Malignant pleural effusion treatment outcomes: pleurodesis via video-assisted thoracic surgery (VATS) versus tube thoracostomy.

STUDY OBJECTIVES: Video-assisted thoracic surgery (VATS) has been widely used in the diagnosis and management of various thoracic diseases. The objective of this retrospective study was to compare the effectiveness of patients undergoing pleurodesis through VATS versus tube thoracostomy for malignant pleural effusion (MPE). Study design was a retrospective review of patients treated in medical centers and hospitals in Taiwan. PATIENTS: One hundred and forty-eight patients with MPE resistant to systemic therapy resulting from various types of carcinomas were retrospectively reviewed. VATS pleurodesis was carried out in 82 and tube thoracostomy with pleurodesis in 66 patients. RESULTS: There were no intraoperative deaths and 4 (2.7 %) in-hospital deaths. One hundred and eighteen (79.7 %) patients were available for follow-up. There were no statistically significant differences in the preoperative characteristics of the two treatment groups, except that the amount of effusion and the percentage of patients with dyspnea were both higher in the VATS treatment group. The duration of chest tube drainage was significantly longer ( P < 0.01) in the tube thoracostomy treatment group (9.1 +/- 3.3 vs. 6.2 +/- 2.3 days). There were no significant differences between the treatment groups with regard to the incidence of surgical complications and perioperative mortality. Median survival was similar in both treatment groups; however, the VATS treatment group had a significantly longer median recurrence-free survival than the tube thoracostomy treatment group. CONCLUSIONS: VATS treatment for MPE appears to be superior to tube thoracostomy for diagnostic accuracy and effectiveness in preventing effusion recurrence; however, the role of these treatments for MPE is palliative, and does not significantly prolong survival time.

Genetic polymorphisms of XRCC1 and risk of the esophageal cancer.

A variety of environmental factors were identified to be associated with the risk of esophageal cancer. The variation in capacity of DNA repair might influence environmental chemical-associated carcinogenesis. We hypothesized that the polymorphic XRCC1 genes might modify cancer susceptibility of the esophagus. To investigate the effect of XRCC1 genetic polymorphisms on codons 194, 280 and 399, we evaluated data from 105 patients of esophageal squamous cell carcinoma and 264 healthy controls, matching with age (+/-3 years), gender and ethnicity. The distribution of the 3 genotypes were not significantly different among patients and controls. However, among alcohol drinkers, the XRCC1399 Arg/Arg genotype was more frequently found in patients with esophageal cancer. After adjustment with other environmental confounders, the OR for the genotype of XRCC1399 Arg/Arg was 2.78 (95% CI =1.15-6.67) as compared with the XRCC1(399) Arg/Gln and XRCC1(399) Gln/Gln genotypes in the alcohol drinkers. Similar trends were observed among cigarette smokers and areca chewers. However, they did not reach a statistical significance. Our findings suggest that the polymorphic XRCC1 genes might modify the risk of alcohol-associated esophageal cancers.

Genetic polymorphisms of p53 and GSTP1,but not NAT2,are associated with susceptibility to squamous-cell carcinoma of the esophagus.

The interaction of genetic and environmental factors can determine an individual's susceptibility to various cancers. We present a hospital-based case-control study, which included 90 patients of esophageal squamous-cell carcinoma (ESCC) and 254 healthy people in Taiwan, to investigate the effects of genetic polymorphisms of p53, GSTP1 and NAT2 on the risk of ESCC. Polymorphisms of p53, NAT2 and GSTP1 were determined by PCR-RFLP. The codon 72 p53 Pro allele was more frequently found in ESCC patients [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.04-3.35 for Arg/Pro genotype and OR 2.56, 95% CI 1.29-5.08 for Pro/Pro genotype]. In cigarette smokers, the frequency of GSTP1 Ile/Ile genotype was higher in ESCC patients (OR 2.8, 95% CI 1.4-5.7). Among alcohol drinkers, borderline significance was also found for GSTP1 Ile/Ile genotype (OR 2.0, 95% CI 0.9-4.4). Results were not similar for the NAT2 genetic polymorphism. Using logistic analyses, we found that individuals with p53 Pro/Pro genotype had a significantly higher risk of developing ESCC than those with Arg/Arg genotype (OR 2.3, 95% CI 1. 1-5.1), after adjusting for other significant environmental risk factors. This result remained similar (OR 2.2, 95% CI 1.0-4.8 for p53 Pro/Pro vs. Arg/Arg), even after further adjustment for NAT2 and GSTP1 polymorphisms. The codon 72 p53 Pro/Pro genotype in the general population and GSTP1 Ile/Ile in cigarette smokers may predict a higher risk of developing ESCC.

