Surgeons' assessment of symptoms suggesting extrathoracic metastases in patients with lung cancer. Canadian Lung Oncology Group.

BACKGROUND: In patients with apparently operable non-small cell lung cancer (NSCLC), clinicians often omit investigation for M disease in asymptomatic patients. Previous investigations have not specified in detail what is meant by "symptomatic," and this could differ between surgeons. We have investigated the extent to which surgeons' criteria differ for presence of symptoms. METHODS: Participating surgeons from seven centers, enrolled patients they judged "asymptomatic" in a randomized trial of investigational strategies for NSCLC. Patients completed a structured questionnaire describing symptoms of the central nervous system (CNS). In 685 patients, we documented CNS symptom recurrence after resectional surgery over 1 year of follow-up. RESULTS: Two centers enrolled only patients without even the mildest symptoms. Three centers took an intermediate approach, occasionally classifying patients with mild symptoms as "asymptomatic" and thus enrolling them in the trial. Two centers classified an appreciable number of patients with minimal symptoms, and occasionally with more than minimal symptoms, as "asymptomatic." Patients with even mild CNS symptoms were more likely to subsequently present with CNS metastases. CONCLUSIONS: Thoracic surgeons differ in their ideas of what may constitute the symptoms of M disease. Patients with structured questionnaire results that suggest symptoms of CNS disease are more likely to have CNS symptom recurrence after resectional surgery.

Reperfusion edema after lung transplantation: radiographic manifestations.

PURPOSE: To characterize the radiographic manifestations of reperfusion edema after lung transplantation and to correlate the severity of the radiographic findings with pulmonary physiology. MATERIALS AND METHODS: Chest radiographs obtained after 45 lung transplantation procedures (20 single, 25 double) were reviewed retrospectively. Physiologic parameters (alveolar-arterial gradient, ratio of partial pressure of oxygen to fraction of inspired oxygen) were noted in patients who underwent intubation. RESULTS: Reperfusion edema appeared on day 1 in 39 transplants and by day 3 in 44. One patient's lungs remained clear. Peak severity occurred by day 4 in 43 of 44 transplants. At peak severity, reperfusion edema appeared as reticular interstitial disease in the upper (19%), middle (33%), and lower (34%) lung zones or air-space disease in the upper (31%), middle (61%), and lower (57%) zones. Reperfusion edema was asymmetric after double-lung transplantation in nine patients. The process cleared by day 10 in five transplants and by day 21 in another seven. There was a poor correlation between the severity of radiographic findings and physiologic measurements. CONCLUSION: Reperfusion edema is almost invariable after lung transplantation and most often appears as air-space disease in the middle and/or lower lung zones. The severity of radiographic findings is a poor indicator of pulmonary physiology.

Simultaneous single-lung transplantation and lung volume reduction.

We report our experience with 2 cases of simultaneous single-lung transplantation and lung volume reduction for emphysema. The lung volume reduction was undertaken electively in an attempt to improve overall lung function above that to be expected from single-lung transplantation alone. There were no postoperative problems related to the addition of lung volume reduction. The pulmonary function at 3 months was greater than that seen in a retrospective group of bilateral lung transplants previously reported from our institution.

Adenoid cystic carcinoma of the airway: thirty-two-year experience.

