General Thoracic Surgery

General Thoracic Surgery

General Thoracic Surgery L. Penfield Faber, MD, FACS pect of the curriculum will only potentiate the momentum that general thoracic surgery has achie...

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General Thoracic Surgery L. Penfield Faber, MD, FACS

pect of the curriculum will only potentiate the momentum that general thoracic surgery has achieved in the past 10 years. The curriculum implementation task force of the Thoracic Surgery Directors Association is moving forward with this curriculum for all training programs. Monitoring of quality care and cost-cutting measures are continually being discussed and implemented. Cardiac surgical costcutting measures have received emphasis in most major medical centers because of volume and length of stay in intensive care units. Publications on cost containment in general thoracic surgery have been minimal. Wright and colleagues described a patient-care pathway that reduced length of stay and hospital costs.3 An important aspect of this study was that unit costs (not hospital charges) were available for items and services used in patient care. The mean length of stay for lobectomy patients was reduced by 3.1 days after the pathway was instituted, and the mean cost reduction was $1,271 per patient. Morbidity and mortality data were similar to those in a group of retrospectively analyzed prepathway lobectomy patients, indicating that quality of care was not hampered by this pathway. General thoracic surgeons must familiarize themselves with these types of cost-cutting measures.

General thoracic surgery is a dynamic specialty, and new techniques and therapies continue to evolve. Basic research is expanding through efforts of the Thoracic Surgery Foundation for Research and Education, and clinical research continues despite managed care. These are interesting times for this very viable specialty. There has been recent concern expressed as to what name we should define ourselves by as a subspecialty of thoracic surgery. The Liaison Committee for Thoracic Surgery was established by the Council of the American Association for Thoracic Surgery, and this committee’s actions and recommendations have resulted in a much clearer definition of the general thoracic surgeon. The term “general thoracic surgery” appears to be a viable and thriving definition of what we are about. Orringer clearly addressed the issue of what we should call ourselves and asked for clarification on who does what to whom.1 The term “general thoracic surgery” appears to be one that will be maintained. The General Thoracic Surgical Club recently celebrated its 10-year anniversary at its annual meeting and continues to thrive. Its membership is represented on many thoracic surgical policy-making committees, and this organization clearly champions the role of general thoracic surgery in our specialty. The Thoracic Surgery Directors Association has published a thoracic surgical curriculum that encompasses adult cardiac, pediatric cardiac, and general thoracic surgery.2 The general thoracic surgical as-

LUNG CANCER The American Joint Commission on Cancer has refined the lung cancer staging system to better reflect longterm prognosis with the various stages4 (Table 1). Stage I has been divided into stage IA and IB, splitting apart the T1 N0 and T2 N0 tumors. This logical separation is a result of the 10–20% difference in survival of these two stage groups. Stage II has been divided into IIA (T1 N1 M0) and IIB (T2 N1

Received October 27, 1997; Accepted October 27, 1997. From Rush Medical College, Rush-Presbyterian St. Luke’s Medical Center, Chicago, IL. Correspondence address: L. Penfield Faber, MD, FACS, 1725 West Harrison Street, Suite 218, Chicago, IL 60612. © 1998 by the American College of Surgeons Published by Elsevier Science Inc.

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Table 1. Revised Stage Grouping of TNM Subset Occult carcinoma Stage 0 Stage IA Stage IB Stage IIA Stage IIB Stage IIIA

Stage IIIB Stage IV

Tumor

Nodes

Metastasis

TX Tis T1 T2 T1 T2 T1 T2 T3 T3 Any T T4 Any T

N0 N0 N0 N0 N1 N1 N2 N2 N1 N2 N3 Any N Any N

M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

M0 and T3 N0 M0). There is similarly a 15% difference in the survival rates between these stage groups. The T3 N0 M0 tumors have been moved up to stage IIB from IIIA because of their improved survival when compared with the other stages of IIIA. Differentiation of central and peripheral T3 N0 tumors still needs to be better staged. The definition of a T4 tumor has been modified to include tumors with separate or satellite nodules in the primary lobe of the lung. A tumor nodule in an ipsilateral but separate lobe is now designated M1. Drings and coauthors analyzed the survival data of 5,155 patients and validated substages IA and IB in both clinical and pathologic staging, but no significant difference was noted in the new stages IB and IIA.5 The prognosis of the substages IIA and IIB was demonstrated to have a significant difference in clinical classification but not pathologic classification. Other stages were significant in their longterm prognosis. Unification of the two major systems of lymph node mapping has been presented by Mountain and Dresler.6 The anatomic landmarks for 14 nodal stations are now clearly defined. The major changes are to designate level-10 lymph nodes as hilar nodes (N1) and all level-4 nodes as N2 or mediastinal. Lower level-4 nodes can be designated as 4i. General thoracic surgeons can now uniformly discuss the same stage of disease in clinical reports. The clinical staging of lung cancer may be enhanced by positron emission tomography (PET), which identifies abnormalities by analyzing metabolic properties rather than anatomic size. Kutlu and coworkers evaluated PET scanning in 20 patients with proven non–small cell lung cancer (NSCLC) in whom routine computed tomography (CT) scans had found 26 additional lesions in the lung, adrenal, liver, kidney, spleen, and pleura.7 The PET scan in-

