Search PubMed⌕ Search

Biomedical subjects

Michael Lanuti

Publications and source records attributed to Michael Lanuti.

3 recordsLinked to original sources

Carinal resection.

There are many challenges in performing carinal resection and, in particular, reconstruction. A better understanding of the safe limits of resection has contributed to the reduced mortality from anastomotic complications. Accurate selection of patients, a meticulous adherence to surgical precision, and optimal postoperative patient care have become mandatory to reduce the risk of the most serious complications, such as noncardiogenic pulmonary edema and suture dehiscence. With carinal resection for bronchogenic carcinoma, contemporary studies suggest that there are reasonable survival rates in the absence of involved mediastinal lymph nodes or distant metastatic disease. The role of neoadjuvant therapy for bronchogenic carcinoma involving the carina deserves further investigation; this type of therapy should be used with caution because of the deleterious effects on anastomotic healing.

Anastomosis, Surgical↗

Management of complications of tracheal surgery.

Basic principles of tracheal reconstruction, which were introduced in the 1960s and 1970s, served to reduce the prevalence of many complications. These principles include thorough preoperative assessment (endoscopic and radiologic) of the tracheal anatomy and glottic function, avoidance of excessive anastomotic tension, preservation of tracheal blood supply, and meticulous dissection and anastomosis. The tracheal surgeon should have access to expert help in radiology and anesthesiology, experienced nursing units, and the help and advice of consultants, especially otolaryngologists. The surgical approach should be meticulously planned. No irreversible maneuvers should be performed until one establishes certainty to proceed to resection. The surgeon should not attempt to exceed the limits of what appears to be reasonably possible. It must be remembered that a permanent tracheal T-tube might be the best solution for a patient with extensive tracheal damage that would defy reconstruction.

Humans↗

Adenovirus-mediated gene transfer of enhanced Herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killing.

The Herpes simplex virus 1 (HSV) thymidine kinase (tk) suicide gene together with ganciclovir (GCV) have been successfully used for the in vivo treatment of various solid tumors and for the ablation of unwanted transfused stem cells in recent clinical trials. With the aim of improving this therapeutic system, we compared the potential efficacy of adenoviral (Ad) vectors expressing enhanced tk mutants in vitro and in vivo. The previously created HSV-tk mutants dm30 and sr39, created by random sequence mutagenesis, were inserted into a standard Ad.RSV E1(-)E3(-) backbone using homologous recombination. GCV killing of Ad.HSV-tk, Ad.dm30-tk and Ad.sr39-tk was assessed in various tumor cell lines with a cell proliferation assay. Cells expressing the two TK mutants were two-to-five-fold more sensitive to GCV when compared with Ad.HSV-tk transduced cells in all cell lines tested (five human mesotheliomas, one human lung cancer, a human cervical carcinoma, a mouse fibrosarcoma, and a rat glioma line) at equal TK expression levels. Flank tumor models, including cell-mixing studies, assessed the in vivo efficacy of the engineered viruses in BALB/C and SCID mice. In all animal studies, Ad.dm30-tk and Ad.sr39-tk showed more tumor growth inhibition than Ad.HSV-tk when GCV was administered. The use of adenovirus-mediated gene transfer of both tk mutants dm30-tk and sr39-tk for cancer suicide gene therapy should provide a more effective and safer alternative to wild-type HSV-tk.

Adenoviridae↗