METHODS: We have reviewed our experience in 38 patients with adenoid cystic carcinoma of the upper airway seen between 1963 and 1995. The mean age was 44.8 years (15 to 80 years) with a male/female ratio of 1:1.1. Thirty-two of the 38 patients were treated by resection and reconstruction (primary anastomosis 28; Marlex mesh prosthesis 4). Twenty-six of the 32 patients undergoing resection received adjuvant radiotherapy. Six patients with unresectable tumors were treated primarily with radiotherapy only. RESULTS: Pathologic examination revealed local invasion beyond the wall of the trachea in all patients. In a majority, microscopic extension was found in submucosal and perineural lymphatics, well beyond the grossly visible or palpable limits of the tumor. Lymphatic metastases were relatively uncommon, occurring in only five of 32 (19%) patients undergoing resection. Metachronous hematogenous metastases occurred in 17 of 38 patients (44%). Thirteen of these 38 patients (33%) had pulmonary metastases. Sixteen of 32 resections were complete and potentially curative. There were two deaths within 30 days of operation. The mean survival in the 14 patients undergoing complete resection was 9.8 years (12 months to 29 years). Sixteen of 32 resections were incomplete (residual tumor at the airway margin on final pathologic examination), with one operative death occurring in this group. The mean survival in the 15 surviving patients was 7.5 years (4 months to 21 years). Six patients were treated with primary radiation only and had a mean survival of 6.2 years (2 months to 14.3 years). In the patients with pulmonary metastases, mean survival was 37 months (4 months to 7 years) from the time of diagnosis of the pulmonary metastasis until their death. CONCLUSION: Adenoid cystic carcinoma of the upper airway is a rare tumor, which is locally invasive and frequently amenable to resection. Although late local recurrence after resection is a feature of this tumor (up to 29 years), excellent long-term palliation is commonly achieved after both complete and incomplete resection. There was a small difference in survival between patients having complete and incomplete resection. Long periods of control can be obtained with radiotherapy alone. The best results, in this series of patients, were obtained by resection. Adjuvant radiotherapy is assumed to favorably influence survival.

Previous intrapleural procedures do not adversely affect lung transplantation.

BACKGROUND: Initially a previous intrapleural procedure causing a partially or completely fused pleural space represented a contraindication to lung transplantation. However, as experience with transplantation increased, particularly in patients with septic lung diseases who frequently have pleural adhesions, a previous intrapleural procedure became a relative rather than an absolute contraindication. The "clam shell" incision, which allows better control of the pleural spaces than a median sternotomy, contributed to this change. METHODS: The outcome of 18 patients with a previous intrapleural procedure was compared with 18 paired controls without previous surgery involving the transplanted pleural space. RESULTS: Five study patients had a predictably fused pleural space from their previous surgery, and four had extensive adhesions (major previous intrapleural procedures). The nine patients with minor previous intrapleural procedures had undergone more limited intrapleural procedures (open lung biopsy or chest tube drainage of a pneumothorax). There was no statistically significant trend for the operating time, blood loss, transfusion requirements, time intubated, and intensive care unit stay to be greater in the study population than in the controls. However, the major previous intrapleural procedure patients were younger, required longer cardiopulmonary bypass, and had a longer intensive care unit stay. The 6- and 12-month forced expiratory volumes in 1 second from the patients with major previous intrapleural procedures were not different from those of either the patients with minor previous intrapleural procedures or the controls. CONCLUSIONS: A previous intrapleural procedure, even when resulting in a fused pleural space, did not have a significant detrimental impact on outcome. Therefore a previous intrapleural procedure should neither preclude listing a patient for transplantation nor significantly influence the choice of recipient when lungs become available for transplantation.

Pleural complications in lung transplant recipients.

