Comparison of survival after mitral valve replacement with biologic and mechanical valves in 1139 patients.

OBJECTIVE: We sought to compare 10-year survival in patients after mitral valve replacement with biologic or mechanical valve prostheses. METHODS: Retrospective survival analysis was performed on data from 1139 consecutive patients older than 18 years of age undergoing mitral valve replacement with Carpentier-Edwards (n = 495; Baxter Healthcare Corp, Irvine, Calif) or St Jude Medical (n = 644; St Jude Medical, Inc, St Paul, Minn) prostheses. RESULTS: The 10-year survival was not statistically different between the patients receiving Carpentier-Edwards valves and those receiving St Jude Medical valves (P =.16). Adjusted survival estimates at 2, 5, and 10 years were 82% +/- 2% (95% confidence intervals, 79%-85%), 69% +/- 2% (95% confidence intervals, 64%-73%), and 42% +/- 3% (95% confidence intervals, 37%-48%), respectively, for the Carpentier-Edwards group and 83% +/- 2% (95% confidence intervals, 80%-86%), 72% +/- 2% (95% confidence intervals, 69%-76%), and 51% +/- 3% (95% confidence intervals, 45%-58%), respectively, for the St Jude Medical group. Predictors of worse survival after mitral valve replacement are older age, lower ejection fraction, presence of class IV congestive heart failure, coronary artery disease, renal disease, smoking history, hypertension, concurrent other valve surgery, and redo heart surgery. CONCLUSION: Choice of biologic or mechanical prosthesis does not significantly affect long-term patient survival after mitral valve replacement.

Efficacy of the internal mammary artery in combined aortic valve replacement-coronary artery bypass grafting.

BACKGROUND: While internal mammary artery (IMA) use predicts improved survival after coronary bypass grafting (CABG), it remains unknown whether patients undergoing concomitant aortic valve replacement (AVR) realize a similar benefit. METHODS: All patients at a single teaching institution, undergoing combined AVR-CABG, which included a graft to the left anterior descending coronary artery (LAD) from 1984 to 1994 (n = 227) were examined retrospectively. RESULTS: Patients receiving an IMA graft (yesIMA, n = 135) and patients receiving only saphenous vein grafts (nonIMA, n = 92) were not different in their presenting symptoms, or in their incidence of preoperative risk factors. The patients with IMA were more likely to be male, have a later year of operation, be younger, and have a greater body surface. Morbidity was not different between groups. IMA use did not affect 30-day mortality. Long-term actuarial survival was greater in the group with IMA (63% +/- 7% vs 42% +/- 6% at 5 years, p < 0.01). A multivariate Cox proportional hazards model demonstrated that use of an IMA graft improved survival, while recent myocardial infarction, diabetes, earlier year of operation, and lower ejection fraction diminished long-term survival. The relative risk of IMA grafting was 0.570. CONCLUSIONS: Within the limits of a retrospective analysis, patients in a modern era of cardiac operation, who undergo combined AVR-CABG, do not suffer increased morbidity from IMA use, and may realize a survival benefit from use of the IMA as a conduit for bypass of the LAD coronary artery.

Mortality and need for reoperation in patients with mild-to-moderate asymptomatic aortic valve disease undergoing coronary artery bypass graft alone.

BACKGROUND: Patients presenting for coronary artery bypass graft (CABG) surgery may have concurrent asymptomatic aortic stenosis (AS) or aortic insufficiency (AI). This retrospective study was performed to evaluate outcomes in patients with aortic valve disease undergoing CABG with or without aortic valve replacement (AVR). METHODS: Study groups included 414 patients undergoing combined AVR and CABG (AVR-CABG group) and 62 patients with asymptomatic mild-to-moderate AS, AI, or both undergoing CABG but not AVR (CABG group). End points included 30-day mortality rate, time to cardiac mortality, time to all-cause mortality, and time to aortic valve reoperation. Reoperation refers to surgery for replacement of the native aortic valve in the CABG group or replacement of the prosthetic aortic valve in the AVR-CABG group. Important patient characteristics affecting outcomes were determined by using Cox proportional-hazard analysis. These variables were then included in multivariable analyses by using logistic regression analysis and Cox proportional-hazard modeling to compare outcomes between each patient group. RESULTS: No difference was seen in any of the mortality end points between the CABG group and the AVR-CABG group after controlling for significant differences between the groups. However, the need for reoperation for AVR was significantly higher for the CABG group than the AVR-CABG group. For patients followed for up to 6 years, the estimated need for aortic valve reoperation was 24.3% in the CABG group versus 3% in the AVR-CABG group. CONCLUSION: On the basis of these results, patients with asymptomatic AS or AI should be considered for AVR at the time of CABG.

