Squamous Cell Cancer

Endoscopic Treatment of Early Gastroesophageal Malignancy: Stomach Lesions

Author(s): Vanessa M. Shami, MD, Irving Waxman, MD

Photodynamic Therapy
Patients are given a light-sensitizing agent incorporated preferentially into cancer cells. Next, a laser probe that emits a low-frequency laser light beam and activates the drug by light of a specific wavelength matched to its absorption spectrum is inserted and causes intracellular free radical formation and cellular destruction of the sensitized tissue. Photodynamic therapy has been applied as experimental treatment in early superficial squamous cell esophageal cancer and in premalignant changes associated with Barrett esophagus.

Hematoporphyrin derivative was the first photosensitizer tested. Endoscopy is performed 2 to 3 days after intravenous administration, when the concentration of the dye between tumoral and healthy tissue is believed to be at its peak. Photofrin (Lederle Pharmaceuticals, Carolina, Puerto Rico), a more purified form, is the only photosensitizer that has received US Food and Drug Administration approval for use in the esophagus. The major problem is the long-term skin photosensitization of 60 to 90 days. A new second-generation photosensitizer being used in trials is 5-ALA. It is administered orally 4 to 6 hours before endoscopy and has the advantage of limiting skin photosensitization to 2 days.

Radu et al. pooled 164 patients from 11 studies who have received photodynamic therapy for superficial squamous cell cancer of the esophagus. A complete response was noted in 50 to 100% of patients, with follow-up that ranged from 1 to 96 months. Major complications such as fistula formation, perforation, and stenosis were seen in 20 (12.2%) of 164.

Ackroyd et al. randomly selected 36 patients with dysplastic Barrett esophagus to receive 5-ALA or placebo. In the photodynamic therapy group, no dysplasia was seen in the columnar epithelium 6, 12, and 24 months later. In contrast, in the placebo group, 12 of 18 patients had persistent low-grade dysplasia. Overholt et al. used photodynamic therapy (sodium porfimer) to treat 100 patients with Barrett and high-grade dysplasia (HGD) or superficial cancer. Squamous re-epithelialization occurred in 75 to 80%, with complete elimination of Barrett mucosa in 43 patients. Dysplasia was eliminated in 78 patients and 10 of the 13 malignancies. In a recent preliminary report, Overholt et al. examined patients with HGD in Barrett esophagus and randomized them to receive photodynamic therapy and omeprazole at 20 mg twice daily (n = 138) or omeprazole alone (n = 70). Those in the photodynamic therapy group received a maximum of three courses. At 6-month follow-up, histologic ablation of HGD was significantly higher in the photodynamic therapy group than in those treated with omeprazole alone (80% vs 40%). Furthermore, at 1 year, there was a trend toward fewer patients with disease progression in the photodynamic therapy group. Gossner et al. reported use of photodynamic therapy in 32 patients with HGD or esophageal cancer using 5-ALA. Dysplasia was eradicated in all ten of ten patients, and mucosal cancer was eradicated in 17 (77%) of 22 at a mean follow-up of 10 months.

There have been no prospective head-to-head trials comparing photosensitizers in early superficial cancer. Maier et al. did report higher success in improving dysphagia, stenosis, and overall performance status in 27 patients who received a hematoporphyrin derivative versus 5-ALA. There have been reports that genetic abnormalities may persist with photodynamic therapy despite phenotypical improvement of dysplasia (aneuploidy, p53 protein overexpression, p53 mutations, and p16 promoter hypermethylation). Again, further studies are needed.


Study of the efficacy of 5 ALA-mediated photodynamic therapy on human larynx squamous cell carcinoma (Hep2c) cell line

Author(s): Khursid, A.; Atif, M.; Firdous, S.; Zaidi, S.; Salman, R.; Ikram, M.

Photodynamic Therapy
5-aminolevulanic acid (ALA), a precursor of Protoporphyrin IX, was evaluated as an inducer of photodamage on Hep2c, human larynx squamous cell carcinoma, cell line. Porphyrins are used as active cytotoxic antitumor agents in photodynamic therapy (PDT). The present study evaluates the effects of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) using human larynx cells as experimental model. Hep2c cell line was irradiated with red light (a diode laser, λ = 635 nm). The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the cellular viability of Hep2c cells were studied. The optimal uptake of photosensitizer ALA in Hep-2c cells was investigated by means of spectrometric measurement. Cells viability was determined by means of neutral red assay (NR). It was observed that sensitizer or light doses have no significant effect on cells viability when studied independently. The spectrometric measurements showed that the maximal cellular uptake of 5-ALA occurred after 7 h in vitro incubation. The photocytotoxic assay showed that light dose of 85 J/cm2 gives effective PDT outcome for Hep2c cell line incubated with 55 μg/ml of 5-ALA with a conclusion that Hep2c cell line is sensitive to ALA-mediated PDT.