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G Alexander Patterson

Publications and source records attributed to G Alexander Patterson.

88 records · Page 5Linked to original sources
PubMed2002

Surgical resection of multifocal non-small cell lung cancer is associated with prolonged survival.

BACKGROUND: Revisions in the international system for the staging of lung cancer, adopted in 1997, assigned the T4 descriptor to separate tumor nodules in the same lobe and the M1 descriptor to tumor nodules in a different lobe. Consequently, these changes shifted the stage of patients with these lesions to stage IIIB or stage IV. The goal of this review was to determine the impact of multifocal non-small cell lung cancer on survival. METHODS: A database analysis of our cardiothoracic surgery tumor registry was performed to identify all patients who underwent surgical resection of non-small cell lung cancer (NSCLC), who were ultimately determined to have pathologically node-negative disease from 1994 to 1999. All pathology reports were individually reviewed. Survival data were collected on each patient from the date of surgery with a mean duration of follow-up of 46.3 months. Kaplan Meier actuarial survival was determined for all patients. RESULTS: Forty-four patients were identified who underwent complete resection of multiple NSCLC tumors. During this same period, 504 patients underwent complete resection of stage I NSCLC tumors. The 3-year actuarial survival for patients with T1/N0/M0 tumors was 79.6%. In comparison with patients with T1/N0/M0 tumors, the 3-year actuarial survival rates of patients with T2/N0/M0 tumors (72.3%, p = 0.056), T4/N0/M0 tumors (66.5%, p = 0.058), and T1 to T2/N0/M1 tumors (63.6%, p = 0.201) were lower. However, these differences did not achieve statistical significance. CONCLUSIONS: Although there was a trend toward decreased survival in patients with multifocal NSCLC compared with patients with stage I NSCLC, this did not achieve statistical significance. Importantly, survival in these subgroups of patients with stage IIIB or stage IV disease (stage determined solely on the basis of multifocal NSCLC) is better than the survival reported in the series that formed the foundation for these staging changes. These data support complete surgical resection of multifocal lung tumors in patients with node-negative NSCLC.

Adenocarcinoma↗
PubMed2002

Thirteen-year experience in lung transplantation for emphysema.

BACKGROUND: Emphysema is the most common indication for lung transplantation. Recipients include younger patients with genetically determined alpha-1 antitrypsin deficiency (AAD) and, more commonly, patients with chronic obstructive pulmonary disease (COPD). We analyzed the results of our single-institution series of lung transplants for emphysema to identify outcome differences and factors predicting mortality and morbidity in these two groups. METHODS: A retrospective analysis was undertaken of the 306 consecutive lung transplants for emphysema performed at our institution between 1988 and 2000 (220 COPD, 86 AAD). Follow-up was complete and averaged 3.7 years. RESULTS: The mean age of AAD recipients (49 +/- 6 years) was less than those with COPD (55 +/- 6 years; p < 0.001). Hospital mortality was 6.2%, with no difference between COPD and AAD, or between single-lung transplants and bilateral-lung transplants. Hospital mortality during the most recent 6 years was significantly lower (3.9% vs 9.5%, p = 0.044). Five-year survival was 58.6% +/- 3.5%, with no difference between COPD (56.8% +/- 4.4%) and AAD (60.5% +/- 5.8%). Five-year survival was better with bilateral-lung transplants (66.7% +/- 4.0%) than with single-lung transplants (44.9% +/- 6.0%, p < 0.005). Independent predictors of mortality by Cox analysis were single lung transplantation (relative hazard = 1.98, p < 0.001), and need for cardiopulmonary bypass during the transplant (relative hazard = 1.84, p = 0.038). CONCLUSIONS: AAD recipients, despite a younger age, do not achieve significantly superior survival results than those with COPD. Bilateral lung transplantation for emphysema results in better long-term survival. Accumulated experience and modifications in perioperative care over our 13-year series may explain recently improved early and long-term survival.

Adult↗
PubMed2002

Special article: physiologic consequences of pneumonectomy. Consequences on the esophageal function. 1999.

