Open Lung Research Articles

Lung Adenocarcinomas Diagnosed by Open Lung or Thoracoscopic vs Bronchoscopic Biopsy

To examine the characteristics of peripheral lung adenocarcinomas diagnosed by open lung or video-assisted thoracoscopic surgery (VATS) biopsy. We used retrospective analysis to compare tumor stage, pleural involvement, central tumor fibrosis, and the number of bronchi or vessels involved with tumors of small peripheral lung adenocarcinomas diagnosed by bronchoscopic biopsy. Subjects had lung adenocarcinomas diagnosed by open lung or VATS (n=22) and those diagnosed by bronchoscopic biopsy (n=22), which were matched by tumor size. The T1N0M0 tumor was notably more frequent in the open lung or VATS group (77.3%) than in the bronchoscopic biopsy group (36.4%) (p<0.01). Tumors invading beyond the pleural surface were less frequent in the open lung or VATS group (4.5%) than in the bronchoscopic biopsy group (40.9%) (p<0.01). The grade of in-tumor central fibrosis--a malignancy factor and the cause of bronchi or vessel involvement with tumors-was significantly lower in the open lung or VATS group than in the bronchoscopic biopsy group (p<0.01). The number of bronchi or vessels involved with tumors was significantly fewer in the open lung or VATS group than in the bronchoscopic biopsy group (p<0.001). (1) Lung adenocarcinomas diagnosed by open lung or VATS biopsy were more frequently T1N0M0 than those diagnosed by bronchoscopic biopsy, which was caused by low grade of central tumor fibrosis rather than small tumor size. (2) They were infrequently diagnosed by bronchoscopic biopsy because few bronchi were involved by tumors due to the low grade of central tumor fibrosis. (3) Small pulmonary nodules not diagnosable by bronchoscopic biopsy should be diagnosed aggressively using VATS biopsy to detect early-stage lung cancer.

Open-lung biopsy in patients with acute respiratory distress syndrome.

It has been suggested that fibrosis present during the fibroproliferative phase of acute respiratory distress syndrome (ARDS) can be treated by corticosteroids. However, neither clinical nor microbiologic criteria permit differentiation of this fibroproliferative phase from a nosocomial pneumonia. The aim of this observational case series was to evaluate the safety and utility of open-lung biopsy (OLB) performed in patients receiving ventilatory support who had persistent ARDS despite negative bacterial cultures. During a 4-yr period, 37 OLBs were performed in 36 of 197 patients receiving ventilatory support who had ARDS. The severity of ARDS was assessed by a lung injury score of 3.1 +/- 0.4 (mean +/- SD) and a median ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of 118 mmHg. Histologic examination; bacterial, fungal, and acid-fast staining; and cultures of the tissue sample were performed. Fibrosis was present in only 41% of the lung specimens obtained by OLB. Only six patients received corticosteroids (17%). In 9 of the 15 patients with fibrosis, cytomegalovirus pneumonia precluded the use of corticosteroids. Histologic cytomegalovirus pneumonia was diagnosed in 18 cases. Histologic bacterial or mycobacterial pneumonia was diagnosed in five cases. No significant change in arterial blood gases was noted as linked to the biopsy procedure except an increase of the PaO2/FiO2 ratio. One pneumothorax was diagnosed on a chest roentgenogram 12 h after OLB. Only one patient required blood transfusion during the 48-h period after OLB (for an hemothorax). Five patients had moderate air leaks from operative chest tubes for 2-10 days. Open lung biopsy appeared to be a useful and acceptably safe diagnostic technique in patients with ARDS. It permitted the diagnosis of unexpected cytomegalovirus pneumonia.

