Mediastinal lymph node sampling following positron emission tomography with fluorodeoxyglucose imaging in lung cancer staging.

OBJECTIVES: To evaluate the predictive accuracy as well as the rates of false-positive and false-negative results of CT and positron emission tomography (PET)-fluorodeoxyglucose (FDG) imaging in detecting the metastatic intrathoracic lymph nodes in patients with suspected or proven non-small cell lung cancer (NSCLC). Our other objective was to determine the need for routine invasive sampling procedure in confirming PET/CT staging results. METHODS: The results of CT and PET-FDG scanning in 77 patients with suspected or proven NSCLC were correlated with the histologic findings of hilar/mediastinal lymph node sampling using mediastinoscopy, open biopsy, thoracotomy, or thoracotomy with resection. Patients were then classified into resectable and unresectable groups based initially on PET results and compared to histologic findings. RESULTS: The sensitivity, specificity, and accuracy of CT and PET for detecting metastatic lymphadenopathy were 68%, 61%, 63%, and 87%, 91%, and 82%, respectively. A change of management with routine sampling following PET was seen in five of six patients (83%) with false-positive findings (13%) but in none of four patients (9%) with false-negative findings. CONCLUSION: The false-positive findings of PET-FDG imaging affected selection of treatment in 83% of patients. However, false-negative results did not change management in any patient. This could potentially prevent unnecessary invasive thoracotomy, mediastinoscopy, or other sampling procedures in patients with negative PET results.

Clinical utility of PET-FDG imaging in differentiation of benign from malignant adrenal masses in lung cancer.

This study was designed to evaluate the sensitivity, specificity, and predictive accuracy of PET-FDG imaging in detecting metastatic disease involvement of adrenal glands in patients with lung cancer. We wanted to compare efficacy of positron emission tomography (PET)-fluorodeoxyglucose (FDG) imaging to computed tomography (CT) scanning in differentiating benign from malignant involvement of adrenal glands in patients with lung cancer. Thirty patients with biopsy-proven lung cancer and abnormal findings on PET and/or CT scanning were studied for presence of adrenal abnormality suggestive of metastatic disease involvement (n = 26) or benign adrenal enlargement (n = 4). The results of PET and CT scanning were compared to histological findings and/or clinical follow-up for at least 1 year for presence or absence of adrenal metastases. PET-FDG imaging correctly detected the presence of metastatic involvement in 17 of 18 patients and excluded metastatic involvement in 11 of 12 patients for sensitivity, specificity, and accuracy of 94.4%, 91.6%, and 93.3%, respectively. CT scanning showed enlarged adrenals without metastases in 8 of 30 patients and normal-sized adrenals in the presence of metastases in 5 of 30 patients. There was a false-positive PET finding in 1 patient and a false-negative PET finding in another patient. PET-FDG imaging is a highly sensitive, specific, and accurate test to differentiate benign from malignant involvement of adrenal glands in patients with lung cancer and often ambiguous findings on CT scanning.

Comparative efficacy of positron emission tomography with fluorodeoxyglucose in evaluation of small (<1 cm), intermediate (1 to 3 cm), and large (>3 cm) lymph node lesions.

PURPOSE: Our objective was to determine if positron emission tomography (PET) with fluorodeoxyglucose (FDG; PET-FDG) imaging is equally efficacious in detection of metastases in small and large mediastinal lymph nodes as compared to CT scanning. MATERIALS AND METHODS: PET-FDG imaging, CT scanning, and histology results of sampled mediastinal lymph nodes were compared in 54 patients of total 118 patients studied. Efficacy of PET and CT was determined and compared in small (< 1 cm), intermediate (1 to 3 cm), and large (> 3 cm) mediastinal lesions. RESULTS: PET was accurate in 94% of patients in characterizing "N" disease as compared to 61% with CT. Overall, sensitivity, specificity, and accuracy of PET for staging mediastinal lymph nodes (n = 168 in 54 patients) was 96, 93, and 94%, as compared to 68, 65, and 66% with CT. Positive and negative predictive value of PET in detecting mediastinal adenopathy was 86% and 98%, as compared to 47% and 82% with CT, respectively. PET was also highly reliable and accurate for detecting lymph nodes < 1 cm, 1 to 3 cm, and > 3 cm in size with superior efficacy than CT. Sensitivity, specificity, and accuracy of PET for detecting malignancy in lymph node lesions < 1 cm in size was 97, 82, and 95%, respectively. CONCLUSION: PET-FDG imaging is equally reliable and accurate for detecting disease in small and large lymph node lesions in patients with suspected or proven lung cancer with better efficacy than CT.

