Operative indications for lung cancer with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is well known to be associated with lung cancer. However, surgical morbidity and mortality in lung cancer patients with IPF remains unclear. METHODS: The data of patients who underwent surgery for non-small cell lung cancer were retrospectively reviewed. RESULTS: Of the 1063 patients with lung cancer, 33 (3.1 %) had IPF. Patients with IPF had significantly higher postoperative pulmonary morbidity and mortality than those without IPF (33.3 vs. 2.0 %; 18.2 vs. 1.3 %, respectively, P < 0.0001). Patients with IPF had a significantly higher incidence of postoperative acute lung injury/acute respiratory distress syndrome (ALI/ARDS) than those without IPF (27.3 vs. 1.3 %, P < 0.0001). IPF patients with postoperative ALI/ARDS had a significantly lower preoperative %FVC than those without postoperative ALI/ARDS (74 +/- 9 vs. 103 +/- 14 %, P < 0.0001). CONCLUSIONS: Lung cancer patients with IPF who have a low preoperative %FVC should be carefully assessed prior to any surgical intervention.

Lung volume reduction surgery and nutritional status in patients with severe emphysema.

OBJECTIVE: We studied the short-term effect of lung volume reduction surgery on nutritional status including body composition and the relationship between preoperative nutritional status and postoperative morbidity. METHODS: Subjects were 28 patients with emphysema who underwent bilateral thoracoscopic lung volume reduction surgery (23 simultaneously, 5 staged). Functional tests, body weight, and body composition were measured before and 6 months after surgery. Fat-free mass and fat mass were assessed by bioelectrical impedance analysis. RESULTS: FEV1.0 improved 35.2% following surgery and maximal oxygen uptake 23.8%. Body weight and fat-free mass increased significantly after surgery, while fat mass was unchanged. Of the 23 undergoing simultaneous bilateral lung volume reduction surgery, 8 had major complications-3 required additional surgery to close air leaks, 3 required mechanical ventilation (> 72 hrs), and 2 developed postoperative infection. The preoperative percentage of ideal body weight and fat-free mass was significantly higher among patients without major complications. CONCLUSIONS: Bilateral lung volume reduction surgery increases fat-free mass and provides functional improvement for underweight patients with severe emphysema. We found fat-free mass and body weight to be good predictors of unacceptable postoperative complications following bilateral lung volume reduction surgery.

The effect of nutritional status on morbidity in COPD patients undergoing bilateral lung reduction surgery.

BACKGROUND: Although candidates for lung reduction surgery (LRS) include malnourished patients with severe chronic obstructive pulmonary disease (COPD), the impact of preoperative nutritional status on surgical outcome has not been clearly elucidated. METHODS: We investigated the relationship between preoperative nutritional status and postoperative morbidity in 23 consecutive patients undergoing LRS. The percentage of ideal body weight (%IBW) and body mass index (BMI) were calculated, and fat-free mass (FFM) and fat mass (FM) were measured using a bioelectrical impedance analyzer. FFM and FM were expressed as height-normalized indices, FFM index [FFM (kg)/height (m)(2), or FFMI] and FM index [FM (kg)/height (m)(2), or FMI]. Serum levels of total protein and albumin were also determined. RESULTS: 8 patients had major complications. Preoperative %IBW and FFMI were significantly lower among patients with major complications, while no significant differences were observed in pulmonary function, FMI or serum protein. The complication rate was significantly higher among patients with low FFMI (FFMI < or = 16) but not with low %IBW or BMI. CONCLUSION: These results suggest that FFM depletion is an excellent predictor of unacceptable postoperative complication following LRS.

Tracheal allotransplantation maintaining cartilage viability with long-term cryopreserved allografts.

