Use of cryotherapy to treat obstructing papilloma of an accessory tracheal bronchus: case report.

BACKGROUND: Tracheal papillomatosis is a relatively rare condition with limited data on successful treatment modalities. To our knowledge, this is the first report to describe a papilloma arising from an accessory bronchus. Furthermore, this case report demonstrates successful treatment with clinical and patient-centered improvements after use of Spray Cryotherapy. CASE PRESENTATION: A 71-year-old woman presented with one year history of recurrent fevers and intermittent hemoptysis. Imaging and video bronchoscopy revealed an obstructing papilloma of an accessory tracheal bronchus to the right upper lobe. She was treated with debridement followed by multiple cryotherapy treatments resulting in complete clinical and radiographic resolution of her post-obstructive pneumonia. CONCLUSIONS: This case report not only supports existing literature on the use of cryotherapy for airway diseases but also presents a unique form of obstructing papilloma confined to an accessory bronchus, the only report of its kind based on extensive literature review.

Sequential 5-Aza 2'-deoxycytidine/depsipeptide FK228 treatment induces tissue factor pathway inhibitor 2 (TFPI-2) expression in cancer cells.

cDNA arrays were used to examine gene induction in CALU-6 and H460 lung cancer cells mediated by sequential 5-aza 2'-deoxycytidine (DAC)/depsipeptide FK228 (DP) exposure in order to identify translational end points for clinical trials evaluating these agents. In both cell lines, sequential DAC/DP treatment induced expression of tissue factor pathway inhibitor-2 (TFPI-2), an inhibitor of Factor VII: tissue factor signal transduction known to diminish the malignant phenotype of cancer cells. TFPI-2 expression was diminished or absent in 16 of 32 cell lines established from thoracic malignancies. Sequential DAC/DP treatment induced TFPI-2 in cancer cells deficient for TFPI-2 expression in the basal state. Promoter methylation coincided with loss of TFPI-2 expression in a number of cancer lines. TFPI-2 promoter methylation was observed in one of five pulmonary adenocarcinomas, and seven of seven esophageal adenocarcinomas, but not corresponding normal tissues. DP enhanced acetylation of TFPI-2-associated histones in CALU-6 cells. DP or PDBU, alone, induced TFPI-2 expression in cancer cells deficient for TFPI-2 expression in the absence of promoter methylation. In these cells, DP-mediated TFPI-2 induction was abrogated by calphostin. Induction of TFPI-2 by distinct, yet cooperative mechanisms involving chromatin remodeling and PKC signaling strengthens the preclinical rationale for sequential administration of DNA demethylating agents and HDAC inhibitors in cancer patients. Furthermore, induction of TFPI-2 may be a useful surrogate marker of treatment response in individuals receiving sequential DAC/DP infusions.

Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: activation of the mitochondria-dependent death-signaling pathway.

OBJECTIVE: Treating cancer cells with depsipeptide, a novel antitumor agent currently in a phase II clinical trial, causes potent upregulation of p21/WAF1 expression and cell arrest at G1 and G2 checkpoints. p21/WAF1 upregulation, however, impedes the ability of depsipeptide to induce significant apoptosis. This study was designed to determine whether flavopiridol, a synthetic cyclin-dependent kinase inhibitor known to inhibit p21 expression in tumor cells, could enhance depsipeptide-mediated apoptosis in cultured lung and esophageal cancer cells. METHODS: Lung or esophageal cancer cells were exposed to depsipeptide, flavopiridol, or a combination of depsipeptide and flavopiridol. Cytotoxicity and apoptosis were quantitated by means of (4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-based assays, respectively. Cytosolic cytochrome c levels, caspase 9 activity, mitochondrial membrane depolarization, and dependence of apoptosis on caspase 9 in treated cells were studied to determine the role of the mitochondria in mediating apoptosis induced by this drug combination. RESULTS: Flavopiridol completely abolished depsipeptide-mediated dose-dependent upregulation of p21/WAF1 expression. Combining flavopiridol with depsipeptide resulted in a 3- to 8-fold reduction of depsipeptide inhibitory concentration of 50% values that was closely paralleled by synergistic enhancement of apoptosis (4- to 10-fold higher than levels of cell death induced by either drug alone) in all cancer cell lines. The essential role of mitochondria in mediating cell death was indicated by robust translocation of cytochrome c from the mitochondria into the cytosol, 2.5- to 5-fold activation of caspase 9, severe disruption of mitochondrial inner membrane potential, and complete inhibition of apoptosis by the selective caspase 9 inhibitor. More important, this drug combination was not toxic to primary normal epithelial cells derived from the airway or skin. CONCLUSION: The depsipeptide plus flavopiridol combination exhibits powerful and selective cytocidal activity against cancer but not normal cells. Apoptosis induced by this combination is mediated by the mitochondria-dependent death pathway.

Juxtathyroidal neck soft tissue angiosarcoma presenting as an undifferentiated thyroid carcinoma.

Angiosarcoma is a malignant growth of endothelial origin, uncommon in the head and neck. We present the case of a 38-year-old woman with long-standing goiter who presented with a rapidly growing 6.0-cm neck mass. Fine-needle aspiration biopsy of the tumor showed features of "undifferentiated thyroid carcinoma (ThyrCa)." Total thyroidectomy resulted in extirpation of all gross disease. Pathology revealed a high-grade angiosarcoma of the neck invading the thyroid gland, coexisting with papillary ThyrCa (follicular variant) in the contralateral lobe. Aggressive external electron beam radiotherapy was initiated for local control. Despite the absence of systemic dissemination initially, bulky neck recurrences, and pulmonary metastases developed rapidly, leading to the patient's demise on postoperative day 41. Autopsy showed metastatic disease involving most organs. This case illustrates that neck angiosarcomas need to be considered in the differential diagnosis of "poorly differentiated" thyroid malignancies. These soft tissue neck tumors may complicate postoperative management due to their bleeding tendency and aggressive infiltrative behavior, and carry a dismal prognosis because of the rapidity of development of local recurrence and distant metastases.