Scott J. Stern

Orbital preservation in maxillectomy

Twenty-eight previously untreated patients with squamous carcinoma of the maxillary sinus underwent maxillectomy with preservation of the orbital contents at the M. D. Anderson Cancer Center between 1971 and 1986. Eighteen patients had part or all of the orbital floor resected; nine patients were treated with radiotherapy, and nine had surgery only. Only 3 of 18 patients in this group (17%) retained significant function in the ipsilateral eye. Furthermore, local recurrence in this group was common (44%), regardless of whether postoperative radiotherapy was used. Ten patients retained the bony orbital floor; If the radiation fields did not include the eye, problems were minimal. Strong consideration should be given to orbital exenteration at the time of surgery, when the orbital floor is resected — Especially if postoperative radiation fields will include the eye.

Osseointegrated implants in the head and neck cancer patient.

Osseointegrated implants allow patients with oromandibular defects to obtain complete or partial dentition via implant‐assisted or implant‐borne prostheses. Implants restore masticatory and occlusal function, improving oral intake and articulation. However, use of implants in head and neck cancer patients has been discouraged due to lack of data supporting their utility in these patients. This study attempts to establish the validity of using osseointegrated implants for dental restoration in head and neck cancer patients.

Cholesteatoma in the pediatric population: Prognostic indicators for surgical decision making†

A review of surgical therapy for pediatric cholesteatoma at the Arkansas Childrens Hospital was performed. Fifty‐three children treated surgically for cholesteatoma were studied over a 10‐year period. Primary acquired, or attic retraction cholesteatomas, were generally treated with a canal up tympanomastoidectomy; there were very few complications or secondary procedures in this group. Middle ear or secondary acquired cholesteatomas were initially treated by both canal up and canal down procedures; however, a large percentage of these patients eventually required an open cavity procedure. The presence of cholesteatoma in the sinus tympani strongly predicted failure to control disease with a canal up procedure (P < .05); conversely, the absence of matrix in the sinus tympani was predictive for success when a canal up procedure was used for attic cholesteatoma (P < .05). Finally, it was determined that follow‐up was not adequate in our patient population. With this in mind, guidelines for the management of pediatric cholesteatoma will be presented.

Neurotoxic Effects of Doxycycline Sclerotherapy

A patient experienced phrenic nerve paralysis after doxycycline sclerotherapy for treatment of chylous fistula at our institution. The purpose of this study is to use physiologic testing to determine whether doxycycline is capable of inducing defects in neural function. A nonrandomized, controlled trial was performed with nerve-conduction studies to determine possible deleterious effects of doxycycline sclerotherapy. Thirty-eight CD rats were used and separated into four groups. Doxycycline was applied to the sciatic nerves of rats by either topical application directly on the nerve or by intraneural injection. Nerve-conduction studies were done before surgery and at 1,7, and 21 days after surgery. The results showed a statistically significant decrement in nerve-conduction velocity and strength of transmitted impulse in those nerves injected with doxycycline solution. Complete nerve block was seen frequently. This effect was not seen with topical application of doxycycline or normal saline solution or with intraneural injection of normal saline solution. This study demonstrates that doxycycline can induce a marked decrement in neural function when applied to the subepineural layers of the sciatic nerve in the rat. Therefore doxycycline sclerotherapy should be used with great caution in situations in which it could become exposed to nerves that have sustained surgical trauma.

Photodynamic Therapy with Chloroaluminum Sulfonated Phthalocyanine in the Rat Window Chamber

The efficacy of photodynamic therapy tumor destruction is dependent upon both the interruption of the tumor vasculature and the resultant production of unstable oxygen species causing cellular oxidation and death. Chloroaluminum sulfonated phthalocyanine (CASP) is a recently developed photosensitizer. In order to study the direct vascular effects of CASP on a non-tumor system, a rat window chamber was utilized. Twelve rats were implanted with the window chamber, and were divided into two groups of six. Three rats served as controls for each group (receiving light alone, CASP alone, or no treatment). The remaining 6 rats received 10 mg/kg CASP intravenously 4 days after chamber placement. Photoactivation with light was performed 24 hours after injection (power density 200 mW/cm2, irradiance 100 J/cm2, lambda = 675 nm). Utilizing integrating sphere measurements and image analysis, marked vascular changes in the form of initial vasospasm followed by vaso-constriction and loss of chamber neovascularization were noted in the CASP-PDT group. The control groups exhibited no significant changes. Manipulation of the chamber vasculature at strategic time-points may translate into improved response rates for photodynamic therapy in a tumor model.