Proliferative Properties and Cytokine Secretion of Lung Fibroblast Cell Lines of the Patients with Idiopathic Pulmonary Fibrosis

Background: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. Subjects and Method: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen Result: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212 0.107 vs , p=0.0922), also there was no significant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower() in IFB than control(, p=0.0429). The IFB secreted significantly higher amount of MCP-l( pg/ml) spontaneously than NFB( pg/ml) and also after the stimulation with TGF-( ng/ml vs ng/ml, p=0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF- stimulation. But after the maximal stimulation with IL-1,8, no significant difference in cytokine secretion was found between IFB and NFB. Conclusion : Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.

Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: Report of two patients, one with distant metastasis, and review of the literature

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a recently recognized malignant neoplasm of the thyroid gland. Two additional cases of this condition which occurred in a 70-year-old woman and a 69-year-old woman are presented. The case of the 70-year-old woman (patient 1) is the first report of distant metastasis, besides lymph node metastasis, for this type of tumor. The patient initially presented with a thyroid mass, and the thyroid gland with surrounding cervical lymph nodes was removed. Because of focal keratin “pearl” formation, the tumor was misinterpreted as a metastatic squamous cell carcinoma to the thyroid. Approximately 4 years later, the patient developed a left supraclavicular mass and lung densities. A pathological fracture of the right humeral head followed, and the left supraclavicular mass recurred along with newly developed subcutaneous nodules on the chest wall and arm. Open lung and bone biopsies revealed metastatic SMECE, which was morphologically identical to that of the thyroid mass. The 69-year-old woman (patient 2) had, in 1983, undergone thyroidectomy with left radical neck dissection; this had been diagnosed as follicular carcinoma of the thyroid with lymph node involvement. After multiple isolated lymph nodes metastases, the patient developed locally extensive, recurrent tumor that showed microscopic features of SMECE. Review of the previous thyroid tumor and lymph nodes revealed the same type of histology. To our knowledge, only a single report containing eight cases of this distinctive carcinoma of the thyroid has been published. Herein we describe characteristic morphological features of two additional cases of this rare malignancy, one with distant metastasis, and we review the related literature.

ARDS: dramatic rises in arterial PO2 with the 'open lung' approach

In a pilot study the 'open lung' concept was applied 22 times in 13 patients of a university medical intensive care unit with ARDS (lung injury score 3.7 ± 0.7) due to sepsis of various origin (APACHE II score 27.4 ± 6.3). Starting with the actual respirator adjustment, peak inspiratory pressure was increased by 10 cmH2O every 3 min up to a mean pressure of 61 ± 9 cmH2O, depending on the hemodynamic state and blood gas results of the patient. PEEP was increased to 15 to 25 cmH2O. After achieving maximal elevation of arterial PaO2, the peak pressure was then lowered to 30, maximal 40, cmH2O and PEEP adjusted just above the alveolar occlusion pressure which guaranteed a tidal volume of about 6 ml/kg body weight. Under this regimen, FiO2 could be significantly lowered from 0.9 to 0.55 with marked rise in oxygenation index from 100 ± 36 to 177 ± 63 mmHg in responders (15 maneuvers in 11 patients). Plain chest X-ray and CT scan showed marked reduction of signs of pulmonary infiltration in a very short time. The 'open lung' approach, though short-lived, might provoke pneumothorax and mediastinal emphysema. However, it enables rapid recruitment of previously atelectatic alveoli, thus resulting in better oxygenation on the one hand, and help avoid oxygen toxicity and protracted volu- and barotrauma on the other hand which are the usual sequel of prolonged ventilation using conventional mode in ARDS. Depending on our experience, the advantages of the concept are far more obvious than its possible risks. Continuous blood gas monitoring systems may help shorten the period of high inspiratory peak pressure. Multicentre studies are required to validate long-term results and possible complications.