BACKGROUND: Cartilage viability of a cryopreserved tracheal allograft seems to affect graft function and durability. We previously reported the influence of warm ischemia and cryopreservation on cartilage viability of tracheal allografts. For the clinical application of tracheal allotransplantation, it is essential to preserve grafts for a long time. In this study, we assessed cartilage viability of tracheal allografts after long-term cryopreservation in transplantation models. METHODS: The tracheas were harvested from Lewis rats. The grafts were frozen to -80 degrees C in a programmable freezer immediately after being harvested and were then stored in liquid nitrogen (-196 degrees C) for different lengths of preservation (1, 2, 6, 9, 12, 18, and 24 months; n for each group = 8). Cartilage viability was evaluated by estimating proteoglycan synthesis. After harvest or thawing of the tracheas, the cartilage was labeled with 4 muCi/mL of Na2 35SO4. Specimens were then hydrolyzed in 0.5 mol/L NaOH, and a solution of the extracts was then counted by a liquid scintillation counter. 35Sulfur incorporation before and after cryopreservation was examined in each group. Tracheal allotransplantation was performed using Lewis rats as donors and Brown Norway rats as recipients. RESULTS: The average 35S incorporation in the cartilage before cryopreservation was 224 +/- 17 disintegrations per minute per milligram of tissue protein. The average 35S incorporation in the cartilage after cryopreservation decreased to 67% to 76% compared with that before cryopreservation. There were no significant differences among the groups in 35S incorporations after cryopreservation. Histologic examination after transplantation revealed normal tracheal cartilage in all groups. CONCLUSIONS: The viability of tracheal cartilage after cryopreservation decreased to 67% to 76%. There were no significant differences in viability of cartilage among the tracheas after different lengths of cryopreservation. Tracheal allotransplantation after long-term cryopreservation can be safely performed in the rat model.

Effects of warm ischemia and cryopreservation on cartilage viability of tracheal allografts.

BACKGROUND: For clinical use of a cryopreserved tracheal allograft, it is important to evaluate cartilage viability. We assessed cell viability of the cartilage in a cryopreserved tracheal allograft by measurement of Na2 35SO4 incorporation. We also investigated the effects of warm ischemic time on tracheal cartilage viability. METHODS: The tracheas from Lewis rats were harvested and preserved at different warm ischemic times from cardiac death to preservation (0, 1, 2, 4, 6, 9, and 12 hours, each group n = 8). The cartilage was labeled with 4 muCi/mL of Na2 35SO4. The specimen was hydrolyzed in 0.5 mol/L NaOH, and a solution of the extracts was then counted by liquid scintillation counter. Tracheas were transplanted into Brown Norway rats. RESULTS: 35Sulfur incorporation in the cartilage decreased as warm ischemic time increased. In addition, 35Sulfur incorporation decreased from 76% to 67% after cryopreservation. Histologic examinations of the normal tracheal cartilage before preservation and after thawing were done in all the groups. After transplantation, the cartilage had severe fibrous changes, and its layer was almost nonobservable in the 9- and 12-hour groups. CONCLUSIONS: The viability of the tracheal cartilage decreased with warm ischemic time and from 76% to 67% after cryopreservation. In the rat tracheal transplantation model, a cryopreserved tracheal allotransplant could be done safely with a graft that was cryopreserved within 6 hours of warm ischemic time.

The change in body composition after bilateral lung volume reduction surgery for underweight patients with severe emphysema.

The aim of this study was to examine the short-term effect of lung volume reduction surgery (LVRS) on body composition and other nutritional indicators in 28 patients with emphysema underwent thoracoscopic LVRS. Functional tests, body weight (BW), and body composition were measured before and 6 months after surgery. Mean daily caloric intake (CI) was estimated by 3-day dietary record as well. Fat-free mass (FFM) and fat mass (FM) were assessed by bioelectrical impedance analysis (BIA). FEV1.0 and VO2max have improved after LVRS by 35.2% and 23.8%, respectively. Preoperatively, 75% of patients were underweight (% ideal body weight (%IBW) <90) with the mean %IBW at 84.5%. BW, CI, and FFM increased significantly after LVRS, whereas FM was unchanged. The change in BW correlated significantly with the change in FEV1.0, MVV, and VO2max (p < 0.01) but not with CI. Bilateral LVRS results in an increase in FFM and functional improvement for underweight patients with severe emphysema, and it may contribute to the improvement in maximal exercise capacity.

Enhanced expression of Tie2, its ligand angiopoietin-1, vascular endothelial growth factor, and CD31 in human non-small cell lung carcinomas.

Expression of angiogenesis-associated genes was compared in 32 primary non-small cell lung carcinoma samples (14 adenocarcinomas, 17 squamous cell carcinomas, and 1 large cell carcinoma) and paired adjacent noncancerous lung tissues using a multiprobe RNase protection assay. Levels of Tie2, angiopoietin (Ang)-1, vascular endothelial growth factor (VEGF), and CD31 mRNAs were higher in cancers than in adjacent noncancerous tissues, in contrast to the fms-like tyrosine kinase (Flt)-1, Flt-4, Tie1, thrombin receptor, endoglin, and VEGF-C, for which no differences were evident. Overexpression did not seem to differ with histological type and pathological stage. Significant positive correlations were found between mRNA expression of Ang-1 and those of Tie2 and CD31, and that of VEGF and those of Flt-1 and CD31. These findings suggest that Ang-1 and VEGF are important angiogenic factors in human non-small cell lung carcinomas.

