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PubMed1996

Activation of lavage lymphocytes in lung injuries caused by radiotherapy for lung cancer.

PURPOSE: Radiation pneumonitis sometimes extends beyond the irradiated area of a lung and can also affect the opposite lung. Some immunological mechanisms, in addition to simple direct injury of the lungs by radiation, seem to be involved in the onset of radiation pneumonitis. To clarify such mechanisms, the effects of radiation on local inflammatory cells in lungs, in particular, lymphocytes, were examined. METHODS AND MATERIALS: A comparison was made of bronchoalveolar lavage fluid (BALF) findings from 13 irradiated patients (RT group) and 15 nonirradiated patients (non-RT group) with lung cancer. Patients who later developed radiation pneumonitis (RP group) and those who did not (RP-free group) were also compared. Using a two-color flowcytometer, radiation-induced changes in local inflammatory cells in lungs were analyzed. This included analyses of human leukocyte-associated antigen (HLADR) and intercellular adhesion molecule-1 (ICAM-1) expression on T-cells, which are though to be involved in cell activation and interactions between cells. RESULTS: The following aspects of BALF were higher in the RT group than in the non-RT group: (a) the percentage of lymphocytes and eosinophiles; (b) the incidence of HLADR-positive CD4+T-cells and HLADR-positive CD8+T-cells; and (c) the incidence of ICAM-1--positive T-cells. The following aspects of BALF were higher in the RP group than in the RP-free group: (a) the total cell counts; (b) the percentage of lymphocytes; and (c) the incidence of ICAM-1-positive T-cells. A significant relationship was seen between the incidence of ICAM-1 expression on T-cells and the number of days from the initiation of radiotherapy to the onset of radiation pneumonitis. CONCLUSION: These data suggest that irradiation can induce accumulation of activated T-cells (HLADR and ICAM-1--positive T-cells) in the lung. This accumulation may be closely linked to radiation-induced lung injury. It is also suggested that the incidence of ICAM-1--positive T-cells in BALF may serve as a useful clinical marker of radiation pneumonitis.

Adult↗
PubMed2004

Computerized scheme for automated detection of lung nodules in low-dose computed tomography images for lung cancer screening.

RATIONALE AND OBJECTIVES: A computerized scheme for automated detection of lung nodules in low-dose computed tomography images for lung cancer screening was developed. MATERIALS AND METHODS: Our scheme is based on a difference-image technique for enhancing the lung nodules and suppressing the majority of background normal structures. The difference image for each computed tomography image was obtained by subtracting the nodule-suppressed image processed with a ring average filter from the nodule-enhanced image with a matched filter. The initial nodule candidates were identified by applying a multiple-gray level thresholding technique to the difference image, where most nodules were well enhanced. A number of false-positives were removed first in entire lung regions and second in divided lung regions by use of the two rule-based schemes on the localized image features related to morphology and gray levels. Some of the remaining false-positives were eliminated by use of a multiple massive training artificial neural network trained for reduction of various types of false-positives. This computerized scheme was applied to a confirmed cancer database of 106 low-dose computed tomography scans with 109 cancer lesions for 73 patients obtained from a lung cancer screening program in Nagano, Japan. RESULTS: This computed-aided diagnosis scheme provided a sensitivity of 83% (91/109) for all cancers with 5.8 false-positives per scan, which included 84% (32/38) for missed cancers with 5.9 false-positives per scan. CONCLUSION: This computerized scheme may be useful for assisting radiologists in detecting lung cancers on low-dose computed tomography images for lung cancer screening.

False Positive Reactions↗
PubMed2006

Ultrasound lung comets: a clinically useful sign of extravascular lung water.