Long-term outcome after biologic versus mechanical aortic valve replacement in 841 patients.

OBJECTIVE: The purpose of this study was to optimize selection criteria of biologic versus mechanical valve prostheses for aortic valve replacement. METHODS: Retrospective analysis was performed for 841 patients undergoing isolated, first-time aortic valve replacement with Carpentier-Edwards (n = 429) or St Jude Medical (n = 412) prostheses. RESULTS: Patients with Carpentier-Edwards and St Jude Medical valves had similar characteristics. Ten-year survival was similar in each group (Carpentier-Edwards 54% 3% versus St Jude Medical 50% 6%; P =.4). Independent predictors of worse survival were older age, renal or lung disease, ejection fraction less than 40%, diabetes, and coronary disease. Carpentier-Edwards versus St Jude Medical prostheses did not affect survival (P =.4). Independent predictors of aortic valve reoperation were younger age and Carpentier-Edwards prosthesis. The linearized rates of thromboembolism were similar, but the linearized rate of hemorrhage was lower with Carpentier-Edwards prostheses (P <.01). Perivalvular leak within 6 months of operation was more likely with St Jude Medical than with Carpentier-Edwards prostheses (P =.02). Estimated 10-year survival free from valve-related morbidity was better for the St Jude Medical valve in patients aged less than 65 years and was better for the Carpentier-Edwards valve in patients aged more than 65 years. Patients with renal disease, lung disease (in patients more than age 60 years), ejection fraction less than 40%, or coronary disease had a life expectancy of less than 10 years. CONCLUSIONS: For first-time, isolated aortic valve replacement, mechanical prostheses should be considered in patients under age 65 years with a life expectancy of at least 10 years. Bioprostheses should be considered in patients over age 65 years or with lung disease (in patients over age 60 years), renal disease, coronary disease, ejection fraction less than 40%, or a life expectancy less than 10 years.

Comparison of omental and pectoralis flaps for poststernotomy mediastinitis.

BACKGROUND: Pectoralis flaps are frequently used to treat poststernotomy mediastinitis. We compared the outcomes of omental transfer, an alternative treatment for mediastinitis, with those of pectoralis flaps. METHODS: Patients treated for poststernotomy mediastinitis with isolated omental flaps (n = 21) were compared with a group of consecutive patients treated with pectoralis flaps (n = 38). Baseline characteristics were equivalent for the two groups, and both early and late outcomes were compared. RESULTS: Length of procedure and length of postoperative hospitalization were reduced significantly and there were significantly fewer early complications in the group treated with omental flaps. Furthermore, there were no early or late flap failures or abscesses in the omental flap group. CONCLUSIONS: This study found that omental flaps had improved early outcomes and are a more effective therapy relative to pectoralis flaps for poststernotomy mediastinitis. Technical considerations for omental transfer that could optimize results are given.

Comparison of open mitral commissurotomy with mitral valve replacement with or without chordal preservation in patients with mitral stenosis.

BACKGROUND: Percutaneous balloon mitral valvuloplasty and durable mitral prostheses have made the role of open mitral commissurotomy (OMC) uncertain. METHODS AND RESULTS: Results from the use of St Jude mitral valve replacement (SJMVR) were compared with those of the use of OMC in 312 consecutive patients with mitral stenosis between 1983 and the present. OMC and SJMVR patients were well matched for age, sex, and comorbidity except that SJMVR patients had more severe stenosis and were more likely to undergo concurrent aortic valve replacement. Compared with OMC, SJMVR without chordal preservation involved a longer pump time (158 +/- 81 versus 87 +/- 41 min, P < 0.05), more frequent in-hospital complications or death (57 of 219 [26%] versus 4 of 52 [8%], P < 0.01), and longer hospital stay (13 +/- 11 versus 10 +/- 6 days, P = 0.001). Preservation of chordae to at least 1 mitral valve leaflet decreased early morbidity and mortality rates of SJMVR to values comparable to those of OMC (3 of 41 [7%]). Survival was greater at 10 years for OMC versus SJMVR (86 +/- 5% versus 67 +/- 4%, P = 0.03). Ten-year freedom from cardiac events was not different between groups (49 +/- 9% for OMC versus 55 +/- 4% for SJMVR, P = 0.7). Freedom from subsequent mitral procedures at 10 years was better for SJMVR (96 +/- 2% versus 58 +/- 8%, P < 0.001). CONCLUSIONS: In the modern era, SJMVR offers significantly greater durability than does OMC. Chordal preservation at the time of SJMVR may reduce perioperative complications to levels comparable to those of OMC.