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dicated that 14 lesions were malignant and 12 were benign. Specific histology of the defined lesions was proved by invasive studies; PET scanning was found to be 89.2% accurate with a sensitivity of 88% and a specificity of 90%. Vansteenkiste and associates evaluated PET scanning as compared with CT scan and invasive surgical staging.8 The PET scan was significantly better compared with the sensitivity, specificity, and accuracy of the CT scan. Implementation of the PET scan with this level of accuracy would have reduced the number of invasive procedures from 37 to 13 in this series of 50 potentially operable NSCLC patients. The conclusion was that the PET scan was significantly more accurate than CT scan in mediastinal staging of lymph nodes. A larger series will be needed to confirm these findings. Scott and colleagues demonstrated that PET scan combined with CT scan was superior to CT scan alone at correctly predicting nodal status in patients with NSCLC.9 Precise location of suspected positive mediastinal nodes will aid in their detection by mediastinoscopy. The use of preoperative systemic therapy with or without concurrent thoracic radiation remains under investigation. Several phase II studies of preoperative chemotherapy or chemoradiotherapy have been performed.10,11 The results of these studies suggested that surgery is feasible after preoperative treatment. The one possible exception was the mitomycin/ vinblastine/cisplatin regimen, which was associated with high treatment-related mortality in one study11 and low lethal toxicity in the other trial.10 Results from other combined-modality trials appear to be better than those observed for radiation alone or surgery alone in patients with stage III NSCLC.12,13 Preoperative treatment using cisplatin-containing chemotherapy with or without radiation therapy is feasible, and surgical procedures can be accomplished with acceptable morbidity and mortality rates. It has been noted that preoperative treatment results in complete clearance of tumor in the resected specimen in approximately 15% of patients,12,13 and these patients have a significantly longer survival. Better survival results also have been noted in patients with metastases to ipsilateral mediastinal lymph nodes identified by mediastinoscopy before treatment, but in whom no tumor is found in the lymph nodes after treatment with chemoradiotherapy and surgical resection. Two small randomized trials have been conducted comparing surgery alone versus three courses of cisplatin-containing chemotherapy followed by

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surgery. Rosell and coworkers used mitomycin, ifosfamide, and cisplatin as the induction regimen.14 Median survival was 8 months for stage IIIA patients undergoing surgical resection alone, but it was 26 months for those receiving chemotherapy before surgery. Roth and associates used a regimen consisting of cyclophosphamide, etoposide, and cisplatin.15 Patients receiving surgery alone had a 15% 3-year survival; those receiving induction chemotherapy before surgery had a 56% 3-year survival. Although both trials had a small number of patients, which approximated 30 in each arm, there was significantly improved survival for patients who received preoperative chemotherapy and then surgery. The major question of whether surgery adds anything to combined-modality therapy consisting of chemotherapy and radiation is being addressed by all of the cooperative groups who have joined an Intergroup Trial (RTOG-9309). Each patient with stage IIIA NSCLC proven by mediastinoscopy is initially treated with cisplatin, etoposide, and simultaneous thoracic radiation. After receiving two courses of chemotherapy and 45 Gy of thoracic radiation, the patients are randomized to either surgery or additional radiation and two additional cycles of chemotherapy. This trial is important to all general thoracic surgeons, and they are encouraged to enter patients with resectable N2 disease if they have access to a cooperative study group. These phase II clinical trials have shown the superiority of combined-modality therapy over surgery or radiation alone in the treatment of stage IIIA (N2) NSCLC. What’s new is that these data indicate that patients with this stage of disease can be given preoperative chemotherapy or chemoradiation followed by surgery in the nonprotocol setting. Phase III trials being conducted in Europe regarding preoperative treatment along with the RTOG-9309 study will provide future information. Clear evidence for postoperative therapy for patients with completely resected stage II or stage IIIA disease has yet to be determined. A recent metaanalysis included all randomized trials testing postoperative chemotherapy or chemoradiotherapy.16 These data showed that the absolute risk of death was reduced by 3% at 2 years and by 5% at 5 years for patients who were treated with postoperative cisplatin-containing regimens compared with patients who were treated with surgery alone (p 5 0.08). There was a 2% absolute reduction in the risk of death in patients treated with postoperative radiation and cisplatin-based chemotherapy compared