Assessment of extravascular lung water is a challenging task for the clinical cardiologist and an elusive target for the echocardiographer. Today chest x-ray is considered the best way to assess extravascular lung water objectively, but this requires radiology facilities and specific reading expertise, uses ionizing energy, and poses a significant logistic burden. Recently, a new method was developed using echocardiography (with cardiac probes) of the lung. An increase in extravascular lung water-as assessed independently by chest computed tomography, chest x-ray, and thermodilution techniques-is mirrored by appearance of ultrasound lung comets (ULCs). ULCs consist of multiple comet tails originating from water-thickened interlobular septa and fanning out from the lung surface. The technique requires ultrasound scanning of the anterior right and left chest, from the second to the fifth intercostal space. It is simple (with a learning curve of < 10 examinations) and fast to perform (requiring < 3 minutes). ULC assessment is independent of the cardiac acoustic window, because the lung on the anterior chest is scanned. It requires very basic 2-D technology imaging, even without a second harmonic or Doppler. ULCs probably represent an ultrasonic equivalent of radiologic Kerley B-lines. On still-frame assessment, cardiogenic watery comets can be difficult to distinguish from pneumogenic fibrotic comets, although the latter are usually more localized and are not dissolved by an acute diuretic challenge. Functionally, ULCs are a sign of distress of the alveolar-capillary membrane, often associated with reduced ejection fraction and increased pulmonary wedge pressure. The ULC sign is quantitative, reproducible, and ideally suited to complement conventional echocardiography in the evaluation of heart failure patients in the emergency department (for the differential diagnosis of dyspnea), in-hospital evaluation (for tailoring diuretic therapy), home care (with portable ultrasound), and stress echocardiography lab (as a sign of acute pulmonary congestion during stress). In conclusion, ULCs represent a useful, practical, and appealingly simple way to image directly extravascular lung water.

Artifacts↗
PubMed2005

Incidental lung cancers identified at coronial autopsy: implications for overdiagnosis of lung cancer by screening.

BACKGROUND: The extent to which overdiagnosis occurs in lung cancer screening programmes has been debated. Overdiagnosis refers to the detection by screening of cancers that would not have become clinically apparent or symptomatic before that individual died of other causes. METHODS: A retrospective review of coronial autopsies performed in Victoria between April 1991 and February 2002 was conducted to determine the rate of incidental lung cancer in individuals who died of natural causes. RESULTS: A total of 24,708 autopsy reports were searched electronically. We estimated that in 56% of these death was from natural causes. Amongst individuals who died naturally there were 167 cases of lung cancer, 47 of these were incidental including five carcinoid tumours, three small cell tumours, 11 cases of carcinoma in situ and 28 invasive nonsmall cell lung cancers. Of the incidental invasive nonsmall cell lung cancers, 86% were stage I. CONCLUSIONS: Although incidental lung cancer is uncommon, there are some lung cancers that remain undetected during life and do not contribute to death. These findings support the hypothesis that some lung cancers detected by screening may never progress to cause symptoms or death in that individual's lifetime and therefore may be overdiagnosed by screening.

Adolescent↗
PubMed2005

Exercise testing determines survival in patients with diffuse parenchymal lung disease evaluated for lung transplantation.

STUDY OBJECTIVES: Diffuse parenchymal lung disease is associated with a high risk of mortality despite early referral and listing for lung transplantation. We hypothesized that cardiopulmonary exercise test results and the distance walked in 6min (6MWTD) would be associated with survival in patients with diffuse parenchymal lung disease referred for lung transplantation. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: We included 51 consecutive patients with diffuse parenchymal lung disease who underwent exercise testing after referral to the Lung Transplant Program at the New York Presbyterian Hospital between January 2000 and December 2002. Thirty-three patients were listed, and 7 underwent transplantation during the study period. There were 17 deaths with 1 death post-transplantation. RESULTS: A 6MWTD < 350 m was associated with an increased risk of death (HR = 4.6, 95% CI 1.5-14.2, P = 0.009). Oxygen saturation with unloaded exercise (HR = 0.91, 95% CI 0.84-0.98, P = 0.015) and oxygen consumption at peak exercise adjusted for weight (HR = 0.88, 95% CI 0.79-0.99, P = 0.039) were also associated with the risk of death. A patient with oxygen saturation <95% during unloaded exercise had a 75% chance of dying on the list for transplantation. A patient with 6MWTD < 350 m had a 67% chance of dying on the list. CONCLUSIONS: Cardiopulmonary exercise test parameters and the 6MWTD were associated with the risk of death. Measures during exercise may be useful for determination of prognosis and for prioritizing patients with diffuse parenchymal lung disease for lung transplantation.