Determinants of 15-year outcome with 1,119 standard Carpentier-Edwards porcine valves.

BACKGROUND: The determinants of long-term outcome 15 years or more after porcine valve replacement are poorly documented. METHODS: A retrospective review was performed of patients undergoing valve replacement with standard Carpentier-Edwards aortic (n = 531), mitral (n = 492), and tricuspid (n = 96) valves. RESULTS: Patient survival was 26%+/-3%, 23%+/-2%, and 31%+/-8% 15 years after aortic, mitral, and tricuspid valve replacements, respectively. Independent determinants of impaired long-term survival for aortic or mitral valve replacement were multiple valve replacement, older age, renal disease, lung disease, or coronary disease. Actual (versus actuarial) freedom from reoperation at 15 years was 86%+/-2%, 76%+/-2%, and 95%+/-2% after aortic, mitral, and tricuspid valve replacement, respectively. Risk factors for reoperation were young age for aortic or mitral valve replacement, previous operation for aortic valve replacement, and large valve size for mitral valve replacement. Freedom from thromboembolism was 77%+/-4%, 62%+/-9%, and 80%+/-5%; from hemorrhage, 95%+/-5%, 87%+/-4%, and 82%+/-6%; and from endocarditis, 94%+/-1%, 96%+/-1%, and 89%+/-5% 15 years after aortic, mitral, and tricuspid valve replacement, respectively. Risk factors for thromboembolism or hemorrhage were multiple valve replacement and age. CONCLUSIONS: The standard Carpentier-Edwards bioprosthesis continues to provide relatively low complication rates at 15 years, especially in the aortic and tricuspid positions, and especially in patients older than 60 years or with significant comorbdity.

Primary malignant melanoma of the esophagus.

A 48-year-old woman presented with a 6-month history of dysphagia, often associated with retrosternal chest pain. Upper endoscopy revealed an unusual pigmented lesion within the middle portion of the esophagus, and multiple biopsies were obtained. The histopathology and immunohistochemical profile of the tissue specimens were diagnostic of malignant melanoma. A thorough clinical and radiographic evaluation was performed, providing no additional findings or alternative primary source. Of approximately 11,500 melanoma patients entered in the Duke University melanoma database since 1970, this represents the only case of primary esophageal melanoma. The case is described and a review of the literature is presented.

Results of valve replacement with mechanical and biological prostheses in chronic renal dialysis patients.

BACKGROUND: Whether biological or mechanical valves should be used in patients on chronic dialysis therapy remains to be clearly defined. METHODS: A retrospective review was performed on 19 consecutive patients from our institution with end-stage renal disease on chronic peritoneal or hemodialysis undergoing aortic (n = 12), mitral (n = 5), or aortic-mitral (n = 2) valve replacement. RESULTS: The 9 biological and 10 mechanical valve patients had similar ages (56.5 versus 56.6 years) and cardiovascular risk factors. The overall estimated Kaplan-Meier survival was 60% +/- 12% at 12 months and 42% +/- 14% at 60 months. Mechanical valve patients had a significantly higher rate of postoperative cerebrovascular accidents or bleeding complications (10/10 versus 0/9; chi 2 = 17.0; p < 0.001). No subsequent reoperations were required for biological valve failure at a mean follow-up of 32 +/- 53 months. CONCLUSIONS: These results demonstrate that in patients with end-stage renal disease, use of mechanical valves is associated with significant risk of complications, whereas biological valve failure from prosthetic dysfunction is unusual. Overall survival is poor in both groups of patients. Therefore, preference should be given to biological valve instead of mechanical valve prostheses in patients on chronic renal dialysis.

Traumatic thoracic fistulas.

This article considers the wide range of fistulas that can result from blunt and penetrating trauma. The mechanisms, physical signs, diagnostic techniques, and nonoperative and operative management strategies for fistulas of the thorax are reviewed. Emphasis is placed on the requirement for a high index of suspicion in specific types of injury in which thoracic fistulas can occur.

Pulmonary abnormalities and PET data analysis: a retrospective study.