Current status of the diagnosis and treatment of thymoma.

Although thymomas are rare neoplasms, they are the most common tumor of the anterior mediastinum in adults. Preferred therapy for these neoplasms is complete surgical resection. If a thymoma cannot be completely resected, postoperative radiotherapy may produce satisfactory results in controlling the tumor. Significant 5- and 10-year survival rates have been recorded for patients with advanced thymomas who have been treated by radiation therapy alone. Chemotherapy may be used in patients with unresectable thymomas as well, but the results are less promising than with radiotherapy. Combinations of radiotherapy and chemotherapy used on patients with unresectable thymomas have produced encouraging results. Surveillance of patients with thymoma should be prolonged because late recurrence (more than 5 years after initial therapy) can be expected in a significant minority of patients. Aggressive therapy of late recurrence, including resection of new tumor masses and pleural metastases, has yielded successive disease-free intervals that validate persistent treatment.

Utilization of muscle flaps in the treatment of bronchopleural fistulas.

This paper reports the results of a series of 5 patients who underwent closure of persistent bronchopleural fistula using extrathoracic muscle flaps over a 6-year period. All patients had failed more conservative treatment. The surgeries were one- or two-stage procedures performed with the collaboration of cardiovascular and reconstructive surgical staffs. There were no associated mortalities. The muscle flaps utilized were the latissimus dorsi, serratus anterior, pectoralis major, pectoralis minor, and trapezius. The results have been encouraging and allowed the complete closure of the bronchopleural fistula in the majority of patients. The authors present the best management of this serious disease, as well as its pathophysiology and clinical aspects.

A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions.

BACKGROUND: The purpose of this study was to compare the effectiveness and safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via tube thoracostomy in the treatment of patients with recurrent symptomatic malignant pleural effusions (MPE). METHODS: In this multi-institutional study conducted between March 1994 and February 1997, 144 patients (61 men and 83 women) were randomized in a 2:1 distribution to either an indwelling pleural catheter or doxycycline pleurodesis. Patients receiving the indwelling catheter drained their effusions via vacuum bottles every other day or as needed for relief of dyspnea. RESULTS: The median hospitalization time was 1.0 day for the catheter group and 6.5 days for the doxycycline group. The degree of symptomatic improvement in dyspnea and the quality of life was comparable in each group. Six of 28 patients who received doxycycline (21%) had a late recurrence of pleural effusion, whereas 12 of 91 patients who had an indwelling catheter (13%) had a late recurrence of their effusions or a blockage of their catheter after the initially successful treatment (P = 0.446). Of the 91 patients sent home with the pleural catheter, 42 (46%) achieved spontaneous pleurodesis at a median of 26.5 days. CONCLUSIONS: A chronic indwelling pleural catheter is an effective treatment for the management of patients with symptomatic, recurrent, malignant pleural effusions. When compared with doxycycline pleurodesis via tube thoracostomy, the pleural catheter requires a shorter hospitalization and can be placed and managed on an outpatient basis.

Chest wall resection and reconstruction.