Pneumonectomy is associated with gross anatomic and physiologic changes of the esophagus. So far, only a few studies have examined the influences of anatomic changes of the esophagus and the resulting physiologic consequences. When pneumonectomy is performed without pulmonary replacement, the esophagus is displaced to the side of pneumonectomy and posteriorly. Indentation of the esophagus by the trachea, bronchus, or aortic arch and dilatation at various levels are present. After pneumonectomy, the peak amplitude of esophageal peristaltic contractions is reduced. This feature is more pronounced in patients who are more than 60 years old and in patients who had their pneumonectomy performed more than 6 years ago. Injury of the vagal nerves, local ischemia, scarring of the esophagus and mediastinum after surgery, and disturbance of the autonomic nervous systems are the major reasons leading to esophageal dysmotility and delayed gastric emptying. Despite the severe morphologic and physiologic changes of the esophagus observed after pneumonectomy, few patients complain of gastrointestinal symptoms after pneumonectomy. Esophageal functional abnormalities may be present in patients with lung cancers before pneumonectomy because of a close anatomic relationship between the esophageal vagal nerve supply and the pulmonary hilum, making the vagal nerves susceptible to disturbances by the tumors or by involved hilar or mediastinal lymph nodes. After pneumonectomy, esophageal dysmotility is exaggerated. After recipient pneumonectomy for thoracic organ transplantation, esophageal dysmotility and delayed gastric emptying are common, but their relationship to gastroesophageal reflux, chronic aspiration, or subsequent development of bronchiectasis and obliterative bronchiolitis is controversial. To reduce the incidence of esophageal dysmotility after pneumonectomy, every effort should be made during surgery to prevent direct injury of the esophagus or the vagal nerves. A prospective study involving a larger patient population is needed to precisely define the problem and its management.

Esophageal Motility Disorders↗
PubMed2002

Intramuscular gene transfer of interleukin-10 reduces neutrophil recruitment and ameliorates lung graft ischemia-reperfusion injury.

Interleukin-10 (IL-10) has potent anti-inflammatory properties but its direct effects on neutrophil trafficking in lung transplant ischemia-reperfusion (I/R) injury are unknown. This study was performed to determine if recipient intramuscular IL-10 gene transfer reduces neutrophil infiltration in lung isografts and ameliorates I/R injury. Twenty-four hours before transplantation, recipient rodents received intramuscular injection with 1 x 10(10) plaque-forming units (pfu) adenovirus encoding human IL-10 (hIL-10), 1 x 10(10) pfu adenovirus control encoding p-galactosidase, or saline. Gene expression in muscle and plasma was confirmed. Lung grafts were harvested, stored at 4 degrees C for 18h, and assessed 24 h after transplantation. Peak muscle and plasma expression of hIL-10 was achieved 24h after gene transfer and returned to baseline by 7 days (p < 0.05 vs. controls). Gene transfer of hIL-10 reduced neutrophil sequestration and emigration in lung grafts as measured by morphometry and myeloperoxidase activity (p < 0.03 vs. controls). Furthermore, hIL-10 improved graft oxygenation and reduced lung edema (p <0.01 vs. controls). Intramuscular gene transfer of hIL-10 releases hIL-10 protein into plasma and reduces neutrophil sequestration and emigration in lung isografts. This is associated with a reduction in I/R injury with improved isograft oxygenation and reduced tissue edema. Intramuscular gene transfer may be a useful strategy to reduce clinical l/R injury.

Animals↗
PubMed2002

Low-dose endobronchial gene transfer to ameliorate lung graft ischemia-reperfusion injury.