PURPOSE: To assess methods of standard uptake ratio (SUR) calculation with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) positron emission tomography (PET) in indeterminate focal pulmonary abnormalities. MATERIALS AND METHODS: One hundred ninety-seven adult patients with indeterminate pulmonary abnormalities had complete FDG PET data, consistent methods of data acquisition, and definitive diagnosis with tissue biopsy or negative 2-year follow-up findings. PET studies were evaluated by using SURs calculated with the average or maximum region-of-interest pixel value in the numerator and with weight, lean body mass, or body surface area in the denominator. RESULTS: One hundred twenty malignant lesions and 77 benign processes were identified. Receiver operating characteristic (ROC) curve areas were statistically significantly larger with the average rather than the maximum pixel value in the calculation of the SUR for any of the three denominators (P < or = .05). SURs calculated with weight versus lean body mass versus body surface area in the denominator showed no statistically significant difference in ROC curve areas. CONCLUSION: SURs determined by using average pixel values provide statistically significant improvement in ROC curve areas over those determined by using maximum pixel values. Weight, lean body mass, and body surface area in the denominator of the SUR calculation provide equivalent ROC curve areas and are therefore equivalent in accuracy in this population.

Effects of valve replacement on ventricular mechanics in mitral regurgitation and aortic stenosis.

BACKGROUND: This study in humans assessed changes in left ventricular function early and late after correction of mitral regurgitation (MR) (n = 9) or aortic stenosis (AS) (n = 10). METHODS: Ventricular function was measured with radionuclide and micromanometer-derived pressure-volume loops during preload manipulation, thermodilution cardiac outputs, and echocardiograms. Late radionuclide and echocardiographic data were acquired at 24 hours and 20 months. RESULTS: Perioperative left ventricular performance (stroke work-end-diastolic volume relationship) did not change for patients with MR or AS. Significant changes in afterload occurred: ejection fraction (MR, 0.49 to 0.37; AS, 0.54 to 0.60; both, p = 0.013), mean left ventricular ejection pressure (MR, 73 to 91 mm Hg; AS, 138 to 93 mm Hg; both, p < 0.01), and end-systolic wall stress (MR, 26 to 42 x 10(3) dynes/cm2; AS, 37 to 22 x 10(3) dynes/cm2; both, p < 0.01). Ejection efficiency improved for MR patients (0.69 +/- 0.26 to 1.0 +/- 0.15; p < 0.05). The 20-month data showed improved New York Heart Association functional class, normal resting ejection fraction, and normal exercise response for both groups. CONCLUSIONS: Early after operation, a significant change in left ventricular load was seen with correction of MR and AS. Data obtained late after operation showed improvement consistent with ventricular remodeling.

Management of microfistula following pulmonary resection.

The symptoms and signs of cough and changes in the air-fluid pattern on chest radiograph are critical as warning signs of bronchopleural fistula. Drainage of the pleural space is a critical first step for all patients to limit endobronchial contamination and prevent drowing. Once nutritional status is optimized and treatment for infection is established, suture reclosure of the bronchial stump with vascularized flap coverage is curative for the acutely presenting fistula, usually fewer than 2 weeks after surgery. Patients who present with bronchopleural fistula at times more remote from resection are unlikely to have direct reclosure of their fistula. These patients may have closure of their fistula by either an anterior, transpericardial approach, thoracotomy with muscle flap to fill the pleural space, or muscle flap coverage of the fistula with a limited thoracoplasty to obliterate the pleural space. Patients who cannot undergo operations of this magnitude may be treated with endoscopically placed tissue adhesives to seal the fistula. These various treatment options are successful in 75% to 100% of cases, and have been responsible for significantly reducing the morbidity and mortality from bronchopleural fistula.

Lung tumor growth correlates with glucose metabolism measured by fluoride-18 fluorodeoxyglucose positron emission tomography.