Pleural complications occurred in 30 (22%) of 138 patients after 53 single and 91 double lung transplants between September 1986 and February 1993. These were defined for the purpose of this study as pneumothorax persisting beyond the first 14 postoperative days, recurrent pneumothorax, or any other pleural process that necessitated diagnostic or therapeutic intervention. Overall, a higher pleural complication rate was seen in double lung transplantation (25 of 30) than in single lung transplantation (5 of 30) with no differences noted in the frequency among preoperative diagnostic groups (p > 0.05). Pneumothorax was the most frequent complication, affecting 14 of 30 patients, with 6 of 14 cases occurring after transbronchial biopsy. All pneumothoraces in single (n = 4) and double lung transplantation (n = 10) resolved spontaneously or with chest tube thoracostomy. One patient required placement of a Clagett window after open lung biopsy and another required thoracotomy and pleural abrasion after transbronchial biopsy. Parapneumonic effusion was observed in 4 of 30 double lung transplantations with spontaneous resolution in all cases. Empyema affected 7 of 30 patients and occurred exclusively in the double lung transplant group. Sepsis developed in three of the patients with this complication and they subsequently died. The risk of empyema was independent of preoperative diagnosis (p > 0.05). Of interest, all patients with cystic fibrosis (n = 3) with complicating empyema had Pseudomonas cepacia in the pleural fluid. Other miscellaneous complications included subpleural hematoma, chylothorax, and hemothorax. The latter two necessitated thoracic duct and bronchial artery ligation, respectively. In summary, a significant proportion of lung transplant recipients will have pleural space complications. The vast majority of these will resolve spontaneously or with conservative procedures. These complications were not related to preoperative diagnosis nor associated with a significant prolongation of hospital stay (p > 0.05). Empyema is the only pleural space complication associated with increased patient mortality and, as such, is an important clinical marker for those at risk for sepsis and death.

Mediastinal invasion by bronchogenic carcinoma: CT signs.

PURPOSE: To determine the accuracy of computed tomographic (CT) signs in assessment of direct mediastinal invasion by primary bronchogenic carcinoma. MATERIALS AND METHODS: In 90 patients with primary bronchogenic carcinoma who underwent CT with thoracic surgical staging and thoracotomy, the pathologic and CT findings in 14 mediastinal structures were compared retrospectively. The degree of contact of the primary tumor with each structure and whether the structure was distorted or contained intraluminal tumor were recorded. A total of 785 mediastinal structures (25 with tumor invasion) were analyzed. RESULTS: When greater than 90 degrees of contact was considered a positive CT finding, the sensitivity of CT was 40% (10 of 25 structures); specificity, 99% (752 of 760 structures); and positive and negative predictive values, 56% and 98%. All structures with > 180 degrees of contact had pathologic involvement, but only 11 of 17 distorted structures (65%) and five of seven structures with intraluminal tumor (71%) were involved. CONCLUSION: CT is insensitive in detection of mediastinal invasion by primary bronchogenic carcinoma. The positive predictive value may be higher, depending on the criteria used.

Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group.

BACKGROUND: The efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit. METHODS: We conducted a prospective multicenter cohort study in which we evaluated potential risk factors for stress ulceration in patients admitted to intensive care units and documented the occurrence of clinically important gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion). RESULTS: Of 2252 patients, 33 (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5 percent in the group with bleeding and 9.1 percent in the group without bleeding (P < 0.001). CONCLUSIONS: Few critically ill patients have clinically important gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be safely withheld from critically ill patients unless they have coagulopathy or require mechanical ventilation.

Staging for M disease.

The presence of distant metastatic disease (M disease) in non-small-cell cancer patients is associated with a poor prognosis, and surgical resection at the primary site is contraindicated. Careful preoperative evaluation to identify the subset of patients presenting with M disease is essential in order to avoid unnecessary surgery. Current indications for the use of diagnostic techniques and the methods utilized to detect metastatic disease at the commonest sites encountered in patients with non-small-cell carcinoma, including the pleura, central nervous system, liver, adrenal glands, and skeletal system, are discussed.

Prospective assessment of a standardized pathologic grading system for acute rejection in lung transplantation.

