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Cytogenetic analysis of mesothelioma cell lines and solid tumors has documented non-random chromosomal abnormalities on the short arm of chromosome 3 from 3p14 to 3p25. We therefore examined nine mesothelioma cell lines, their corresponding tumors, and 15 additional mesothelioma tumors for loss of heterozygosity on 3p from 3p13 to 3p25.5 by polymerase chain reaction and restriction fragment length polymorphism analysis at 8 loci: D3S3, D3S30, D3S6, D3S2, D3S32, D3F15S2, THRB, and VHL. Loss of heterozygosity was documented by loss of one of two alleles in the tumor DNA whose corresponding normal DNA was heterozygous and was documented in four of nine mesothelioma cell lines and six of 15 mesothelioma tumors or a total of 42% of the mesotheliomas evaluated. This study suggests the involvement of a gene on the short arm of chromosome 3 in the development of mesotheliomas

Pulmonary mycoses can be life threatening in patients who are in an immunocompromised state stemming from defective host defenses or the use of certain treatment regimens. In 36 immunosuppressed patients undergoing thoracotomy for the treatment of pulmonary fungal disease, the underlying cause of immunosuppression was malignancy (n = 9), Wegener's granulomatosis (n = 4), hematologic disorders (aplastic anemia, 5-Q minus syndrome, or myelofibrosis) (n = 6), or chronic granulomatous disease of childhood (n = 17). The mean age of the patients was 25 years, and 89% were symptomatic (fever, n = 27; cough, n = 20; chest pain, n = 14; and other, n = 13). Chest x-ray studies revealed the presence of cavitary disease (n = 7), a mass (n = 8), infiltrates (n = 20), or cavity and infiltrate (n = 1). A preoperative diagnosis was lacking in 23 of the 36 patients. Procedures included wedge biopsy (n = 13), segmentectomy with or without wedge or chest wall resection (n = 5), lobectomy with or without chest wall resection (n = 16), wedge resection plus completion pneumonectomy (n = 1), and segmentectomy plus completion pneumonectomy (n = 1). Fungi identified included Aspergillus (n = 23), Zygomycetes (n = 4), Cryptococcus (n = 3), and other (n = 6; 1 each), and specific antifungal treatment was instituted in 34 of the patients (94%). The 31% operative (ie, < 30-day or inhospital) mortality was chiefly due to multiorgan system failure (9/11).(ABSTRACT TRUNCATED AT 250 WORDS)

The cellular and molecular biology of mesothelioma is a complicated, multifactorial, incompletely understood process of carcinogenesis. Normal mesothelial cells can be transformed into a malignant phenotype by multiple factors, usually asbestos. Several tumor suppressor genes may be lost, and several oncogenes can be activated. A local environment of inflammation with associated release of cytokines may promote deregulated cell growth. The release of immunosuppressive substances such as nitric oxide may contribute to this process. The interaction of asbestos and viral DNA incorporation is unclear but warrants further investigation. In the majority of mesothelioma patients, present standard therapies have little effect on survival. Clinical trials studying a variety of innovative treatment strategies are being performed at centers with a significant referral base for the disease. Future treatments, however, must be based on understanding of the biology of mesothelioma

BACKGROUND. Suramin is an antiparasitic agent that is currently being evaluated for antineoplastic activity. Documented toxicities of suramin include adrenal and renal insufficiency, coagulation factor abnormalities, immunosuppression, and polyneuropathy. These adverse effects have potential for contributing to postoperative morbidity in surgical patients. Because no experience with suramin has been reported in the surgical literature, this 5-year retrospective review of postoperative complications in patients receiving suramin was performed. METHODS. From a review of 171 charts, 14 patients were identified who had undergone a major surgical procedure either while receiving intravenous suramin or within 1 year after its administration. Primary diagnoses included prostate cancer (six), lymphoma (four), ovarian cancer (two), colon cancer (one), and glioblastoma (one). All patients received replacement dose hydrocortisone at the initiation of suramin therapy and thereafter. RESULTS. Eighteen major surgical procedures were performed with 18 complications occurring in five patients. The predominant complications encountered were hemorrhage (five), impaired wound healing (three), and bowel dysmotility (two). A highly significant relationship existed between the incidence of complications and interval from completion of suramin therapy to the time of operation (p < 0.0005), with 17 of the 18 morbidities occurring within the first month. The length of operation (p < 0.05) and amount of blood transfused during the procedure were related to postoperative morbidity (p < 0.05). No other factors evaluated were correlated to complications. CONCLUSIONS. This experience suggests the avoidance of elective procedures during the first month after suramin therapy and a heightened awareness of the potential for bleeding and wound healing problems in patients receiving suramin who do require an emergent procedure