Use of esophagectomy to treat recurrent hyperplastic tissue obstruction caused by multiple metallic stent insertion for corrosive stricture.

We report a case of a 75-year-old woman who received repeated metallic stent insertion for corrosive esophageal injury. She underwent esophagectomy and gastric tube reconstruction about 3 years after injury because both stents were occluded in turn by overgrowth of granulation tissue. The gross and microscopic changes of the esophagus secondary to prolonged stent insertion are described. In the literature, no reports of similar cases have been recorded. Our limited experience revealed that using metallic stents to treat benign esophageal stricture should be handled very cautiously because of the complications which can commonly occur and are difficult to manage. Repeated stent insertion, although effective for temporarily relieving dysphagia, is ineffective in the long run and can create complications. We suggest that the feasibility of esophagectomy should be evaluated after the improvement of the general condition of the patient.

The effects of inhaled nitric oxide, gabexate mesilate, and retrograde flush in the lung graft from non-heart beating minipig donors.

BACKGROUND: The use of lung grafts from non-heart-beating donors (NHBD) is one way of solving the donor organ shortage problem. In this experiment, we studied the effect of retrograde flush (RF) from the left atrium before harvest, inhaled nitric oxide (NO), and gabexate mesilate (FOY), a protease inhibitor, in the lung grafts from NHBD. METHODS: Forty-eight Lee-Sung, small-ear, miniature pigs (15-20 kg) were divided into 24 pairs (donor and recipient) and four groups. The donor lungs were flushed and harvested 90 min after cardiac arrest. No i.v. heparin was administered until the time before flush and harvest. Left single lung transplantation was undertaken, and the recipients were observed for 18 hr. The grafts warm and cold ischemia times were 90 (controlled) and 183+/-23.4 min. Group 1 (untreated control, UC, n=6) had core perfusion through a Swan-Ganz catheter followed by a single, antegrade flush with modified Euro-Collin's solution containing heparin, urokinase, and PGE1. Group 2 (RF group, n=6) had the same as group 1, except that one additive retrograde flush through the left atrium was administered. Group 3 (NO group, n=6) had the same as group 1, except that 20 parts per million (ppm) inhaled NO was administered for the cadaver donors before the graft harvest, and for the recipients after the grafts reperfusion. Group 4 (FOY group, n=6) had the same as group 1, except that the recipients received FOY i.v. infusion from the beginning of the recipient's operation and continuously throughout the experiments. RESULTS: Compared with the group 1 (control), group 2 (RF) had significantly (P<0.05) lower mean pulmonary artery pressure, pulmonary vascular resistance (PVR), lung wet/dry ratio, histological lung injury score, and higher PaO2/FiO2 and pulmonary dynamic compliance. Group 3 (NO) had significantly lower mean pulmonary arterial pressure, PVR, lung injury score, degree of tissue neutrophils infiltration (histological and myeloperoxidase assay), bronchoalveolar lavage fluid protein content and neutrophils (PMNs) percentage, and higher PaO2/FiO2 and pulmonary dynamic compliance. Group 4 (FOY) had significantly lower PMNs infiltration, lung injury score, wet/dry ratio, bronchoalveolar lavage fluid protein and PMNs percentage, and higher PaO2/FiO2. Group 2 (RF) revealed better gas exchange (PaO2/FiO2) than the control (group 1) at earlier reperfusion periods (1st and 5th hr). On the contrary, group 4 (FOY) had higher PaO2/FiO2 than group 1 only at later period (18th hr). Pathologically, retrograde flush (group 2, RF) inhibited the intravascular thrombi formation more effectively than the NO or FOY treatment. However, the NO or FOY treatment inhibited the neutrophil infiltration more effectively than did the retrograde flush. CONCLUSION: The retrograde flush, inhaled NO and FOY infusion are beneficial to the protection of the NHBD lung grafts at an early reperfusion period, through different mechanisms. The use of these treatments in combination might help us to find a better way to protect the NHBD grafts against the preservation and reperfusion injury.

