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A new experimental therapy for squamous carcinoma was tested by sensitizing human tumor cells with light-sensitive anticancer drugs followed by laser illumination at visible or infrared wavelengths. The anthrapyrazole DUP-941 and the isoquinoline derivative DUP-840 were compared with the dianthraquinone hypericin. P3 human squamous carcinoma cells were incubated for 2 h with the drugs at escalating doses ranging from 5 to 100 micrograms/ml, then exposed to visible green 532-nm or infrared 1064-nm light at 300 J output from a KTP/Nd:YAG laser. Tumor cell toxicity measured by in vitro MTT viability assays was minimal after DUP-840 uptake but was slightly enhanced by infrared laser emissions. By contrast, the strong tumoricidal effects seen after DUP-941 uptake were amplified over 10-fold by 532-nm light and up to 2-fold by 1064-nm light. Hypericin-sensitized tumor cells were killed after 532 nm irradiation even at the lowest drug dose but were not affected by 1064-nm illumination. The results suggest that laser chemotherapy with drugs sensitive to photothermal energy could become a useful new treatment modality for cancer.

Photodynamic therapy (PDT) with lasers and new dyes has gained popularity in recent years as a minimally invasive technique with high tumoricidal effects in vitro and in some cancer patients. However, because new laser dyes are not FDA approved at present, the clinical evaluation of PDT may be years away. During the past 6 years we have used laser alone for photothermal ablation in both preclinical studies and in a large number of patients with an observed 60% tumor response rate. The 40% treatment failure led us to explore the possibility of combined therapy with lasers and standard chemotherapeutic drugs. We have recently tested a promising preclinical alternative using implantation of a bare 600-microns KTP 532 laser fiberoptic in multiple tumor sites 30 min after intratumor injection of the anthrapyrazole DUP-941. As a control, this drug was injected in 3 sites of P3 human squamous cell tumor transplants in nude mice, which led to tumor stasis without regression. Similar 400-600 mm3 tumors exposed to laser illumination alone (0.8 W for 5 sec) at multiple sites resulted in tumor regrowth after 10 weeks in 80% of the animals. However, combining interstitial laser illumination with intratumor DUP-941 injections led to complete tumor regression in 85% of the mice. We propose that intratumor drug injection followed by interstitial laser fiberoptic treatment represents a potentially useful new method for tumor ablation in advanced cancer patients.

Imaging-guided palliative therapy of recurrent and/or inaccessible head and neck tumors may soon become clinically practical since sensitive and noninvasive monitoring techniques of energy deposition in tissues are now available. Interstitial tumor therapy (ITT) is a technique whereby a source of energy (laser, radiofrequency, ultrasonic, cryoenergy, etc.) is directly applied into tumors at various depths. Recent studies have demonstrated the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real and/or "near" real time tumor and vessel identification as well as monitoring and quantifying energy-induced tissue damage. We now report our initial clinical experience with patients in which UTZ and/or MRI-guided ITT techniques were successfully applied for the treatment of recurrent, nonresectable, local, and/or metastatic head and neck carcinomas. Patients were treated on an outpatient basis either in the operating room or in an upgraded specially equipped SIGNA 1.5T MR suite. Most patients tolerated these procedures well and were successfully palliated for periods ranging from 3 months to 5 years posttreatment. The upgrades introduced in a standard MRI suite, the clinical experience, and future perspectives will be reviewed.

Extramedullary plasmacytomas (EMP) constitute only 1% of all head and neck malignancies, with the vast majority occurring in the upper respiratory tract. The diagnosis of laryngeal EMP can be difficult since the symptoms are non-specific and the tumor usually mucosally covered. This paper discusses the successful combination of jet Venturi ventilation technique with suspension microlaryngoscopy and contact Nd:YAG laser for tissue diagnosis in a patient presenting with a large subglottic mass. Previous attempts using standard endotracheal intubation and forceps technique for biopsy failed to reach the diagnosis and resulted in significant bleeding from the biopsy site. A review of the disease and technique is presented.

Syringomas are benign tumors of eccrine origin that occur primarily in the lower eyelid region of females. Since they do not involute and are typically refractory to conventional forms of therapy, they may grow to become considerable, chronic cosmetic and functional deficits. The current study reports on a patient with familial syringomas, previously refractory to two different standard therapies, who was successfully treated with the superpulsed CO 2 laser. A simple, accurate, and reproducible method of dosimetry of laser energy was used to treat these lesions with the Sharplan 700 CO 2 laser connected to the operating microscope. Each lesion was irradiated separately with single pulses at a calculated energy density of 1 J/cm 2. Superficial scabbing was observed 1 week postoperatively, with no edema or pain. Mild erythema persisted for 1 month, with complete healing thereafter. No recurrences were noted after a 2 year follow-up. There was no evidence of scarring, ectropion, or changes in pigmentation. The disease and methods of treatment are reviewed.