BACKGROUND: The growth rate, or doubling time, of radiographically indeterminate pulmonary abnormalities is an important determinant of malignancy. Prospective calculation of doubling time, however, delays diagnosis and treatment. Positron emission tomography (PET) using the glucose analogue fluoride-18 fluorodeoxyglucose (FDG) measures the enhanced glucose uptake characteristic of neoplastic cells. We postulated that if FDG activity correlates with doubling time, then PET may allow prompt diagnosis of lung cancer. METHODS: From March 1992 to July 1993, all patients with indeterminate focal pulmonary abnormalities were eligible for FDG PET imaging. In 53 patients, serial chest radiographs or computed tomograms were available and doubling time was computed. The FDG activity within the lesion was expressed as a standardized uptake ratio. RESULTS: The mean standardized uptake ratio (+/- SD) was 5.9 +/- 2.7 in 34 patients with cancer, versus 2.0 +/- 1.7 in 19 with benign disease (p < 0.001). Using a criterion of standardized uptake ratio 2.5 or greater for malignancy, the accuracy of PET was 92% (49 of 53). The standardized uptake ratio was significantly correlated with doubling time (r = -0.89; p = 0.002). CONCLUSION: These data suggest a direct relation between tumor growth and FDG uptake in lung cancer. The technique of FDG PET demonstrates exceptional accuracy and may permit prompt diagnosis of lung cancer.

Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence.

BACKGROUND: Nonsmall cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths in women and men in the United States, with more than 157,000 estimated deaths in 1995. Surgical resection remains the mainstay of therapy in Stage I and II disease. However, local and distant recurrence account for the disappointing survival rates after resection. Appropriate selection of surgical procedures and effective use of adjuvant therapies will depend upon the elucidation of prognostic factors that predict for recurrence. METHODS: A detailed analysis was undertaken to evaluate surgical therapy and to define risk factors associated with recurrence and cancer death in 289 consecutive patients with NSCLC who were diagnosed, resected and followed at the Duke University Medical Center from January 1, 1980, until December 31, 1988. These patients had no evidence of metastases on head and chest/abdominal computed tomograms and radionuclide bone scans before resection. Resected specimens from these patients pathologic verification of Stage I disease. Follow-up was complete in all cases through 8/1/94 (median, 61 months). Variables analyzed included age, sex, smoking history, presenting signs and symptoms, operative procedure, histopathology, hospital course including complications, and the time and location of any recurrence or cancer death. RESULTS: The 30-day mortality rate was 5 of 289 (1.7%), with minor and major morbidity rates of 17% and 9%, respectively. Statistical comparison of lobectomy (193) wedge resection (75) and pneumonectomy (21) revealed significantly (P < 0.04) smaller tumors (T1), more comorbidity, and fewer complications for wedge resection patients. A trend (P < 0.09) toward an increased rate of local/regional recurrence and no difference in survival was also observed for wedge resection. One hundred five patients died of cancer (13-month median time to recurrence) for an actual 5-year survival of 63%. Significant univariate predictors of early recurrence and decreased survival (P < 0.01) were: male sex, the presence of symptoms, hemoptysis, chest pain, type of cough, tumor size in cm and by T-classification, visceral pleural invasion, high mitotic index, and vascular invasion. Significant (P < 0.05) multivariate independent variables for early recurrence and cancer death were the presence of symptoms, vascular invasion, pleural invasion, high mitotic index, and tumor size greater than 3 cm. CONCLUSION: Current surgical therapy for stage I NSCLC has an acceptable morbidity and mortality rate. The current data also stratify patients with Stage I NSCLC into high and low risk populations that can be used in future randomized trials of adjuvant therapy.

Detection of primary and recurrent lung cancer by means of F-18 fluorodeoxyglucose positron emission tomography (FDG PET).

Positron emission tomography (PET), with the glucose analog F-18 fluoro-deoxyglucose (FDG), takes advantage of the enhanced glucose uptake observed in neoplastic cells. We examined whether the detection of preferential FDG uptake with PET permits differentiation between benign and malignant focal pulmonary lesions in patients with suspected primary or recurrent lung cancer. Between November 1991 and September 1993, 100 patients with indeterminate focal pulmonary abnormalities including 16 patients who had previous lung resections for cancer were prospectively studied. Tissue diagnosis was obtained by transbronchial or percutaneous biopsy (n = 49) and open biopsy or resection (n = 35). Three patients underwent extended observation (> 2 years) alone. Excluded were 13 patients lacking firm pathologic diagnoses and less than 2-year follow-up. FDG activity in the lesion was expressed as a calculated standardized uptake ratio. Mean standardized uptake ratio (+/- standard deviation) was 6.6 (+/- 3.1) in 59 patients with cancer versus 2.0 (+/- 1.6) in 28 with benign disease (p = 0.0001; unpaired t test, two-sided). With a standardized uptake ratio > or = 2.5 used for detecting malignancy, sensitivity, specificity, and accuracy were 97% (57/59), 82% (23/28), and 92% (80/87), respectively. Notably, in patients evaluated for pulmonary abnormalities after lung resection for cancer, all chest recurrences were correctly identified. The exceptional sensitivity of FDG PET demonstrates that malignant pulmonary lesions preferentially accumulate FDG, which results in a standardized uptake ratio > or = 2.5. PET may be useful for distinguishing recurrent tumor from postoperative, or postradiation, changes. If performed in all patients before open biopsy, PET increases the diagnostic yield by reducing the number of patients who have benign lesions at operation. Moreover, by lowering expenditures for hospitalization and other diagnostic procedures, FDG PET may significantly reduce health care costs.

