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Background: Despite vigorous efforts at curbing tobacco consumption and aggressive combined-modality treatment programs, both the incidence of and the mortality from lung cancer have remained virtually unchanged in the last 10 years. More effective innovative therapies are clearly needed. The direct transfer into tumor cells of tumor suppressor genes or toxic gene products that specifically promote tumor cell death and spare nonmalignant cells is a potentially novel anticancer treatment approach that should be investigated. Purpose: On the basis of compelling preclinical data, we initiated a phase I study involving six patients with inoperable lung cancer and an endobronchial lesion accessible by bronchoscopy. Our purpose was to evaluate the feasibility, tolerance, and clinical, biologic, and immunologic effects of the intratumoral administration of a recombinant, replication-deficient adenovirus (rAd.RSV[beta]-gal), using the Rous sarcoma virus promoter to drive transcription of the Escherichia coli lacZ marker gene that encodes for the bacterial enzyme [beta]-galactosidase ([beta]-gal). Methods: From June 1994 through April 1995, six patients (five males and one female) were enrolled in the trial. A single dose of recombinant virus suspension containing [10.sup.7] or [10.sup.8] plaque-forming units (PFU) was injected intratumorally into two successive cohorts of three patients. Eligible patients received concomitant chemotherapy. Patients were kept under isolation conditions from 3 days before the injection was given until virus excretion was undetectable. Biopsy specimens of the tumor and surrounding mucosa were collected on the 8th day and at 1, 2, and 3 months after injection. They were analyzed by cell culture, polymerase chain reaction TPCRI, and ff@gal expression for the presence of recombinant adenovirus. So that the risk of virus recombination or complementation could be minimized, wildtype adenovirus carriers among the hospital staff (identified by PCR) were excluded from contact with patients who were potentially excreting recombinant virus. Results: [beta]-gal was expressed in tumor biopsy specimens of three patients tone who received the [10.sup.7] PFU dose level and two who received [10.sup.8]). Bronchoalveolar lavage specimens collected immediately after injection were positive for recombinant adenovirus when analyzed in culture and by PCR. All biologic fluids were negative for recombinant virus as judged by PCR after day 12, with the exception of bronchoalveolar lavage specimens (positive PCR up to 90 days in two of three patients treated with [10.sup.8] PFU). The blood samples obtained from the three patients treated with [10.sup.8] PFU showed positive PCR results immediately after virus injection. Patients were kept in isolation for a median of 17 days. The most common toxic effects were moderate bleeding (occurring in two patients) during bronchoscopy and fever (seen in four patients). Endoseopic and clinically objective antitumor responses were seen in four patients, including one patient who showed a complete response by pathologic evaluation. The median survival for the patients was 12.5 months (range, 3-16+ months). Throughout the study, hospital staff remained negative for recombinant adenovirus infection. Conclusions: This ongoing phase I study has demonstrated that a recombinant adenovirus-mediated marker gene, such as rAd.RSV[beta]-gal, can be safely introduced into humans and that the gene product is expressed by lung tumor cells of the host.

Background. Surgical resection of pulmonary metastases (PMs) has been shown to produce approximately a 35% 5-year survival rate, but specific data about late survival are not available in the literature. Methods. A retrospective review and survival analysis of 186 adult patients who underwent surgery for PMs at a single center before June 1984 is presented. Results. Of the 186 patients who had surgery, of whom 34 (18%) had an incomplete resection, the 10-year survival rate (Kaplan-Meier) was 23% (95% CI, 16-30%), and 36 patients, with PMs from nine different primary sites, were still at risk at 10 years. Two patients died of their primary disease more than 10 years after the first thoracotomy, and two are alive with uncontrolled disease. Thirty-one patients are currently alive and disease free. Comparison between the 36 10-year survivors and the 150 nonsurvivors revealed that only the percentage of incomplete resections and the mean number of resections per patient were significantly different between the two groups (P < 0.001); the histologic type of the primary tumor, the disease-free interval, and the number of resected PMs at the first thoracotomy were not found to be statistically significant prognostic factors. Conclusions. The 23% 10-year survival and the high rate of disease free 10-year survivors in this study constitute support for complete resection as an efficient therapeutic approach in patients with isolated PMs. Relevant criteria to select more precisely those patients who will benefit from resection remain to be developed. Cancer 1994; 74:2791-7.

Malacoplakia is a rare granulomatous disease well described in the urinary tract but which rarely involves the lung. We report for the first time, to our knowledge, tracheal localization of [...]

A 36-year-old patient was found to have severe left mainstem bronchial stenosis two years after bronchial artery embolization (BAE) for hemoptysis. Embolization-induced bronchial ischemia appeared to be the only potential [...]