Chest wall reconstruction has been refined and expanded in recent years so that almost any defect may be repaired with an excellent cosmetic and physiological result. The first step in a good reconstruction is an appropriate and thorough resection that leaves healthy, viable margins to which the materials and tissues used in a reconstruction may be anchored securely. In most instances, chest wall stabilization will not be necessary. In some cases in which large areas of chest wall will be removed or a lateral aspect of a chest wall needs to be resected, stabilization may be necessary. Stabilization may also be required in patients who suffer from debilitating lung disease and need a chest wall resection and reconstruction. Soft tissue coverage completes the reconstruction by moving healthy, viable tissue to fill the defect. In most instances, pedicled muscular, musculocutaneous, and omental flaps will provide adequate soft tissue coverage. Very infrequently, a free flap will be necessary to achieve total closure of a chest wall defect. The soft tissue coverage is completed by using meshed, split thickness skin grafts to provide epithelialization of any exposed muscle or omentum.

Current management of thymoma.

Patients with thymoma present rarely even on active thoracic surgery services. These patients may suffer from many associated conditions but the most common is myasthenia gravis. Aggressive surgical resection is the mainstay of initial therapy. Radiation therapy has a role in patients who are left with retained neoplasm after surgical resection. Recurrence may occur at prolonged intervals but should be treated aggressively.

Positron emission tomographic imaging with fluorodeoxyglucose isefficacious in evaluating malignant pulmonary disease.

OBJECTIVE: Positron emission tomography (PET), when used with the intravenously administered radiopharmaceutical F-18 fluorodeoxyglucose (FDG), has the potential to help in the evaluation of patients with lung cancer because the radiopharmaceutical is concentrated by metabolically active cells. We conducted a retrospective study of PET-FDG in 96 patients evaluated at our institution over the past 2 years for suspected primary pulmonary neoplasms. PET-FDG results were compared with the findings of computed tomographic scans on the same patients. All patients underwent surgical exploration with or without resection of the malignant tumors. Sites of potential malignancy were subjected to biopsy and/or excision, with subsequent pathologic evaluation. RESULTS: A total of 96 patients with suspected or proven primary pulmonary malignant disease were evaluated. Sixty-six patients had histologically confirmed malignant tumors, and 30 had benign masses histologically. PET-FDG had an accuracy of detecting malignancy in pulmonary lesions of 92% (sensitivity 97%; specificity 89%). A total of 111 surgically sampled sites were from lymph nodes. PET-FDG was accurate in predicting the malignancy of nodes in 91% of instances, whereas computed tomography was correct in 64%. The sensitivity, specificity, and predictive accuracy of PET in detecting metastatic lymphadenopathy in mediastinal lymph nodes were 98%, 94%, and 95%, respectively. PET-FDG also changed the M stage in 8 (12%) patients (6 with and 2 without metastases). The 6 malignant (positive) lesions were correctly identified by PET-FDG, and the 2 without tumor were accurately predicted as benign (negative). CONCLUSION: These initial results suggest that PET-FDG is highly accurate in identifying and staging lung cancer. PET-FDG also appears to be more accurate in detecting metastatic mediastinal lymphadenopathy than computed tomographic scan.

Comparative efficacy of positron emission tomography with FDG and computed tomographic scanning in preoperative staging of non-small cell lung cancer.

OBJECTIVE: To determine the sensitivity, specificity, and accuracy of positron emission tomography with 2-fluorine-18-fluorodeoxyglucose (PET-FDG) in the preoperative staging (N and M staging) of patients with lung cancer. The authors wanted to compare the efficacy of PET scanning with currently used computed tomography (CT) scanning. MATERIALS AND METHODS: Results of whole-body PET-FDG imaging and CT scans were compared with histologic findings for the presence or absence of lymph node disease or metastatic sites. Sampling of mediastinal lymph nodes was performed using mediastinoscopy or thoracotomy. RESULTS: PET-FDG imaging was significantly more sensitive, specific, and accurate for detecting N disease than CT. PET changed N staging in 35% and M staging in 11% of patients. CT scans helped in accurate anatomic localization of 6/57 PET lymph node abnormalities. CONCLUSION: PET-FDG is a reliable method for preoperative staging of patients with lung cancer and would help to optimize management of these patients. Accurate lymph node staging of lung cancer may be ideally performed by simultaneous review of PET and CT scans.

Dynamic positron emission tomography with F-18 fluorodeoxyglucose imaging in differentiation of benign from malignant lung/mediastinal lesions.