Effects of gabexate mesilate (FOY) on ischemia-reperfusion-induced acute lung injury in dogs.

BACKGROUND: To assess the effects of gabexate mesilate (FOY), a protease inhibitor, on a canine model of pulmonary ischemia-reperfusion injury. FOY has been applied clinically to treat acute pancreatitis and disseminated intravascular coagulation (DIC) and has been found to suppress some leukocyte-mediated tissue injuries in both in vitro and in vivo studies. DESIGN: Comparison of four experimental groups: group 1 (untreated control, n = 8), unilateral (left) pulmonary ischemia due to perfusion and ventilation obstruction followed by reperfusion, without receiving any specific treatment; group 2 (negative control, sham operation, n = 8), left pulmonary hilar dissection without ischemia; group 3 (FOY posttreatment, n = 8), FOY treatment during the reperfusion stage only; and group 4 (FOY pretreatment, n = 8), FOY treatment before ischemia and then continued during reperfusion. SETTING: University animal laboratory. SUBJECTS: Heart-worm-free mongrel dogs (12 to 15 kg body wt) were anesthetized with pentobarbital and mechanically ventilated. INVESTIGATIONS: Lung ischemia was made by snaring the left pulmonary artery and veins and clamping the bronchus with peribronchial tissue for 90 min followed by reperfusion for 18 h. Animals of the two treatment groups received a 1 mg/kg bolus of FOY at the beginning of reperfusion, with infusion of 2 mg/kg/h of FOY continuously starting 30 min before ischemia (group 4) or after reperfusion (group 3). During this study the following were measured: hemodynamics and aerodynamics, blood gas, bronchoalveolar lavage (BAL) fluid neutrophil percentage and protein concentration, lung wet to dry weight ratio (W/D ratio), myeloperoxidase (MPO) activity of the lung tissue, alveolar neutrophil infiltration, and degree of injury. RESULTS: This model of lung ischemia-reperfusion induced significant pulmonary hypertension, increased pulmonary vascular resistance, decreased pulmonary dynamic compliance and arterial hypoxemia, increased BAL fluid total protein amount and neutrophil percentage, and increased alveolar neutrophil infiltration, histological injury score, and lung tissue MPO assay (group 1). Animals of the sham operation (negative control, group 2) showed only minimal changes in the above parameters. Treatment with FOY significantly attenuated the injury by decreasing the lung W/D ratio, alveolar neutrophil infiltration, histological injury score, lung tissue MPO assay, BAL fluid neutrophil percentage, and protein amount. Pretreatment with FOY (group 4) attenuated the injury to a significantly greater degree than it did when administered at the reperfusion stage only (group 3), which was reflected by the above-mentioned parameters, and as well significantly improved gas exchange function. FOY treatment was found to have little effect in altering hemodynamics and aerodynamics at most time points in this model of lung injury. CONCLUSIONS: FOY can attenuate the ischemia-reperfusion-induced acute lung injury in dogs by ameliorating the degree of alveolar membrane permeability change, neutrophil aggregation, and activation. FOY treatment starting before ischemia attenuated this injury to a significantly higher degree than its use after ischemia. However, the effect of FOY may be partial because it cannot alter the hemodynamics or aerodynamics as prominently as other parameters in this type of lung injury. Concomitant use of FOY with other agents will have additive or synergic effects in preventing lung ischemia-reperfusion injury.

Significance of P53 and Rb protein expression in surgically treated non-small cell lung cancers.