Adult↗
PubMed2004

Incidence of primary neoplasms in explanted lungs: long-term follow-up from 214 lung transplant patients.

BACKGROUND: Undetected neoplasms in explanted lungs at transplantation are an unusual occurrence that may significantly complicate both the short- and long-term outcome of these patients. The incidence and survival of undetected primary neoplasms in explanted lungs with clinical and radiologic correlation have not been studied in a large cohort of patients. METHODS: We reviewed the files of 214 consecutive lung transplants from the Transplant Center at the Cleveland Clinic Foundation from 1991 to 2000. Data collected included age, gender, pathology of explanted lung, and survival. Retrospective review of all imaging studies was performed in those cases where a primary neoplasm was detected after transplant. RESULTS: One hundred thirteen males and 101 females underwent lung transplantation for the following diagnoses: emphysema, 118; cystic fibrosis, 35; primary pulmonary hypertension, 27; usual interstitial pneumonia, 26; lymphangioleiomyomatosis, 4; sarcoidosis, 2; and pneumoconiosis, 2. Four neoplasms were found in the explanted lungs, representing a 2% incidence. All four neoplasms were bronchogenic carcinomas, including three adenocarcinomas and one squamous cell carcinoma. Three of four neoplasms were found in the setting of emphysema and were detected at an early stage (stage I), and the fourth presented as stage IV in the setting of usual interstitial fibrosis. No recurrence of tumor was seen in the stage I cases. The stage IV case died in the perioperative period. Retrospective review of the imaging studies showed that, in all four cases, a portable chest radiograph performed immediately before transplant failed to identify the lesions. A chest computerized tomogram was performed in all four cases from 3 to 27 months prior to transplantation and revealed a suspicious lesion in one of the four. CONCLUSIONS: Undetected neoplasms in explanted lungs at transplantation are uncommon, with an incidence of 2% at our institution. Adenocarcinoma was the most common cell type. In long-term survivors, no recurrences were found. The 3-year survival was 50% and this approaches the 3-year survival of transplant recipients without lung tumors (58.8%) at our institution. Chest radiographs appear to have a very low sensitivity for the detection of small lesions suspicious for a neoplasm. Chest computerized tomograms performed immediately prior to transplantation may be of benefit in detecting these neoplasms.

Adenocarcinoma↗
PubMed2004

Discrepancy between severity of lung impairment and seniority on the lung transplantation list.

BACKGROUND: Organ allocation for lung transplantation, based mainly on accrued time on a waiting list, may not be an equitable system of organ allocation. To provide an objective view of the current practice concerning lung allocation, and timing for transplantation, we examined illness severity and list seniority in patients on a lung transplantation waiting list. METHODS: Adult patients awaiting lung transplantation underwent testing for mean pulmonary artery pressure (mPpa), maximum oxygen consumption (VO2 max), 6-minute walk distance (6MWD), forced expiratory volume in 1 second, mean partial pressure of carbon dioxide, partial pressure of oxygen/fractional concentration of inspired oxygen, and diffusing capacity of the lung for carbon monoxide. Relationships between physiological variables and waiting list rankings were then determined. RESULTS: Thirty-four patients were tested and there was no correlation between time spent waiting on the list and mPpa (r=0.01; P=.94), VO2 max percentage predicted (r=0.07; P=.71), or 6MWD (r=0.15; P=.42). Many patients with functional impairments as indicated by low maximum VO2 or by short 6MWD are scheduled to receive their transplant after patients with levels that indicate a lower degree of risk. When compared with a hypothetical reranking based on mean Ppa, 24 of the 34 patients (71%) on our current waiting list were found to be 5 positions higher or lower than this new risk-based ranking. Sixteen patients (47%) were 10 or more positions away from their hypothetical severity-based ranking, and 9 (26%) were at least 15 positions out of place. Sixteen of the 34 patients were ranked lower than they would be based on a severity of illness using the pulmonary artery pressure alone, 17 were ranked higher than "should be" based on pulmonary artery mean, and only 1 patient (ranked in position 15) was appropriately positioned based on seniority and severity of disease based on PA mean. CONCLUSION: Rank order for lung transplantation has no relationship with illness severity, and the discrepancy between disease severity and seniority on the lung waiting list may compromise overall outcomes in the lung transplantation population.