PURPOSE: This study was done to evaluate the diagnostic utility of dynamic positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) imaging in patients with suspected malignant pulmonary lesions. We wanted to test the hypothesis that the rate of FDG uptake (FDG influx constant values) would differentiate malignant from benign lung or mediastinal lesions. MATERIALS AND METHODS: We performed segmental dynamic PET imaging studies following administration of FDG in 19 patients with indeterminate pulmonary lesions based on chest radiograph and/or CT scans. Patlak analysis was done to compute Ki (FDG influx constant) values and compared with FDG standardized uptake values (SUVs) and histology. RESULTS: FDG Ki values (mean+/-SD) were significantly greater (p < 0.01) in all 12 malignant lesions (0.029+/-0.02) as compared with 7 benign lesions (0.0024+/-0.0011) with good correlation to the SUV values. Distinct time activity curve patterns were identified in malignant and benign lesions with continued uptake in malignant lesions. CONCLUSION: Dynamic PET-FDG imaging accurately differentiates malignant from benign pulmonary lesions. In certain cases with equivocal findings on visual analysis and SUV values, dynamic imaging may be further helpful in differentiating benign and malignant lesions.

Right ventricular endocarditis due to infection of pacemaker apparatus.

This article describes an unusual case of endocarditis in a 73-year-old man with a permanent pacemaker. Echocardiography revealed vegetations in the right ventricle below the tricuspid valve only, and he required open heart surgery for removal of the pacemaker system. This case demonstrates the potentially protracted course of infective endocarditis many years after pacemaker insertion. It also emphasizes the importance of echocardiography in diagnosing right ventricular vegetations; and the need for total replacement of the endocardial pacing system whenever it becomes infected.

Arachidonic acid metabolism by adult human osteoblast-like cells exhibits sexually dimorphic characteristics.

The eicosanoids, including prostaglandin E2 (PGE2) and other bioactive arachidonic acid metabolites, are important local mediators of bone remodeling. Presumably, the limited or excessive synthesis of the eicosanoids could compromise bone homeostasis. We have noted that the stimulated release of arachidonic acid by adult male donor derived human osteoblast-like (hOB) cells exceeded the stimulated release measured for female-derived hOB cells by 1.5-fold. Assays of PGE2 biosynthesis by cytokine-stimulated hOB cells also demonstrated a sex-linked difference, such that male hOB cell PGE2 production exceeded female cell production by 1.6-2.2-fold. The calcium-dependent cytoplasmic phospholipase A2 activity in subcellular fractions prepared from hOB cell homogenates was higher in both the cytosolic (1.6-fold) and particulate (1.5-fold) fractions from the male cells than in those prepared from female hOB cells, suggesting a molecular basis for the observed sexually dimorphic characteristics related to arachidonic acid metabolism by hOB cells. The relatively limited capacity of the female cells may limit needed intracellular and intercellular signaling during bone remodeling, thereby contributing to the development of bone pathology.

Right atrial metastatic melanoma in a patient with transient ischemic attacks.

A 65-year-old-man was admitted for evaluation of a transient ischemic attack. A 4.5 x 5.3-cm right atrial mass and a patent foramen ovale were identified by echocardiography. A 0.5-cm lesion was identified in the left temporal lobe of the brain by magnetic resonance imaging. Positron emission tomography was used to differentiate a tumor from an infarct in the brain. The cardiac and the brain lesions were successfully resected. Histopathologic study of the atrial and cerebral tissue demonstrated that these were metastases from a previously excised scalp desmoplastic malignant melanoma. The patient remains well at 14 months' follow-up.

1,25-Dihydroxyvitamin D3 pretreatment limits prostaglandin biosynthesis by cytokine-stimulated adult human osteoblast-like cells.