Cellular Autofluorescent Pigment and Interstitial Fibrosis Smoker's Lung

The mechanisms by which cigarette smoking lead to bronchopulmonary diseases are incompletely understood. The most characteristic lesion is a chronic macrophage-alveolitis accompanied by slight fibrosis and emphysema. The macrophages contain a ceroid-like granular autofluorescent pigment in their lysosomes. Using immunohistochemical methods, open lung-, transbronchial biopsies and cells obtained by broncho-alveolar lavage from cigarette smokers were studied: anti-human macrophage serum and anti-human elastase, immune sera against type I, type III collagens and fibronectin were used in the demonstration of the cellular components of alveolitis and the connective tissue constituents of fibrosis. The characteristic red-brown autofluorescent pigment of the macrophages was also found in an extra-alveolar location mainly in peribronchial, septal and pleural scars. Similar emission colour occurred focally in the elastic laminae of fibrotic alveoli and sclerotic arteries. Granular fluorescent pigment was found in many bronchial epithelial cells. The epithelial pigmentation was associated with increased transcription of nucleic acid proteins, revealed by colloid silver (AgNOR) reaction. The results suggest that the autofluorescent pigment substances in macrophages may indicate or also play a role in the development of pathological connective tissue and epithelial changes of smoker's lung, in addition to the known mediators and enzymes.

Drug-related pulmonary toxicity in non-Hodgkin's lymphoma. Comparative results with three different treatment regimens

Pulmonary toxicity may complicate the treatment of non-Hodgkin's lymphoma (NHL). The possible drug-related cause of pulmonary toxicity was investigated retrospectively in 207 NHL patients treated between 1981 and 1988 with three regimens containing cyclophosphamide with and without methotrexate or bleomycin: methotrexate, calcium, leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) (n = 134); methotrexate, calcium, leucovorin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-ACOD) (n = 43); or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 30) chemotherapy. These regimens contained the same drugs and were administered in the same schedule; the regimens differed primarily in the addition of bleomycin or methotrexate. Pulmonary toxicity occurred in 24 of 134 (18%) m-BACOD-treated and in six of 43 (14%) m-ACOD-treated patients (P = 0.65). Chest radiography revealed diffuse pulmonary infiltrates in 16 (67%) and six (100%) of the m-BACOD-treated and m-ACOD-treated patients with pulmonary toxicity, respectively. None of the CHOP-treated patients had pulmonary toxicity. The clinical features of pulmonary toxicity and the amount of chemotherapy administered before it occurred did not differ in patients treated with m-BACOD or m-ACOD, although the toxicity tended to be more severe in the m-BACOD group. Open lung or transbronchial biopsies done in six (38%) of the m-BACOD-treated and three (50%) of the m-ACOD-treated patients with pulmonary infiltrates revealed nonspecific pneumonitis compatible with drug-related toxicity. In summary, these results showed that pulmonary toxicity during m-BACOD and m-ACOD therapy occurred with similar frequency and clinicopathologic features. This suggested that bleomycin was not responsible uniquely for the pulmonary toxicity in m-BACOD-treated patients. That pulmonary toxicity was not observed in patients treated with CHOP suggested that methotrexate may play an important role in the pathogenesis of the pulmonary toxicity.

Removal of abdominal sources of caudal mediastinal node lymph in anesthetized sheep

We investigated the conditions for and the quantity of abdominal contributions to caudal mediastinal node (CMN) efferent lymph in 15 anesthetized sheep with open thorax and lung lymph fistulas. Contractions of the diaphragm by phrenic nerve stimulation increased lymph flow by 29%. Adding large volumes (10 ml/kg) of 5% albumin solution to the peritoneal cavity increased lymph flow by 19 and 28% during diaphragm contraction. Tracer albumin specific activity in lymph indicated that about half the lymph flow increment came from the peritoneal liquid. Raising hepatic vein pressure 19 cmH2O increased CMN lymph flow 178%. Lymph protein concentration also increased markedly, from 0.72 to 0.91 of the plasma concentration. We devised a simple procedure to cauterize across the pleural surface of the diaphragm to destroy the aberrant lymphatics. This procedure markedly diminished both abdominal cavity and portal system contributions.

Amiodarone and pulmonary fibrosis.