Adult↗
PubMed2000

A randomized, controlled trial comparing thoracoscopy and limited thoracotomy for lung biopsy in interstitial lung disease.

BACKGROUND: Lung biopsies are frequently needed to diagnose diffuse interstitial lung diseases. A prospective randomized, controlled trial comparing limited thoracotomy (open lung biopsy) and thoracoscopy for lung biopsy was done. METHODS: Ambulatory patients with a clinical diagnosis of diffuse interstitial lung disease were randomized to thoracoscopy or limited thoracotomy. Data on postoperative pain, narcotic requirements, operating room time, adequacy of biopsy, duration of chest tube drainage, length of hospital stay, spirometry, and complications were collected. RESULTS: A total of 42 randomized patients underwent lung biopsy (thoracoscopy 20, thoracotomy 22). The two study groups were comparable with respect to age, gender, corticosteroid use, and preoperative spirometry. Visual analog scale pain scores were nearly identical in the two groups (p = 0.397). Total morphine dose was 50.8 +/- 27.3 mg in the thoracoscopy group and 52.5 +/- 25.6 mg in the thoracotomy group (p = 0.86). Spirometry (FEV1) values in the two groups were not significantly different on postoperative days 1, 2, 14, and 28 (p = 0.665). Duration of operation was similar in both groups (thoracoscopy 40 +/- 30 minutes, thoracotomy 37 +/- 15 minutes; p = 0.67). The thoracoscopy and thoracotomy groups had equivalent duration of chest tube drainage (thoracoscopy 38 +/- 28 hours, thoracotomy 31 +/- 26 hours; p = 0.47) and length of hospital stay (thoracoscopy 77 +/- 82 hours, thoracotomy 69 +/- 55 hours; p = 0.72). Definitive pathologic diagnoses were made in all patients. CONCLUSIONS: There is no clinical or statistical difference in outcomes for thoracoscopic and thoracotomy approaches. Both thoracoscopy and thoracotomy are acceptable procedures for diagnostic lung biopsy in diffuse interstitial lung disease.

Biopsy↗
PubMed2002

Lung and heart-lung transplantation in patients with end-stage cystic fibrosis: the Stanford experience.

BACKGROUND: Bilateral lung (BLTx) and heart-lung transplantation have gained wide acceptance as treatment of end-stage lung disease from cystic fibrosis. We reviewed our 13-year experience with thoracic transplantation for cystic fibrosis with an operative approach that favors use of cardiopulmonary bypass for BLTx. METHODS: Sixty-four patients with cystic fibrosis underwent heart-lung transplantation (n = 22, 34.4%) or BLTx (n = 42, 65.6%) between 1988 and 2000. Mean age and weight at transplantation were 29 +/- 8 years and 51 +/- 11 kg, respectively. Mean follow-up for survivors was 4.4 +/- 3.6 years. Immunosuppression regimen included cyclosporine, tapered corticosteroids, azathioprine, and induction therapy with OKT3 (murine monoclonal antibodies) or rabbit antithymocyte globulin. Cardiopulmonary bypass was used in all but 5 patients (7.8%). However, in 8 (19%) of the 42 patients having BLTx, only the grafting of the second lung was performed with cardiopulmonary bypass. RESULTS: The operative mortality rate was 1.6%. The actuarial survival rates at 1 year, 3 years, 5 years and 10 years were 93.2%, 77.7%, 61.8%, and 48.1%, respectively, with no significant difference between BLTx and heart-lung transplantation. The major hospital complications were pneumonia (n = 11, 17.2%) and bleeding (n = 8, 12.5%). Clinically significant reperfusion injury was observed in 6 patients, 3 of whom required reintubation. Freedom from acute lung rejection beyond 1 year was 47.7%. One patient underwent late retransplantation, and 4 required bronchial stenting. Obliterative bronchiolitis accounted for eight (50.0%) of 16 late deaths. CONCLUSIONS: Though postoperative bleeding and pneumonia are still of concern, satisfactory early and intermediate-term results can be expected in patients undergoing BLTx or heart-lung transplantation for cystic fibrosis. Cardiopulmonary bypass can be used for BLTx with no adverse impact on intermediate and long-term outcomes.