BACKGROUND: Alterations of the P53 or Rb gene are among the most frequently observed genetic changes in primary lung cancer. Nevertheless, there has been no final conclusion on the relationship between P53 or Rb protein expression and clinico-pathological parameters in primary lung cancer. A large-scale study was performed to examine the clinicopathological and prognostic significance of P53 and Rb expressions in 207 surgically resected non-small cell lung cancer (NSCLC) patients. METHODS: Tumor specimens were obtained from 207 primary NSCLC surgically resected from January 1990 through December 1994. The avidin-biotin-peroxidase method was used to determine the expression of P53 or Rb of tumor cells using anti-P53 or anti-Rb monoclonal antibodies. The relationships between P53 or Rb protein expression and the clinicopathological parameters were analyzed. RESULTS: Expression of P53 or Rb protein was detected in 115 (55.6%) and 136 (65.7%) of the 207 lung tumors, respectively. P53 had significantly higher positive results in patients with regional lymph node metastasis and advanced tumor stage. Rb expression was significantly lower in lung cancers with a macro- or microscopic picture of tumor necrosis. Additionally, an inverse correlation between the expression of Rb and P53 was found. By multiple variate analysis, P53 expression and pathological stage were independent, significant prognostic factors. Further analysis demonstrated P53 expression was an independent prognostic factor in stage 1, but not in other stages. CONCLUSIONS: P53 expression is especially useful as a prognostic factor in stage 1 lung cancer.

Lung transplantation for patients with end-stage Sauropus androgynus-induced bronchiolitis obliterans (SABO) syndrome.

Sauropus androgymus (SA), a vegetable of the Euphorbiaceae family, is a common food source in Malaysia. In Taiwan, over 30 patients have developed progressive respiratory failure after consuming the extract from raw SA leaves as a means of losing weight. Symptoms consistent with a severe obstructive ventilatory defect progressed, despite cessation of SA intake and treatment with bronchodilators, corticosteroids, cytotoxic agents and plasmaphresis. Five patients with end-stage Sauropus androgynus-induced bronchiolitis obliterans (SABO) syndrome underwent lung transplantation. There was no early mortality. One patient died of post-transplant lymphoproliferative disorder and another patient died of bronchial stenosis with infection, 5 and 3.5 months, respectively, post-transplantation. The remaining 3 patients have been followed from 29 to 34 months, with improved general condition and pulmonary function. Perfusion/ventilation scans revealed that these improvements were exclusively attributed to the functional grafts. We believe that lung transplantation is the only effective modality of treatment for patients with end-stage SABO syndrome.

Surgical treatment for pulmonary aspergilloma: a 28 year experience.

BACKGROUND: Pulmonary aspergilloma has been treated surgically for many years but the mortality rates of larger surgical series, varying from 7% to 23%, is not considered acceptable by today's standards. The authors report their experience in the surgical treatment of pulmonary aspergilloma and present a review of the literature. METHODS: Sixty seven patients who underwent thoracotomy for pulmonary aspergilloma from 1968 to 1995 were studied retrospectively by reviewing their medical records. RESULTS: The most common clinical presentation of pulmonary aspergilloma was haemoptysis which occurred in 61 patients (91.0%). Tuberculosis was the most common pre-existing disease, occurring in 54 patients (80.6%). The plain chest radiograph showed the typical "air-crescent" sign in 36 patients (53.7%). Systemic antifungal therapy neither palliated the clinical symptoms nor eradicated the aspergilloma, and transarterial embolisation was also unsuccessful. Surgery offered the only chance of cure for both unilateral and bilateral disease. Procedures varied from segmentectomy to pneumonectomy with most (61.4%) undergoing lobectomy. There was one death following surgery from pneumonia and 15 postoperative complications occurred in 12 patients-empyema (7), massive bleeding (3), bronchopleural fistula (2), wound infection (2), and Horner's syndrome (1). Postoperatively, most of the patients were symptom-free. CONCLUSIONS: With appropriate preoperative evaluation and judicious surgical technique, surgery is the preferred treatment for pulmonary aspergilloma, both for eradicating the tumour and for curing the underlying disease.

The optimal tidal volume delivered by ventilator after pulmonary resection: its effect on cardiopulmonary hemodynamics.