The steroid derivative 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a regulator of bone biology, and there is evidence that 1,25(OH)2D3 modulates arachidonic acid metabolism in osteoblastic cell model systems and in bone organ cultures. In the present studies, 1,25(OH)2D3 decreased prostaglandin (PG) biosynthesis by normal adult human osteoblast-like (hOB) cell cultures by about 30%. The decrease was observed under basal incubation conditions, or in specimens stimulated by transforming growth factor-beta 1 (TGF-beta) or by tumor necrosis factor-alpha (TNF). The inhibition of the TGF-beta-stimulated PG production appeared to reflect a diminished efficiency of arachidonic acid conversion into PGs by the cells, while the efficiency of substrate utilization for PG biosynthesis was unaffected by 1,25(OH)2D3 pretreatment in the unstimulated samples, or in samples stimulated with TNF or with TNF plus TGF-beta. Free arachidonic acid levels were decreased following 1,25(OH)2D3 pretreatment in the TNF stimulated samples. hOB cell phospholipase A2 activity was measured in subcellular fractions, and this activity was decreased by 20-25% in the 1,25(OH)2D3 pretreated samples. The addition of the selective inhibitor AACOCF3 to the phospholipase A2 assays provided evidence that it was the cytoplasmic isoform of the enzyme that was affected by the 1,25(OH)2D3 pretreatment of the hOB cells. Thus, 1,25(OH)2D3 regulation of hOB cell biology includes significant effects on arachidonic acid metabolism. In turn, this could influence the effects of other hormones and cytokines whose actions include the stimulated production of bioactive arachidonic acid metabolites.

Esophageal injuries.

Esophageal injuries may accompany any type of trauma. A high index of suspicion that esophageal injury has occurred is the most important first step in diagnosing and treating these injuries. Various diagnostic modalities are available to evaluate esophageal injuries, and all should be used judiciously in diagnosing the position and extent of the injury. Therapy depends on the extent of the injury, its anatomic location in the esophagus, and the elapsed time between the injury and repair.

Cytokine regulation of adult human osteoblast-like cell prostaglandin biosynthesis.

Prostaglandin (PG) biosynthesis by cytokine stimulated normal adult human osteoblast-like (hOB) cells was evaluated by thin layer chromatography, high performance liquid chromatography, and specific immunoassays. PGE2 was the predominant PG formed under all incubation conditions tested. Control samples produced measurable amounts of PGE2, and the measured level of this metabolite increased by 22-fold (from 7 to 152 ng/ml) following a 20 h treatment with the combination of TGF beta and tumor necrosis factor-alpha(TNF). The production of 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) and of PGF2 alpha were each increased by about five-fold (from about 0.5 to 2.5 ng/ml) in samples treated with the cytokines. Thus, TGF beta and TNF exerted a regulation of hOB cell PG biosynthesis that was principally directed towards an increased PGE2 biosynthesis, with lesser effects on the production of other PG metabolites. COX-2 mRNA levels were increased within 2 h of cytokine stimulation, reached a maximum at 6-12 h, and levels had appreciably diminished by 24 h after treatment. Both TGF beta and TNF could independently increase COX-2 mRNA levels and PG biosynthesis. However, the increased production of PGE2 resulting from TNF stimulation was blocked by the addition of an interleukin-1 beta (IL-1 beta) neutralizing antibody, suggesting that TNF regulation of hOB cell PG synthesis was secondary to its capacity to increase hOB cell IL-1 beta production. TGF beta regulation of PG production was not affected by the addition of the neutralizing antibody. These studies support the proposition that PGs can be important autocrine/paracrine mediators of bone biology, whose production by hOB cells is responsively regulated by osteotropic cytokines.

Estrogen pretreatment increases arachidonic acid release by bradykinin stimulated normal human osteoblast-like cells.