Interstitial laser phototherapy (ILP) is a technique whereby laser energy is directly applied into tumors at variable depths. This technique is attractive, since it is minimally invasive and carries a low morbidity. It may allow treatment of deep and difficult to reach tumors in the head and neck and other areas when improved noninvasive monitoring techniques of laser-tissue interactions are developed. Recent studies demonstrate, respectively, the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real time interstitial needle placement in tumors, identification of vessels, monitoring and quantifying laser-induced tissue damages. We present a case in which a patient with recurrent, metastatic base of skull carcinoma has managed successfully with repeat ILP using MRI and UTZ guidance. Under heavy sedation, needles were placed in the tumor using MRI or UTZ guidance. Tumors were treated with a 600 mum flexible Nd:YAG laser fiberoptic passed through the needles. Laser-induced tissue photoablation was monitored using real time color flow Doppler UTZ or near real time fast spin-echo T2-weighted MRI. Posttreatment fine needle aspiration cytologic study demonstrated the presence of cellular debris and no viable cancer cells. Posttreatment follow-up MRI scans showed significant reduction of tumor size, and positron emission tomography (PET) revealed interval decrease in tumor metabolism. Treatments were accompanied by pain relief and improved functional abilities. ILP has now evolved into minimally invasive outpatient surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adriamycin and daunomycin anticancer drugs are detectable in leukemias and solid tumors by cell fluorescence. We observed initial cytoplasmic fluorescence followed by slow nuclear localization of adriamycin and daunomycin after incubation with cultured human squamous cell (P3, FADU) and adenocarcinoma (HT29, SW620) lines by digital video imaging microscopy. Tumor cells incubated with 10 mug/ml of these drugs exhibited increased uptake for more than 3 h with intracellular levels in the range 0.5-2.5 mug/10 6 cells measured by dimethyl sulfoxide (DMSO) extraction and fluorescence spectrophotometry. Daunomycin had 10- to 100-fold higher toxicity for these carcinoma cells than for normal human epithelial keratinocytes measured by in vitro MTT tetrazolium assays. The viability of daunomycin-sensitized carcinoma cells was decreased 2- to 10-fold further by argon laser illumination at 488 nm (5W, T max = 8 degrees C) for 2-3 minutes. The results suggest that adriamycin derivatives may be useful targeting agents for adjuvant treatment and chemophototherapy of human solid tumors by MR-guided laser fiberoptic endoscopy.

Attempts to improve human tumor detection by non-radioactive magnetic resonance techniques have led several investigators to develop antibody-linked paramagnetic contrast agents. Initial studies focused on gadolinium conjugated to monoclonal antibodies. However, very high levels of this contrast agent were needed to significantly reduce proton relaxation times and obtain improved MR images. The use of magnetite (Fe 3O 4) as an MR contrast agent provides a magnetic moment that is approximately one order of magnitude larger than gadolinium. In this study monoclonal antibodies 44 x 14 (specific for squamous cell carcinoma) and 436G10 (specific for melanoma) were obtained from ammonium sulfate precipitation of tumor ascitic fluid. Equal volumes of magnetite solution (1.87 mg Fe/ml) and antibody solution 44 x 14 (5.24 mg protein/ml) and 436G10 (0.64 mg protein/ml) were mixed and sonicated. The 44 x 14-magnetite and 436G10-magnetite solutions were then added to equal volumes of M20 and P3 squamous cell carcinoma cell lines. T1 and T2 values were obtained on a Praxis II NMR spectrometer equipped with a 10 mm probe and 0.25 Tesla permanent magnet. The T2 relaxation times of the magnetite-antibody-cell mixtures were 31 ms with an R = 0.985 for both experimental samples. Our results demonstrate a significant decrease in T2 by binding of the magnetite-coated antibodies to these melanoma and carcinoma cells in vitro. The possibility of detecting subclinical local and metastatic disease with magnetite linked to monoclonal antibodies followed by MRI guided laser tumor ablation therapy may render this technique clinically attractive for treatment of deep-seated tumors.