Pulmonary function and gas exchange deteriorate after pulmonary resection. The vital capacity, tidal volume, and functional capacity decrease after pulmonary resection because of loss of effective lung volume and, therefore, affect the setting of the ventilator. Nineteen patients undergoing pulmonary resection were included in this study on the optimal tidal volume delivered by a ventilator. Five patients received mediastinal surgery or wedge resection of the lung, 4 had pneumonectomy, and 10 had lobectomy. Immediately after the pulmonary surgery, they were maintained with ventilatory support. Subsequently, a different setting of tidal volume on the ventilator was given for each patient, i.e., 6 ml/kg, 8 ml/kg, 10 mg/kg, and 14 ml/kg. For each setting of tidal volume, a hemodynamic study was performed including cardiac output and other parameters. With the examination of Wilk's Lambda test, there was no difference in association with different settings of tidal volume on blood pressure (F = 0.92, p = 0.51), pulmonary artery pressure (F = 0.95, p = 0.43), pulmonary vascular resistance (F = 0.24, p = 0.97), systemic vascular resistance (F = 0.42, p = 0.78), and cardiac output (F = 0.35, p = 0.93) in 3 different groups of patients. It is concluded that after pulmonary resection a patient's lungs can be inflated with a tidal volume to 14 ml/kg during ventilatory support without compromise of cardiovascular performance.

Using titanium plate or meshplate for chest wall reconstruction: report of 6 cases and literature review.

Titanium plate has been widely used in several surgical fields, such as craniofacial reconstruction and orthopedic prosthesis. This prosthesis has been proved not only with good biocompatibility and mechanical strength, but also with light weight and low radiological interference. From October 1991 to May 1995, 6 patients underwent thoracic cage reconstruction with titanium plate in our hospital. They included 5 females and 1 male, with ages ranging from 26 to 62 years. Four of them suffered from primary chest wall tumors (2 desmoid tumors, a chondrosarcoma, and 1 hemangioma), one had a recurrent chest wall tumor from breast carcinoma, and one had thoracic hypoplasia. The thoracic cage defect ranged from 5 x 6 cm to 10 x 15 cm, and 1 to 3 titanium plates were used for the reconstruction. No paradoxical movement or other prosthesis-related complications have occurred during the follow-up period. We conclude that titanium plate is a good material for thoracic cage reconstruction.

The role of video-assisted thoracic surgery in the diagnosis and treatment of indeterminate pulmonary lesion.

Patients with indeterminate pulmonary lesions usually require a definite diagnosis for proper management. The conventional diagnostic procedures such as bronchoscopy and transthoracic needle biopsy sometimes fail to obtain a decisive answer, thus a more aggressive diagnostic procedure will be needed. Video-assisted thoracic surgery (VATS) has provided an alternative for open thoracotomy for definite diagnosis in these conditions. Thirty-three patients with indeterminate pulmonary lesions received VATS in National Taiwan University Hospital. Of these patients, twenty-eight manifested with coin lesion and five had diffuse pulmonary infiltration before operation. Traditional diagnostic procedures, i.e. bronchoscopy or transthoracic needle biopsy, could not give a definite diagnosis for these patients. A definite diagnosis was obtained after thoracoscopy in all of these patients. The mean operation time was 129 minutes (range, 180 to 45 minutes). The mean duration of chest tube drainage was 4.1 days (range, 1 to 7 days). The mean postoperative hospital stay of elective surgery without subsequent chemotherapy or radiotherapy was 9.5 days (range, 5 to 14 days). The patients received 2.4 times parental narcotics injection for analgesia on average (range, 0 to 6 times). There is no operation-related death in this series. Three patients had prolonged air leak with seven days of chest tube drainage. Two patients, with CMV and chronic interstitial pneumonia, have mortality from their underlying disease later. VATS is a safe and effective procedure not only for diagnosis, but also for treatment in the management of indeterminate pulmonary lesions.

Videothoracoscopic treatment of spontaneous pneumothorax.

Thoracoscopic surgery has been well accepted as a treatment for spontaneous pneumothorax and other intrathoracic diseases. Seventy-four patients with primary or secondary pneumothorax underwent thoracoscopic operation in this hospital. There was no postoperative mortality or major morbidity. Only two (2.7%) patients developed recurrent pneumothorax postoperatively, but this never reappeared after using bullae resection and mechanical pleurodesis in place of electroablation only at an earlier period. Three patients had residual pleural effusion or air space, and two patients had persistent air-leak postoperatively; all of them recovered after conservative treatment. The mean operation time, intensive care unit stay, and total hospital stay were decreased significantly when compared with open thoracotomy. The low recurrence rate and shorter hospital stay also made this procedure much superior to tube thoracostomy and chemical pleurodesis only. Approaches to make working ports, bullectomy, and pleurodesis are also discussed here. We concluded that thoracoscopic surgery is highly effective and minimally invasive for patients with spontaneous pneumothorax, but may not be suitable for patients with generalized emphysematous change of lungs or dense adhesion of the pleural spaces.