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with patients who received only postoperative radiation (p 5 0.46). These results only suggest that cisplatin chemotherapy regimens given postoperatively may slightly improve survival. A potentially important postoperative adjuvant trial has recently accrued 462 patients. This was an Eastern Cooperative Oncology Group based phase III clinical trial comparing the role of adjuvant radiation therapy to that of concurrent chemotherapy plus radiation in patients who had undergone complete resection of stage II and IIIA NSCLC. Patients with enlarged mediastinal lymph nodes on preoperative chest CT scan or with preoperative histologic confirmation of mediastinal lymph node metastasis were excluded from the study. This trial is important because a large number of patients were entered, all NSCLC histologies were included, and a complete lymph node dissection was done on each patient. Several trials are currently underway to test postoperative chemotherapy in patients with completely resected NSCLC, and two ongoing European trials are evaluating postoperative chemotherapy in patients with stage I through IIIA disease. Investigators in the Cancer and Leukemia Group B study (CLB-9633) are comparing carboplatin/ paclitaxel versus observation alone after the resection of T2 N0 lung cancers. Emphasis on metastatic disease to regional lymph nodes in stage I NSCLC continues. Takizawa and coauthors evaluated 575 patients with clinical stage I NSCLC who had lobectomy and systemic mediastinal lymphadenectomy.17 Mediastinal lymph nodes were positive in 79 patients (14%), and 33% of patients with positive N2 nodes had negative N1 nodes. The lobar location of the primary tumor correlated well with the location of positive regional lymph nodes. The investigators concluded that systematic staging of mediastinal lymph nodes is necessary for patients with resectable clinical stage I lung cancer. This conclusion was based on the finding that 54 patients (68%) had only microscopic positive disease in grossly appearing mediastinal lymph nodes. Oda and associates evaluated the role of mediastinal lymph node dissection for clinical stage I resected NSCLC with respect to tumor diameter, histology, and mediastinal lymph node metastasis.18 There were 526 patients with clinical stage I NSCLC who underwent lung resection with systematic mediastinal lymph node dissection. Clinical nodal status was evaluated by CT scan in all patients. Seventythree patients had N2 or N3 disease; 36 patients had single-level metastasis and 37 patients had multilevel metastasis. The metastatic levels were widely distrib-

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uted, and metastatic nodes in 31 patients were out of reach of the mediastinoscope. Among 37 patients with squamous cell tumors measuring , 2 cm, only two patients had positive N1 disease. Patients with adenocarcinoma , 1 cm in size did not have positive nodal disease. The investigators concluded that systematic mediastinal lymph node dissection should be performed for clinical stage I lung cancer because of the variability and locations of multilevel nodal metastases. General thoracic surgeons await a proposed American College of Surgeons randomized trial to evaluate the longterm benefits of complete lymphadenectomy versus lymph node sampling. The peripheral small cell carcinoma should be considered for surgical resection. If diagnosed preoperatively, clinical staging would include CT scans of the head, chest, and upper abdomen, plus radionuclide bone scanning. Mediastinoscopy is mandatory because surgical resection is not indicated for mediastinal node-positive (N2) NSCLC. If a peripheral small cell carcinoma is identified at the time of surgery, a complete parenchymal resection and lymphadenectomy are indicated. Lymphadenectomy completely stages the disease pathologically and ensures a more complete resection. Postoperative chemotherapy is indicated in all patients with resected peripheral NSCLC and is related to the biology of this disease. Five-year survival rates of 50–60% can be achieved.19 It has not been determined yet whether surgery plus chemotherapy is superior to chemotherapy plus radiation therapy in node-negative tumors.20 Surgical therapy provides no benefit for centrally located small cell lung cancer.21 Thoracic surgeons should be familiar with the new chemotherapeutic agents that are now being used in the management of NSCLC. Vinorelbine is a new semisynthetic vinca alkaloid with a mechanism of action similar to that of the other vinca alkaloids and is more active than vinblastine and vincristine. This drug is active in combination with cisplatin and has been evaluated in randomized phase III trials, with positive results.22 Paclitaxel is cytotoxic and is also a radiationsensitizing agent. Paclitaxel and cisplatin have demonstrated synergistic cytotoxicity.23 Systemic toxicity consists of neutropenia and hypersensitivity reactions. Caution should be taken when paclitaxelcontaining chemotherapy is used with radiation therapy preoperatively. Faber and colleagues reported that 6 of 16 patients had serious postoperative complications, with one death from adult respiratory dis-