OBJECTIVE: This study was undertaken to determine whether low-dose endobronchial transfer to the donor of the gene for human interleukin 10 would decrease ischemia-reperfusion injury in lung transplantation. METHODS: Experiments used male Fischer rats. Donor animals underwent right thoracotomy. A catheter was introduced into the left main bronchus, and vector was instilled. Group I (n = 6) received 2 x 10(7) plaque-forming units of adenovirus encoding human interleukin 10, group II (n = 6) received an adenovirus control encoding beta-galactosidase, and group III (n = 6) received saline solution. After instillation the left main bronchus was clamped for 60 minutes. Lungs were removed 24 hours later and stored in low-potassium dextran glucose solution for 18 hours before left lung transplantation. Graft function was assessed at 24 hours immediately before the animals were killed. Ratio of wet to dry weight and tissue myeloperoxidase activity were measured. Transgenic expression of human interleukin 10 was evaluated by means of enzyme-linked immunosorbent assay and immunohistochemical assay. RESULTS: Arterial oxygenation was significantly improved in group I relative to groups II and III (257.6 +/- 59.7 mm Hg vs 114.6 +/- 66.9 mm Hg and 118.6 +/- 91.1 mm Hg, P =.008 and P =.007, respectively). Neutrophil sequestration, as measured by myeloperoxidase activity, was also significantly reduced in group I relative to groups II and III (0.141 +/- 0.025 vs 0.304 +/- 0.130 and 0.367 +/- 0.153 Delta optical density units/[min. mg protein], P =.029 and P =.004, respectively). Enzyme-linked immunosorbent assay and immunohistochemical assay demonstrated the expression of human interleukin 10 in transfected lungs only. CONCLUSIONS: Low-dose endobronchial transfer to the donor of the gene for human interleukin 10 ameliorated ischemia-reperfusion injury in rodent lung transplantation by improving graft oxygenation and reducing neutrophil sequestration. Only 2 x 10(7) plaque-forming units of adenoviral vector were required for functional transgenic expression. Endobronchial gene transfer to lung grafts may be a useful delivery route even at low doses.

Animals↗
PubMed2002

Impact of comorbidity on survival after surgical resection in patients with stage I non-small cell lung cancer.

OBJECTIVE: As the mean age in patients with non-small cell lung cancer increases, the proportion of patients with serious comorbidity who are considered for surgical resection also increases. Patients with non-small cell lung cancer have been shown to have a higher burden of comorbidity than do patients with tumors of other sites, such as breast, prostate, colon, and head and neck. The goal of this review was to determine the impact of comorbidity on postoperative and long-term survival after surgical resection in patients with stage I non-small cell lung cancer. METHODS: A database analysis of our hospital's tumor registry included 451 patients who underwent surgical resection for pathologic stage I non-small cell lung cancer between January 1, 1994, and December 31, 1999. Comorbidity severity was prospectively determined with the Kaplan-Feinstein Index. Survival data were collected for each patient from the date of operation, with a mean duration of follow-up of 35.7 months. Bivariate statistics and Cox proportional hazards model analyses were used. RESULTS: The mean age was 64.4 years, and 249 (55%) patients were male. The distribution of overall comorbidity severity was none, 142 (31.5%); mild, 150 (33.3%); moderate, 115 (25.5%); and severe, 44 (9.8%). The overall in-hospital mortality was 2.2% (n = 10/451). There was a nonsignificant trend toward higher hospital mortality with greater comorbidity: none, 0.7% (n = 1/142); mild, 3.3% (n = 5/150); moderate, 0.9% (n = 1/115); and severe, 6.8% (n = 3/44, P =.055). Kaplan-Meier estimated survivals at 3 years for each level of comorbidity were as follows: none, 85.6%; mild, 74.8%; moderate, 68.8%; and severe, 70.0% (P <.002). After adjustment for age, sex, T status, and tumor histologic type, the relative risks of death as a function of comorbidity were mild, 1.44 (95% confidence interval 0.89-2.34); moderate, 2.28 (95% confidence interval 1.43-3.65); and severe; 1.94 (95% confidence interval 1.023-3.70). CONCLUSIONS: Comorbidity has a significant impact on survival after surgical resection of patients with stage I non-small cell lung cancer. These data may help to explain the lower than expected survival results for patients after surgical resection for stage I non-small cell lung cancer.

Actuarial Analysis↗
PubMed2002

Molecular staging of lung cancer: real-time polymerase chain reaction estimation of lymph node micrometastatic tumor cell burden in stage I non-small cell lung cancer--preliminary results of Cancer and Leukemia Group B Trial 9761.