Adult↗
PubMed1985

The effect of hypothermic preservation of the heart and lungs on cardiorespiratory function following canine heart-lung transplantation.

The effect of hypothermic preservation of the heart and lungs with a crystalloid solution was evaluated in 12 mongrel dogs receiving heart-lung allografts. Six animals served as controls and received an immediate heart-lung transplant. Six animals were in the experimental group and received a heart-lung transplant after 5 hours of preservation at 4 degrees C following perfusion of both organs with a crystalloid solution. Physiological function of the heart and lungs was studied for 20 hours after transplantation. While cardiac function was minimally depressed following preservation, pulmonary function testing demonstrated significantly greater increases in extravascular lung water in experimental animals, suggesting that an ischemic lung injury occurred with this preservation technique. The model allows for future evaluation of other methods of combined preservation of both the heart and lungs for transplantation.

Airway Resistance↗
PubMed1989

Lung asbestos burden in shipyard and construction workers with mesothelioma: comparison with burdens in subjects with asbestosis or lung cancer.

Although mesothelioma is generally considered to be caused by asbestos, epidemiologic studies indicate that some cases have another cause. In order to determine whether pulmonary asbestos burden can be used to define asbestos-related mesotheliomas, asbestos burden was quantified in 27 shipyard or construction workers with diffuse malignant mesothelioma of the pleura or peritoneum and a history of asbestos exposure. Their burden was significantly greater than the burden found in 19 unexposed men (P less than 0.001). The burdens were also compared to those of previously reported subjects with asbestosis or lung cancer. The median concentration for total amphibole fibers (2.7 million/g dry lung) in subjects with mesothelioma did not differ significantly from our previously reported median values for 14 subjects with asbestosis (1.3 million/g dry lung) or for 60 asbestos workers with lung cancer (1.3 million/g dry lung). Fiber size distribution for amosite, the most prevalent fiber type, was similar in all three subject groups. Fifteen of 25 (60%) subjects with mesothelioma had mild asbestosis. Asbestos body (AB) concentrations were greater than or equal to 1900/g dry lung, and total amphibole fiber concentrations were greater than or equal to 390,000/g dry lung. Counts of ABs greater than or equal to 0.5/cm2 in histologic sections always signified both of these concentrations in extracts. Thus, histologic sections showing greater than or equal to 0.5 ABs/cm2 or extracts containing asbestos body or amphibole fiber concentrations of at least 1900 or 390,000/g dry lung, respectively, will confirm an asbestos-related mesothelioma.

Aged↗
PubMed1997

Inhaled nitric oxide and pentoxifylline in rat lung transplantation from non-heart-beating donors. The Paris-Sud University Lung Transplantation Group.

BACKGROUND: In non-heart-beating donor lung transplantation, postmortem warm ischemia poses a special challenge. Inhaled nitric oxide and pentoxifylline have been shown to attenuate ischemia-reperfusion injury after lung transplantation. We hypothesized that concomitant administration of inhaled nitric oxide and pentoxifylline would result in a synergistic effect on ischemia-reperfusion lung injury. METHODS: Lungs were harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia, flushed, and stored for 2 hours at 4 degrees C before left lung transplantation in rats. Inhaled nitric oxide (30 ppm) was added during cadaver ventilation and reperfusion; pentoxifylline was given intravenously throughout reperfusion. The following groups were studied (n = 8 each): control, pentoxifylline, nitric oxide, and nitric oxide+pentoxifylline. Hemodynamic indices and arterial blood gases were obtained after ligation of the right pulmonary artery. Lung myeloperoxidase and wet/dry ratio were measured after death. RESULTS: All rats that did not receive nitric oxide died within 10 minutes after ligation. Inhaled nitric oxide significantly decreased pulmonary vascular resistance and improved recipient survival. Nitric oxide + pentoxifylline improved pulmonary vascular resistance, arterial oxygen tension, and survival even further and reduced lung myeloperoxidase as compared with the group that received nitric oxide only. Preservation solution flush time was significantly decreased in both groups receiving nitric oxide, suggesting that inhaled nitric oxide used during cadaver ventilation allows for a more even distribution of the preservation solution. CONCLUSIONS: We conclude that treatment with inhaled nitric oxide + pentoxifylline results in a synergistic protection from ischemia-reperfusion injury after non-heart-beating donor lung transplantation. This is likely the result of a dual action on the graft vasculature and neutrophil sequestration.