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tress syndrome, when this agent was used preoperatively.24 The relatively high incidence of postoperative pulmonary complications suggests that simultaneous paclitaxel and radiation may increase lung toxicity. Docetaxel has similar cytotoxic effects as paclitaxel and has potent radiation-sensitizing properties. Hematologic and nonhematologic toxicities are substantial even with reduced dosages. Gemcitabine has been shown to exhibit schedule-dependent cytotoxicity. Toxicity includes myelosuppression and flulike syndrome with fever and hypertension. This drug has demonstrated synergistic cytotoxicity with cisplatin and etoposide. Studies in the chemotherapeutic treatment of lung cancer with these newer agents will be forthcoming. Their benefits may include the opportunity for outpatient treatment, less toxicity, and improved tumor response in the preoperative setting. MESOTHELIOMA The International Mesothelioma Interest Group has presented a new international staging system for malignant pleural mesothelioma.25 This staging system was devised after analyzing the impact of tumor and nodal status on survival. The tumor descriptors use four different T gradings that provide better anatomic definition of the local extent of the mesothelioma. The N descriptors are similar to those used for the International Lung Cancer staging system. The stage groupings now recognize the better prognosis of T1 and N0 tumors and classify these tumors into stages I and II. The adverse effect of nodal metastasis on survival places N-positive tumors into stage III. Locally advanced unresectable (T4) tumors and extrathoracic disease (N3 or M1) are classified as stage IV. Diffuse malignant mesothelioma is difficult to stage, and thoracic surgeons should familiarize themselves with this system for future reporting of information. Sugarbaker and colleagues have recommended a staging system with four stages of disease that considers resectability and nodal status.26 Patients with stage I disease have resectable tumors and negative nodes; stage II refers to resectable tumors with positive nodes; stage III represents unresectable nodes; stage IV represents metastatic disease. The reported results of Sugarbaker and colleagues have renewed the interest in extrapleural pneumonectomy for diffuse malignant mesothelioma.26 Candidates must have resectable disease, be physiologically capable of withstanding extrapleural pneumonectomy, and demonstrate a satisfactory per-

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formance status. The patients undergo extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy. Carboplatin and paclitaxel are the chemotherapeutic agents used, and radiation therapy is given to the entire hemithorax and mediastinum to a cumulative dose of 54 Gy. Improved results were reported in 120 patients who underwent this multimodality therapeutic protocol, and the mortality rate was 5%. The survival at 2 and 5 years was 45% and 22%, respectively, with 21 months as the median survival. Two- and 5-year survival rates of 74% and 39%, respectively, were achieved in patients with epithelial histology and negative lymph nodes. Sarcomatous histology was associated with a poor prognosis, as described previously. It appears that the prognosis is best for patients with epithelial histology and localized disease without lymph node involvement. Smythe and associates demonstrated the feasibility of adenovirus administration into the pleural space of patients with malignant mesothelioma with evidence of gene transfer.27 This experimental work in rodents and subhuman primates has demonstrated the possible efficacy of this gene therapy. Thoracic surgeons await further reports on this mode of treatment.28 LUNG VOLUME REDUCTION SURGERY Lung volume reduction surgery (LVRS) is now being performed predominantly in the centers selected for the National Institutes of Health trial. Occasionally, third-party payers or health maintenance organizations will permit the procedure to be done in a nondesignated center, but the incidence of the procedure has been curtailed sharply by the National Institutes of Health trial and by Medicare’s unwillingness to reimburse hospitals and surgeons for the procedure. Cooper and coauthors reported on 150 consecutive bilateral lung volume reduction patients with severe emphysema.29 The patients had an average forced expiratory volume in 1 second (FEV1) of 25% of predicted, and the average residual volume was 283% of predicted. The 90-day operative mortality rate was 4%, and prolonged air leaks were the major complication. The 6-month results demonstrated a 51% increase in the FEV1 and a 28% reduction of residual volume. It was noted that among patients who previously needed supplemental oxygen, 70% no longer had this requirement. There was a significant reduction in dyspnea, and 1- and 2-year evaluations after the procedure showed that the benefits

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were maintained. Patient selection is obviously of great importance. McKenna and colleagues compared the results of unilateral and bilateral stapled LVRS.30 There was a 3.5% mortality rate for the unilateral procedure and a 2.5% mortality rate for the bilateral operation. It was noted that the bilateral procedures resulted in a mean improvement in the FEV1 of 57%, as compared with a 31% improvement for the unilateral operation. Unilateral procedures in compromised patients demonstrated a higher 1-year mortality rate because of late respiratory failure. The conclusion was that the bilateral operation is the procedure of choice. Unilateral LVRS can be an option in patients who have had a previous thoracotomy, asymmetric emphysema, or contraindications to sternotomy. Twenty-eight patients underwent unilateral LVRS for these indications, with an operative mortality rate of 3.6% (1 of 28). Patients having the unilateral approach demonstrated a mean improvement of 28% in FEV1 and 29% in forced vital capacity. The 6-minute walk distance was also improved.31 Discussion continues regarding the merits of video-assisted thoracic surgery (VATS) for LVRS versus sternotomy and bilateral stapling of the lungs. The results, complications, and morbidity and mortality rates are reported to be similar with these two techniques. Wisser and coworkers compared the perioperative data and functional results in 15 patients having sternotomy and 15 patients having a videoendoscopic approach.32 Mortality rates and levels of improvement in spirometry were similar in the two groups, with nearly identical lengths of hospital stay, chest tube duration, and morbidity. Kotloff and associates compared the VATS technique and open approach and described less morbidity with the thoracoscopic technique, with similar levels of functional improvement.33 Data in 1997 indicated that LVRS is beneficial for carefully selected patients with symptoms of severe emphysema. Results were similar for the open and VATS techniques. A randomized prospective study to compare the thoracoscopic and median sternotomy approaches to medical management with and without LVRS was begun in 1997 by the National Institutes of Health. Thoracic surgeons will await these results. VIDEO-ASSISTED THORACIC SURGERY The excitement over VATS seems to have settled, and the advantages and disadvantages of various