OBJECTIVE: The 5-year survival for patients with surgically resected stage I non-small cell lung cancer is only 60% to 70%, probably because of undetected systemic occult micrometastases. Detection of occult micrometastases in lymph nodes by reverse-transcriptase polymerase chain reaction for carcinoembryonic antigen messenger RNA in non-small cell lung cancer has not been reported. Detection of occult micrometastases by standard reverse-transcriptase polymerase chain reaction provides only yes or no answers about their presence, whereas quantitative real-time reverse-transcriptase polymerase chain reaction permits reproducible quantitation of target molecules. This study evaluated the ability of quantitative reverse-transcriptase polymerase chain reaction to quantitate lymph node occult metastases with carcinoembryonic antigen messenger RNA as a tumor marker. METHODS: Standard reverse-transcriptase polymerase chain reaction and quantitative reverse-transcriptase polymerase chain reaction for carcinoembryonic antigen messenger RNA were performed on 232 lymph nodes from 53 patients with stage I disease (node negative according to histologic examination). Quantitative reverse-transcriptase polymerase chain reaction determined carcinoembryonic antigen messenger RNA quantity by detecting fluorescence increase at a threshold polymerase chain reaction cycle. Threshold polymerase chain reaction cycle values were correlated with standard curves created from serially diluted carcinoembryonic antigen-positive HTB-174 tumor cells to estimate the number of micrometastatic tumor cells in a lymph node. RESULTS: Detection rates of occult metastases were similar for standard reverse-transcriptase polymerase chain reaction and quantitative reverse-transcriptase polymerase chain reaction at 38 of 232 (16.4 %) and 59 of 232 (25.4 %), respectively. Upstaging rates among 53 cases of stage I non-small cell lung cancer were also similar for standard reverse-transcriptase polymerase chain reaction and quantitative reverse-transcriptase polymerase chain reaction at 23 of 53 (43.4 %) and 30 of 53 (56.6%), respectively. Comparison of positive lymph node stations according to quantitative reverse-transcriptase polymerase chain reaction (threshold polymerase chain reaction cycle <45) with HTB-174 tumor cell standard curves yielded estimates of metastatic tumor cell burden of 1.07 x 10(3)to 3.24 x 10(5)cells per lymph node station (median 7190 tumor cells per lymph node station). CONCLUSIONS: Standard and quantitative real-time reverse-transcriptase polymerase chain reaction for carcinoembryonic antigen detected occult metastases in patients with stage I non-small cell lung cancer at similar rates; both upstaged about 50% of cases. Quantitative reverse-transcriptase polymerase chain reaction allows estimation of the number of metastatic cells per lymph node, however, which potentially allows greater precision in predicting recurrence risk.

Adenocarcinoma↗
PubMed2002

Does donor cause of death affect the outcome of lung transplantation?

BACKGROUND: Accumulating evidence suggests that the donor's cause of death may influence posttransplantation allograft function. We conducted a retrospective analysis of our adult lung transplant experience to investigate the influence of donor traumatic brain injury versus nontraumatic brain injury on posttransplantation outcome. METHODS: We retrospectively reviewed donor records and recipient medical charts for 500 consecutive lung transplants performed between July 1988 and December 1999. Recipient follow-up was complete, with a minimum follow-up of 1 year of survival. RESULTS: There were 295 and 205 donors in the traumatic and nontraumatic brain injury groups, respectively. Young male donors predominated in the traumatic brain injury group. Recipients receiving donor lungs from the traumatic and nontraumatic brain injury groups did not differ by age, sex, diagnosis, type of transplant (single-lung versus double-lung) or requirement for pretransplantation mechanical ventilatory assistance. Recipients did not differ in immediate or 24-hour PaO (2)/inspired oxygen ratio, ventilation time, hospital stay, hospital mortality, or overall survival. Recipients of organs from donors who died of traumatic brain injury showed a higher severity and frequency of rejection episodes during the first year after transplantation. Freedoms from bronchiolitis obliterans syndrome at 5 years were 34.5% and 50.8% for recipients of organs from donors who died of traumatic and nontraumatic brain injury, respectively (P =.002). CONCLUSIONS: The cause of donor brain death does not appear to influence early results of lung transplantation. Traumatic brain injury, or some phenomenon associated with it, may predispose a transplanted lung and its recipient toward more severe early rejection episodes and subsequent development of bronchiolitis obliterans syndrome.

Adult↗
PubMed2002

Recipient intramuscular cotransfection of naked plasmid transforming growth factor beta1 and interleukin 10 ameliorates lung graft ischemia-reperfusion injury.