Using the recent standardization of the pathologic definitions for acute lung rejection, we prospectively evaluated 66 consecutive bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) specimens in 32 patients after lung transplantation. Clinical indications for bronchoscopies were surveillance (n = 44), rejection (n = 18), and infection (n = 4). Bronchoalveolar lavages were obtained from the right middle lobe or lingula in single lung transplant and from both sites in double lung transplant recipients. Cytosmears for differential cell counts were performed and 400 to 500 cells were counted. Five to eight TBB specimens were taken from two different lobes and stained with hematoxylin-eosin, elastic trichrome, and silver methenamine. Sixty-four of 66 sets of biopsy specimens were satisfactory, but 3 were eliminated because of presence of cytomegalovirus cytopathic changes. Of the remaining 61, rejection was presented in 45 (74 percent): grade 1 in 23 (38 percent), grade 2 in 19 (31 percent), and grade 3 in 3 (5 percent). In 30 of 42 (71 percent) surveillance biopsy specimens, rejection was present, grade 1 in 18 (43 percent) and grade 2 or 3 in 12 (28 percent). In TBBs performed for clinical suspicion of rejection, 15 of 18 TBB specimens (83 percent) showed rejection, grade 1 in 5 (28 percent) and grade 2 or 3 in 10 (55 percent). Of four biopsies performed for suspicion of infection, one was normal and three showed rejection in addition to infection. These three were eliminated from further analysis due to the limitation of the Lung Rejection Study Group criteria in distinguishing rejection from infection. Of the 45 episodes of rejection, 24 (53 percent) occurred during the first 3 months posttransplantation, 8 (18 percent) between 3 and 6 months and 13 (29 percent) after 6 months. Percentage of BAL lymphocytosis was significantly elevated in grade 2 or 3 rejection (28 +/- 4) when compared with grade 1 (15 +/- 3) or grade 0 (10 +/- 3) (p < 0.001). Bronchoalveolar lavage lymphocytosis also correlated with severity of rejection (r = 0.6). We conclude that according to the standardized criteria of the Lung Rejection Study Group, acute lung rejection occurs more frequently than clinically suspected early and late after transplantation and that BAL lymphocytosis correlates with the presence and severity of histologically proven rejection.

Unilateral donor lung dysfunction does not preclude successful contralateral single lung transplantation.

Single lung transplantation remains limited by a severe shortage of suitable donor lungs. Potential lung donors are often deemed unsuitable because accepted criteria (both lungs clear on the chest roentgenogram, arterial oxygen tension greater than 300 mm Hg with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 5 cm H2O, and no purulent secretions) do not distinguish between unilateral and bilateral pulmonary disease. Many adequate single lung grafts may be discarded as a result of contralateral aspiration or pulmonary trauma. We have recently used intraoperative unilateral ventilation and perfusion to assess single lung function in potential donors with contralateral lung disease. In the 11-month period ending October 1, 1990, we performed 18 single lung transplants. In four of these cases (22%), the donor chest roentgenogram or bronchoscopic examination demonstrated significant unilateral lung injury. Donor arterial oxygen tension, (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) was below the accepted level in each case (246 +/- 47 mm Hg, mean +/- standard deviation). Through the sternotomy used for multiple organ harvest, the pulmonary artery to the injured lung was clamped. A double-lumen endotracheal tube or endobronchial balloon occlusion catheter was used to permit ventilation of the uninjured lung alone. A second measurement of arterial oxygen tension (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) revealed excellent unilateral lung function in all four cases (499.5 +/- 43 mm Hg; p less than 0.0004). These single lung grafts (three right, one left) were transplanted uneventfully into four recipients (three with pulmonary fibrosis and one with primary pulmonary hypertension). Lung function early after transplantation was adequate in all patients. Two patients were extubated within 24 hours. There were two late deaths, one caused by rejection and Aspergillus infection and the other caused by cytomegalovirus 6 months after transplantation. Two patients are alive and doing well. We conclude that assessment of unilateral lung function in potential lung donors is indicated in selected cases, may be quickly and easily performed, and may significantly increase the availability of single lung grafts.

Infectious complications following isolated lung transplantation.

