Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy.

PURPOSE: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. RESULTS: Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. CONCLUSION: p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.

Modern thirty-day operative mortality for surgical resections in lung cancer.

Modern postoperative mortality rates for resectional operations for lung cancer are not readily available. In recent publications estimating the risk factors for surgical resection, mortality rates of 10% to 15% for pneumonectomy and 5% to 7% for lobectomy are frequently quoted. In order to determine modern operative mortality rates (up to 30 days postoperatively), the Lung Cancer Study Group (LCSG) analyzed the surgical mortality rates of the various participating centers during the years 1979 to 1981. A total of 2,200 resections for lung cancer were available for analysis. Of the 2,220 resections performed, 1,058 were lobectomies, 569 were pneumonectomies, and 143 were lesser resections (segmental or wedge). Eighty-one postoperative deaths occurred from among the 2,220 resections (3.7%). The mortality rate for pneumonectomy was 6.2% and for lobectomy, 2.9%. Lesser resections carried a 1.4% mortality rate, not statistically different from lobectomy. In patients under the age of 60 years, the mortality rate was 1.3%, 60 to 69 years, 4.1%, and over 70 years, 7.1%, all significantly different (p less than 0.01). The postoperative mortality rate for patients 70 years or older was 7.1% (pneumonectomy 5.9% and lobectomy 7.3%). It is obvious that greater care was taken in selection among the older pneumonectomy patients. The striking similarity of postoperative mortality rates for resectional operations for lung cancer among the various centers of the LCSG and among the various institutions within these centers suggest that these data are a reasonably accurate analysis of modern surgical mortality rates in the treatment of lung cancer.

Continuous paravertebral extrapleural infusion for post-thoracotomy pain management.

BACKGROUND: Continuous thoracic epidural analgesia is considered by many the gold standard for post-thoracotomy pain control but is associated with its own complications. In this study we compare continuous paravertebral extrapleural to epidural infusion for post-thoracotomy pain control. METHODS: In a prospective fashion, 50 patients were randomized to receive either paravertebral or epidural infusion for post-thoracotomy pain control. The anesthesia department placed epidurals, and the operative surgeon placed unilateral paravertebral catheters. Patients were evaluated for analgesic efficacy and postoperative complications. RESULTS: We found that both methods of analgesia provide adequate postoperative pain control. Epidural infusion demonstrated an improved efficacy early in the postoperative course but provided statistically similar analgesia to paravertebral by postoperative day 2. Neither group demonstrated a greater number of pain-related complications. Narcotic-induced complications such as pruritus, nausea/vomiting, and postural hypotension/mental status changes/respiratory depression were seen with statistically similar frequency in both epidural and paravertebral arms. Urinary retention, however, was noted to be significantly more frequent in patients with epidural catheters. Drug toxicity was not observed with either epidural or paravertebral infusion. CONCLUSIONS: We recommend continuous paravertebral infusion as an improved method of post-thoracotomy analgesia that can be placed and managed by the surgeon.

The solitary pulmonary nodule in the patient with breast cancer.

A solitary pulmonary nodule appearing in a patient with breast cancer, either past or present, is most likely to be a second primary cancer originating in the lung rather than a metastasis from the breast cancer. Between 1970 and 1983 there were at this institution 1416 patients with breast cancer and 579 patients with bronchogenic cancer, 198 of whom were women. Among the patients with breast cancer, 42 (or 3% of all of the patients with breast cancer) had a solitary pulmonary nodule either at the time of presentation of their breast cancer or during the follow-up period. Fifty-two percent of the solitary pulmonary nodules proved to be a primary lung tumor, 5% proved to be benign lesions, and only 43% proved to be metastatic breast cancer. Patients with breast cancer with solitary pulmonary nodules should have a diagnostic workup appropriate for lung cancer. Since adenocarcinoma has become the most common lung cancer cell type, the usual diagnostic tests may not allow a firm differentiation between primary lung and secondary breast cancer. Therefore if malignancy is proved or suspected, thoracotomy with appropriate resection is the treatment of choice in most patients with breast cancer, even at the initial appearance of the breast cancer.

Intraoperative fine needle aspiration biopsy of thoracic lesions.

Forty-one intraoperative fine needle aspiration biopsies were performed on 35 patients during exploratory thoracotomy (33 patients) or mediastinoscopy (2 patients). Each biopsy was done with a 22 gauge needle. Smears were prepared at the operating table, air-dried, sent directly to the laboratory, stained, and interpreted immediately by the pathologist. Preparation and reporting time averaged ten minutes. Surgical decisions were made on the basis of the pathologist's reports. Intraoperative fine needle aspiration biopsy was 100% accurate in differentiating inflammatory from neoplastic lesions. Ninety-five percent diagnostic accuracy for malignancy (39 out of 41 specimens) was obtained. It permitted quick biopsy of lesions deep within the lung parenchyma without the need to cut across uninvolved tissue, thus permitting appropriate resection in each patient. There were no deaths related to the procedure.

Thoracoscopic implantation of cancer with a fatal outcome.

