Faculty Bibliography

A variety of imaging procedures were performed in 28 patients with ectopic adrenocorticotropic hormone (ACTH) syndrome in an attempt to localize the ACTH-producing tumor. Diagnosis was made on the basis of removal of an ACTH-producing tumor or biopsy of metastases in the 19 patients with a proved source and the absence of ACTH gradients in bilateral samples of the inferior petrosal sinuses in the nine patients in whom an ACTH-secreting tumor had not been localized. Eleven bronchial carcinoids, two thymic carcinoids, three pheochromocytomas, and three islet-cell tumors constituted the proved sources. The condition has been cured in eight patients, six are alive with residual tumor, and five have died. Of the nine patients with undetected sites of ACTH production, one has died of pneumocystis pneumonia and eight are being treated medically or with bilateral adrenalectomy. Computed tomography (CT) of the chest and abdomen was the most helpful study in the detection of these tumors. Selective arteriography (bronchial and visceral), systemic and portal venous sampling, and iodine-131 meta-iodobenzylguanidine scintigraphy failed to demonstrate tumors when findings at CT were negative. Bronchial carcinoids constituted most of the ACTH-secreting tumors in this study (58%) and in a review of four large series (47%). To assure early detection of these potentially malignant tumors, pulmonary CT should be performed every 6 months, even after hypercortisolism has been medically or surgically controlled

Tracheoesophageal fistula (TEF) occurs only rarely in the patient with lymphoma. Two cases are presented to illustrate the challenges in managing TEF in this patient population. Most of the 38 previously reported cases have occurred in patients who have undergone radiation therapy, although several patients have had TEF as an initial manifestation of lymphoma. TEF is usually, but not universally, associated with the presence of active lymphoma. The surgical approach should be individualized, based on the patient's overall condition, the site and size of the fistula, and sites of disease. Often a conservative surgical approach is warranted with the expectation that many of these fistulas will close after radiation therapy or chemotherapy. Patients with lymphoma-related TEF have a better prognosis than do those with TEF caused by carcinoma of the lung or esophagus

The use of monochlorobimane (MCIB) as a fluorescence label for glutathione (GSH) quantitation was investigated in human tumor cell lines. When MCIB was used with a hamster fibroblast cell line under conditions where GSH was either depleted or elevated, an excellent correlation between bimane-GSH fluorescence and the standard cyclic GSH reductase assay (Tietze's) was accomplished. When the MCIB technique was applied to a human lung adenocarcinoma cell line, little or no GSH labeling was noted even at MCIB levels 10X higher than that used for the hamster line. HPLC analysis suggested that the source of the problem may be the affinity for MCIB to glutathione S-transferase. By using higher dye concentrations and longer staining times, adequate staining was possible. While the MCIB technique may have problems quantitating GSH levels between cell types, the possibility of examining GSH heterogeneity in solid tumor biopsies remains feasible

Between 1982 and 1987, 74 patients (46 men and 28 women) had exploration for presumed metastases from high-grade soft tissue sarcoma of the head/neck, extremity, or trunk. Ages ranged from 11 to 75 years (median 38 years). Thirty (41%) had multiple procedures for recurrences (range two to six explorations). Median postthoracotomy time for the group of patients with histologically confirmed sarcoma (n = 63) was 20.3 months. Patients rendered free of disease at initial thoracotomy had significantly longer postthoracotomy survival times (26.8 months median) than those with unresectable metastatic disease (9 months median); p2 less than 0.0001). The prognostic significance of age, sex, location of primary tumor, disease-free interval, number of nodules on preoperative computed tomograms or conventional linear tomograms, number of metastases resected, and the use of postoperative chemotherapy were analyzed. In a univariate analysis, sex, age, and location of the primary tumor did not impact significantly on survival, nor did the use of postoperative chemotherapy. Initial disease-free interval of 1 year or less was associated with a significantly shorter survival time, and patients with five nodules or fewer on preoperative computed tomography had significantly longer survival times than patients with six nodules or more. Patients with three nodules or fewer on linear tomography had a longer postthoracotomy survival time than patients with four nodules or more. In patients whose malignant disease could be completely resected, the number of nodules resected at thoracotomy did not impact on long-term survival. According to proportional-hazards modeling, disease-free interval, sex, resectability, and truncal location were found to associate with length of survival after metastasis removal. We conclude that pulmonary metastasis resection in patients with soft tissue sarcoma is associated with long-term survival, and consistent indicators can define which patients may benefit from these interventions

