Detection of trisomy 7 in nonmalignant bronchial epithelium from lung cancer patients and individuals at risk for lung cancer.

Early identification and subsequent intervention are needed to decrease the high mortality rate associated with lung cancer. The examination of bronchial epithelium for genetic changes could be a valuable approach to identify individuals at greatest risk. The purpose of this investigation was to assay cells recovered from nonmalignant bronchial epithelium by fluorescence in situ hybridization for trisomy of chromosome 7, an alteration common in non-small cell lung cancer. Bronchial epithelium was collected during bronchoscopy from 16 cigarette smokers undergoing clinical evaluation for possible lung cancer and from seven individuals with a prior history of underground uranium mining. Normal bronchial epithelium was obtained from individuals without a prior history of smoking (never smokers). Bronchial cells were collected from a segmental bronchus in up to four different lung lobes for cytology and tissue culture. Twelve of 16 smokers were diagnosed with lung cancer. Cytological changes found in bronchial epithelium included squamous metaplasia, hyperplasia, and atypical glandular cells. These changes were present in 33, 12, and 47% of sites from lung cancer patients, smokers, and former uranium miners, respectively. Less than 10% of cells recovered from the diagnostic brush had cytological changes, and in several cases, these changes were present within different lobes from the same patient. Background frequencies for trisomy 7 were 1.4 +/- 0.3% in bronchial epithelial cells from never smokers. Eighteen of 42 bronchial sites from lung cancer patients showed significantly elevated frequencies of trisomy 7 compared to never smoker controls. Six of the sites positive for trisomy 7 also contained cytological abnormalities. Trisomy 7 was found in six of seven patients diagnosed with squamous cell carcinoma, one of one patient with adenosquamous cell carcinoma, but in only one of four patients with adenocarcinoma. A significant increase in trisomy 7 frequency was detected in cytologically normal bronchial epithelium collected from four sites in one cancer-free smoker, whereas epithelium from the other smokers did not contain this chromosome abnormality. Finally, trisomy 7 was observed in almost half of the former uranium miners; three of seven sites positive for trisomy 7 also exhibited hyperplasia. Two of the former uranium miners who were positive for trisomy 7 developed squamous cell carcinoma 2 years after collection of bronchial cells. To determine whether the increased frequency of trisomy 7 reflects generalized aneuploidy or specific chromosomal duplication, a subgroup of samples was evaluated for trisomy of chromosome 2; the frequency was not elevated in any of the cases as compared with controls. The studies described in this report are the first to detect and quantify the presence of trisomy 7 in subjects at risk for lung cancer. These results also demonstrate the ability to detect genetic changes in cytologically normal cells, suggesting that molecular analyses may enhance the power for detecting premalignant changes in bronchial epithelium in high-risk individuals.

Intrapleural fibrinolytics in management of empyema thoracis.

STUDY OBJECTIVE: To determine the success and complication rates of fibrinolytic therapy (FL) in the treatment of thoracic empyema. DESIGN AND PATIENTS: Between December 1992 and November 1994, all patients referred with empyema thoracis (ET) were offered FL. FL consisted of streptokinase (275,000 +/- 170,000 IU) or urokinase (121,000 +/- 57,000 IU) daily for a mean of 6.2 +/- 2.1 days. SETTING: The University of New Mexico Health Sciences Center and the Albuquerque Veterans Affairs Medical Center. RESULTS: Twenty-six patients were treated. Sixty-two percent (16/26) had complete resolution (CR) of symptoms, near or complete normalization of chest radiographic findings, and required no surgery or empyema tubes. Eight percent (2/26) had relief of symptoms and partial resolution (PR) of radiographic abnormalities and were discharged from the hospital with empyema tubes in place. All patients with PR had empyema tubes removed within 30 days of hospital discharge. Thirty-one percent (8/26) of patients failed to completely improve clinically or radiographically (nonresponse) and were treated with decortication or empyema tubes for greater than 30 days. Bleeding occurred in a single patient (4%). There was no mortality associated with FL use. CONCLUSIONS: The use of FL is associated with resolution of ET in 69% (18/26) of patients. This modality is safe, effective, and spares most patients with empyema the morbidity and mortality of thoracotomy.

Lung biopsy: is it necessary?

