Contralateral Pneumonectomy Research Articles

Single-Lung Transplantation for Cystic Fibrosis and Metachronus Pneumonectomy: Case Reports

Three patients with end-stage cystic fibrosis (CF) underwent single lung transplantation (SLT) with contralateral pneumonectomy. In the first case, contralateral pneumonectomy (CP) was performed before SLT. The patient is alive with no signs of infection or rejection. For the other 2 cases, CP was performed after SLT. One patient died 8 months later with septicemia; the other patient died after 10 days because of complicated bronchopleural fistula and infection of the pneumonectomy space. SLT can be a good option for some patients with CF. The outcome is good when CP is done before SLT. However, CP must be done simultaneously with SLTX.

Successful Video-assisted Thoracic Surgery Lobectomy in a Single-lung Patient

In terms of perioperative management, it is extremely difficult to perform a video-assisted thoracic surgery lobectomy for primary lung cancer in patients previously undergoing a contralateral pneumonectomy. We herein describe the successful video-assisted thoracic surgery lobectomy with systematic mediastinal lymph node dissection in a single-lung patient with clinical stage IA nonsmall cell lung cancer. Our experience indicates surgeons may consider the procedure if the following conditions are met: (1) satisfactory pulmonary function, (2) the selective bronchial blockade of the lobe to be resected, and (3) the effective retraction of the inflated lung.

Accuracy of CT-guided transthoracic needle biopsy of lung lesions: Results of 612 consecutive procedures

18022 Background: CT-guided transthoracic needle biopsy (TNB) is commonly used in diagnostic work-up of lung lesions. The availability of a on-site pathologist at the time of the procedure ameliorate its sensitivity, reduce the number of biopsies and false negatives. Methods: 612 procedures (608 patients with a CT-documented central or peripheral pulmonary lesion) performed at S. Luigi Hospital between November 2002 and August 2005 were prospectively analyzed; 66% males, median age was 66 years (range 29–87). Ineligibility criteria for the procedure included severe coagulopathy, previous contralateral pneumonectomy, lesions with a maximum diameter less than 5 mm or the impossibility to understand the procedure or to maintain the clinostatism for the time of the procedure. The on-site pathologist assigned to each specimen a semiquantitative score: 0 for bloody sample without other cells, 1 for aspecific benign or inflammatory cells, 2 for malignant cells without histotype characterization and 3 for well established benign or malignant histotype. Results: Most of the procedures was performed by fine needle aspiration biopsy, while in a minority of cases a tru-cut biopsy was requested. In 57.2% of the cases a single transthoracic access (range 1–4) was used and in 31% the procedure was repeated on the basis of the radiologist/pathologist judgment. In 154 patients a surgical resection was subsequently performed, while 454 were patients non-surgical. A score of 3 was obtained in 71% of cases (88% malignancies), 2 in 12.5%, 1 in 7.5% and 0 in 9%. A definitive diagnosis was made in 83.5% of procedures, while a score of 0–1 was assigned in 101 cases. Among 458 malignancies there were 411 lung cancer, 7 non-epithelial cancers and 40 metastases with only 1 false positive. The diagnostic accuracy for benign and malignant lesions was 67% and 92%, respectively (Pearson’s test p<0.005) with overall diagnostic accuracy of 83.3%. The variables affecting diagnostic accuracy were final diagnosis (benign 67%, malignant 92%, p<0.001) and lesion size (lesion 5 cm 78%, p<0.05). The presence of cavitation or necrotic areas and location of the lesion didn’t affect the diagnostic accuracy. Conclusion: In consecutive cases of CT-guided TNB final diagnosis and lesion size affect diagnostic accuracy. No significant financial relationships to disclose.

Urgent Contralateral Pneumonectomy After Single Lung Transplantation for Lymphangioleiomyomatosis

Left single lung transplantation in a 33-year-old woman affected by end-stage lymphangioleiomyomatosis was complicated by spontaneous and diffuse bleeding from the right lung at the end of the procedure. The right lung was completely deteriorated and the only option to stop the bleeding was a right pneumonectomy. At 14 months after transplantation, the single allograft showed good lung function with acceptable volumes. Single lung transplant and contralateral pneumonectomy can be considered a safe procedure in case of complications related to native lung either in case of lymphangioleiomyomatosis than for other lung diseases (emphysema, cystic fibrosis).