Thoracoscopic lung volume reduction surgery for emphysema. Evaluation using ventilation-perfusion scintigraphy.

Thoracoscopic lung volume reduction surgery was conducted in 28 consecutive patients (bilateral 21, unilateral 7). The bilateral procedure was conducted simultaneously in 16 and as a planned staged approach in 5, using stapler resection with Nd:YAG laser ablation. Perfusion and ventilation scintigraphy were used to evaluate status before and after surgery. One operative death (3.6%) due to pneumonia occurred after a simultaneous bilateral procedure. Three to 6 months after surgery, the forced expiratory volume in 1 second (FEV1.0) had improved an average of 44% after the bilateral procedure and 17% after unilateral. Improved ventilation and perfusion distribution in the lower lung field correlated significantly with improved dyspnea scale (p < 0.01). Mean transit time was shortened significantly in each lung field (p < 0.01). Improved mean transit time correlated significantly with improved FEV1.0 and maximum oxygen consumption (VO2max) (p < 0.05). In conclusion, we found that bilateral thoracoscopic lung volume reduction surgery produces short-term functional outcomes superior to those of the unilateral procedure, and should be considered the procedure of choice for most patients. Ventilation and perfusion scintigraphy are useful both in determining target areas for resection and in evaluating lung volume reduction surgery effects.

[Thoracoscopic lung volume reduction surgery for emphysema].

In recent years, several institutions have been performing lung volume reduction surgery (LVRS) for emphysema, and have reported that LVRS is effective for patients with emphysema that is resistant to other forms of therapy. However, questions remain about the relationship between the extent of resection and the therapeutic benefits. In our study, 15 men with emphysema underwent thoracoscopic LVRS. We analyzed the effects of LVRS on pulmonary function, exercise performance, and subjective symptoms after both bilateral and unilateral procedures. The patients who underwent the bilateral procedure, demonstrated significantly improved pulmonary function and exercise performance and relief of their subjective symptoms. Those who underwent the unilateral procedure, demonstrated significantly improved pulmonary function and relief of their subjective symptoms. Forced expiratory volume in 1.0 second increased by an average of 51% after the bilateral procedure, and 17% after the unilateral procedure. We conclude that thoracoscopic LVRS is an effective treatment for emphysema, especially with the bilateral procedure.

Epithelial regeneration and preservation of tracheal cartilage after tracheal replacement with cryopreserved allograft in the rat.

OBJECTIVE: We investigated the origin of the epithelium in transplanted cryopreserved tracheal allografts in rats and tried to clarify the mechanism by which immunogenicity is reduced in this procedure. METHODS: Tracheal transplantation was performed with PVG rats (allele at the RT1 locus: c) used as donors and ACI rats (allele at the RT1 locus: a) as recipients. After resection of a 5-ring segment of the cervical trachea of an ACI rat, the trachea was reconstructed with the cryopreserved tracheal segment of a PVG rat (n = 6). No immunosuppressive agents or steroids were given. Histologic changes were determined and immunohistochemical staining was performed to investigate major histocompatibility complex class I antigens of the transplanted tracheal segment. RESULTS: Two months after tracheal transplantation, 6 surviving ACI rats were killed. Histologically, the epithelium and tracheal cartilage of the transplanted cryopreserved segment displayed normal structure. Immunohistochemical staining showed that the major histocompatibility complex class I antigen of the ACI rat was expressed in the epithelium of the transplanted segment and that the class I antigen of the PVG rat was expressed in the cartilage of the transplanted segment. CONCLUSIONS: After transplantation of the cryopreserved trachea, the epithelium of the transplanted cryopreserved segment originated from the recipient epithelium whereas the cartilage retained the structure of the donor trachea. We hypothesize that transplantation of a cryopreserved trachea leads to the growth of the recipient's epithelium over the donor trachea, thereby reducing the antigenicity of the transplant.

Tracheal replacement with cryopreserved tracheal allograft: experiment in dogs.