OBJECTIVE: Lung biopsy is associated with substantial mortality rates. We reviewed our experience with this operation, primarily in patients with immunocompetence, to determine whether the results justify the continued performance of this procedure. METHODS: We conducted a retrospective review of all diagnostic lung biopsies performed at 3 university-affiliated hospitals between July 1, 1992, and December 31, 1998. RESULTS: There were 75 patients: 25 patients were treated electively, 17 were treated on an urgent basis, 27 patients on an emergency basis, and the urgency was unclear in 6 patients. Significant beneficial therapeutic changes were made in 15 of 25 elective procedures (60%), in 16 of 17 urgent procedures (94%), and in 11 of 27 emergency procedures (41%; P =.001). Significant beneficial therapeutic changes consisted of immunosuppression in 13 of 15 (87%) patients treated on an elective basis, in 9 of 16 (56%) treated on an urgent basis, and in 9 of 11 (82%) treated on an emergency basis in whom therapy was altered (P =.14). Operative death was 0 of 25 for elective operations (0%), 3 of 17 for urgent operations (18%), and 14 of 26 for emergency operations (54%). Multivariable analysis of operative death showed urgency to be the only significant predictor of death (P =.002). CONCLUSIONS: In patients with immunocompetence, elective and urgent lung biopsies have acceptable operative mortality rates and frequently result in important beneficial therapeutic changes. Consequently biopsies are appropriate in these patients. Emergency biopsies are associated with high operative mortality rates and rarely result in a therapeutic change other than immunosuppression. These patients should not undergo lung biopsy if they are in stable condition and should be treated empirically with immunosuppression without operation if their condition is deteriorating.

The use of adenosine for repair of penetrating cardiac injuries: a novel method.

The use of intravenous administration of adenosine to expedite cardiorrhaphy in penetrating cardiac trauma by inducing temporary asystole is described. It is quicker, more effective, and safer than the traditional methods.

Aortoesophageal fistula after repair of descending aortic dissection.

The development of aortoesophageal fistula after aortic repair is rare. We describe a patient who presented with hematemesis 4 months after emergent repair of a descending thoracic aortic dissection using a prosthetic graft. Diagnosis was supported by computed tomographic, angiographic, and endoscopic findings. Resection of the involved graft was performed through a left thoracotomy after placement of an ascending aorta-to-abdominal aorta conduit through an anterior approach. The patient died of uncontrollable bleeding a few hours after the procedure. Surgical intervention offers the potential for cure in this otherwise uniformly fatal condition. But like medical therapy, operative management has thus far been associated with 100% mortality.

Transhiatal esophagectomy in a patient with aberrant right subclavian artery.

During transhiatal esophagectomy, the esophagus is generally safely and easily dissected posteriorly. However, in 1% to 2% of patients, an aberrant right subclavian artery passes between the esophagus and spine. We demonstrate that transhiatal esophagectomy may be safely performed in these patients when recognition and careful dissection are performed. Thoracic surgeons must be aware of this anomaly in order to prevent laceration of the aberrant right subclavian artery with catastrophic hemorrhage.

Herniation of the lung after video-assisted thoracic surgery.

We report a case of lung herniation occurring following video-assisted thoracic surgery. Although lung hernias are rare, the widespread application of video-assisted thoracic surgery to patients at risk for lung hernia will likely result in more reports in the future. Consequently, pulmonologists and thoracic surgeons must be aware of this condition, risk factors for development, and potential methods of prevention in order to minimize the occurrence of this complication.

Sequestration of the lung arising from the circumflex coronary artery.

Sequestration is an unusual pulmonary malformation. Systemic blood supply is commonly from the thoracic aorta, but arteries may occasionally arise from other sites including the abdominal aorta or the intercostal vessels. We report a rare form of sequestration with origin from the circumflex coronary artery. Knowledge of uncommon vascular origins, particularly from coronary arteries, is important to avoid injury and possible ischemia, infarction, exsanguination, or death.

Fissureless lobectomy.

Traditional lobectomy techniques describe division of pulmonary parenchyma within the fissures for access to the pulmonary artery. This results in air leaks, which may prolong chest tube drainage and hospitalization times. We describe a technique for lobectomy in which all lung parenchyma is divided using a stapler.