Eicosanoids are multifunctional autocrine/paracrine regulators of bone that are enzymatically derived from arachidonic acid (AA). The rate-limiting step in the eicosanoid biosynthetic pathways may be the release of AA from membrane glycerophospholipids by activated phospholipases. Free AA can serve as the substrate for cyclooxygenase(s) or lipoxygenases that catalyze the commitive steps in eicosanoid synthesis; alternatively, free AA may be used in reacylation processes, resulting in its reincorporation into cellular lipids. The hormones 17 beta-estradiol (17 beta-E2), dexamethasone (a synthetic glucocorticoid), and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) have been identified as regulators of AA metabolism, at various levels, in several tissues including bone. The possibility that these osteotropic steroids modulate the availability of free AA in bone cells was studied in the human osteoblast-like (hOB) cell model system. Following a 48-h steroid pretreatment, bradykinin or the calcium ionophore A23187 were used as agonists to stimulate hOB cell release of AA. The principal findings from these investigations were that (1) 17 beta-E2 pretreatment potentiated the appearance of free AA following bradykinin stimulation of the cells but, did not alter their response to A23187 stimulation; (2) dexamethasone pretreatment limited bradykinin-induced increases in free AA levels but did not alter cell response to A23187 stimulation; (3) hOB cells derived from different trabecular bone compartments (manubrium of the sternum, femoral head) differed quantitatively in their responses to bradykinin stimulation of AA release; and (4) 1,25(OH)2D3 did not effect AA release stimulated by either agonist. The ability of the steroids to modulate AA release by hOB cells suggests that these hormones may indirectly mediate bone cell responses to other osteotropic hormones that act through eicosanoid-dependent processes.

Thorascopic staging of stomal recurrence.

BACKGROUND: Squamous cell carcinoma of the low cervical area may be secondary to stomal recurrence following laryngectomy, low cervical esophageal disease, or peritracheal metastasis. Most often patients with disease in this area have already received both surgery and radiotherapy. Prior to Sisson's description of the trans-sternal radical neck dissection or mediastinal dissection the management and prognosis was uniformly poor. Since then, a number of authors have reported their experience with mediastinal dissection. Survival remains poor but palliation has been acceptable. Unfortunately, resectability of the disease cannot often be determined prior to the actual surgical procedure. A number of patients are explored only to have the procedure terminated. Thoracoscopy is a procedure that involves insertion of two or three trocars into the right thoracic cavity with collapse of the right lung. A form of endoscopic surgery, it permits visualization and dissection of the important structures of the mediastinum. Tracheal, esophageal, and great vessel invasion by tumor can be evaluated. METHODS: Prospectively, all patients initially seen with stomal recurrence from 1991 to 1994 were evaluated. CT scans, MRIs as well as thoracoscopy were performed when indicated. RESULTS: One patient required conversion to a minithoracotomy involving a 7-cm chest incision. The patient was found to have unresectable disease with tumor involving the great vessels of the mediastinum. A second patient was found to have unresectable disease with tumor encasing the subclavian artery. The third patient was found to have no mediastinum involvement. The patient with no mediastinum involvement underwent a stomal resection with mediastinal dissection. Reconstruction with a pectoralis major myogenous flap was performed. The patient has remained disease free to date. The remaining two patients were judged to have unresectable disease and were offered palliative treatment. Both of these patients died of the disease within 6 months. CONCLUSIONS: Thoracoscopy provides important information in judging the surgical resectability of patients with stomal recurrence. This procedure has not been previously described in the otolaryngologic literature. We provide some suggestions for its use in the evaluation of the mediastinal extent of disease.

Biatrial approach to cardiac myxomas: a 30-year clinical experience.

Early surgical intervention for atrial myxomas mitigates morbidity and usually offers cure. The operative approach to resect these tumors is controversial. The purpose of this study was to review our experience with the biatrial approach between 1964 and 1994. The location of the myxoma was left atrium in 17 and right atrium in 3. Mean preoperative New York Heart Association functional classification was 2.7. Surgical approach to the tumor was biatrial in all patients. There were no perioperative strokes, myocardial infarctions, or deaths. Mean follow-up was 7.5 years (range, 2 mo to 27 years) with a postoperative New York Heart Association functional classification of 1.4. One late death occurred, which was unrelated to the myxoma. Advantages of biatrial approach include (1) definition of tumor pedicle by direct visualization, (2) minimal manipulation of the tumor, (3) adequate margins of excision, (4) inspection of all heart chambers, and (5) secure closure of the atrial septal defect. Long-term follow-up demonstrates the efficacy of this operative approach to atrial myxomas.