Animals↗
PubMed1998

Controlled reperfusion after lung ischemia: implications for improved function after lung transplantation.

OBJECTIVES: Despite improvements in organ preservation, reperfusion injury remains a major source of morbidity and mortality after lung transplantation. This pilot study was designed to investigate the effects of controlled reperfusion after lung ischemia. METHODS: Twenty adult pigs underwent 2 hours of warm lung ischemia by crossclamping the left bronchus and pulmonary artery. In five (group 1), the clamp was simply removed at the end of ischemia (uncontrolled reperfusion). The 15 other pigs underwent modified reperfusion using blood from the femoral artery to perfuse the lung through the pulmonary artery (pressure 40 to 50 mm Hg) for 10 minutes before removing the pulmonary artery clamp. In five (group 2), the blood was mixed with crystalloid, resulting in a substrate-enriched, hypocalcemic, hyperosmolar, alkaline solution. In five (group 3), the blood was circulated through a leukocyte-depleting filter, and the last five (group 4) underwent reperfusion with both a modified solution and white blood cell filter. Lung function was assessed 60 minutes after reperfusion, and biopsy specimens were taken. RESULTS: Controlled reperfusion with both a white blood cell filter and modified solution (group 4) completely eliminated the reperfusion injury that occurred with uncontrolled reperfusion (group 1), resulting in complete preservation of compliance (98% +/- 1% vs 77% +/- 1%; p < 0.001, and arterial/alveolar ratio (97% +/- 2% vs 27% +/- 2%; p < 0.001); no increase in pulmonary vascular resistance (106% +/- 1% vs 198% +/- 1%; p < 0.001); lowered tissue edema (82.1% +/- 0.4% vs 84.3% +/- 0.2%; p < 0.001), and myeloperoxidase activity (0.18 +/- 0.02 vs 0.35 +/- 0.02 deltaOD/min/mg protein; p < 0.001). In contrast, using either a white blood cell filter or modified solution separately improved but did not avoid the reperfusion injury, resulting in pulmonary function and tissue edema levels that were intermediate between group 1 (uncontrolled reperfusion) and group 4 (white blood cell filter and modified solution). CONCLUSION: After 2 hours of warm pulmonary ischemia, (1) a severe lung injury occurs after uncontrolled reperfusion, (2) controlled reperfusion with either a modified reperfusion solution or white blood cell filter limits, but does not avoid, a lung reperfusion injury, (3) reperfusion using both a modified reperfusate and white blood cell filter results in complete preservation of pulmonary function. We therefore believe surgeons should control the reperfusate after lung transplantation to improve postoperative pulmonary function.

Animals↗
PubMed2001

The clinical value of lung imaging fluorescence endoscopy for detecting synchronous lung cancer.

Some patients with non-small cell lung cancer (NSCLC) will also have a synchronous malignant lesion. The lung imaging fluorescence endoscopy (LIFE) has proven better than conventional white light bronchoscopy (WLB) for visualizing premalignant lesions or early stages of lung cancer. In this study, the additional value of LIFE in diagnosing synchronous lung cancers as well as the impact of these findings on definite therapy was analyzed. Seventy-two patients with recently diagnosed NSCLC or pulmonary lesions highly suspect of lung cancer were studied. Patients underwent WLB, followed by LIFE. Apart from the primary lesions, additional abnormal and suspicious lesions seen at WLB and LIFE were scored separately and biopsied. Sixty-nine patients had NSCLC and three patients had small cell lung carcinoma. Apart from the primary lesion, one up to six additional endobronchial lesions were visualized in 48 patients by WLB and/or LIFE. High-grade dysplastic lesions were detected in ten patients, three of whom were eligible for surgery of the primary tumor after completion of the investigations. Three other patients (4.3%) had synchronous cancers (NSCLC). In one patient, the lesion was visualized by LIFE and by WLB. The other two malignant lesions were detected only by LIFE. In these three latter patients, diagnostic work-up and definite treatment was changed, as a result of detection of synchronous lesions. In conclusion, LIFE has additional value in detecting synchronous malignant lesions in patients with primary lung cancer. The detection of these lesions changed diagnostic work-up and definite treatment plan. Therefore, LIFE should be used in the work-up of patients with primary lung cancer.