Digitonin enhances the antitumor effect of cisplatin during isolated lung perfusion

Background. The antitumor effect of isolated lung perfusion with cisplatin was limited because the intracellular platinum concentration did not increase sufficiently. To solve this problem, digitonin, a detergent, was chosen to increase cell permeability and enhance intracellular uptake and antitumor effect. This study was designed to investigate toxicity, pharmacokinetics, and efficacy of isolated lung perfusion with the combined use of digitonin and cisplatin in Fischer 344 rats. Methods. Systemic and local toxicities of isolated lung perfusion treatment were evaluated on the basis of body weight change, survival rate, and histologic findings. The maximal tolerated dose of digitonin was determined by assessing survival on day 21 after contralateral pneumonectomy, body weight change, and histologic findings. Pharmacokinetics were observed in a solitary lung tumor nodule model by measuring platinum concentration in tumor and normal lung tissue. The antitumor effect was evaluated by the number of tumor nodules in the left lung 21 days after isolated lung perfusion. Isolated lung perfusion was performed 7 days after 1.0 × 10 6 methylcholanthrene sarcoma cells were injected into the external jugular vein. Results. The maximal tolerated dose of digitonin was 20 μmol/L. Platinum concentration of tumor nodules in the digitonin-cisplatin–treated rats was 20% higher than in the cisplatin-only group (5.48 ± 0.64 μg/g tissue versus 4.50 ± 1.09 μg/g tissue; p = 0.067). The number of pulmonary nodules decreased significantly by digitonin use (1.3 ± 1.5 versus 9.7 ± 2; p < 0.0001). Conclusions. Isolated lung perfusion with digitonin and cisplatin in combination was performed safely and enhanced the antitumor effect. These drugs in combination show promise for enhancing the effect of clinical isolated lung perfusion.

Electronmicroscopic observations on the visceral and parietal rat's pleura after contralateral pneumonectomy.

The mechanism of compensatory growth and healing of the pleura remains unresolved. Contralateral visceral and parietal (diaphragmatic and costal) pleura were investigated by transmission electron microscopy, following an experimental pneumonectomy (EP). Fifteen young-adult Wistar rats were divided into three groups and with survival times of 1, 5 and 8 days respectively after EP. Three sham-operated (thoracic cavity opened and closed) and three unoperated rats served as controls. One day following EP the superficial mesothelial cells have more microvilli and microvesicles, but a lower number of specialized contacts. Multiplication of extravasal cells leads to an increase of the thickness of the layer over the basal lamina and of the submesothelial layer. Five days after EP the superficial cells show a stratified arrangement in longer sectors of both pleural sheets. Along with typical mesothelial cells there are three new populations of cells: (1) with an abundant granular endoplasmic reticulum and secretory granules, (2) with fibroblast-like characteristics and (3) with a more extensive lysosomal system. The submesothelial layer is thickened due to newly formed blood vessels and collagen bundles. Eight days after EP the mesothelial cells build multi-row arrangement sectors and surround intercellular dilatations covered with microvilli. 'Activated' high mesothelial cells characterize the monolayer sectors. The submesothelial layer remains thicker due to larger collagen bundles and elastic fibers. The changes in the mesothelium and in the connective tissue layer suggest the existence of two periods. The first one is characterized by different mesothelial cell populations, new vasculogenesis and starting of fibrillogenesis. In the second period there are 'activated' mesothelial cells, pleural villi, groups of lymphatic lacunae and significant fibrillogenesis.