OBJECTIVE: Multiple gene transfer might permit modulation of concurrent biochemical pathways involved in lung graft ischemia-reperfusion injury. In this study we analyzed whether recipient intramuscular naked plasmid cotransfection of transforming growth factor beta(1) and interleukin 10 would result in amelioration of lung graft ischemia-reperfusion injury. METHODS: Forty-eight hours before transplantation, 6 groups (n = 6) of F344 rats received intramuscular injection of naked plasmid encoding chloramphenicol acetyltransferase, chloramphenicol acetyltransferase plus beta-galactosidase, transforming growth factor beta(1), interleukin 10, or transforming growth factor beta(1) plus interleukin 10 or were not treated. Donor lungs were flushed and stored for 18 hours at 4 degrees C before transplantation. Twenty-four hours later, grafts were assessed immediately before the animals were killed. Arterial oxygenation, wet/dry ratio, myeloperoxidase, and proinflammatory cytokines (interleukin 1, tumor necrosis factor alpha, interferon gamma, and interleukin 2) were measured, and immunohistochemistry was performed. RESULTS: For lung graft function, the arterial oxygenation was considerably higher in the cotransfected group receiving transforming growth factor beta(1) plus interleukin 10 compared with that in all other groups (P < or =.03). The wet/dry ratio, reflecting lung edema, was reduced in the cotransfected group compared with that in control animals (nontreated, P <.02; chloramphenicol acetyltransferase, P <.03; chloramphenicol acetyltransferase plus beta-galactosidase, P <.01). Myeloperoxidase, which measures neutrophil sequestration, was also reduced with cotransfection compared with that seen in control animals (P < or =.03). All proinflammatory cytokines were decreased in the cotransfected group compared with those in all other groups (interleukin 1beta, P <.04; tumor necrosis factor alpha, P <.002; interferon gamma, P <.0001; interleukin 2, P <.03). These results indicate that cotransfection provides a synergistic benefit in graft function versus either cytokine alone, neutrophil sequestration, or inflammatory cytokine expression. Immunohistochemistry showed positive staining of transforming growth factor beta(1) plus interleukin 10 in type I and II pneumocytes and localized edema fluid. CONCLUSIONS: Recipient intramuscular naked plasmid cotransfection of transforming growth factor beta(1) and interleukin 10 provides a synergistic effect in ameliorating lung reperfusion injury after prolonged ischemia.

Analysis of Variance↗
PubMed2002

Intratracheal adenovirus-mediated gene transfer is optimal in experimental lung transplantation.

OBJECTIVE: Gene transfer to experimental lung grafts has been shown to reduce ischemia-reperfusion injury and acute rejection. The optimal delivery route should produce high lung expression with no inflammation and minimal systemic expression. The goal of this study was to determine the optimal gene transfer route for use in experimental lung transplantation. METHODS: F344 rats were injected with 2.9 x 10(10) plaque-forming units of adenovirus vector encoding beta-galactosidase through intratracheal, intravenous, intraperitoneal, or intramuscular delivery routes and killed 48 hours later. Gene expression was measured by means of enzyme-linked immunosorbent assay. RESULTS: Intratracheal delivery produces significantly greater gene expression in the lung (75,350 +/- 47,288 pg/100 microg of protein, P <.001 vs intravenous, intraperitoneal, and intramuscular routes) and minimal systemic expression (nonsignificant in serum, kidney, liver, spleen, and muscle vs that seen in control animals, P =.016 for heart). Immunohistochemistry staining showed beta-galactosidase expression in the bronchial epithelium of lungs transfected through the intratracheal route with mild inflammation. CONCLUSIONS: Intratracheal gene transfer provides significant expression in the lung with mild to no inflammation and minimal systemic expression. This delivery strategy has tremendous potential in experimental lung transplant models to reduce ischemia-reperfusion injury and acute allograft rejection and should be investigated further.

Adenoviridae↗
PubMed2002

Lung transplantation in children.