The significance of c-erb B-2 and p53 immunoreactivity in patients with adenocarcinoma of the esophagus.

OBJECTIVE: Studies in breast cancer suggest that p53 and c-erb B2 protein overexpression are predictive of outcome. The authors determined whether these molecular markers correlated with treatment response and survival in patients with adenocarcinoma of the esophagus and esophagogastric junction. METHOD: Immunostaining for p53 and c-erb B2 was performed on paraffin-embedded specimens from 42 patients with esophageal adenocarcinoma. All patients received neoadjuvant chemotherapy (cisplatin and fluorouracil [5-FU] x 3 cycles) and irradiation (4500 rads) followed by resection. RESULTS: In this cohort of patients, 79% (33/42) were positive for p53, and 43% (18/42) were positive for c-erb B2. p53 positivity correlated with residual disease in the resection specimen but not with disease-free survival. Although c-erb B2 negatively correlated with residual disease after resection and a 5-year survival of 10%, c-erb B2 positivity was associated with a 5-year actuarial survival of 60%. CONCLUSIONS: Although p53 protein overexpression is commonly observed in adenocarcinoma of the esophagus, its prognostic value appears limited. In contrast, c-erb B2 protein expression predicts a favorable response to therapy and improved survival.

In-hospital and long-term outcome after porcine tricuspid valve replacement.

Porcine bioprostheses are often used for tricuspid valve replacement, yet the long-term outcome after this procedure is not well documented. Therefore, the records of 129 patients undergoing tricuspid valve replacement with Carpentier-Edwards (n = 88) or Hancock (n = 41) prostheses between 1975 and 1993 were reviewed. The operation required a repeat median sternotomy in 66 of 129 (51%) patients, whereas 67 of 129 (52%) underwent double or triple valve replacement. Operative mortality was 14% (2/14) in patients undergoing first-time isolated tricuspid valve replacement and 27% (35/129) overall. Survival at 5, 10, and 14 years was 56% +/- 5%, 48% +/- 5%, and 31% +/- 9%, and freedom from tricuspid reoperation at 5, 10, and 14 years was 96% +/- 3%, 93% +/- 4%, and 49% +/- 17%. No valve thrombosis was observed. In this largest reported series of porcine bioprostheses in the tricuspid position, long-term freedom from valve-related events was excellent because of a low incidence of valve thrombosis and a valve durability of 13 to 15 years in a population with limited life expectancy.

A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression.

In order to construct a multivariate model for predicting early recurrence and cancer death for patients with stage I non-small cell lung cancer, 271 consecutive patients (mean age, 63 +/- 8 years) who were diagnosed, treated, and followed at one institution were studied. All patients were clinical stage I with head and chest/abdominal computed tomograms and radionuclide bone scans without evidence of metastatic disease. Pathological material after resection was reviewed to verify histological staging. Follow-up documented the time and location of any recurrence, was a median 56 months in duration, and was complete in all cases. Data recorded included age, sex, smoking history, presenting symptoms, pathological description, and oncoprotein staining for erbB-2 (HER-2/neu), p53, and KI-67 proliferation protein. Immunohistochemistry of oncogene expression was performed on two separate archived paraffin tumor blocks for each patient, with normal lung as control. All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Data, including immunohistochemistry, were complete for all 271 patients. Actual 5-year survival was 63% and actuarial 10-year survival was 58%. Significant univariate predictors (P < 0.05) of early recurrence and cancer-death were: male sex; the presence of symptoms; chest pain; type of cough; hemoptysis; tumor size > 3 cm diameter (T2); poor differentiation; vascular invasion; erbB-2 expression; p53 expression; and a higher KI-67 proliferation index (> 5%). An additive oncogene expression curve demonstrated a 5-year survival of 72% for 136 patients without p53 or erbB-2, 58% for 108 patients who expressed either oncogene, and 38% for 27 who expressed both (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)