Adult↗
PubMed2002

Expression of cytokeratin 8 in lung cancer cell lines and measurement of serum cytokeratin 8 in lung cancer patients.

It has been reported that cytokeratin 8 (CK8) can be expressed in several cancers and expression of CK8 is correlated with increased invasiveness of the tumor in vitro and in vivo. In the present study, we investigated expressions of CK8 in human lung cancer cell lines. In addition, we also evaluated the clinical significance of CK8 measurements in sera of patients with lung cancer. Expression of mRNA for CK8 was semi-quantitatively evaluated by the competitive reverse transcriptase-polymerase chain reaction (competitive RT-PCR), using human lung cancer cell lines. The level of CK8 protein in culture supernatants of lung cancer cell lines and 70 sera of patients with lung cancer was measured by enzyme-linked immunosorbent assay (ELISA). Levels of serum CK8 according to clinical parameters were also examined. The level of expression of CK8 mRNA in non-small cell lung cancer (NSCLC) cell lines was significantly high compared with that of small cell lung cancer (SCLC) cell lines (P<0.05). The level of CK8 in culture supernatants in NSCLC was significantly high compared with that of SCLC. The level of serum CK8 in patients with NSCLC was significantly high compared with that of normal non-smokers and compared with that of SCLC (P<0.05). Patients with a CK8 value of 50.0 ng/ml, or higher, had a statistically significant diminished survival compared with those patients whose CK8 values were lower. In conclusion, CK8 was preferentially expressed in NSCLC. Increasing values of CK8 were significantly associated with tumor progression and decreased survival in patients with NSCLC. Therefore, CK8 in sera may become a novel tumor marker in patients with lung cancer.

Adult↗
PubMed2002

Results of lung metastasectomy from breast cancer: prognostic criteria on the basis of 467 cases of the International Registry of Lung Metastases.

OBJECTIVE: Metastatic breast cancer is still defined as an incurable disease. Although the prognosis after resection of isolated metastases to the lung is much better than after chemotherapy most oncologists and gynecologists disapprove of lung metastasectomy. METHODS: In order to summarize the experience of pulmonary metastatic surgery and to achieve more relevant data by an increased number of cases, we evaluate the data of the International Registry of Lung Metastases of 467 patients having lung metastases from breast cancer with regard to long-term survival and prognostic factors. RESULTS: In 84% a complete metastatic resection was possible. The survival rates are 38% after 5 years, 22% after 10 years, and 20% after 15 years. Prognostic factors are a disease-free interval of > or = 36 months with 5-year survival of 45%, a 10-year survival of 26% and a 15-year survival of 21% (P=0.0001), solitary lung metastasis is associated with a survival rate of 44% after 5 years and of 23% after 10 and 15 years, but this is not statistically significant compared to multiple metastases. When establishing prognostic groups as suggested by Pastorino and the International Registry of Lung Metastases based on the risk factors disease-free interval, number of metastases and complete resection the group with the best prognosis showed 5-year survival of 50%, 10- and 15-year survival of 26% with a median survival of 59 months. CONCLUSION: Considering the low morbidity and mortality rate, we think that lung metastasectomy today is the best treatment option in selected cases of lung metastases from breast cancer.

Breast Neoplasms↗
PubMed1999

Lung infections in pediatric lung transplantation: experience in 49 cases.