Videothoracoscopic treatment of hepatic hydrothorax.

Hepatic hydrothorax occurs frequently in ascites arising from communications in the diaphragm between peritoneal and pleural cavities. Numerous treatments have been described but are of limited utility due to invasiveness and poor success rate. We describe a case of hepatic hydrothorax in which the pore in the diaphragm was documented photographically and in which successful resolution was achieved with videothoracoscopic suture ligation and talc pleurodesis.

Heterotopic pancreas of the esophagus masquerading as Boerhaave's syndrome.

Heterotopic pancreas (HP) of the esophagus is rare. We report a patient with HP of the esophagus and review the presentation, treatment, and results of the nine previously reported cases. Two patients had cancer. This high incidence raises concerns that HP of the esophagus may be premalignant. Because surveillance endoscopy is not possible, all known or suspected esophageal HP should be treated surgically.

Esophago-airway fistula in AIDS.

Fistula formation between the esophagus and airway in acquired immunodeficiency syndrome is extremely unusual. We report 2 cases, the first in a patient who did not undergo definitive surgical management and died shortly after diagnosis. The second patient was managed successfully for 5 months by insertion of a Celestin endoesophageal prosthesis. This procedure can be performed with low morbidity and mortality, and may become the treatment of choice for this complex problem.

Air embolus complicating transthoracic percutaneous needle biopsy.

Transthoracic percutaneous needle biopsy has become popular for evaluation of pulmonary nodules. However, it is a procedure with morbidity and mortality that is not negligible. In this article, we report massive air embolus complicating needle biopsy in a patient with amyloidosis. A negative biopsy does not exclude malignancy, and if surgical excision will be performed regardless of the result, preoperative assessment using this technique may not be necessary.

Internal fixation of high tracheal stents.

A technique for internal fixation of a silicone elastomer tracheal stent is described. This technique allows the use of a short stent in situations where complex stent placement otherwise would be necessary. The procedure was used successfully to manage a postresection stricture in the subglottic trachea.

The lingula is an appropriate site for lung biopsy.

BACKGROUND: Lung biopsy is commonly performed for diagnosis of diffuse pulmonary disease. The lingula offers technical advantages for biopsy, however the quality of tissue obtained by lingula biopsy has been questioned. We sought to determine whether lingula biopsy was a satisfactory site for biopsy in terms of diagnostic yield, therapeutic interventions, and survival results. METHODS: All diagnostic lung biopsies performed for diffuse lung disease at 3 university affiliated hospitals between July 1, 1992 and December 31, 1998 were retrospectively reviewed. Patients were divided into 2 groups, depending upon site of biopsy: patients with lingula biopsy only and those with biopsies from other sites. RESULTS: There were 75 patients; 20 underwent biopsy of the lingula alone, 48 had biopsy of other sites with or without biopsy of the lingula, and location of biopsy was unknown in 7 patients. Histologic diagnosis was achieved in all patients. Significant beneficial therapeutic changes were made in 14 lingula patients, and consisted of immunosuppression in 12 cases. Three patients died in the hospital or within 30 days. Fourteen patients survived 1 year. There was no significant difference between patients that had biopsy of the lingula alone and those that had biopsies from other sites in urgency, technique, histologic diagnosis, rate of therapeutic interventions, hospital mortality, or 1 year survival. CONCLUSIONS: Lung biopsy of the lingula compared to other anatomic sites has equivalent diagnostic yield, therapeutic significance, and survival. Given the technical ease of biopsy, when disease is present radiographically it is the preferred site for lung biopsy.

Multiple polyposis and adenocarcinoma arising in Barrett's esophagus.

Adenomatous polyps of the esophagus are rare in comparison with those of the lower gastrointestinal tract. Like adenomatous colon polyps, they have been associated with malignancy. We describe a case of early adenocarcinoma and multiple polyposis of the esophagus arising in a Barrett's epithelium, treated with surgical resection.

Selective protection of gray and white matter during spinal cord ischemic injury.

