G. Alexander Patterson

Staging: The key to rational management of lung cancer

Staging is the quantitative assessment of malignant disease and allows logical groupings of patients with a similar extent of disease for prognostic, therapeutic, and analytic purposes. In bronchogenic carcinoma a stage is assigned based on size, location, and the extent of invasion of the primary tumor, as well as the presence of any regional or metastatic disease. Selecting the most appropriate treatment for a patient with bronchogenic carcinoma depends on precise staging. The extent of local invasion and presence of metastatic disease will determine the likelihood of complete resection and possible cure. Careful assessment of the history, blood chemistry, radiographic studies, bronchoscopy, mediastinoscopy, and exploration (thoracotomy) are all important staging tools. Routine radionuclide scans have no useful role when there is no clinical or laboratory evidence of metastases. The T status of a tumor is best judged by bronchoscopy and at thoracotomy. Thoracic surgeons must be familiar with the techniques available to determine T status intraoperatively and use this information when planning resection. Computed tomography of the chest has fallen short in predicting direct invasion of the mediastinum and chest wall. Cervical and anterior mediastinoscopy remain important tools in determining operability. Intraoperative assessment of node involvement determines the extent of resection and likelihood of cure.

Major Histocompatibility Complex Expression and Lung Ischemia-Reperfusion in Rats

BACKGROUND Clinical studies in kidney and liver transplantation have suggested that poor early function is associated with increased graft loss due to rejection. Ischemia-reperfusion injury may contribute to rejection by enhancing graft immunogenicity. METHODS A rat model of unilateral in situ pulmonary ischemia-reperfusion was used to examine class II major histocompatibility complex (MHC) antigen expression. The effects of deflation during ischemia (which augments subsequent injury) as well as concurrent allostimulation were also examined. Major histocompatibility complex expression was examined 9 days after ischemia using the binding of radiolabeled anti-class II antibody and immunohistochemistry. RESULTS Four hours of ischemia in full inflation or 2 hours of atelectatic ischemia both led to severe lung injury. Ischemia-reperfusion injury led to greater MHC expression in the ischemic lung compared with the nonischemic side. Allostimulation with mononuclear cells did not increase MHC expression in the nonischemic lung but did enhance the increase found in the ischemic lung. This was not due to a graft-versus-host response because allostimulation with F1 cells also led to a significant increase. CONCLUSIONS Severe ischemic lung injury leads to significant increases in MHC expression, detectable after 9 days of reperfusion. Deflation during ischemia, which augments lung injury, also augments increased MHC expression. Concurrent allostimulation with foreign mononuclear cells appears to potentiate increased MHC expression after ischemia. Increases in graft MHC expression may enhance immunogenicity and increase the rejection response.

Precision Cautery Excision of Pulmonary Lesions

We have used a cautery dissection technique, initially described by Perelman, to facilitate nonanatomical pulmonary resections in certain instances in which the anatomical location of the lesion made wedge excision by standard methods difficult or impossible. With the precision cautery technique, the raw surface of the lung is left charred and allows minimum or no air leakage following the procedure. We have found this method a useful addition to existing techniques for pulmonary resection.

Improved tracheal allograft viability in immunosuppressed rats.

Airway ischemia has been a common cause of morbidity and mortality in clinical lung transplantation. The present study examined the effects of cyclosporin A (CsA) and methylprednisolone (MP) on the viability of the devascularized trachea after heterotopic transplantation and omentopexy. Thirty-six tracheal segments were harvested from 18 donor Lewis rats, wrapped in omentum, and heterotopically implanted into the abdomen of recipient rats. Tracheal segments were randomly allocated into one of six recipient groups (n = 6): Lewis syngeneic controls, and five groups of Brown Norway recipients, receiving either no treatment, CsA alone (5 mg.kg-1.day-1 or 15 mg.kg-1.day-1), or CsA in combination with MP (5 mg CsA + 1 mg MP per kg/day or 15 mg CsA + 2 mg MP per kg/day, respectively). After 14 days, the tracheal segments were histologically evaluated. Epithelial thickness and the degree of epithelial regeneration were significantly different (p < 0.05) between the syngeneic control group and the untreated Brown Norway group. Without immunosuppression there was virtually no epithelium, whereas low-dose immunosuppression yielded intermediate viability, and with high dose CsA and MP we observed improved tracheal viability. In this high-dose group, the epithelium was thicker than in even the syngeneic control group. These results indicate that, in heterotopic tracheal allografts, viability may be improved with an optimum combination of CsA and MP.

Pericardial repair of a tracheal laceration during transhiatal esophagectomy

Transhiatal esophagectomy has recently been popularized for both benign and malignant esophageal disease. While we were performing a transhiatal esophagectomy for a squamous cell cancer of the upper third of the esophagus, a tear in the membranous trachea near the carina occurred. This was repaired through the cervical incision with a free pericardial patch. This solution to a potentially catastrophic complication of transhiatal esophagectomy gave a satisfactory result without early or late postoperative respiratory complications.