Electronmicroscopic Observations on the Visceral and Parietal Rat’s Pleura after Contralateral Pneumonectomy

Electronmicroscopic Observations on the Visceral and Parietal Rat’s Pleura after Contralateral Pneumonectomy

Isolated lung perfusion with melphalan and tumor necrosis factor for metastatic pulmonary adenocarcinoma

Background. Isolated left lung perfusion with melphalan and human tumor necrosis factor-α for pulmonary metastatic adenocarcinoma in the WAG/Rij rat was studied. Methods. Survival was determined for melphalan, human tumor necrosis-α. Lung, pulmonary effluent, and serum melphalan were analyzed by chromatography after isolated lung perfusion or intravenous injection. On day 0, rats were injected with 2.0 × 10 6 CC531S cells intravenously. On day 7, rats underwent sham thoracotomy, received melphalan intravenously, or underwent isolated left lung perfusion with saline, melphalan, tumor necrosis factor, and a combination of the latter two. On day 14, tumor nodules were counted. Results. For the doses of 400 μg tumor necrosis factor, 1,000 μg tumor necrosis factor, or both melphalan and tumor necrosis factor (2 mg + 200 μg), survival rates after contralateral pneumonectomy were 33%, 17%, and 80%, respectively. Survival in all other groups was 100%. Left lung melphalan level was significantly higher after isolated lung perfusion compared to intravenous administration. Significantly fewer left lung nodules were found for 0.5 mg isolated lung perfusion with melphalan (28 ± 17) compared to isolated administration (200 ± 0) ( p = 0.001), and for 1.0 mg intravenous lung perfusion with melphalan (16 ± 10) compared to controls (171 ± 65) ( p = 0.00047). Tumor necrosis factor showed no significant effect. Conclusions. Isolated lung perfusion with melphalan is an effective treatment for pulmonary metastases from adenocarcinoma in the rat.

Angiotensin-converting enzyme inhibition delays pulmonary vascular neointimal formation.

Primary pulmonary hypertension (PPH) is a disease characterized pathologically by pulmonary artery medial hypertrophy, adventitial thickening, and neointimal proliferation. Increasing recognition of the importance of remodeling to the pathogenesis of PPH suggests new therapeutic possibilities, but it will be necessary to (1) identify essential mediators of remodeling, and (2) demonstrate that inhibiting those mediators suppresses remodeling before new antiremodeling therapies can be considered feasible. The effect of angiotensin-converting enzyme (ACE) inhibition on pulmonary vascular remodeling was studied in a newly developed rat model in which neointimal lesions develop between 3 and 5 wk after monocrotaline injury is coupled with increased pulmonary artery blood flow after contralateral pneumonectomy. Neointimal formation was significantly suppressed at 5 wk by ACE inhibition whether it was started 10 d before or 3 wk after remodeling was initiated, although medial hypertrophy and adventitial thickening still developed. By 11 wk, the extent of neointimal formation in rats treated with ACE inhibition was similar to rats without ACE inhibition at 5 wk. Pulmonary artery pressures and right ventricular weights correlated with the extent of neointimal formation. Northern blot analysis and in situ hybridization demonstrated marked suppression of lung tropoelastin and type I procollagen gene expression in the presence of ACE inhibition. An angiotensin II type I receptor antagonist partially, but not completely, replicated the effects of ACE inhibition. These data suggest that the tissue angiotensin system may be a target for therapeutic efforts to suppress the vascular remodeling that is characteristic of primary pulmonary hypertension.

Isolated lung perfusion with melphalan for the treatment of metastatic pulmonary sarcoma