Of 25 cases of idiopathic pulmonary fibrosis, confirmed by open chest lung biopsy between January 1979 and July 1981, 5 patients had been taking amiodarone in doses less than 600 mg daily for 1 to 6 years. No lung disease had been observed in any patient before the administration of amiodarone, and other drugs, factors and diseases thought to play a role in the causation of pulmonary fibrosis were ruled out. Two patients died of respiratory insufficiency, and only 1 does not now suffer from serious sequelae. Review of a further 5 cases reported in the literature and the present data suggest a causal link between administration of amiodarone and pulmonary fibrosis, and tend to indicate a hypersensitivity mechanism.

Transbronchial lung biopsy in the diagnosis of lymphangitic carcinomatosis

The clinical diagnosis of lymphangitic carcinomatosis of the lung has generally been confirmed by open lung or transthoracic needle biopsy, precedures with significant morbidity and mortality, particularly in patients with respiratory insufficiency. We present six cases of lymphangitic carcinomatosis diagnosed by transbronchial biopsy. Autopsy confirmation was obtained in 4 patients and ultrastructural confirmation of intralymphatic location of tumor in one. The diffuse bronchial and peribronchial lymphatic involvement demonstrated here suggests that this relatively noninvasive technique should be the procedure of choice in the diagnosis of lymphangitic carcinomatosis of the lung.

Effects of lung inflation on pulmonary arterial blood volume in intact dogs.

The isolated effects of alterations of lung inflation and transmural pulmonary arterial pressure (pressure difference between intravascular and pleural pressure) on pulmonary arterial blood volume (Vpa) were investigated in anesthetized intact dogs. Using transvenous phrenic nerve stimulation, changes in transmural pulmonary arterial pressure (Ptm) at a fixed transpulmonary pressure (Ptp) were produced by the Mueller maneuver, and increases in Ptp at relatively constant Ptm by a quasi-Valsalva maneuver. Also, both Ptm and Ptp were allowed to change during open airway lung inflation. Vpa was determined during these three maneuvers by multiplying pulmonary blood flow by pulmonary arterial mean transit time obtained by an ether plethysmographic method. During open airway lung inflation, mean (plus or minus SD) Ptp increased by 7.2 (plus or minus 3.7) cmH2O and Ptm by 4.3 (plus or minus 3.4) cmH2O for a mean increase in Vpa by 26.2 (plus or minus 10.7) ml. A pulmonary arterial compliance term (Delta Vpa/Delta Ptm) calculated from the Mueller maneuver was 3.9 ml/cmH2O and an interdependence term (Delta Vpa/Delta Ptp) calculated from the quasi-Valsalva maneuver was 2.5 ml/cmH2O for a 19% increase in lung volume, and 1.2 ml/cmH2O for an increase in lung volume from 19% to 35%. These findings indicate that in normal anesthetized dogs near FRC for a given change in Ptp and Ptm the latter results in a greater increase of Vpa.

Biopsy Techniques in the Diagnosis of Intrathoracic Lesions

1)Ideal therapy of intrathoracic lesions cannot be undertaken without an accurate histological diagnosis. 2)The role of bronchoscopic and esophagoscopic biopsy in the investigation of thoracic lesions has long been firmly established and the necessity for early exploratory thoracotomy in the management of undiagnosed unilateral solid pulmonary infiltrates suspected of representing bronchogenic carcinoma has been widely accepted in recent years. 3)There are other biopsy techniques available for the study of intrathoracic disease that do not appear to have been generally utilized. These include: (a) Resection of the deep cervical fat pad and its contained nodes, (b) mediastinal biopsy at open thoracotomy and (c) lung biopsy at open thoracotomy. We have used each of these methods in an appreciable series of cases and in practically every instance it has been possible to establish a definite histological diagnosis. The procedures have occasioned minimal morbidity and no mortality. They appear to merit more widespread use in the investigation of chest lesions posing difficult diagnostic problems. 4)Cases are reported to illustrate the use of each of the three foregoing methods.