reconstruction at 24 months. No patient died or lost a limb due to occlusion of the vascular reconstruction. CONCLUSION: Contemporary reconstructive vascular procedures permit resection of tumors that involve major vascular structures with acceptable early and late morbidity and mortality.

Lung cancer and cyclooxygenase-2.

Lung cancer is by far the leading cause of cancer-related death. Overall survival is poor and has not improved substantially over the last half century. It is clear that new approaches are needed and these should include prevention, screening for early detection, and novel treatments based on our understanding of the molecular biology of this disease. Recently attention has been drawn to the role of the cyclooxygenase (COX) enzyme and its involvement in tumorigenesis. Investigations have documented two isoforms, COX-1 and COX-2, encoded by different genes. COX-1 is constitutively expressed in most tissues and appears to be responsible for the production of prostaglandins mediating normal physiologic functions, such as the maintenance of gastric mucosa and regulation of renal blood flow. In contrast, COX-2 is normally undetectable in most tissues, and is induced by cytokines, growth factors, oncogenes, and tumor promoters. A growing body of evidence indicates COX-2 plays a key role in lung cancer, and can serve as a potential marker of prognosis in this disease. Furthermore, the recent availability of COX-2 inhibitor medications offers a unique opportunity to interfere with the development of lung cancer and the progression of metastasis. Because COX-2 inhibitors have been demonstrated to interfere with tumorigenesis, the COX-2 enzyme may be an attractive target for therapeutic and chemoprotective strategies in lung cancer patients.

Clinical importance of the "seat belt sign" in blunt trauma to the neck.

Currently a carotid duplex scan is the initial screening modality routinely used to evaluate occult extracranial carotid artery injuries secondary to blunt neck trauma. The objective of this study was to investigate the role of carotid artery duplex scanning in patients who suffered blunt trauma to the neck with a "seat belt sign." The medical records of 131 consecutive patients who sustained blunt trauma to the neck from a motor vehicle accident were reviewed. Patients with the cervical seat belt sign underwent a complete physical examination and carotid duplex scan in an accredited vascular laboratory. An intimal flap with severe carotid artery stenosis was found in one of 131 patients (0.76%). This patient has multiple injuries to the face, head, chest, lateralizing neurological signs, and a Glasgow Coma Scale score of 8. In an era of cost containment, resource consumption should target appropriate populations. A cervical seat belt sign should not serve as a sole indicator for evaluation of the carotid artery in the absence of other pertinent signs or symptoms.