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Biomedical subjects

Mark Varvares

Publications and source records attributed to Mark Varvares.

6 recordsLinked to original sources
PubMed2006

Proton beam radiation therapy for skull base adenoid cystic carcinoma.

OBJECTIVE: To determine the treatment outcome and prognostic factors in patients with adenoid cystic carcinoma of the skull base treated with proton beam radiation therapy. DESIGN: Retrospective analysis. SETTING: Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary, and Harvard Medical School, Boston. PATIENTS: From 1991 to 2002, 23 patients with newly diagnosed adenoid cystic carcinoma with skull base extension were treated with combined proton and photon radiotherapy. There was tumor involvement of the sphenoid sinus in 61% of patients (14), nasopharynx in 61% (14), clivus in 48% (11), and cavernous sinus in 74% (17). The extent of surgery was biopsy alone in 48% (11), partial resection in 39% (9), and gross total resection with positive margins in 13% (3). The median total dose to the primary site was 75.9 cobalt-gray equivalent. The median follow-up of all surviving patients was 64 months. MAIN OUTCOME MEASURES: Locoregional control and disease-free survival and overall survival rates. RESULTS: Tumors recurred locally in 2 patients at 33 and 68 months, respectively. No patients developed neck recurrence. Eight patients had distant metastasis as the first site of recurrence. The local control rate at 5 years was 93%. The rate of freedom from distant metastasis at 5 years was 62%. The disease-free and overall survival rates at 5 years were 56% and 77%, respectively. In multivariate analysis, significant adverse factors predictive for overall survival were change in vision at presentation (P = .02) and involvement of sphenoid sinus and clivus (P = .01). CONCLUSIONS: High-dose conformal proton beam radiation therapy results in a very encouraging local control rate in patients with adenoid cystic carcinoma of the skull base. Changes in vision at presentation and tumor involvement of the sphenoid sinus and clivus are important prognostic factors.

Adult↗
PubMed2006

Successful myoblast transplantation in rat tongue reconstruction.

BACKGROUND: Controversy exists regarding the success of myoblast transplantation. The purpose of this study was to determine the survival of transplanted myoblasts in a rat tongue reconstruction model by using fluorescently labeled myoblasts and surgical stains to mark the location of the pocket into which transplanted cells were delivered. We evaluated tongue histology after myoblast transplantation under the hypothesis that myoblast transplantation will promote muscle regeneration and result in minimal scar tissue formation. METHODS: Sterile solutions of 1:10 India ink, 1% methylene blue, and 1% crystal violet were applied to the inner lining of a left-sided mucosa-sparing hemiglossectomy pocket. After air-drying, the hemiglossectomy defect was filled with collagen gel and closed. The tongues were evaluated histologically at 6 weeks. Next, myoblasts were cultured and labeled with three commercially available fluorescent dyes, 5-chloromethyl-fluorescein diacetate (CMFDA), chloromethylbenzamido (CM-DiI), and fluorescently labeled microspheres (FLMs), to determine which would optimally label myoblasts in a tongue reconstruction model. Next, Lewis rats underwent left hemiglossectomy, and the created pockets were coated with 1:10 India ink. Control animals received collagen gel alone, whereas experimental animals received labeled myoblast/collagen constructs into the tongue defect. Tongues were harvested at intervals to determine the presence of labeled fluorescent cells, the relative numbers of viable myoblasts, and the degree of scarring. RESULTS: India ink coating of the hemiglossectomy pocket caused minimal inflammation and lasted longer than the other tested dyes. CMFDA and FLMs both successfully label myoblasts for transplantation. In vivo, donor cells were observed in all specimens at week 0 with increasing numbers of cells and muscle formation, determined by desmin immunofluorescence, after 6 weeks. There was less scar tissue contracture in the experimental group and a significant increase in the amount of desmin-stained muscle in the surgical defect. CONCLUSIONS: India ink is an appropriate vehicle for intra-operative marking of a hemiglossectomy cavity. The introduction of myoblast/collagen constructs into the rat hemiglossectomy defect increases the amount of regenerated muscle, results in less scar contracture, and may increase meaningful tongue function.