A case is presented in which an indeterminate lung lesion was extracted through an accessory incision during a video-assisted thoracic surgical lung biopsy. The lesion was malignant, and a completion lobectomy was performed. An incisional recurrence developed 5 months later, and this was treated with a wide chest wall resection and reconstruction. However, there was a second massive chest wall recurrence that proved fatal. We believe that tumor seeding to the chest wall occurred at thoracoscopy. To prevent such tumor seeding, thoracoscopic biopsy specimens should be removed in some sort of receptacle when cancer is suspected.

Funnel stitch closure of the limited pulmonary excision defect.

A technique to close small defects in lung tissue resulting from local excision of lung lesions is described. The technique, called the spiral funnel stitch, is a conical suture started in the depth of the defect and tied at the surface. It minimizes air leaks.

Intercostal hemangioma presenting as a chest wall tumor.

Skeletal muscle hemangiomas are uncommonly described in a variety of locations. This report details the diagnosis and management of a 39-year-old woman with a right chest wall mass detected on physical examination. After a negative diagnostic evaluation, exploratory thoracotomy revealed an intercostal hemangioma, undescribed in recent literature. The lesion was excised.

Site of recurrence in patients with stages I and II carcinoma of the lung resected for cure.

Ninety-nine patients with Stage I or II lung carcinoma that was other than the small cell type and who survived for more than 30 days after a "curative" resection were followed for five years or until death if it occurred prior to the five-year anniversary. Recurrent disease developed in 44 patients. Clinical data and data from postmortem examination were reviewed in these 44 patients in an attempt to classify each recurrence as either initially local or distinct metastatic disease. The site of the first documented recurrence was local in 18 patients and distance metastases in 26. When the patients with recurrence were separated into TNM categories, it was apparent that in those patients without lymph nodes metastases demonstrated in the resected specimen (N0), the initial recurrence tended to be a distant metastases, whereas in those with such involvement (N1), the initial occurrence was more often local. In light of these data, selection of appropriate initial adjuvant therapeutic modalities may be different for each type of patient.

Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer.

BACKGROUND: Lymph node metastases are the most significant prognostic factor in localized non-small cell lung cancer (NSCLC). Nodal micrometastases may not be detected. Identification of the first nodal drainage site (sentinel node) may improve detection of metastatic nodes. We performed intraoperative Technetium 99m sentinel lymph node (SN) mapping in patients with resectable NSCLC. METHODS: Fifty-two patients (31 men, 21 women) with resectable suspected NSCLC were enrolled. At thoracotomy, the primary tumor was injected with 2 mCi Tc-99. After dissection, scintographic readings of both the primary tumor and lymph nodes were obtained with a handheld gamma counter. Resection with mediastinal node dissection was performed and findings were correlated with histologic examination. RESULTS: Seven of the 52 patients did not have NSCLC (5 benign lesions, and 2 metastatic tumors) and were excluded. Forty-five patients had NSCLC completely resected. Mean time from injection of the radionucleide to identification of sentinel nodes was 63 minutes (range 23 to 170). Thirty-seven patients (82%) had a SN identified; 12 (32%) had metastatic disease. 35 of the 37 SNs (94%) were classified as true positive with no metastases found in other intrathoracic lymph nodes without concurrent SN involvement. Two inaccurately identified SNs were encountered (5%). SNs were mediastinal (N2) in 8 patients (22%). CONCLUSIONS: Intraoperative SN mapping with Tc-99 is an accurate way to identify the first site of potential nodal metastases of NSCLC. This method may improve the precision of pathologic staging and limit the need for mediastinal node dissection in selected patients.

Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study.

BACKGROUND: The last two decades have seen changes in the prevalence, histologic type, and management algorithms for patients with esophageal cancer. The purpose of this study was to evaluate the presentation, stage distribution, and treatment of patients with esophageal cancer using the National Cancer Database of the American College of Surgeons. STUDY DESIGN: Consecutively accessed patients (n = 5,044) with esophageal cancer from 828 hospitals during 1994 were evaluated in 1997 for case mix, diagnostic tests, and treatment modalities. RESULTS: The mean age of patients was 67.3 years with a male to female ratio of 3:1; non-Hispanic Caucasians made up most patients. Only 16.6% reported no tobacco use. Dysphagia (74%), weight loss (57.3%), gastrointestinal reflux (20.5%), odynophagia (16.6%), and dyspnea (12.1%) were the most common symptoms. Approximately 50% of patients had the tumor in the lower third of the esophagus. Of all patients, 51.6% had squamous cell histology and 41.9% had adenocarcinoma. Barrett's esophagus occurred in 777 patients, or 39% of those with adenocarcinoma. Of those patients that underwent surgery initially, pathology revealed stage I (13.3%), II (34.7%), III (35.7%), and IV (12.3%) disease. For patients with various stages of squamous cell cancer, radiation therapy plus chemotherapy were the most common treatment modalities (39.5%) compared with surgery plus adjuvant therapy (13.2%). For patients with adenocarcinoma, surgery plus adjuvant therapy were the most common treatment methods. Disease-specific overall survival at 1 year was 43%, ranging from 70% to 18% from stages I to IV. CONCLUSIONS: Cancer of the esophagus shows an increasing occurrence of adenocarcinoma in the lower third of the esophagus and is frequently associated with Barrett's esophagus. Choice of treatment was influenced by tumor histology and tumor site. Multimodality (neoadjuvant) therapy was the most common treatment method for patients with esophageal adenocarcinoma. The use of multimodality treatment did not appear to increase postoperative morbidity.