Objective: Isolated lung perfusion allows the delivery of high-dose chemotherapy to the perfused lung and is an efficacious modality in the treatment of pulmonary metastases in the rat. Melphalan activity in this model was investigated. Methods: Toxicity study: Maximum tolerated dose of melphalan delivered by means of isolated lung perfusion was determined by survival after contralateral pneumonectomy. Pharmacokinetics study: Nineteen rats were treated with melphalan administered either by isolated lung perfusion (2 mg) or intravenously (2 mg or 1 mg). Lung, pulmonary effluent, and serum melphalan were analyzed by high-pressure liquid chromatography. Efficacy study: On day 0, 41 rats received an intravenous injection of 5 × 10 6 methylcholanthrene induced sarcoma cells. On day 7, rats either received intravenous melphalan (2 mg [ n = 10]; 1 mg [ n = 8]) or underwent left isolated lung perfusion with 2 mg of melphalan ( n = 12). Isolated lung perfusion with buffered hetastarch in sodium chloride (Hespan, n = 11) was used as control. On day 14, pulmonary nodules were counted. Results: Toxicity: Maximum tolerated dose of melphalan delivered buy means of isolated lung perfusion was 2 mg. Pharmacokinetics: Left lung melphalan level was significantly higher in the isolated lung perfusion group (62.2 ± 34.3 μg/gm lung) than in the intravenous treatment groups (6.9 ± 1.9 μg/gm lung and 3.3 ± 0.9 μ g/gm lung, respectively) ( p = 0.0002). Efficacy: Significantly fewer left lung nodules were found in animals receiving melphalan by means of isolated lung perfusion (7 ± 10) than in the groups receiving intravenous melphalan (60 ± 21) or buffered hetastarch by isolated lung perfusion (84 ± 52) ( p = 0.01 and p = 0.0001, respectively). Conclusion: Isolated lung perfusion with melphalan is safe and effective in the treatment of pulmonary sarcoma metastases in the rat. (J T horac C ardiovasc S urg 1996;112:1542-8)

Contralateral pneumonectomy after single-lung transplantation for emphysema

An intractable contralateral air leak developed in a 46-year-old woman after right single-lung transplantation for emphysema. A left pneumonectomy was performed on postoperative day 17, leaving the patient with only one transplanted lung. Fifteen months postoperatively the patient is well and has satisfactory pulmonary function. Survival with a good quality of life is possible after single-lung transplantation and bilateral sequential pneumonectomies.

Efficacy of topical cooling in lung preservation: Is a reapprisal due?

The aim of the present study was to test the efficacy of topical cooling as the only viable lung preservation method using the most challenging evaluation method, namely single-lung transplantation followed by immediate contralateral pneumonectomy. Ten domestic pigs (5 donors and 5 recipients) with a mean body weight of 57 kg (range, 53 to 59 kg) were used. After we administered systemic heparin (4 mg/kg), the lungs were harvested and placed in an atelectatic state under cold (8 ° to 9 °C) low-potassium-dextran solution for 12 hours. Left lung transplantation was then done in the recipient pig followed by right pneumonectomy, thus making the recipient 100% dependent on the transplanted donor lung. No operative mortality or morbidity occurred. All animals were in excellent condition throughout the 24-hour observation period. They had normal blood gases which did not differ significantly from the preoperative blood gases obtained from the 5 recipients before transplantation (ie, when they had their own two lungs). A moderate increase ( p < 0.05) in pulmonary vascular resistance was seen as compared with sham-operated animals. To conclude, topical cooling to 8 °C provides excellent lung preservation for 12 hours in pigs. If similar results can be obtained with other species, the currently accepted 6-hour limit for safe clinical lung preservation may be extended to 12 hours. It seems also warranted to critically reconsider which factors, apart from cooling alone, actually contribute favorably to 12-hour lung preservation.

Pulmonary vascular resistance related to endothelial function after lung transplantation

In 8 donor pigs, flush perfusion was performed with a low-potassium-dextran solution. Ring segments were taken from a smalt intralobar pulmonary artery in the right lung immediately after perfusion and after 24 hours of cold storage for studies in organ baths. Stable vasoconstriction was induced with the thromboxane mimic U-46619, and acelylcholine was used to induce endothelium-dependent relaxation. The maximum relaxation was significantly reduced after flush perfusion compared with fresh nonperfused controls, and a significant additional reduction was seen after the 24-hour storage period. The left donor lung was transplanted into a recipient after 24 hours of cold storage. Contralateral pneumonectomy was then performed, making the recipient entirely dependent on the transplanted lung for survival. All 8 pigs were in good condition throughout the 24-hour observation period, with arterial oxygen tension of around 165 mm Hg (range, 80 to 275 mm Hg; inspired oxygen fraction, 0.5) and pulmonary vascular resistance of around 450 dyne · s · cm −5 (range, 260 to 730 dyne · s · cm −5). The maximum endothelium-dependent relaxation for each donor was checked for correlation (to pulmonary vascular resistance and to systolic, mean, and diaslolic pulmonary artery pressures as recorded at 4-hour intervals. Regression analyses showed arterial oxygen tension to be unrelated to pulmonary vascular resistance and endothelial dysfunction to be unrelated to pulmonary artery pressure but to correlate to pulmonary vascular resistance, this correlation being significant after reperfusicn for 16 hours ( p < 0.05) and highly significant after 24 hours ( p < 0.001). Thus, endothelial dysfunction appears to contribute to the increase in pulmonary vascular resistance after transplantation.