Induction of mesothelioma in the rat is an important animal model for assessing the carcinogenic potential of fibers and for understanding the molecular basis underlying the development of these tumors. Mesotheliomas and nephroblastoma (Wilms' tumor) have many developmental, biochemical, and histological similarities; however, the expression of the Wilms' tumor suppressor gene, WT-1, has not been well characterized in the rat, and its expression pattern in rat or human mesothelioma has not been described. We report that WT-1 transcripts (3.2 kilobases) could be detected by Northern analysis in adult rat testis, spleen, kidney, lung, heart, and glomerular mesangial cells. Normal adult mesothelial cells also expressed this gene. Rat mesothelioma cell lines expressed WT-1 transcripts of 3.2 kilobases and an additional 2.8-kilobase transcript, previously only reported to be expressed in the testis. Normal and transformed rat mesothelial cells expressed all four of the WT-1 splice variants, except testis, which only expressed WT-1 splice variants containing exon 5. Seven of seven human mesothelioma cell lines examined also expressed WT-1 transcripts, suggesting that expression of this gene may be useful in the diagnosis of these tumors

Mesotheliomas are pleural, pericardial, or peritoneal neoplasms frequently associated with asbestos exposure, and it is estimated that over the next twenty years up to 80,000 new cases are expected in the USA alone. We found simian virus 40-like DNA sequences in 29 of 48 mesotheliomas studied (60%) and demonstrated simian virus large-T antigen expression in 13 of 16 specimens. The matching lung samples did not contain simian virus 40-like sequences; however, they contained asbestos. These findings are to our knowledge the first demonstration of a physical link between DNA virus-like sequences and human mesothelioma. We suggest that a simian virus 40-like virus may act independently or as a co-carcinogen with asbestos. Moreover, the selective large T antigen expression by mesothelioma and not by the surrounding pulmonary parenchyma may have both diagnostic and therapeutic implications

Isolated lung perfusion with tumor necrosis factor (TNF) potentially could deliver high doses of drug and avoid systemic toxicity in patients with unresectable lung cancer or metastases. We investigated the feasibility of isolated lung perfusion with TNF in a pig model. Eleven animals had left-sided isolated lung perfusion with no TNF (n = 3), 40 micrograms/kg TNF (n = 2), 80 micrograms/kg TNF (n = 3), and 40 micrograms/kg TNF at moderate (39.5 degrees C) hyperthermia (n = 3). Hemodynamic monitoring and measurement of systemic and pulmonary circuit TNF levels were performed. Surviving animals were electively sacrificed a minimum of 6 months after isolated lung perfusion. All sham-perfused pigs survived. Isolated lung perfusion elevated pulmonary artery pressure, decreased cardiac output, and had minimal effects on mean pressure (15 +/- 0 versus 32 +/- 8 mm Hg, 4.5 +/- 1.1 versus 3.03 +/- 0.03 L/min, 67 +/- 11 versus 61 +/- 2 mm Hg; before versus after 90 minutes of isolated lung perfusion). Both 40 micrograms/kg animals and 2 of the 3 hyperthermic perfusion pigs survived, with 1 requiring pneumonectomy. Of the three 80 micrograms/kg animals, 1 survived, 1 died, and 1 required pneumonectomy. Survivors, compared with dying animals, had lower systemic/pulmonary TNF ratios and lower peak systemic TNF levels. All surviving pigs were electively sacrificed. These data justify phase I human protocols of isolated lung perfusion with TNF and hyperthermia; however, intraoperative leak rates must be monitored to ensure pulmonary isolation because systemic TNF levels may dictate treatment morbidity/mortality

Pericardial effusion can be treated effectively by the technique of subxiphoid pericardial window. We present a case in which the Cooper retractor designed for transcervical thymectomy facilitated this operation. When available, the Cooper retractor can be useful in selected patients