Faculty Bibliography

Photodynamic therapy (PDT) is a potential treatment for peritoneal carcinomatosis. However, little data is available regarding the relative distribution of sensitizer to tumor and intra-abdominal organs, optimal route of sensitizer administration, and maximal tolerated light dose. Tumor and normal tissue sensitizer levels were measured by tissue extraction 3, 24, 48 and 72 h after 10 mg/kg of Photofrin II was given intraperitoneally (IP) or intravenously (IV) in a mouse peritoneal tumor model, and the maximal tolerated PDT light dose determined. Equivalent tumor sensitizer levels were obtained regardless of the route of sensitizer administration. Route of administration, however, did affect the kinetics of tumor sensitizer elimination, with the half-time for elimination (T1/2) 113.6 h for IP drug and 60.6 h for IV drug. Route of administration also affected sensitizer levels in several intra-abdominal organs, resulting in somewhat higher tumor to liver and kidney levels at 24 and 72 h after IP sensitizer administration. Despite these tissue distribution differences, route of sensitizer administration did not significantly affect PDT toxicity or mortality when mice were treated with 630 nm light. The maximum tolerated light dose was 1.04 J/cm2. These parameters will prove helpful in designing large scale animal trials assessing the efficacy and safety of intra-abdominal PDT

Adrenocorticotrophic hormone (ACTH)-producing bronchial carcinoid tumors tend to occur in the middle third of the lung adjacent to pulmonary vessels. Because they cause signs and symptoms when quite small (by virtue of their ACTH production), they may not be detected by CT. MR imaging was performed in 10 consecutive patients with surgically proved ACTH-producing bronchial carcinoid tumors in order to test the ability of MR to clarify equivocal or indeterminate findings on CT examinations. All bronchial carcinoid tumors had high signal intensity on T2-weighted and short-inversion-time inversion-recovery images, facilitating their distinction from pulmonary vasculature. In eight patients, the CT and MR images were equivalent in the detection of bronchial carcinoid tumors. In two patients, MR showed tumors in the middle third of the lung that were equivocal on CT. MR imaging may distinguish small bronchial carcinoid tumors from adjacent pulmonary vessels in the central third of the lung at a time when the CT study is nondiagnostic or equivocal

Despite recommended preoperative preparation with alpha-adrenergic blockers, severe hemodynamic instability may occur during operations to resect pheochromocytoma. We combined the alpha-blocker phenoxybenzamine with the tyrosine hydroxylase inhibitor metyrosine in an attempt to better manage the hypertension of patients with pheochromocytoma undergoing surgical resection. This report reviews the cases of 25 consecutive patients undergoing surgery for known intra-abdominal pheochromocytoma. Each patient had elevated serum or urine levels of catecholamines or their metabolites. Nineteen patients were prepared before operation with phenoxybenzamine and metyrosine and six patients were given phenoxybenzamine alone. There were no significant differences in maximum, minimum, or mean blood pressure before or after tumor resection between patients who received metyrosine and those who did not. However careful review suggested that those who received metyrosine had more severe disease as judged by biochemical criteria. Study of selected patients matched for age and severity of disease suggested that the intraoperative blood pressure management of patients prepared with phenoxybenzamine and metyrosine was facilitated. In addition metyrosine-prepared patients lost less blood and required less volume replacement during surgery than did non-metyrosine-prepared patients. There were no apparent differences in postoperative fluid requirements. Although the study is not a prospective randomized trial, a retrospective review of patients managed with the combination of phenoxybenzamine and metyrosine suggests that surgery to resect pheochromocytoma can be better performed with both drugs than with phenoxybenzamine alone. The combination regimen appears to result in better blood pressure control, less blood loss, and the need for less intraoperative fluid replacement than does the traditional method of single-agent alpha-adrenergic blockade

A total of 63 patients with metastatic renal cell carcinoma with the primary kidney tumor in place was accepted as candidates for immunotherapy at the Surgery Branch of the National Cancer Institute. Of the 63 patients 54 underwent nephrectomy and 9 were treated with the primary kidney tumor in place. Many of the patients underwent associated procedures, such as regional lymphadenectomy (11), venacavotomy with extraction of tumor thrombus (9), hepatic resection (2), pulmonary wedge resection (2), cholecystectomy (2), splenectomy (2), distal pancreatectomy (1), omentectomy (1) and contralateral adrenalectomy (1). Of the 54 patients 20 were not able to enter therapy because of tumor-related (17) or other medical (3) reasons that developed between the operation and therapy, while 34 were able to receive immunotherapy postoperatively. The 20 patients who were treated with either high dose interleukin-2 or interleukin-2 plus lymphokine activated killer cells soon postoperatively (mean 2.1 months) were able to tolerate roughly the same amount of interleukin-2 as the 74 who had undergone nephrectomy before referral to our institute and who were treated for a mean of 22 months after nephrectomy. Further studies, including a prospective, randomized trial, will be required to define the role of nephrectomy in patients with advanced renal cell carcinoma before treatment with interleukin-2 based immunotherapies

Chronic granulomatous disease (CGD) is a rare, genetically transmitted disorder characterized by recurrent, life-threatening infections with catalase-positive micro-organisms and excessive inflammatory reactions that lead to granuloma formation. Long-term prophylactic antimicrobial agents and aggressive surgical management are the mainstays of therapy. The authors provided anesthetics for 17 patients with CGD undergoing 55 surgical procedures. These patients presented to surgery with multiple organ system involvement and were at significant risk for complications in the perioperative period. Granulomatous lesions of the gastrointestinal (GI) tract may predispose such patients to regurgitation and aspiration

The relative sensitivities of different cancer histologies in a single site to photodynamic therapy (PDT) are unknown and methods to predict PDT sensitivity have not been described. The in vitro response to PDT of six established human lung cancer cell lines and one normal lung fibroblast cell line was studied using the clonogenic assay. Dose-response curves were determined for cells incubated in 25 micrograms/ml of Photofrin II for 2 h, followed by exposure to 630-nm light to total energies of 0-3150 J/m2. None of the cell lines were sensitive to sensitizer alone or light alone. Differences in inherent PDT sensitivities as evaluated by survival curve parameters n, Do, and light dose to yield 1% survival were observed among the cell lines. No clear correlation was found when inherent PDT sensitivity was compared with sensitizer uptake; however, a general association was noted between PDT sensitivity and the plating efficiency of the cell line. These data illustrate that differences in inherent PDT exist for in vitro systems. Such differences may explain some of the failures seen in clinical PDT

The frequency of atypical pathologic manifestations of Pneumocystis carinii pneumonia (PCP) were studied in 123 lung biopsy specimens from 76 National Institutes of Health patients with the acquired immune deficiency syndrome. The following atypical features were observed: interstitial (63%) and intraluminal (36%) fibrosis, absence of alveolar exudate (19%), numerous alveolar macrophages (9%), granulomatous inflammation (5%), hyaline membranes (4%), marked interstitial pneumonitis (3%), parenchymal cavities (2%), interstitial microcalcification (2%), minimal histologic reaction (2%), and vascular invasion with vasculitis (1%). These atypical features are discussed with emphasis on the significance of cavities, vascular invasion, vasculitis, and granulomas. Immunohistochemical staining with monoclonal antibodies to the 2G2 and 6B8 antigens of P carinii in paraffin-embedded lung biopsy specimens did not indicate any diagnostic advantage over routine methenamine silver stains. This study provides an important reminder that a wide variety of pathologic manifestations may occur in PCP in human immunodeficiency virus-infected patients and that atypical features should be sought in lung biopsies from patients at risk for PCP