BACKGROUND: It has been difficult to perform tracheal allotransplantation without immunosuppression. To determine whether cryopreserved trachea can be used in tracheal replacement, we evaluated the viability of cryopreserved tracheal allografts in a canine model of immunosuppressant-free transplantation. METHODS: Cryopreserved tracheal allografts, which had been frozen to -80 degrees C in a programmed freezer and then stored in liquid nitrogen (-196 degrees C) (group 1, n = 6), fresh tracheal autografts (group 2, n = 5), and fresh tracheal allografts (group 3, n = 4) were transplanted into the thoracic segment of the trachea using an omental flap without immunosuppressive agents. RESULTS: All dogs in groups 1 and 2 survived, but in group 3, all 4 died of airway obstruction between 1 month and 2 months after operation. Histologically, the cryopreserved allografts displayed normal epithelium and cartilage, but the fresh allografts showed chronic inflammatory changes, no epithelium, and no cartilage. CONCLUSIONS: Cryopreserved tracheal allografts maintain their structural integrity after transplantation. The cryopreservation process seems to reduce the allogenic response of the trachea in canine models. Therefore, we believe the cryopreserved tracheal allograft is an excellent choice for tracheal replacement.

Recovery and limitation of exercise capacity after lung resection for lung cancer.

OBJECTIVE: To assess the effects of pulmonary resection for lung cancer on postoperative recovery and limitation of exercise capacity. METHODS: Eighty-two patients (20 pneumonectomies, 62 lobectomies) underwent spirometric pulmonary tests and exercise capacity tests preoperatively, and at 3 months and more than 6 months after the operation. RESULTS: In the lobectomy group, FEV1 vital capacity (VC), and maximum oxygen consumption (VO2max) decreased significantly 3 months after the operation and improved after more than 6 months, but did not reach the preoperative values. In the pneumonectomy group, FEV1 VC, and VO2max decreased 3 months after the surgery and the values did not recover thereafter. In comparison with preoperative values, the functional percentage losses after more than 6 months for lobectomies and pneumonectomies were 11.2% and 36.1% for FEV1, 11.6% and 40.1% for VC, and 13.3% and 28.1% for VO2max, respectively. Postoperatively, maximal minute ventilation (VEmax), the maximal heart rate percentage, and maximal O2 pulse during the exercise test significantly decreased in both the lobectomy and pneumonectomy groups. Nevertheless, VEmax and O2 pulse improved more than 6 months after lobectomy compared with the value at 3 months, but not after pneumonectomy. Breathing reserve did not differ before and after surgery in the lobectomy group, although it decreased significantly after surgery in the pneumonectomy group. Subjectively, postoperative exercise after lobectomy was limited by leg discomfort (64% at more than 6 months after surgery); after pneumonectomy, exercise was limited by dyspnea (60%). CONCLUSIONS: These results suggest that there are differences between lobectomy and pneumonectomy for lung cancer in terms of recovery and limitation of exercise capacity.

Frequent expression of the vascular endothelial growth factor in human non-small-cell lung cancers.

BACKGROUND: Angiogenesis is an essential factor for progression and metastases in solid tumors. It has been reported that several angiogenic factors play a role in the regulation of angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most important molecules in angiogenesis. We investigated expressions of VEGF in a series of lung carcinomas with regard to clinicopathological factors. METHOD: VEGF expression was investigated by use of immunohistochemical studies and Northern blot analysis, using 155 primary and 26 metastatic lung carcinomas for the immunohistochemical studies and 10 primary and two metastatic lung carcinomas for the Northern blot analysis. All lesions were resected at surgery. RESULTS: The frequencies for positive VEGF expression were 64 of 74 (86.5%) adenocarcinomas, 38 of 67 (56.7%) squamous cell carcinomas, four of four (100%) large cell carcinomas, two of three (66.7%) adenosquamous carcinomas and one of five (20%) small-cell carcinomas, the degree of positivity generally being greater in well differentiated tumors. The majority of metastatic foci from adenocarcinomas and squamous cell carcinomas at other sites were also positive (76.5 and 66.7%, respectively). VEGF expression did not correlate with clinicopathological factors such as tumor size or pathological stage, but pathological stage I adenocarcinoma cases positive for VEGF demonstrated a shorter disease-free period when followed up for 48 months than those cases expressing VEGF negatively. CONCLUSIONS: The results indicated that VEGF expression was frequently detected in non-small-cell lung cancers and suggested that VEGF might relate to the disease-free period of the patients with early adenocarcinomas.

[Clipping of the thoracic duct with video-assisted thoracic surgery in the treatment of chylothorax after pulmonary resection].

We describe a procedure for video-assisted thoracoscopic clipping of the thoracic duct to treat postoperative chylothorax. This technique was successfully performed on a 62-year-old man who developed chylothorax following right lower lobectomy and partial resection of the 11th and 12th vertebral bodies for squamous cell lung cancer. Because conservative therapy for 7 days failed to reduce the amount of pleural effusion, we performed thoracoscopic examination of the thoracic duct and found a site leaking chylous fluid. The thoracic duct was successfully and easily clipped resulting in complete elimination of the effusion in 2 days. Generally, chylothorax complicating pulmonary resection has been managed by medical treatment first, followed by surgical intervention in case that fail to respond to initial therapy. The newly designed video-assisted thoracic surgery procedure reduces the trauma, shortens the drainage period and hospital stay, and provides better exposure of the thoracic duct. We believe that this procedure can be carried out shortly after the occurrence of chylothorax.