Production and reversibility of right ventricular hypertrophy and right heart failure in dogs

Combined heart-lung transplantation has been used for end-stage primary pulmonary hypertension. Experience with single-lung transplantation for other conditions suggested that associated severe right ventricular dysfunction resulting from increased afterload would recover after placement of a satisfactory lung allograft. Early experience with the application of single-lung transplantation for pulmonary hypertension supports this contention. We devised a reversible canine model of chronic progressive pressure-overloaded right heart failure by pulmonary artery banding to study the echocardiographic, hemodynamic, and pathological reversibility of the failing right heart. Clinical right heart failure was defined as the development of ascites and pleural effusions. Right heart failure developed in 23 dogs 67 to 348 days after banding, and they were divided into two groups to determine its early and long-term effects. Group 1 dogs (n = 11) were either sacrificed immediately after the onset of right heart failure (n = 5) or unbanded (n = 6); group 2 dogs (n = 12) were maintained in right heart failure for 3 months and then either sacrificed (n = 6) or unbanded. Unbanded dogs in both groups were observed for 4 additional months before sacrifice. A control group of 6 normal dogs was sacrificed for pathological comparisons. After unbanding, the right ventricular systolic pressure fell from 97 +/- 17 mm Hg (group 1) and 88 +/- 31 mm Hg (group 2) to 44 +/- 11 mm Hg and 47 +/- 13 mm Hg, respectively. Despite this persistent gradient across the pulmonary artery, echocardiographic and hemodynamic measures of right ventricular function returned to normal, albeit more slowly in the group 2 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodilution reduces early reperfusion injury in an ex vivo rabbit lung preservation model

We sought to reduce early ischemia-reperfusion injury after lung preservation by an initial brief period of hemodilute reperfusion. Left lungs of New Zealand White rabbits were ventilated with room air and reperfused in an ex vivo ventilation-perfusion apparatus after 18 hours of storage at 10 degrees C. Lungs were randomly assigned to one of three groups (n = 6) according to the composition of initial reperfusate. In group 1 (control), preserved lungs were reperfused with whole blood for 20 minutes (hematocrit, 38%). In the experimental groups, blood was diluted to a hematocrit of 10% with Ringers lactate (group 2) or low-potassium-dextran solution (group 3) for the first 10 minutes of reperfusion, followed immediately by whole blood for 10 minutes. Oxygen tension of left ventricular effluent at the end of the 20-minute assessment period was significantly higher in both hemodiluted groups (mean +/- standard error of the mean: group 2, 81.3 +/- 6.6 mmHg; group 3, 77.0 +/- 9.5 mmHg, versus Group 1, 46.3 +/- 7.4 mmHg; p < 0.006). Similarly, mean tracheal airway pressure was reduced in the hemodiluted groups, suggesting improved compliance (group 2; 3.1 +/- 0.3 mmHg; group 3, 2.8 +/- 0.6 mmHg; versus group 1, 6.5 +/- 1.4 mm Hg; p < 0.05). An initial 10-minute period of hemodilute reperfusion appears to reduce early pulmonary ischemia-reperfusion injury in this 18-hour ex vivo rabbit lung preservation model.

Effect of methylprednisolone on angiogenesis in syngeneic rat tracheal grafts

Airway anastomotic complications remain a cause of morbidity after clinical lung transplantation. The use of corticosteroid therapy to control pulmonary rejection has raised concern over delayed airway healing. We therefore investigated the hypothesis that the effects of methylprednisolone (MP) impair the revascularization and epithelial regeneration of heterotopic syngeneic tracheal isografts. Lewis rat tracheal segments were wrapped in omentum and implanted in the abdomen of recipient rats. All recipients received cyclosporin A (CsA) (5 mg.kg-1.day-1) and were randomly allocated into three groups of 12 rats each according to the daily MP dose: group II, no MP; group III, 1 mg.kg-1.day-1; and group IV, 2 mg.kg-1.day-1. In each group, 6 animals were sacrificed after 7 and 14 days. Normal, untreated rats served as controls (group I). Epithelial regeneration was assessed histologically by a blinded subjective scoring system and by measurement of epithelial thickness. Tracheal revascularization was quantitated in terms of the number of blood vessels per square millimeter of tracheal wall and the vessel area was quantitated in terms of the percentage of the tracheal wall area. In animals treated with MP and CsA, the trachea exhibited significantly better regeneration after 14 days than it did in animals treated only with CsA. Epithelial regeneration was improved between 7 and 14 days in the groups treated with MP (group III, p = 0.01; group IV, p = 0.04). The epithelial thickness for all three study groups was significantly greater than that in the control group and returned toward normal after 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

A short course of FK506 can induce limited donor-specific graft acceptance

To examine the hypothesis that a short course of FK506 would induce permanent graft acceptance after lung transplantation, left lung allotransplantation was performed in 14 mongrel dogs. In group 1 (control; n = 3), no immunosuppressive agent was given. In group 2 (n = 7), FK506 (1.2 mg/kg intramuscularly) was given on posttransplantation days 0, 1, and 2. In group 3 (n = 4), FK506 was given at the same dose on posttransplantation days 0, 1, and 2 as well as on days 29 and 30. Allograft function was evaluated by temporarily occluding the right pulmonary artery. A mixed lymphocyte reaction study was performed preoperatively and monthly thereafter. Control lungs were all rejected within 8 days. Group 2 dogs showed improved survival, with a median survival of 49.5 days. One dog in group 2 lived more than 400 days after transplantation. The mixed lymphocyte reaction data suggests that some donor-specific unresponsiveness occurs, which lasts for only a limited time. Supplemental doses of FK506 did not significantly improve survival (median, 74 days). The whole blood level of FK506 was 17.7 +/- 3.98 ng/mL on day 15; however, on day 29 the FK506 level was almost undetectable. We conclude that a 3-day course of 1.2 mg/kg of FK506 can induce donor-specific graft acceptance, but this acceptance is not permanent.