Isolated single lung perfusion with doxorubicin is effective in eradicating soft tissue sarcoma lung metastases in a rat model

The only effective therapy for patients with metastatic soft tissue sarcoma in the lung is surgical resection, with a 5-year survival of approximately 25%. Because systemic chemotherapy has not significantly affected survival in these patients, we began to investigate locoregional chemotherapy. We have previously shown that isolated single lung perfusion with doxorubicin in the rat results in higher lung tissue levels and lower systemic toxicity than does high-dose intravenous therapy. In the present study, we examined the safety of isolated lung perfusion with doxorubicin and its efficacy in the treatment of experimental pulmonary metastases from soft tissue sarcoma. In experiment 1, 15 F344 rats were randomized into three groups ( n = 5): group I had isolated left lung perfusion with doxorubicin 320 μg/ml in saline solution; group II had left isolated lung perfusion with doxorubicin 480 μg/ml and group III with doxorubicin 640 μg/ml. All perfusions with doxorubicin were at 0.5 ml/min for 10 minutes followed by perfusion of saline solution for 5 minutes. On day 21, all animals underwent right (contralateral) pneumonectomy and were observed for over 10 days. In experiment 2, two groups of F344 rats were injected intravenously with 107viable methylcholanthrene-induced sarcoma cells on day 0. On day 7, group I ( n = 12) had left isolated lung perfusion with saline solution only and group II ( n = 15) had isolated lung perfusion with doxorubicin 320 μg/ml. On day 21, all animals were killed, and their lungs were stained for metastases. Routine histologic sections from three animals from group II were examined. In experiment 1, 80% of the animals in group I survived contralateral pneumonectomy. There were no survivors in groups II and III. In experiment 2, three animals died after isolated lung perfusion (one from group I and two from group II), and one animal (group I) was excluded because of mediastinal tumor. All animals in both groups had massive tumor replacement of the right (untreated) lung. Group I animals had massive tumor replacement of the left (treated) lung, whereas animals in group II had eradication of metastases in nine of ten cases; no microscopic evidence of tumor was detected in all three animals evaluated for microscopic disease. Isolated lung perfusion with doxorubicin 320 μg/ml is safe and effective in eradicating experimental pulmonary sarcoma metastases in this model. (J T HORAC C ARDIOVASCSURG1994;107:50-4)

Contralateral pneumonectomy after single-lung transplantation for emphysema

An intractable contralateral air leak developed in a 46-year-old woman after right single-lung transplantation for emphysema. A left pneumonectomy was performed on postoperative day 17, leaving the patient with only one transplanted lung. Fifteen months postoperatively the patient is well and has satisfactory pulmonary function. Survival with a good quality of life is possible after single-lung transplantation and bilateral sequential pneumonectomies.

Simplified rat lung transplantation using a cuff technique

A cuff technique is introduced to anastomose pulmonary vein and pulmonary artery in rat lung transplantation. In 11 consecutive cases, the average graft ischemic time was 13.5 +/- 2.0 minutes and operating time 100.7 +/- 4.8 minutes: The time for ischemia was less than one third of previous reports and the time for operation one half of previous reports. Excluding two operative deaths, the survival rate was 88.8% (8/9) on postoperative day 11, when contralateral pneumonectomy revealed excellent graft function supporting the oxygenation of the animals.

Hemodynamic pulmonary edema in dog lungs after contralateral pneumonectomy and mediastinal lymphatic interruption.