Nucleolar organizer regions as a prognostic factor in surgically treated lung cancer patients.

The prognostic value of the number of nucleolar organizer regions (NORs) (DNA loops in the nucleus) in tumor cells from various kinds of malignancies has been widely studied in recent years. During the period 1989 to 1992, a total of 73 primary lung tumors was examined for the number of NORs by silver staining AgNOR proteins on the stump smear of resected specimens in this hospital. The relations of the mean number of AgNOR per cell with other factors such as sex, age, habit of smoking, performance status, tumor location, tumor size, pathological stage, histological type, degree of differentiation, and whether histologically vascular or lymphatic invasion were analysed. It was found that the mean number of AgNOR was significantly different between positives and negatives of histologically vascular or lymphatic invasion (6.4 +/- 0.4 vs 5.5 +/- 0.2) (p < 0.05). Both single and multiple-variate analysis of patient survival revealed that the mean number of AgNOR was a significant prognostic factor, as were pathological stage, histological type, and performance status of the patient. Patients with a higher mean number of AgNOR (> 7) had a significantly worse prognosis compared with those with less AgNOR (< or = 7) (median survival 28 versus 43 months) (p < 0.05). It was concluded that the mean number of AgNOR of tumor cells is a significant prognostic factor in surgically treated lung cancer patients.

Surgical treatment of second primary lung cancer: report of eight cases.

Of 312 patients undergoing resection for lung cancer at National Taiwan University Hospital during 1980 to 1990, eight presented with second primary lung cancer. One patient had synchronous and seven patients had metachronous primaries. There were five males and three females with ages ranging from 41 to 77 years. In the metachronous group, two patients had a different histology between the first and the second tumor, and the intervals between the two tumors varied from 12 to 60 months. The initial resections included pneumonectomy in one and lobectomy in six patients. At the second operation, the surgical procedures included lobectomy in three, completed pneumonectomy in one, segmentectomy in another, and wedge resection in two patients. There was no operative mortality and all patients were regularly followed up from 6 months to 6 years after the second operation. Two patients died, one from repeated respiratory tract infection and the other from brain metastasis. Kaplan-Meier analysis showed 2-year and 3-year survivals of 80% and 60%, respectively. It can be concluded that surgical resection for second primary lung cancer is justified, as it can prolong the patient's survival. Lobectomy can be performed for patients with a second primary lung cancer and sufficient lung reserve, but limited resection should be chosen for patients with poor lung reserve.

Adjuvant immunotherapy with intrapleural Streptococcus pyogenes (OK-432) in lung cancer patients after resection.

A prospective randomized study to evaluate the effect of adjuvant intrapleural OK-432 immunotherapy after resection of lung tumor was conducted in 93 patients with primary lung cancer. Among them, 46 patients had had intrapleural OK-432 injection, 47 had not. In the meantime, serial measurements of serum immunosuppressive acidic protein, of serum interleukin-2 receptor and of the subpopulation of the peripheral blood cells and lymphocytes were performed in all these patients. Patient characteristics in these two groups (sex, age, histological type, pathological stage, type of operation, and performance status) were compatible. The results showed that adjuvant intrapleural OK-432 injection after resection had no beneficial effect on a patient's survival time. Patients who received intrapleural OK-432, had an increase in blood leukocytes, granulocytes and monocytes and serum immunosuppressive acidic protein level. But the cell numbers of total T cells, suppressor/cytoxic cells, helper/inducer cells and natural killer cells of peripheral blood were decreased in the OK-432 positive group. Over half of the patients had transient 1- or 2-day febrile reactions after intrapleural OK-432 injection. It was concluded that neither clinical observation nor immunological monitoring of peripheral blood could demonstrate a beneficial effect from intrapleural OK-432 immunotherapy after complete resection of the tumor.