Faculty Bibliography

BACKGROUND: S-Adenosylmethionine (AdoMet) is a major methyl donor for transmethylation reactions and propylamine donor for the biosynthesis of polyamines in biological systems, and therefore may play a role in lung cancer development. We hypothesized that AdoMet levels were elevated in patients with lung cancer and may prove useful as a biomarker for early lung cancer. METHODS: High-performance liquid chromatography was used to analyze plasma AdoMet levels in triplicate samples from 68 patients. This included 13 patients with lung cancer, 33 smokers with benign lung disease, and 22 healthy nonsmokers. The three groups of subjects were compared with respect to the distribution of demographic and disease characteristics and AdoMet levels. Distributions were examined using summary statistics and box plots, and nonparametric analysis of variance procedures. RESULTS: Serum AdoMet levels were elevated in patients with lung cancer as compared to smokers with benign lung disorders and healthy nonsmokers. There were no significant correlations between AdoMet levels and tumor cell types, nodule size, or other demographic variables. CONCLUSIONS: Our data demonstrate that plasma levels of AdoMet are significantly elevated in patients with lung cancer. Plasma AdoMet levels may prove to be a useful tool for the diagnosis of early lung cancer, in combination with chest CT. Registered at: clinicaltrials.gov (NCT00301119)

BACKGROUND: Lymph node (LN) involvement predicts recurrence in patients who have undergone resection of apparently localized nonsmall cell lung carcinoma (NSCLC). Standard detection methods for LN disease have a low sensitivity, and many patients with apparent N0 disease status develop recurrent disease. Molecular techniques can improve the detection of micrometastases, whereas sentinel lymph node (SLN) mapping can indicate which LN may contain micrometastases. These methods, although potentially complementary, have not, to the authors' knowledge, been used together previously. METHODS: The authors used SLN mapping and molecular staging to improve the detection of LN micrometastases in patients with NSCLC. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for cytokeratin-7 (CK7), expressed both in normal lung and in malignant lung, was used to identify tumor-derived material in LN. RESULTS: SLN mapping was performed in 13 patients, with 1-3 SLNs identified in each patient, and sufficient RNA for RT-PCR was obtained in 12 of these 13 patients. Eleven of 12 tumors expressed CK7. Overall, 32 LNs were positive for CK7, including 13 of 21 SLNs. Ten of 11 patients with evaluable SLNs had at least 1 CK7-positive SLN. Routine pathology showed Stage I disease in eight patients, T3N0 disease in one patient, and LN-positive disease in two patients. Of the nine patients with N0 disease according to routine pathology that was evaluable by RT-PCR, eight patients were upstaged by this technique. All patients with positive LN status by routine pathology who were evaluable by RT-PCR analysis had positive RT-PCR results. CONCLUSIONS: LN micrometastases were common in resected NSCLC, including patients with N0 disease according to routine pathology. SLN mapping was useful for identifying disease-containing LNs. This approach may be useful for stratifying histologically N0 patients into higher risk and lower risk groups

Between 1986 and 1994 we identified 57 patients who underwent carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) during the same hospitalization. Simultaneous CABG and CEA was performed in 28 patients (mean age 70.5 years, 58% male). Indications for CABG in these patients were myocardial infarction in two crescendo angina in 19, congestive heart failure in two and left main or triple-vessel coronary artery disease noted during carotid preoperative evaluation in five. Indications for CEA were transient ischemic attack (TIA) in 12, crescendo TIA in six, cerebrovascular accident (CVA) in five, and asymptomatic stenosis in five. There were no postoperative myocardial infarctions or perioperative deaths. Two patients developed atrial fibrillation, and four patients had CVAs (two were ipsilateral to the side of CEA). Twenty-nine patients underwent staged procedures (i.e., not performed concomitantly but during the same hospitalization). Indications for CABG and CEA were comparable to those in the group undergoing simultaneous procedures. In 17 patients CEA was performed before CABG. There was a single CVA, the result of an intracerebral hemorrhage. Five of the 17 patients had a myocardial infarction and two died; one patient had first-degree heart block requiring a pacemaker. Four additional patients developed atrial fibrillation, one of whom required cardioversion. The remaining 12 patients had CABG followed by CEA. There were no CVAs, myocardial infarctions, arrhythmias, or deaths in this subgroup. These data demonstrate that the performance of simultaneous CABG and CEA procedures is associated with increased neurologic morbidity (14.3%), both ipsilateral and contralateral to the side of carotid surgery in contrast to staged CABG and CEA (3.4%). In addition, when staged carotid surgery preceded coronary revascularization in those with severe coronary artery disease, the combined cardiac complication and mortality rate was significantly higher than when coronary revascularization preceded CEA. This evidence suggests that when CABG and CEA must be performed during the same hospitalization, the procedures should be staged with CABG preceding CEA

The anterior approach to the thoracic and lumbar spine for neoplastic disease is now a well-accepted procedure, with results, for the most part, superior to those achieved with laminectomy. However, the specific indications for anterior decompression and the selection of reconstruction techniques based on the location and extent of bony destruction have received surprisingly little attention. The authors report their experience with the operative management of 33 patients with benign and malignant tumors of the thoracic and lumbar spine, using the anterior transthoracic or retroperitoneal approach. The role of stabilization and the relative indications for anterior or posterior instrumentation are emphasized. The mean age of patients was 58 years. Twenty-three patients were male. Five patients had benign tumors, and the remainder had a variety of metastatic lesions. Twenty-nine patients had lower extremity motor deficits, although 25 were ambulatory preoperatively. Thirty-seven noncontiguous resections were performed in 33 patients. In 13 patients, the resected vertebral body was replaced with acrylic or bone without instrumentation; in 18, the acrylic was supplemented with anterior instrumentation; and in 6, both anterior and posterior instrumentation were used. Above T11, vertebral reconstruction techniques were used to restore stability after decompression. Between T11 and L4, anterior instrumentation was used to supplement vertebral reconstruction in all patients. Supplemental posterior instrumentation was used for three-column involvement. Motor function was stabilized or improved in 94% of patients, and 88% of patients were ambulatory postoperatively. Of 28 patients with malignant disease, 23 died after a mean survival of 10.2 months (range, 2-51 mo) and 5 are alive a mean of 34.4 months since their operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous pneumothorax in patients with acquired immunodeficiency syndrome (AIDS) may require prolonged therapy for treatment of a persistent bronchopleural fistula, and treatment by standard methods often fails. This pilot study was done to test the effectiveness of aggressive surgical therapy for definitive treatment of persistent bronchopleural fistula in patients with AIDS. Between March 1989 and September 1991, 44 patients with AIDS were treated for spontaneous pneumothorax with closed tube thoracostomy; 14 of these patients had development of persistent bronchopleural fistula for more than 10 days, and 2 patients had subsequent bronchopleural fistula on the opposite side. Operative therapy in 14 patients included 15 thoracotomies and one sternotomy. The bronchopleural fistula was closed directly with suture or staples in 15 procedures and resected by lobectomy in 1 patient. All 14 patients received adjuvant parietal pleurectomy. Operative mortality was 7% (1 of 14 patients). The fistula was closed in all survivors and 13 patients were discharged between 7 and 28 days postoperatively. Pathologic examination confirmed Pneumocystis carinii in 13 patients with a high incidence of diffuse involvement and subpleural necrosis, further demonstrating the need for pleurectomy. These data suggest that in selected patients bronchopleural fistulas associated with AIDS can be effectively controlled by surgical closure combined with pleurectomy