STUDY OBJECTIVE: To ascertain the incidence, types, morbidity, and mortality of infectious episodes in isolated lung transplant recipients. DESIGN: Retrospective chart review of patients who have undergone transplants over a six-year period in one institution. PATIENTS: Twenty-three single and 17 double lung transplants followed up between 2 and 68 months. RESULTS: Fifty-one episodes of infection occurred in the group with a slight predominance in the double lung transplants. The 32 episodes of bacterial infection constituted the largest group of infection and more than half of these were pneumonias. Organisms identified were predominantly Gram negative. While bacterial processes made up the bulk of infections, fatalities were rare. Viral and fungal infections were less common, but more often fatal. Of six cases of viral pneumonitis, two were fatal; two of five cases of invasive fungal infection were also fatal. Overall, six patients died of infection. CONCLUSION: Our findings support previous reports from heart-lung centers documenting a high rate of infectious complications, particularly pneumonia, in recipients of lung grafts. In our experience, bacterial infections are the most common (two of three infections), but have the lowest mortality. Efforts should be directed toward establishing effective prophylaxis programs and early detection of infection.

Bilateral lung transplantation for cystic fibrosis. The Toronto Lung Transplant Group.

Between March 1988 and March 1991, 17 patients underwent bilateral lung transplantation for end-stage lung disease caused by cystic fibrosis. There were 11 male and six female patients. Ages ranged from 19 to 41 years (mean age 28 years). Preoperative mean arterial oxygen tension with the patient breathing room air was 54 +/- 6 mm Hg; forced vital capacity, 1.8 +/- 0.7 L; forced expiratory volume in 1 second, 0.9 +/- 0.3 L; and 6-minute walk test, 506 +/- 44 m. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone. Induction immunosuppression was obtained with Minnesota antilymphocyte globulin. All patients received perioperative antibiotics according to sputum cultures and sensitivities. There were six operative deaths, four of which resulted from bacterial infection. Two patients required a second transplantation, one receiving a single lung and one undergoing bilateral lung replacement. Significant functional improvement was observed in all survivors. At 3 months follow-up, mean arterial oxygen tension on room air was 95 +/- 6 mm Hg (p less than 0.01); forced vital capacity, 3 +/- 0.8 L (p less than 0.01); forced expiratory volume in 1 second, 2.6 +/- 0.9 L (p less than 0.01); and 6-minute walk test, 678 +/- 47 m (p less than 0.01). The actuarial survival rate was 66% at 3 months and 58% at 6, 12, and 24 months. The most frequent cause of morbidity and mortality was acute pneumonia resulting from Pseudomonas cepacia. For patients with respiratory failure caused by cystic fibrosis, bilateral lung transplantation is an effective treatment option associated with significant functional improvement.

Pulmonary transplantation. Early and late results. The Toronto Lung Transplant Group.

Between November 1983 and March 1991, we performed 50 single and 40 double lung transplants in 82 recipients. Early deaths occurred in six (13%) single and in eight (21%) double lung transplant recipients. Late deaths occurred in 11 (28%) single and in one (3%) double lung recipients. Twenty-three of 37 (62%) single and 17 of 24 (71%) double lung transplant recipients have survived at least 1 year after the operation. In patients surviving at least 3 months after the operation (36 of 47 single lung transplant [77%] and 28 of 37 double lung transplant recipients [76%]), significant improvement occurred in arterial blood gases, pulmonary function tests, and exercise capacity. During our initial experience, airway anastomotic complications were the main cause of early morbidity and mortality. With newer surgical techniques and improved perioperative care, airway complications are now uncommon. Infectious complications, either bacterial (Pseudomonas cepacia) or viral (cytomegalovirus), are now the main cause of early mortality. Chronic rejection in the form of obliterative bronchiolitis has become a frequent cause of late morbidity.

Single-lung transplantation for pulmonary vascular disease.

Six patients with end-stage pulmonary vascular disease received right SLTs. Though patients generally had difficult early postoperative courses, four of the six have survived from 3 to 23 months and have achieved good recovery of right ventricular function and good functional results. SLT is a viable option in selected patients with severe pulmonary hypertension even when right ventricular function is severely impaired.