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VATS procedures are being defined more clearly. A questionnaire on the appropriate applications, advantages, and limitations of VATS was sent to members of the General Thoracic Surgical Club by Mack and coauthors.34 There was an 87.3% (200 of 229) response to the questionnaire by practicing general thoracic surgeons. Respondents designated VATS as the preferred procedure for the management and diagnosis of pleural disease, lung biopsy, recurrent pneumothorax, and sympathectomy. It was deemed an acceptable approach for diagnosis of the indeterminate pulmonary nodule and anterior and posterior mediastinal masses. It was also acceptable for the management of early empyema, clotted hemothorax, secondary pneumothorax, limited lung cancers, and benign esophageal disease. It was thought to be unacceptable for thymectomy, lobectomy, and LVRS. Lung volume reduction operations by experienced VATS surgeons, however, seem to contradict this latter point. The survey indicated that the use of VATS will increase over the coming years as surgeons gain more experience and techniques are refined. Longterm data on lung cancer resections and volume reduction surgery will also become available. Now that it is a more mature procedure, VATS has become a valuable addition to the practice of general thoracic surgery. Lewis and coworkers reported the results of 100 video-assisted surgical simultaneously stapled lobectomies without rib spreading.35 This technique entails simultaneous stapling of the vascular structures and bronchus to complete the lobectomy. Indications for this technique included a negative bronchoscopy and a negative mediastinoscopy when lymph nodes . 1 cm were noted on the CT scan. Visible lymph nodes were resected by the VATS technique when cancer was present. Nine patients had positive N1 nodes and two patients had positive N2 nodes. All of the various lobes were resected, and three patients had bilobectomies. Ninety patients had a primary lung cancer and six patients subsequently died of their cancer. Another six patients have had recurrence. Of the six patients who died, four demonstrated vascular spread and two had positive N1 nodes. All bronchial margins were free of microscopic invasion. Described advantages included shorter hospital stay, less postoperative pain, decreased hospital costs, and improved patient satisfaction. Kirby’s invited commentary on this article questioned the lobectomies done for benign disease, the low incidence of N2 disease identified at the time of SS lobectomy, and the lack of true substantiation

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of the described advantages of the simultaneously stapled lobectomy.36 For those thoracic surgeons who prefer mediastinal lymphadenectomy with resections of primary lung cancer, the adequacy of a VATS lymphadenectomy remains in question. Heniford and associates described 25 patients who had a clotted hemothorax or pleural infection associated with trauma treated by thoracoscopic techniques.37 In 19 patients (76%), the pleural cavity was evacuated satisfactorily by the thoracoscopic technique, and in four patients, open thoracotomy was necessary. Two additional patients required further procedures for drainage. The investigators concluded that the VATS technique was a safe and reliable operative therapy to evacuate retained thoracic collections. Thymectomy for patients with myasthenia gravis has been accomplished by the VATS approach. Mack and coauthors described 32 patients who had total thymectomy by the VATS technique.38 There was no mortality or longterm morbidity, and one patient required conversion to a lateral thoracotomy. Mean followup has been approximately 24 months, and clinical improvement was identified in 87.9% (29 of 33) of patients. No complete remissions have been noted. Techniques of the procedure are clearly described in this manuscript. The investigators stated that the results were similar to those of other techniques for resection of the thymus gland for myasthenia and further asserted that “the improved cosmesis of the video-assisted approach ideally will lead to earlier thymectomy in patients with myasthenia gravis.”38 Further followup will determine the longterm benefit for these patients. The adequacy of this technique for the removal of all thymic tissue does remain in question. Total thoracic esophagectomy with mediastinal lymphadenectomy has been described by Akaishi and colleagues.39 The esophagus and mediastinal lymph nodes were removed by the VATS technique. Laparotomy was accomplished to complete the dissection of the stomach, and a cervical anastomosis of the stomach to the esophagus was completed. Harvested lymph nodes approximated 20 in number, and 17 patients (45%) had positive lymph nodes. There was no 30-day hospital mortality. The investigators concluded that thoracoscopic mediastinal lymphadenectomy was feasible and completeness was comparable to that of open techniques. Extensive laboratory experience had been obtained by carrying out thoracoscopic esophagectomy on pigs before clinical trials were begun, and it is obvious