BACKGROUND: Ischemic injury in the gray matter is associated with excitatory amino acid neurotransmitters (EAA) release, and in the white matter is associated with intracellular sodium accumulation. We investigated the protective effect during spinal ischemia of the EAA antagonist, 2-carboxypiperazinyl-propylphosphonic acid (CPP), and the sodium channel blocker (2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX). METHODS: Sprague-Dawley rats were randomized in four groups, received intrathecally 10 microL of saline, CPP, QX, or QX/CPP, and underwent balloon occlusion of the aorta. Proximal pressure was lowered by exsanguination. In the acute protocol, 28 rats were used to calculate the length of occlusion, resulting in paraplegia in 50% of animals (P50). In the chronic study, 60 rats underwent 11' occlusion. The chronic animals were scored daily for 28 days and submitted to cord histology. RESULTS: The P50 of QX (11'22") and QX/CPP (11'54") were longer than saline (10'39"), suggesting a beneficial effect. Neurologic scores of all treatment groups (p = 0.0001) and histologic scores of CPP (p = 0.003) and QX/CPP (p = 0.002) were better than saline. CONCLUSIONS: Protection of spinal cord during ischemia can be achieved with intrathecal administration of selective agents directed to the gray and white matter.

Catastrophic hemorrhage on sternal reentry: still a dreaded complication?

BACKGROUND: To define the incidence of catastrophic hemorrhage (CH) during reoperations, the experience of the University of New Mexico was reviewed and compared with the practice of surgeons contacted by questionnaire. METHODS: At the University of New Mexico, 610 reoperations were reviewed and 210 deemed high risk because of multiple reoperation, aneurysm, patent grafts, chamber's enlargement, conduit or previous mediastinitis. In the questionnaire, we asked about reentry technique, occurrence and outcome of CH, and precautions for high-risk patients. RESULTS: At the University of New Mexico there were 4 CH with 1 death, and in the questionnaire there were 2,046 CH with 392 deaths. Our rate per surgeon was lower than that of the questionnaire. Rate of CH according to the saw was 2.09 for reciprocating, 2.0 for sagittal, and 1.74 for stryker in the questionnaire. Our rate was lower (0.65) with a micro sagittal saw. High-risk category predicted CH during sternotomy (p = 0.01) but only conduit (p = 0.005) was significant by univariate analysis. CONCLUSIONS: The risk of CH could be as high as 1%. The sagittal micro oscillating saw is the safest reported to date. Presence of a conduit increases the risk by 2.5 fold.

Intrapulmonary lymph nodes masquerading as renal cell carcinoma metastases.

Clinically apparent intrapulmonary lymph nodes are rare but may be incorrectly diagnosed as pulmonary metastatic disease. We report on a 65-year-old man who presented with a left renal mass and left lower lobe pulmonary nodules that were interpreted radiographically to be consistent with metastatic disease. Surgical pathologic examination confirmed intrapulmonary lymph nodes and a Stage II renal cell carcinoma. Failure to diagnose intrapulmonary lymph nodes may result in erroneous diagnosis of metastatic disease and preclude potentially curative treatment.

Individuals at high risk for lung cancer have airway epithelial cells with chromosome aberrations frequently found in lung tumor cells.

Identification of individuals at greatest risk of developing lung cancer could enhance the efficacy of intervention modalities, thereby greatly reducing mortality from this disease. One strategy for identifying these people is to establish molecular markers which reflect the severity of their cancerization field. Thus, investigations were initiated to determine of cells with chromosome aberrations frequently exhibited by lung tumor cells, i.e., trisomy 7, trisomy 20, and deletion of 9p23, are prevalent within the uninvolved airways of cancer patients. As a result, cells containing these aberrations were consistently found at significantly elevated levels by using fluorescence in situ hybridization (FISH). In contrast, cells collected from non-smokers who had never smoked were normal by this assay. The next objective was to determine of cells exhibiting these alterations are also present in upper airways of exposed, but cancer-free smokers and ex-uranium miners. The results showed that, although only a subset of these people will develop lung cancer in their lifetimes, they universally harbor increased numbers of abnormal cells within their airway epithelium. However, the number of sites with multiple verities of abnormal cells tended to be fewer compared with the cancer patients. Thus, quantifying cells with molecular alterations within the cancerization field of a smoker may delineate those with a lesser grade of damage, and these individuals may be at a lesser risk of developing disease. However, differences in the extent of genetic damage afforded by these assays may not clearly define individuals with pending disease, and additional molecular assays must be devised.