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.

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.

Ten-year survey of lung cancer treatment and survival in hospitals in the United States: a national cancer data base report.

BACKGROUND: Primary lung cancer accounts for approximately 14% of all new cancers and 28% of cancer deaths in the U.S. Previous reviews have shown limited progress in the management or outcome of this devastating disease. METHODS: Reports described in the current study were 713,043 primary lung malignancies diagnosed between 1985 and 1995 and submitted to the National Cancer Data Base. Demographic, tumor, and treatment patterns for 1995 were compared with those for 1985-1987, 1988-1991, and 1992-1994. Ten-year relative survival rates were presented for selected demographic and histologic groups and 5-year relative survival rates were presented by stage and dominant treatment modalities for major carcinoma histologies. RESULTS: Previously observed demographic trends were evident, with increasing proportions of patients being older, female, and African American, and more cases reported to be adenocarcinomas. There was a substantial shift toward more complete staging but no change in the distribution of staged cases. Compared with earlier patients, fewer 1995 patients received cancer-directed treatment. More surgical patients underwent lymph node dissection, and radiation treatment was supplemented more often with chemotherapy. The overall 10-year relative survival rate was 7%. The 5-year survival for American Joint Committee on Cancer Stage I surgical patients was >50% for all nonsmall cell histologic groups. CONCLUSIONS: Recent shifts in treatment, although minimal, are consistent with current literature concerning the effectiveness of lung carcinoma treatment. The authors believe that the overall poor survival of lung carcinoma patients points to a continuing need for improved prevention and treatment measures. The comparatively superior survival of Stage I nonsmall cell lung carcinoma surgical patients indicates that a substantial number of patients have the potential to be treated successfully.

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.

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.

Complications from induction regimens for thoracic malignancies. Perioperative considerations.

The treatment of locoregionally advanced non-small cell lung cancer is evolving rapidly, and we as surgeons should continue to take a prominent role, from the pretreatment evaluation phase, through reassessment after induction therapy and intraoperative decision making, to vigilant postoperative care. These are by far the most challenging thoracic oncologic patients to care for. The multidisciplinary team formula required for optimal results and mandates the leadership that we, as surgeons familiar with all facets of patient care, can provide.

Amplification of residual DNA sequences in sterile bronchoscopes leading to false-positive PCR results.

PCR has been used successfully for the direct detection of Mycobacterium tuberculosis in uncultured patient samples. Its potential is hindered by the risk of false-positive results as a result of either amplicon carryover of cross-contamination between patient samples. In the present study, we investigated whether residual amplifiable human or M. tuberculosis DNA could remain in sterile bronchoscopes and potentially be a cause of false-positive PCR results in subsequent patient samples. Sterilized bronchoscopes were flushed with sterile saline, and the collected eluate was submitted for PCR amplification of IS6110 sequences and exon 8 of the human p53 gene. Of a total of 55 washes of sterile bronchoscopes from two institutions, 2 (3.6%) contained amplifiable M. tuberculosis DNA and 11 (20%) contained residual human DNA. These findings indicate that residual DNA can remain in sterilized bronchoscopes and can be a source of false-positive PCR results.

The National Cancer Data Base report on lung cancer.

BACKGROUND: Previous Commission on Cancer data from the National Cancer Data Base (NCDB) have examined time trends in stage of disease, treatment patterns, and survival for selected cancers. The most current (1992) data for lung cancer are described here. METHODS: Four Calls for Data have yielded a total of 560,455 lung cancer cases diagnosed in 1986-1987 and 599,597 cancer cases diagnosed in 1992, from hospital cancer registries across the United States. RESULTS: A total of 91,115 lung cancer cases diagnosed in 1986-1987 and 92,182 diagnosed in 1992 were reported from cancer registries across the United States. Lung cancer occurs mainly in patients between the ages of 50 and 80 years. There was an increasing relative frequency of adenocarcinoma, and of lung cancer in women, and a noteworthy poor prognosis among African Americans. Lung cancer patients were reported from all types and sizes of hospitals in America, from smaller community hospitals to major teaching centers. Treatment by surgical resection occurred more frequently in the major cancer centers. The overall prognosis for lung cancer remains extremely poor. CONCLUSIONS: For a selective category of patients (Stage I), cancer-directed surgery offers reasonable cure rates, but these data underline the need for earlier diagnosis and improved treatment modalities in the overall management of lung cancer patients.

Thoracic incisions.

There are many ways to gain access to the chest. In recent years, there has been a rediscovery of the clamshell incision, an evolving concept of the utility incision for video-assisted thoracic surgery (VATS), and a continued emphasis on the importance and usefulness of the muscle-sparing axillary thoracotomy, which continues to be the author's most frequently used incision.

Parietal pleurectomy for malignant pleural effusion.

BACKGROUND: Malignant pleural effusions are seen frequently in clinical practice and are most commonly caused by breast cancer and lung cancer. Standard treatment usually consists of complete drainage of the pleural space via a chest tube and instillation of a pleural irritant to obtain pleural symphysis. In a majority of instances, such treatment effectively controls the pleural space; however, standard treatment fails in some cases. METHODS: Twenty-four patients who did not respond to standard treatment for malignant pleural effusion were subjects for parietal pleurectomy, which was usually performed through an axillary thoracotomy. In several cases, decortication was also necessary. The study population was composed of 18 women and six men. Twelve of the patients had carcinoma of the breast, five carcinoma of the lung, and four carcinoma of the ovary. RESULTS: Three patients died in the perioperative period to give an operative mortality of 12.5%. The other 21 patients all had satisfactory control of their recurrent malignant effusions. Their survival time ranged from 2 to 30 months (average 10.6). CONCLUSIONS: Parietal pleurectomy is an effective operation for recurrent malignant pleural effusion. However, because of its significant morbidity and mortality, it should be reserved for failures of standard treatment, and patient selection is important.

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.

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.

Spontaneous pneumothorax.

Most cases of spontaneous pneumothorax can be handled either expectantly or by tube thoracostomy with good results. When surgical intervention is required, good results from treatment can be expected with minimal morbidity, a very low recurrence rate, and a mortality rate near zero. The traditional surgical approach has been a transaxillary thoracotomy with bleb resection and apical mechanical pleurodesis. A similar procedure, however, can be performed by VATS and may ultimately replace thoracotomy as the technique of choice.

Imaging manifestations of pleural tumors.

Although radiologic assessment of pleural tumors may be accomplished with several imaging modalities, the standard noninvasive techniques include chest radiography and computed tomography (CT). These examinations may be supplemented with magnetic resonance imaging and occasionally with ultrasound. Depending on the location, size, and underlying histologic features, pleural tumors may produce a spectrum of findings. CT is particularly useful in defining the location and extent of these masses. The authors present a review of basic pleural anatomy and imaging features of both benign and malignant pleural neoplasms. The pleural may be involved by one of several primary or metastatic tumors. Specific cell types are diffuse malignant mesothelioma (the most common plain radiographic findings are unilateral pleural effusion and pleural thickening), localized fibrous tumor (circumscribed, spherical or ovoid, noncalcified lesions arising in the pleural surface), metastatic disease (radiographic findings may mimic those of malignant mesothelioma), and uncommon neoplasms including thymoma and lymphoma. Among these various pleural tumors, metastatic disease represents the most common neoplasm.

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.

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.

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.