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that thoracoscopic expertise is required for this procedure. In summary, VATS surgery is finding its rightful place in the armamentarium of the general thoracic surgeon. METASTATIC DISEASE TO THE LUNG The International Registry of Lung Metastases was established in 1991 to assess the longterm results of pulmonary metastasectomy.40 This registry was begun among major centers of thoracic surgery in Europe and the United States with the establishment of a common data base. The initial report consisted of 5,206 cases of lung metastasectomy, with complete surgical resection accomplished in 4,572 patients. Incomplete resection in 634 was due to residual disease at the margin or in the lung tissue. Actuarial survival after complete resection was 36% at 5 years, 26% at 10 years, and 22% at 15 years. Survival was better for patients with a disease-free interval from time of resection of the primary tumor of . 36 months. There was a 43% actuarial 5-year survival for single lesions and a 27% actuarial survival for four or more lesions. Five-year survival was 44% for patients having a second metastasectomy. The best prognosis was for resection of metastatic germ cell tumors, and the worst prognosis was for the resection of metastatic melanoma to the lung. Robert and coworkers reported on factors influencing longterm survival after resection of metastatic disease to the lung.41 They reported 276 consecutive patients who underwent curative removal of metastatic disease. There were 63 patients who had a second-stage operation; 12 had three procedures and two patients had four operations. The actuarial survival was 69% at 2 years and 48% at 5 years. An interesting finding was that survival was not related to disease-free interval, multiple lung metastases, or tumors recurring after a first or second procedure. Isolated lung perfusion with chemotherapeutic agents is an exciting new technique for the treatment of pulmonary metastatic cancers. Abolhoda and associates designed a rat model for developing sarcoma in the lung.42 After injection of sarcoma cells into the pulmonary artery, a group of rats underwent isolated lung perfusion with doxorubicin. Control groups were perfused with buffered hetastarch in 0.9% sodium chloride or were untreated. Rats in the untreated and hetastarch in 0.9% sodium chlorideinfused groups had a median survival time of approximately 20 days, but the median survival time

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was 36 days for the animals undergoing isolated lung perfusion with doxorubicin (p , 0.00001). Two of the rats had tumor-free lungs at 6 weeks. These experiments have led to the development of human trials in which isolated lung perfusion is used as adjuvant therapy at the time of surgical resection of pulmonary metastasis. This technique has been used in patients, and these results will be forthcoming. LUNG TRANSPLANTATION There remains some controversy regarding single-lung transplantation versus double-lung transplantation for patients with emphysema. In a retrospective study, Sundaresan and colleagues analyzed 119 consecutive lung transplantations done for emphysema.43 Fifty patients received a single lung transplant and 69 received bilateral transplants. Evaluation of their data showed that the bilateral procedure was not associated with an increase in mortality or morbidity and did achieve better results in oxygenation, exercise tolerance, and longterm survival. Bronchiolitis obliterans occurred in both groups, with a higher incidence in the single-lung transplant group than with bilateral transplantation (51% versus 33%). Longer followup was available in the single-lung transplant group. Final recommendations were that single-lung transplantation is mainly indicated for older patients and those with smaller body size. Bilateral transplantation was indicated for younger patients who are in a better physiologic condition. Bavaria and coauthors compared the results of 29 patients who underwent bilateral-lung transplantation and 47 patients who underwent single-lung transplantation for chronic obstructive pulmonary disease.44 Sixty-day mortality was 21.3% for the single-lung transplantation group versus 3.5% for bilateral-lung transplantation (p 5 0.03). This difference in mortality was believed to be related to reduced primary graft failure in the bilateral transplant group. The 2-year survival was 63.3% after single-lung transplantation and 90% after bilaterallung transplantation (Kaplan-Meier analysis). Longer followup is necessary to complete this analysis, but bilateral-lung transplantation is now recommended for patients under the age of 55 because the 6-minute walk test and FEV1 were significantly improved in the bilateral group. The scarcity of donors continues to plague lung transplant surgeons. Starnes and associates reported on 38 living-donor lobar lung transplants in 27 adult