Animals↗
PubMed2003

Tissue engineered muscle implantation for tongue reconstruction: a preliminary report.

OBJECTIVES/HYPOTHESIS: Because current tongue reconstructive methods introduce adynamic, variably sensate tissue into the mouth, the critical functions of the tongue in articulation and deglutition may be compromised. The objective of this work was to introduce a combination of myoblasts and scaffolding material into rat hemiglossectomy defects and to examine the extent of neomuscle formation in the reconstructed area, under the hypothesis that the presence of myoblasts leads to formation of new muscle. STUDY DESIGN: Randomized, prospective animal study. METHODS: Myoblasts were harvested from neonatal Lewis rats, and a growth factor enriched collagen gel was prepared. Syngeneic adult animals received either hemiglossectomy alone or reconstruction with one of four experimental reconstructive preparations: collagen gel alone, collagen gel with suspended myoblasts, the gel-cell combination in undifferentiated muscle construct form by way of tissue culture for 7 days in a preformed mold, or differentiated constructs, cultured in myoblast fusion medium. After 6 or 16 weeks, animal weight gain was recorded, animals were killed, and the tongues harvested. The tissue was examined histologically, and quality of the muscular regenerate was rated on a scale according to predefined criteria. RESULTS: Animals in all groups gained weight appropriately. In groups receiving hemiglossectomy alone or acellular (gel only) reconstruction, there was significant scarring and lack of neomuscle formation. In groups receiving myoblast transplantation, either by way of gel suspension or in the form of undifferentiated or differentiated constructs, muscle quality was superior to controls. CONCLUSIONS: Myoblast transplantation into hemiglossectomy defects appears to lead to new muscle formation and does not inhibit normal weight gain in animals after tongue implantation.

Animals↗
PubMedDate not supplied

Muscle tissue engineering for partial glossectomy defects.

BACKGROUND: Tongue reconstruction represents a difficult reconstructive problem, based on the tongue's complex multimodality function. Existing methods of tongue reconstruction often result in significant deficits in speech and deglutition. A functional neotongue requires adequate soft tissue bulk and restoration of coordinated muscle function. Tissue engineering, a scientific approach that allows introduction of isolated cell populations of interest within 3-dimensional polymer scaffolds to create new tissue, may allow the generation of more highly functional tissue in tongue reconstruction. OBJECTIVES: To apply muscle-tissue engineering techniques in the reconstruction of partial glossectomy defects in rats, and to compare the gross and histological nature of tissue found after reconstruction of the hemiglossectomy defect with acellular vs tissue-engineered composite material. MATERIALS AND METHODS: Thirty mature Lewis rats underwent a left-sided mucosa-sparing partial glossectomy. The defects were then filled with 1 of the following 3 substances: isotonic sodium chloride solution, a collagen-rich hydrogel, or hydrogel containing a suspension of neonatal myoblasts from syngeneic rats. The animals were killed after 6 weeks and the tongues were harvested. The control and operated-on tongue halves were evaluated for weight differences and histological features. RESULTS: The group receiving the hydrogel-myoblast composite injections demonstrated a statistically significant increase in tongue weight of the operated-on side compared with the control side. In contrast, the isotonic sodium chloride solution and hydrogel groups demonstrated loss of tongue weight. These findings correlated with the results of the histological evaluation. Hemitongues from the composite group demonstrated formation of new tissue with areas of musclelike tissue extending from islands of residual hydrogel, and we found evidence of neovascularization and possible neurotization. In contrast, the isotonic sodium chloride solution group exhibited dense fibrous scar with loss of muscle architecture and dramatic loss of tongue volume. The hydrogel group demonstrated preservation of tongue volume with persistent islands of gel, but no clear evidence of new tissue formation. CONCLUSIONS: The introduction of a hydrogel into the rat hemiglossectomy pocket appears to promote volume preservation and/or muscle regeneration. The addition of myoblasts suspended in collagen gel supports the development of new tissue that preserves weight and volume after hemiglossectomy and may possess muscle properties similar to the tissue desired. This tissue-engineering approach represents a promising new strategy in tongue reconstruction and merits further investigation into the possible functional advantages it offers compared with current techniques.

Animals↗