Thoracoscopic wedge resection of blebs under local anesthesia with sedation for treatment of a spontaneous pneumothorax.

We performed thoracoscopic wedge resections of blebs with a stapling device under local anesthesia with sedation in 34 consecutive patients who presented with spontaneous pneumothoraces. The indications for surgery included the absence of parietal pleural adhesions and knowledge of the precise bleb location prior to the procedure. Prior to surgery, 0.5% lidocaine was administered into the pleural space, and IV butorphanol tartrate and diazepam were administered to reduce pain and anxiety during the procedure. In our series, the thoracoscopic procedure resulted in favorable outcomes in all but two patients. There was no evidence of hemodynamic instability or arterial blood gas abnormalities encountered during the procedure. Minor postoperative complications were seen in only three patients (two with air leakage and one with transient atelectasis). One patient had a recurrence of his spontaneous pneumothorax 3 months following the procedure. Therefore, the overall success rate was 91%. We compared the results of this therapeutic modality (group 1) with those of 38 patients who underwent the procedure under general anesthesia (group 2) during the same period. The length of hospital stay was shorter in group 1 than in group 2 (4.5 +/- 1.3 vs 5.8 +/- 1.1 days; p < 0.01). Thoracoscopic wedge resections under local anesthesia are safe and offer the benefit of shorter hospital stays. We believe that this thoracoscopic technique will further simplify the surgical treatment of pneumothoraces without incremental risks.

[A case of mucoepidermoid carcinoma of the thymus].

A 19-year-old man was admitted to our hospital with anterior mediastinal cystic tumor. Subtotal thymectomy with the tumor was performed. The tumor was localized inside the thymus without outer infiltration. It weighed 145 g and measured 9 x 8 x 5 cm. The cut surface was cystic and spongy, partially with a solid focus. Pathological findings of the solid area was compatible with mucoepidermoid carcinoma of the thymus. The histogenesis of mucoepidermoid carcinoma of the thymus was discussed.

Flow cytometric analysis of the DNA content of thymomas.

In this study, the prognostic value of determining the nuclear DNA content of thymomas by flow cytometry was evaluated. Of a total 31 resected thymomas, 10 (32%) showed DNA aneuploidy, the presence of which was significantly correlated with an advanced clinical stage of disease. The patients with an aneuploid tumor had a poorer prognosis than those with a diploid tumor, demonstrating a survival rate of 50% at 7 postoperative years, which was considerably less favorable than that of the patients with a diploid tumor, being 100% in the same period (p < 0.05). Moreover, patients with a high DNA index (DI), i.e., a DI >or= 1.5, tended to have a poorer prognosis than those with a low DI. These findings indicated that the DNA content can be an important prognostic index in patients with thymomas.

Protection against lipid peroxidation induced during preservation of lungs for transplantation.

The questions of whether oxygen-derived free radicals are induced during preservation of lungs and, if so, how such radicals might relate to reperfusion injury were investigated by means of an isolated canine lung model. Lungs were obtained from 16 mongrel dogs and divided into groups 1 (n = 6), 2 (n = 5), and 3 (n = 5). The lungs of groups 1, 2, and 3 were flushed through the pulmonary artery with Euro-Collins solution alone, the solution with superoxide dismutase (120,000 U/L), and the solution with allopurinol (1 mmol/L), respectively, at 4 degrees C and then stored for 4 hours in the respective solutions at 4 degrees C with clamped bronchi. They were then reperfused for 2 hours by means of an isolated lung model. Lung lipid peroxidation was sequentially determined. The lung functional status was assessed by systolic pulmonary arterial pressure and end-inspiratory airway pressure. The lung edema was assessed by lung wet/dry weight ratio. Lipid peroxidation was induced after 1 hour of preservation and the first 30 minutes of the reperfusion in group 1 and only 2 hours of the reperfusion in group 2, whereas no induction was observed in group 3. Values for systolic pulmonary arterial pressure and end-inspiratory pressure in group 1 were significantly higher than those in group 3 (p < 0.05). The lung wet/dry weight ratio in group 1 was significantly higher than that in groups 2 and 3 (p < 0.05). The present results indicate that the administration of free radical scavengers in the preservation may effectively improve conditions for lung transplantation.