James H. Hill

PHOTODYNAMIC THERAPY OF HEAD and NECK SQUAMOUS CELL CARCINOMA: OPTICAL DOSIMETRY and CLINICAL TRIAL

Abstract This paper reports the retrospective comparison of a PDT dosimetry model with the current results of an ongoing clinical trial on photodynamic therapy (PDT) for head and neck squamous cell carcinoma (HNSCC). The model is based on the assumption that tumor eradication requires a minimum absorption of radiant energy by the tumor‐localized porphyrins. The diffusion approximation was employed to calculate the incident light dose required to attain the minimum absorbed energy density at tumor boundaries most distant from the light source. Dosimetry tables for HNSCC were calculated with estimated tissue parameters, giving the PDT light dose for front surface exposure (FS) and illumination by interstitial cylindrical diffuser fibers (CI) in terms of the tumor dimensions. The model includes a correction for the photobleaching of the localized photosensitizer by the therapeutic light. The PDT trial was carried out on nine patients with previously untreated or recurrent early stage tumors and one patient with a recurrent advanced stage tumor. A complete response was obtained in 83% (10/12) of the sites treated. The calculated doses for FS and CI exposures vary from comparable with to three‐fold lower than the actual doses for each complete response tumor site.

Primary mandibular reconstruction using the ao reconstruction plate

Primary reconstruction of segmental defects of the mandible following cancer resection remains a major problem. In 1976, a stainless steel plate was developed by AO/ASIF (Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation) for mandibular reconstruction. This plate completely stabilizes both mandibular stumps without the need for intermaxillary or external fixation. In addition, when bone grafting is performed, the design of this plate promotes revascularization by allowing maximal contact between grafted cancellous bone and surrounding soft tissue.

Panendoscopy in screening for synchronous primary malignancies.

The entire upper aerodigestive tract must be evaluated at the time of initial tumor evaluation in patients with squamous cell carcinoma of the head and neck. The necessity of panendoscopy (laryngoscopy, bronchoscopy, esophagoscopy) in this evaluation has not been demonstrated convincingly. Between January 1, 1984 and December 31, 1985, 208 patients with previously untreated squamous cell carcinoma of the head and neck were analyzed prospectively. These patients underwent head and neck examination, chest radiograph, barium esophagram, and panendoscopy. Fifteen (7.2%) had synchronous malignancies of the upper aerodigestive tract. In four patients (1.9%) the synchronous primary tumor was found only by endoscopy. Three patients (1.4%) had cancers of the hypopharynx. One patient (0.5%) had a bronchial cancer detected only on bronchoscopy. No tumors were detected by esophagoscopy that were not also seen on barium esophagram. We conclude that endoscopic examination of the hypopharynx is very helpful in screening for additional tumors in head and neck cancer patients, but routine esophagoscopy cannot be supported. Screening bronchoscopy cannot be strongly supported due to its very low yield.

The conservation neck dissection

This study compares the neck tumor recurrence rate between patients treated with radical neck dissection and those treated with conservation neck dissection. A standard radical neck dissection modified by sparing at least the internal jugular vein or the spinal accessory nerve is defined as a conservation dissection. Six hundred ninety‐one neck dissections performed on 631 patients in the Department of Otolaryngology‐Head and Neck Surgery of the University of Illinois College of Medicine at Chicago were reviewed retrospectively. All patients had been followed postoperatively for at least 24 months. Group I consisted of 422 radical neck dissections. Group II contained 269 conservation neck dissections.

Enlargement of the vestibular aqueduct.

Enlarged vestibular aqueduct, a recently identified anomaly, is typified by an enlarged vestibule, dilation of the ampullated portions of the horizontal and superior semicircular canals, an abnormal cochlea, and hearing loss. In the case described a 16-year-old boy had congenital hearing loss, episodic vertigo, and abnormal vestibular function testing. Tomograms and CT scans confirmed the diagnosis of bilaterally enlarged vestibular aqueducts. The vertiginous episodes decreased in frequency and severity with a no-salt-added diet. The authors conclude that the enlarged vestibular aqueduct is associated not only with other structural inner ear abnormalities and hearing loss, but also with abnormal vestibular function.