OBJECTIVE: To report the authors' experience with pediatric lung transplantation (LTX) to provide an overview of patients selected for this procedure and their outcomes. SUMMARY BACKGROUND DATA: Pediatric LTX differs from adults in many ways, including recipient size, indications, posttransplant care, and rehabilitation. METHODS: Two hundred seven isolated lung transplants on 190 children under the age of 18 years were performed from 1990 to the present. This represents the single largest series of lung transplants in children in the world. Thirty-two patients were less than 1 year of age, 22 were 1 to 5 years of age, 32 were 5 to 10 years of age, and 121 were 10 to 18 years old. The groups by major diagnostic category were cystic fibrosis (n = 89), pulmonary vascular disease (n = 44), bronchiolitis obliterans (n = 21), pulmonary alveolar proteinosis (n = 12), pulmonary fibrosis (n = 15), and other (n = 26). The average age at the time of transplant was 9.5 +/- 5.9 years (range 36 days to 18 years). RESULTS: Survival by Kaplan-Meier analysis was 77% at 1 year, 62% at 3 years, and 55% at 5 years. There was no significant difference in survival according to primary diagnosis leading to LTX or age at LTX. There were 25 early (<60 days) and 61 late deaths. The most common cause of early deaths was graft failure (13/25, 52%). The most common causes of late death were bronchiolitis obliterans (35/61, 57%), infection (13/61, 21%), and posttransplant malignancies (11/61, 18%). No patient died of acute rejection. In those surviving greater than 3 months (mean follow-up 3.5 years, range 3 months to 11 years), the overall rate of occurrence of bronchiolitis obliterans was 46% (80/175) and the overall incidence of posttransplant malignancies was 24/175 (14%). Major risk factors for the development of bronchiolitis obliterans were age older than 3 years, more than two episodes of acute rejection, and organ ischemic time longer than 180 minutes. CONCLUSIONS: In children, LTX is a high-risk but viable treatment for end-stage pulmonary parenchymal and vascular disease. The major hurdle to overcome in long-term survival is bronchiolitis obliterans.

Adolescent↗
PubMed2000

Outcome of patients with cystic fibrosis awaiting lung transplantation.

Cystic fibrosis is a common indication for lung transplantation. Under the current organ allocation system, donor lungs are distributed to patients based solely on their accrued waiting time, and the death rate on the waiting list has been high. Physiologic parameters have been used to guide the referral, but risk factors for death while awaiting transplantation have not been well defined. This study aimed to identify factors at the time of evaluation that were associated with death on the waiting list. A consecutive cohort of 146 patients with cystic fibrosis who were listed for lung transplantation was retrospectively reviewed. Characteristics of patients who died awaiting transplantation were compared with those of patients who survived until transplantation or the end of the study. Thirty-seven patients died while waiting, 76 underwent transplantation, and 33 were alive and still waiting. Actuarial survival rates for the entire cohort were 81% at 1 yr, 67% at 2 yr, and 59% at 3 yr. Although a multivariate Cox proportional hazards model (chi(2) = 29.6; p < 0.001) identified shorter six-minute walk distance (50 m increments; RR, 0.69; 95% CI, 0.57 to 0.84), higher systolic pulmonary artery pressure (5 mm Hg increments; RR, 1.41; 95% CI, 1.11 to 1.80), and diabetes mellitus (RR, 1.57; 95% CI, 1.06 to 2.32) as significant risk factors for death on the waiting list, these factors and other features overlapped considerably between the group of patients who died waiting and the group who lived until transplantation or the end of the study. The transplant evaluation selects a rather homogeneous cohort of patients for the waiting list. Unless outcome on the waiting list can be reliably predicted, establishing criteria to allocate donor lungs according to medical urgency may not be feasible.

Adult↗
PubMedDate not supplied

Critical care aspects of lung transplantation.

Lung transplantation currently is the preferred treatment option for a variety of end-stage pulmonary diseases. Remarkable progress has occurred through refinements in technique and improved understanding of transplant immunology and microbiology. As a result, recipients are surviving longer after their transplant. Despite improvements in short- and intermediate-term survival, long-term success with lung transplantation remains limited by chronic allograft rejection, also known as bronchiolitis obliterans syndrome. Despite its long-term limitations, lung transplantation remains the only hope for many with end-stage pulmonary disease, and during the past 20 years, it has become increasingly accepted and used. As a result, clinicians working in an intensive care unit (ICU) are more likely to be exposed to these patients both in the immediate postoperative period as well as throughout their remaining lives. It is thus important that the ICU team have a working knowledge of the common complications, when these complications are most likely to occur, and how best to treat them when they do arise. The main focus of this review is to address the variety of potential graft and life-threatening problems that may occur in lung transplant recipients. Because the ICU is also the most common setting where a potential donor is identified, donor issues will briefly be addressed.

Bronchiolitis Obliterans↗