Malignant bone tumors of the chest wall.

Malignant bone tumors constitute only 0.2% of all tumors. Bone sarcomas occur at a rate approximately one tenth that of sarcomas of the soft tissue. Malignant bone tumors of the chest wall and sternum are even more rare because most bone tumors occur in the long bones or joints. Because of the relative paucity of experience treating these malignancies, progress in successful therapies has been limited. Chondrosarcomas remain the most common bony malignant chest wall lesions and are discussed elsewhere in this issue. Other lesions in descending order of incidence include Ewing's sarcoma, osteosarcoma, malignant fibrous histiocytoma, solitary plasmacytoma, and Askin tumors. This article reviews these remaining five malignant bony chest wall tumors, along with their symptoms, presentations, and current approaches to therapy.

Biopsy of lesions of the thorax.

Bronchoscopy, thoracocentesis, and fine needle aspiration are the three most useful biopsy techniques for thoracic lesions. Minimally invasive procedures, such as mediastinoscopy and thoracoscopy, must readily be available. As biopsy techniques and the lesions to be biopsied become more complex, the surgeon should make the decision regarding the particular technique. Exploratory thoracotomy remains the ultimate thoracic biopsy.

Axillary thoracotomy.

The axillary thoracotomy should be the incision of choice for most uncomplicated general thoracic surgical procedures. It can be performed rapidly, avoids major muscle transection, and by employing a double lumen endotracheal tube will permit segmental resection as well as lobectomy without technical problem. One hundred consecutive, elective axillary thoracotomies were performed with minimal morbidity and only one mortality. Twenty-five of the patients were of high surgical risk. The larger posterolateral thoracotomy is reserved for repeat thoracotomy, Pancoast tumors, difficult procedures such as bronchoplasty and/or radical pneumonectomy, and when pleural symphysis is expected. Sometimes called lateral thoracotomy or mini-thoracotomy, the axillary thoracotomy is our most common incision.

Emergency subxiphoid pericardial decompression for malignant pericardial effusion.

Malignant pericardial effusion can result in acute cardiac tamponade with serious hemodynamic compromise. This condition requires prompt pericardial decompression for relief of symptoms; however, the risks of general anesthesia in this setting are considerable. In a series of 12 patients, all operated on under local anesthesia without operative mortality, there were six patients with malignant pericardial effusion secondary to lung carcinoma; four patients, secondary to breast carcinoma; one patient, secondary to squamous cell carcinoma of the oral cavity; and one patient, secondary to an unknown primary. The clinical presentation of each was abrupt and echocardiography was definitive. The procedure is performed through an upper abdominal midline incision. The xiphoid process is excised, the diaphragm is visualized, and a pericardial window is created through which two chest tubes are placed through separate stab incisions. The tubes are removed when the drainage has subsided, usually 3-7 days. No medication or irritant is instilled. There was no recurrence following this treatment. The average survival time was 27 weeks with a range of 2-153 weeks. This operation should be part of the repertoire of the general surgeon who treats breast cancer and of the thoracic surgeon who treats lung cancer.

Angiogenic nature of the "intravascular bronchioloalveolar tumor" of the lung: an electron microscopic study.

An intravascular bronchioloalveolar tumor of lung (IVBAT) was studied with electron microscopy. Based on ultrastructural evidence and information obtained from the literature, we propose the following: (1) IVBAT is a true pulmonary neoplasm with distinctive morphologic features; (2) it consists of cells with endothelial characteristics and is probably derived from multipotential mesenchymal reserve cells; (3) it is not related to the typical bronchioloalveolar tumor of lung; (4) a more appropriate designation for this unusual pulmonary neoplasm is "sclerosing angiogenic tumor."

Evolution of pulmonary pseudolymphomas: clinical and radiologic manifestations.

Solitary or multifocal pulmonary pseudolymphoma developed in two men and two women between 59 and 76 years of age. The lesions were detected incidentally in three patients and following a respiratory infection in the fourth. Follow-up radiographs and chest CT revealed gradual expansion of the opacities without cavitation, calcification, or pleural involvement. Histopathologic sections from open lung biopsies or resected segments showed dense alveolar and peribronchial infiltration by numerous mature lymphocytes and plasma cells surrounding reactive lymphoid follicles with true germinal centers. Their benign nature was confirmed by immunofluorescent studies showing polyclonal cell populations. No recurrence or malignant change occurred during 4- to 9-year periods of observation. The clinical and radiologic features of pulmonary pseudolymphoma are presented with a brief review of 54 previously reported cases.