Photodynamic therapy is a recently introduced treatment for surface malignancies. Since January 1987, 10 patients with endobronchial neoplasms have had bronchoscopic photodynamic therapy at similar dose rates (400 mW/cm) for total atelectasis (2), carinal narrowing with respiratory insufficiency (2), or partial obstruction without collapse (4). Two patients underwent photodynamic therapy as a preliminary to immunotherapy. Histologies included endobronchial metastases (colon, ovary, melanoma, and sarcoma, 1 each; and renal cell, 3) and primary lung cancer (3). The 2 patients with total atelectasis had complete reexpansion after photodynamic therapy, which permitted eventual sleeve lobectomy in 1. Carinal narrowing was ameliorated in the 2 patients seen with inspiratory stridor, thereby permitting hospital discharge. Endoscopically resected fragments after photodynamic therapy exhibited avascular necrosis. These data support further controlled studies of photodynamic therapy by thoracic surgical oncologists to define its limitations as well as to improve and expand its efficacy as a palliative or surgical adjuvant

A case of ruptured gastroepiploic artery aneurysm associated with thoracic aortic aneurysm is presented. Gastroepiploic artery aneurysms are rare, but the association of visceral artery aneurysm and aortic aneurysm is clinically significant and is emphasized in this report

The influence of light dose-rate delivery was studied in human lung adenocarcinoma A549 cells treated with hematoporphyrin derivative (Photofrin II)-based photodynamic therapy. Clonogenic cell survival curves were generated for cells treated for 2 h with 25 micrograms/ml of Photofrin II followed by exposure to light delivered at 0.3, 0.15, 0.075, or 0.0375 milliwatts/cm2. Cellular sensitizer levels, as determined by fluorescence measurements, remained constant over the entire time course of all light exposures. As the dose rate of light delivery was decreased, a significant increase in cell survival was observed at equal light energies (225 mJ/cm2). The enhancement in survival from the highest to the lowest dose rate used was 1.6-fold (at the 50% survival level). These findings may have important clinical implications relating to photodynamic therapy of tumors and may provide a partial explanation for treatment failure

Lung cancer cells are susceptible to photodynamic therapy (PDT) using 630 nm light and dihematoporphyrin ether (DHE). A light scattering media, intralipid (IL), was compared to balanced salt solution (PBS) for PDT of A549 human lung cancer cells. Differences in cellular DHE content after IL or PBS exposure were determined. Cells were incubated in 25 micrograms/ml DHE for 2 hr and then incubated in various concentrations of IL or PBS at room temperature for 2.5 to 10.0 min. Significant amounts of DHE were lost from IL-incubated cells compared to cells incubated in PBS. After 5 min in 1% IL, cellular DHE content was 0.32 +/- 0.04 microgram DHE/10(6) cells compared to 0.56 +/- 0.11 microgram DHE/10(6) cells in PBS-incubated cells (P less than 0.05). Despite this, superior PDT cytotoxicity was noted when cells were treated in IL with energy densities greater than or equal to 105 mJ/cm2. At an energy density of 210 mJ/cm2, the survival fraction (SF) of cells treated in 1% IL was 0.004 +/- 0.001 compared to 0.071 +/- 0.022 in PBS-treated cells (P less than 0.05). SF was dependent upon the IL concentration with the greatest cell killing noted with 1% IL. An apparent loss of cellular DHE ('DHE washout') was confirmed by demonstration of a higher SF of cells incubated in IL, rinsed, and subsequently PDT-treated in PBS with 157.5 mJ/cm2 (SF = 0.85 +/- 0.11) compared to cells incubated and treated in PBS (SF = 0.50 +/- 0.03, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cunninghamella bertholletiae, an uncommon cause of human infection, has been reported with increasing frequency in recent years. C. bertholletiae belongs to the order Mucorales and produces infections similar to those produced by the other agents of mucormycosis. Infections with this group of organisms have typically been seen either in patients with diabetes mellitus or in those receiving chemotherapy. Recent reports of mucormycosis in dialysis patients receiving deferoxamine for iron or aluminum overload have raised the possibility that deferoxamine therapy is a risk factor for mucormycosis. A case of C. bertholletiae infection in a patient receiving deferoxamine for iron overload unrelated to hemodialysis was investigated in detail, and possible explanations for this patient's infection were assessed

The use of preoperative computed tomographic (CT) scans of the chest in carcinoma of the esophagus to associate preoperative staging with postoperative survival is controversial. Thirty-two patients who underwent esophagectomy and reconstruction were examined with respect to a variety of variables available on preoperative evaluation, including lesion width on CT scan, lesion length on CT scan, and barium esophagogram. Each variable was evaluated for its ability to predict the presence of extraesophageal spread of tumor, as determined pathologically by logistic regression analysis. Lesions greater than 3.0 cm in width by CT scan were associated with a significantly higher incidence of extraesophageal spread. Tumor location, gender, histologic grade, presence of in situ lesions, vascular invasion, eosinophilia, nodal metastases, and preoperative chemotherapy had no predictive value for survival. Duration of survival was affected by the presence of esophageal spread of disease and lesion width. These results indicate that preoperative CT scanning can predict extraesophageal spread of tumor, and this is associated with overall survival