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and 10 pediatric patients.45 The cause of death in 14 of 37 patients was infection, related to the large group of patients with cystic fibrosis. These were bilateral transplantations that required 76 donors. Complications in the donor group included postpericardiotomy syndrome and atrial fibrillation, and three patients underwent reoperation for empyema, bleeding, and persistent air leak. Fifteen patients had 1-year followup, and their FEV1 was 73% of predicted. These results were thought to be encouraging, but because of donor risk, this procedure should be limited to patients in a severely critical condition and should be carried out at a center with extensive experience in lung transplantation. In an experimental model using immature swine, Binns and colleagues compared the results with a size-matched immature whole left-lung transplant versus a mature-sized upper- or lower-lobe transplant.46 Their data revealed that the oversized mature lobar graft provided improved hemodynamics as compared with the size-matched grafts. Obliterated bronchitis continues to be a major complication after heart-lung and lung transplantation. Reichenspurner and coworkers reviewed 135 heart-lung transplantations and 61 isolated lung transplantations for obliterative bronchiolitis.47 The overall incidence of obliterative bronchiolitis in these patients was 64% and 68%, respectively. Major risk factors were the frequency and severity of acute rejection episodes and lymphocytic bronchiolitis defined on transbronchial lung biopsy. The major cause of death in these patients was lung infection. The conclusion in this review was that transbronchial biopsy for early diagnosis is important, as immediate rejection treatment can improve results. Newer immunosuppressive agents may have the ability to minimize this complication of lung transplantation. The scarcity of donors has continued to spur investigators to analyze the use of non–heart-beating donors to retrieve organs for transplantation. D’Armini and associates have studied this problem extensively.48 Van Raemdonck and coauthors evaluated lung function after various amounts of deflation or inflation with varying types of ventilation after delayed hypothermic crystalloid flush.49 They concluded that alveolar collapse was a critical factor in protecting the lung from warm ischemic damage related to donor retrieval from a cadaver. Murakami and colleagues studied the use of nitric oxide for the ventilation of ischemic lungs retrieved from non– heart-beating donor rats.50 Their data indicated that inhaled nitric oxide reduced ischemia-reperfusion in-

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jury in the lungs harvested from non–heart-beating donors. In experiments in rabbits, Kuang and coworkers demonstrated that the rapid cooling of perfused lungs prevented ischemia-reperfusion injury and maintained good graft function after retrieval from the non–heart-beating donor.51 ESOPHAGUS Clinical staging of esophageal cancer is receiving greater emphasis to provide better selection of patients for therapy by surgery alone or neoadjuvant therapy followed by surgery for more advanced disease. Continuing use of endoscopic esophageal ultrasonography indicates its superiority to CT scan for defining depth of tumor penetration in the wall of the esophagus and regional lymph node status.52 Esophageal ultrasonography has been shown effective in identifying advanced esophageal disease that precludes surgery, identifying patients with T4 disease who are predicted to have a poor prognosis regardless of treatment, and predicting survival in patients undergoing brachytherapy and external irradiation. Esophageal ultrasonography can be used to identify patients with disease confined to the esophageal wall without lymph node metastasis, and these patients can be considered for surgical therapy alone. Patients with more advanced disease are considered for multimodality therapy. Thoracoscopy has been described to be of benefit in the staging of patients with esophageal cancer. Unnecessary thoracotomy can be avoided by defining T4 tumors, and metastatic disease to mediastinal lymph nodes can be defined. Laparoscopic staging has been added recently to the thoracoscopic staging for esophageal cancer, as described by Krasna.53 The accuracy in detecting lymph node metastasis in 18 patients was 94% (17 of 18). The accuracy of thoracoscopy in detecting lymph node involvement was 94% (29 of 31). Positron emission tomography also has been described as a staging tool for esophageal carcinoma. Block and colleagues reported on 58 patients with biopsy-proved esophageal cancer who were evaluated by PET scanning and CT scanning.54 Metastatic disease was identified in 17 patients who were then deemed nonresectable; CT was positive for metastasis in only 5 of these 17. Resection was accomplished in 35 patients, and positive lymph nodes were found in 21. The PET scan identified these nodes in 11 patients and the CT scan in 6. Scanning with PET appears to be superior to CT scanning in detecting