Dynamic computerized tomography in the assessment of hemangioma

Three hemangiomas of the face and orbit are studied with dynamic computerized tomography (CT). This noninvasive technique has the advantage of simultaneous bone and soft tissue visualization at the time of peak contrast enhancement, and it precludes the potential complications of arteriography and biopsy. The hemangiomas are precisely delineated with intense contrast; the sharp peak and rapid uninterrupted runoff of the computer-generated plot of contrast concentration (CT number) versus time is characteristic of this lesion. It is suggested that the progress of hemangioma involution may be documented by the change in contrast distribution in sequential dynamic CT studies. Dynamic CT is recommended for the evaluation of head and neck vascular tumors.

A phase II study of adriamycin in previously untreated squamous cell carcinoma of the head and neck

Twenty patients with squamous cell carcinoma of the head and neck (SCC H/N) were treated with Adriamycin (doxorubicin) at a dosage of 60 mg/m2 at 3‐week intervals. No patient had received surgery, radiation, or chemotherapy before treatment with Adriamycin. Responses were observed in 44% of 18 evaluable tumors. We conclude that Adriamycin is a highly active drug in SCC H/N when no prior treatment has been administered.

Primary culture of squamous head and neck cancer with and without 3T3 fibroblasts and effect of clinical tumor characteristics on growth in vitro.

Twenty‐one tumors from patients with squamous cell carcinoma of the head and neck (SCC H/N) were cultured with and without 3T3 fibroblasts in order to determine whether, on the basis of improved tissue culture medium, 3T3 cells could be deleted without altering growth and cloning efficiency. Thirty‐five additional primary SCC H/N specimens, cultured in the presence of 3T3 fibroblasts, were studied to assess the effect of tumor differentiation, site of primary tumor, and site of specimen procurement on growth. The authors conclude that 3T3 cells remain essential for optimal growth and cloning efficiency. Also, 3T3 cells improved the number of successful cultures by 33% to 100% depending on the plating density, and cloning efficiency was improved by 50% in the presence of 3T3 cells. Growth did not correlate with tumor differentiation or site of origin of the tumor specimen. Culture of specimens from the primary site resulted in growth significantly more frequently than culture of specimens obtained from metastatic neck nodes.

Light dosimetry in animal models: Application to photodynamic therapy in otolaryngology

Photodynamic therapy (PDT) for treatment of head and neck cancer uses a photoactive compound that is illuminated with 630 nm (red) light. The effectiveness of PDT depends on the penetration of light into tissue that is both tissue and wavelength dependent. The characterization of the optical properties of an animal oral mucosa and skin has been done to determine the amount of light below these tissues available to be used for photodynamic therapy. The tissue absorbance of visible light from 400 nm to 700 nm has been determined in vitro for hamster cheek pouch mucosa and for athymic mouse skin. The pattern of absorbance is similar for both tissues and demonstrates greater transmission at the longer wavelengths. The diffuse transmittance of light in vivo for these animal models was measured with an interstitial fiberoptic probe. At 630 nm the diffuse transmittance for nude mouse skin averages 10% of the incident light energy, and that for the hamster mucosa almost 50% of the incident light energy.

Fluorescent microscopy of hematoporphyrin derivative in the nude mouse tumor model

Mechanisms for localization of hematoporphyrin derivative (HPD) within malignant tissue and for tumor necrosis after photodynamic therapy have not yet been established with certainty. We describe a modified freeze-drying technique to study these mechanisms. Normal tissues and squamous cell carcinoma xenografts were examined in nude mice after administration of HPD. Skin reveals marked fluorescence in connective tissue cells. No fluorescence is visible in surface epithelial cells or keratin. Liver shows diffuse fluorescence only in cells lining sinusoids. In tumor, malignant cells do not fluoresce and connective tissue cells fluoresce brilliantly. This technique provides a clear view of HPD fluorescence, frozen instantaneously in location and time. Fluorescence from connective tissue cells in skin and tumor suggests that localization and photodynamic action may be targeted in part at cells that critically support malignant epithelial cell growth as well as at malignant epithelial cells directly.