Histologic effect of doxycycline sclerotheraphy on rat femoral nerve

This study stems from an encounter with a phrenic nerve paralysis in a patient following doxycycline sclerotherapy for treatment of chylous fistula. The purpose of this study is to identify possible histologic evidence of doxycycline‐induced nerve injury.

Salivary gland tumors.

Salivary gland cancers continue to pose both diagnostic and treatment dilemmas. Over the past year, a great deal has been written concerning salivary gland tumors in children, fine needle aspiration for salivary gland neoplasms, prognostic factors, and pathologic evaluation and treatment. Some of the more important findings include imaging studies and approaches to the human immunodeficiency virus-positive patient with parotid enlargement, the molecular biology of salivary cancer, and the pitfalls of fine needle aspiration cytology. The necessity of facial nerve sacrifice in parotid surgery for malignancy is debated, and the classification of tumors is clarified.

Er:YAG laser-induced changes in skin in vivo and transdermal drug delivery

It has been shown that laser ablation of stratum corneum, in vitro, can result in an increased uptake of topically applied pharmaceuticals. We have performed measurements of drug permeation, using an in vitro model of human skin, that involves a portable Er:YAG laser used to ablate the stratum corneum. For the first time, this method of drug administration was tested in vivo in human volunteers, whereby a hydrocortisone blanching assay was used to assess the efficiency of the procedure. The results show that this is a safe and efficient way to ablate stratum corneum for the purpose of enhanced transcutaneous drug administration.

Photofrin and 5-aminolevulinic acid permeation through oral mucosa in vitro

Photofrin and 5-aminolevulinic acid are photosensitizers that show promise in the photodynamic treatment of cancer, port-wine stains, atherosclerosis and viral lesions. Photofrin is a mixture of porphyrins which, upon the absorption of light, become temporarily cytotoxic. One side-effect associated with the use of Photofrin is long-term cutaneous photosensitivity. It is possible that topical application of this photosensitizing dye will ameliorate such a side-effect. Another way to avoid the cutaneous photosensitivity in photodynamic therapy is to use 5- aminolevulinic acid, which is a porphyrin precursor that causes an increase in the synthesis and concentration of the photosensitizer protoporphyrin IX. 5-aminolevulinic acid is usually applied topically, and so minimizes cutaneous photosensitivity while maximizing the local protoporphyrin concentration. There are a host of disorders in oral mucosa that are potentially treatable by photodynamic therapy. However, since stratum corneum presents an impermeable barrier to many pharmaceuticals, it is not clear that topical application of the photosensitizer will result in a clinically relevant tissue concentration. We have therefore studied the permeation behavior of Photofrin and 5-aminolevulinic acid by applying them to the surface of ex vivo oral mucosa tissue positioned by a Franz diffusion cell. In order to increase the permeability of the photosensitizer across the stratum corneum, we studied the effects of four different drug carriers: phosphate buffered saline, dimethylsulfoxide, ethanol and Azone with isopropyl alcohol.

An implantable tumor-window chamber model for the study of photodynamic therapy.

In order to study both the anti-tumor effects and early vascular events in photodynamic therapy, a useful animal model has been developed. A window chamber is surgically placed on the dorsum of the Fischer-344 rat, and 500-μm fragments of the rat mammary adenocarcinoma 13672 are placed under direct vision into the subcutaneous tissue. Implantation of the chamber has been successfully completed in more than 50 rats. The operative procedure Is straightforward and is accomplished in less than 1 hour. Using tumor fragments, tumor viability has been 60%. We have demonstrated obvious and reproducible neovascularization occurring as soon as 1 day after implantation. The application of this system to an experimental protocol comparing the photosensitizes dihematoporphyrin ether (DHE) and chloroaluminum sulfonated phthalocyanine (CASP) has yielded important information on early vascular events resulting from photodynamic therapy.