The effect of pneumonectomy and mediastinal lymphatic interruption on gravimetrically measured extravascular lung water was studied in dogs. Raising left atrial pressure to 23 mm Hg caused a significant increase in extravascular lung water in normal dogs compared to controls. The same hemodynamic challenge, however, when applied to pneumonectomized dogs caused a significantly greater increase in extravascular lung water than in the hemodynamically challenged normal dogs. When a moderate mediastinal lymphatic interruption was added to the pneumonectomy, there was no additional increase in extravascular lung water. We suggest that the remaining lungs after contralateral pneumonectomy are more prone to extravascular fluid development when subjected to a significant hemodynamic challenge because of the combination of an increase in transmembrane fluid transudation into the interstitium of the remaining lung and loss of parenchymal/hilar lymphatic drainage routes. In this situation, lymphatic clearance thresholds are more easily exceeded, extravascular fluid accumulates and pulmonary edema is the result.

Reoperation for recurrent bronchogenic carcinoma.

From a total of 869 patients primarily operated on for bronchogenic carcinoma, nine underwent a second operation for recurrence of the tumour. The median interval between the operations was 16 months. In four patients the second operation consisted of resection of ipsilateral residual lung after primary segmental resection or lobectomy. One patient underwent contralateral pneumonectomy after primary segmental resection. In the four remaining cases a contralateral lobectomy or segmental resection was performed after primary lobectomy. Four of the nine patients are still alive but, after a short observation time, only two are tumour-free. On the basis of these findings we cannot recommend reoperation for bronchogenic carcinoma, except in very rare, individually selected cases.

Single lung transplantation with cyclosporin immunosuppression: Evaluation of canine and human recipients

Cyclosporin, a potent new immunosuppressive agent, was used (alone or in combination with other drugs) in 28 canine single lung allograft recipients. Mean recipient survival with good allograft function was 155 days with cyclosporin and far exceeded that obtained in previous single lung allograft recipients treated with standard immunosuppression (15 to 22 days). The results of these experiments were as follows: (1) 20% of the recipient animals exhibited no evidence of rejection whatsoever; (2) four of 28 animals survived more than 350 days with good allograft function; (3) 79% of the animals exhibited some evidence of rejection that was easily reversed in 74% of instances with corticosteroids; (4) 10 of 28 animals exhibited good lung allograft function 5 months or more after operation; (5) in cyclosporin-treated lung allograft recipients, rejection was diagnosed by the presence of infiltrate on chest roentgenogram, analysis of the cellular content of bronchoalveolar lavage samples, and decreased perfusion on 99mtechnetium lung scan; (6) complete healing without stenosis of the bronchial anastomosis occurred in 82% of the animals studied. One of two patients treated with cyclosporin after undergoing single lung allografting survived 7 weeks after transplantation and 4 weeks after contralateral pneumonectomy. Episodes of rejection were reversible, and the bronchial anastomosis healed normally. This overall experience indicates that cyclosporin, although not a perfect immunosuppressive agent, increases the likelihood of success with therapeutic single lung transplantation.

Isolated lung perfusion with Adriamycin. A preclinical study.

Isolated in vivo single-lung perfusion with an Adriamycin-containing whole-blood perfusate was performed in three groups of dogs after establishing adequate controls. The procedure, performed through a left thoracotomy, was followed two weeks later by a contralateral pneumonectomy. Survival following pneumonectomy was used as the ultimate end point in assessing perfusion toxicity. Groups I and II had high mortality rates but provided valuable information concerning perfusion methods, venous drainage techniques, drug dosage schedules, and perfusate flow rates. The group III study consisted of five dogs perfused for 45 minutes at flow rates sufficient to maintain mean pulmonary artery pressure at 12-15 mm Hg. An initial Adriamycin (Adr) dosage of 0.5 micrograms/ml in the plasma perfusate resulted in mean peak Adr lung tissue levels of 3.8 +/- 1.06 micrograms/g. All animals survived right pneumonectomy 19 +/- 4 days later. Three dogs have been killed and histologic examination showed only mild focal pleural and subpleural interstitial fibrosis. Based on these studies it is concluded that isolated single-lung perfusion is a reproducibly safe technique and that a dosage of Adr has been identified which produces no apparent toxity in a large animal model. A clinical trial is currently in progress.