OBJECTIVES: Pulmonary infections, and particularly cytomegalovirus (CMV) infections, are a major cause of morbidity after lung transplantation. We report here our results in 49 pediatric lung transplantations. METHODS: Between may 1988 and 1997, we have done 49 lung transplantations in 42 children (en bloc double lung transplantation (DLT):10, HLTx:7, sequential bilateral sequential-lung transplantation (BSLT):31, single-lung transplantation (SLT): 1). In seven, it was a retransplantation. Among these, 34 were cystic fibrosis (CF) patients, all with multiresistant organisms (Pseudomonas aeruginosa, Burkholderia cepacia, Achromobacter xylososydans, Staphylococcus aureus). All patients were treated with multiantibiotic prophylaxy adapted to the preoperative cultures. Donor-recipient CMV matching was possible in only 31 cases. CMV prophylaxy and immunosuppression protocols have evolved with time, with a current protocol of IV Gancyclovir prophylaxy for 3 months and triple drug immunosuppression without post-operative rabbit anti-thymocyte globulin (RATG) induction. There was no perioperative mortality in the primary transplantations and three early deaths in the whole group (6.1%). RESULTS: Only five patients had no pulmonary infection. The patients presented 3.2 infection episodes per year, 75% localized on the lungs, 41% during the first 3 months. Among the 13 deaths in the 1st year, 10 were directly related to infection, 60% due to CMV. After the 1st year, in all patients dying of pulmonary dysfunction or obliterative bronchiolitis (OB), bacterial infections were associated. There was no serious fungal infection. Actuarial survival at 3 months, 1, 3, 5 years were 85, 65.7, 47.5 and 28.5%, respectively. There was a significant difference in 3 year survival between patients receiving CMV negative organs (40%) and CMV positive organs (17%). CONCLUSION: In our experience, as in other's, pulmonary infection risk is important in lung transplantation. Bacterial infections were mainly an aggravating factor of secondary pulmonary dysfunction or OB, and were not the primary cause of death. CMV infections have been very severe and lead us, despite the scarcity of donors, to avoid positive donors in negative recipients, this leads to disastrous mid-term results in our experience, despite prophylaxis.

Adolescent↗
PubMed1999

Causes of allograft dysfunction after single lung transplantation for emphysema: extrinsic restriction versus intrinsic obstruction. Brigham and Women's Hospital Lung Transplantation Group.

BACKGROUND: A subset of patients with emphysema who have undergone single lung transplantation (SLT) may subsequently present with dyspnea, worsening airways obstruction, hypoxemia, and progressive chronic native lung hyperinflation. The leading cause of late allograft dysfunction is bronchiolitis obliterans syndrome (BOS). However, extrinsic restriction manifests with a similar clinical presentation and is an additional mechanism to consider. We describe the use of the inspiratory lung resistance (RLi) to distinguish a decline in respiratory status due predominantly to either extrinsic restriction or BOS. METHODS: We studied five patients who underwent SLT for emphysema between 1992 and 1995, in whom the diagnoses of BOS and extrinsic restriction were subsequently entertained. Forced expiratory volume in 1 second (FEV1), RLi, static lung compliance, elastic recoil pressure at total lung capacity (TLC), and the slope of the maximum flow static recoil (MFSR) plot were measured. RESULTS: All patients had severe airflow obstruction, with mean FEV1 0.98 +/- 0.24 liter (26 +/- 5% predicted), elevated static lung compliance, reduced elastic recoil pressure at TLC, and reduced slope of the MFSR plot. Three patients had "low" RLi (9.3-12.8 cm H20/L/sec). Obstruction was attributed predominantly to extrinsic restriction. These patients underwent lung volume reduction surgery (LVRS) on the native lung; improvements in pulmonary mechanics were observed at 6 months. In contrast, two patients had markedly elevated RLi (17.3 and 17.4 cm H2O/L/sec). Obstruction was attributed predominantly to intrinsic airway disease from BOS that was subsequently documented at autopsy. CONCLUSIONS: The RLi appears to be a useful adjunct to the clinical history in distinguishing a decline in respiratory status due predominantly to either BOS or extrinsic restriction in patients who have undergone SLT for emphysema. Determination of the mechanism of allograft dysfunction may allow the selection of an appropriate subset of patients who would benefit from LVRS.

Airway Resistance↗