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both distant metastatic disease and lymph node involvement. Luketich and coauthors reported similar findings in their study investigating PET scanning for the staging of esophageal cancer.55 Data are now demonstrating that combination chemotherapy and irradiation followed by surgery improve the survival of patients with advanced esophageal carcinoma. Jones and associates reported on 66 patients who were treated with chemotherapy concurrently with radiation, followed by esophagectomy.56 Actuarial survival at 36 months was 32%, and a pathologic complete response rate of 41% was achieved. Statistical significance was achieved for the complete-responding patients in recurrence-free survival time. The Michigan Group has provided an updated analysis on their randomized series of patients with esophageal cancer who underwent a chemoradiotherapy regimen followed by surgery or surgery alone.57 The pathologic complete remission rate in the neoadjuvant group was 28%, and with a median followup of 5.6 years, there was a decrease in the risk of death for patients receiving preoperative combination chemoradiotherapy. Before this treatment program can become the standard of care, continuing followup data will be required from these phase II trials, along with a larger phase III trial comparing chemoradiotherapy followed by surgery with surgery alone. In the meantime, it does appear to be of benefit in esophageal cancer patients with operable disease. Chemotherapy alone followed by surgery is currently not of benefit for treating esophageal cancer. Ellis and coworkers reviewed a 24-year experience with 454 operations for carcinoma of the esophagus and cardia.58 Hospital mortality was 3.7%, with an overall 5-year survival of 24.7%. Modifications in staging are presented in this manuscript and should be reviewed by those interested in the clinical staging and treatment of esophageal cancer. Laparoscopic fundoplication continues to gain momentum, and indications for this technique are being clearly defined. Peters and DeMeester59 emphasized the many benefits of this technique for thoracic surgeons and stressed the need for thoracic surgeons to be involved in laparoscopic techniques. Increasing laparoscopic experience of general thoracic surgeons is enabling them to perform many of these procedures. Indications for this technique in patients with gastroesophageal reflux disease include a normal length of esophagus and normal contractility and wave progression. Patients with questionable esophageal length, decreased contractility, or abnormal esophageal wave progression are considered for

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the transthoracic approach. In a review of 100 patients, DeMeester reported that the primary symptoms of gastroesophageal reflux were relieved in 91% of patients by the laparoscopic Nissen fundoplication.60 DeMeester stated that “laparoscopic Nissen fundoplication has become the preferred surgical procedure for patients with uncomplicated gastroesophageal reflux disease.” Pearson stressed that the results of the open fundoplication operation should be the same as for the laparoscopic fundoplication.61 Indications for the open procedure include a short esophagus, abdominal adhesions, previous failed antireflux surgery, and laparoscopic intraoperative complications. Esophageal myotomy and partial fundoplication are now being accomplished by laparoscopic techniques. Graham and colleagues reported on 26 patients with achalasia and dysphagia who underwent this procedure.62 The mean operative time was 3.5 hours, and one patient had an intraoperative esophageal perforation. This perforation was repaired laparoscopically by suturing techniques, and the stomach was wrapped over the repair. The fundoplication is accomplished by loosely rolling the stomach over the lower esophagus and anchoring it in place between the fundus, the right myotomized esophageal muscle, and the right crust of the diaphragm. Postoperatively, 14 of 21 patients reported no dysphagia and six had dysphagia of less than one episode per week. One patient had dysphagia more than once per week. The reason for the failure to relieve dysphagia remained unclear to the authors. Postoperative symptoms of reflux were mild, but only a few patients underwent postoperative 24-hour pH studies. Longer followup is obviously required for this group of patients, but general thoracic surgeons must be familiar with this technique of laparoscopic esophageal myotomy. References 1. Orringer MB. What shall we call ourselves? The time for standardization. Ann Thorac Surg 1997;64:596–598. 2. Comprehensive Thoracic Surgery Curriculum. A program for study and clinical activity during thoracic surgery residency. Thoracic Surgery Directors Association, 1994. 3. Wright CD, Wain JC, Grillo HC, et al. Pulmonary lobectomy patient care pathway: a model to control cost and maintain quality. Ann Thorac Surg 1997;64:299–302. 4. Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997;111:1710–1717. 5. Drings P, Bulzebruck H, and Vogt-Moykopf I. Prognostic impact of the new 5th edition of the TNM classification for lung cancer (1997). Lung Cancer 1997;18(suppl 1):215. 6. Mountain CF, and Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997;111:1718–1723.

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in patients with resectable esophageal cancer: updated analysis. Proc Am Soc Clin Oncol 1997;16:277. Ellis FH Jr, Heatley GJ, Krasna MJ, et al. Esophagogastrectomy for carcinoma of the esophagus and cardia: a comparison of findings and results after standard resection in three consecutive eightyear intervals with improved staging criteria. J Thorac Cardiovasc Surg 1997;113:836–848. Peters JH, and DeMeester TR. Indications, benefits and outcome of laparoscopic Nissen fundoplication. Dig Dis Sci 1996;14:169– 179. DeMeester TR. Preoperative assessment and operative management of gastroesophageal reflux: laparoscopic fundoplication. ACS Postgraduate Course, General Thoracic Surgery 1997;8:38– 40. Pearson FG. Preoperative assessment and operative management of gastroesophageal reflux: open fundoplication. ACS Postgraduate Course, General Thoracic Surgery 1997;8:41–42. Graham AJ, Finley RJ, Worsley DF, et al. Laparoscopic esophageal myotomy and anterior partial fundoplication for the treatment of achalasia. Ann Thorac Surg 1997;64:785–789.