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Biomedical subjects

P Mlkvy

Publications and source records attributed to P Mlkvy.

9 recordsLinked to original sources

In vivo fluorescence diagnostics and photodynamic therapy of gastrointestinal superficial polyps with aminolevulinic acid. A clinical and spectroscopic study.

In the present study initial results of clinical study related to the treatment of patients having different types of precancerous lesions in the area of esophagus, stomach and intestine by photodynamic therapy (PDT) based on aminolevulinic acid (ALA-PDT) are reported. The procedure was performed by laser fibre system with the light guides introduced through biopsy channel of an endoscope. In addition, in vivo fluorescent diagnostics and spectral analyses of biopsies were performed. Each patient had a positive response to therapy. In two cases there was a total response and in other five cases more than sixty percent of suspected area was removed. Additionally, sigilocellular carcinoma of stomach was revealed in one case. It appears from the results of this study, that the treatment of precancerous lesions with ALA-PDT could be successful treatment modality.

Aminolevulinic Acid↗

Barrett's esophagus.

Patients with Barrett's esophagus have 30-40 times higher risk of developing adenocarcinoma of distal esophagus. Treatment of Barrett's esophagus without dysplasia is identical with treatment of gastroesophageal reflux disease. (Tab. 1, Ref. 5.).

Adenocarcinoma↗

Etiology, epidemiology and diagnosis of esophageal cancer.

The data from the National Cancer Registry in Slovakia showed 306 esophageal cancers in 1999 (288 men and 18 women). There has been a 5-fold increase in the incidence of esophageal cancer among men in the past 30 years as compared to women in whom no significant chance occurred. The reported 1999 raw incidence of esophageal cancer (per 100000) was 11.0 and 0.6 among men and women in Slovakia, respectively. (Tab. 1, Ref. 8.).

Adult↗

Laser and photodynamic therapy for esophageal cancer.

Esophageal cancer has a poor prognosis. The diagnosis in clinical practise is often made in advanced stages when curative treatment is impossible. Overall five year survival is reached only in 10% of patients and a palliative treatment is indicated in 60% of patients. From these patients one year survival could be observed in 55% and five year survival only in about 20% of patients. Progressive dysphagia is responsible for the poor quality of life. (Ref. 4.).

Adult↗

Endoscopic ultrasound in esophageal cancer.

The first prototype of an endoscopic ultrasound (EUS) was constructed in Japan in 1980. The evolution continued quickly and within the past ten years this method became available in routine practice. One of the most significant indications of EUS in esophagus are locoregional staging and posttherapeutic monitoring of the esophageal cancer. (Ref. 4.).

Endosonography↗

Palliative endoscopic therapy of esophageal cancer: self-expanding stents.

Esophageal cancer is the tenth most common malignancy. Recently, there has been an increase in the incidence of carcinoma of distal esophagus. Unfortunately, early esophageal cancer is commonly asymptomatic and inaccessible to examinstion during regular physical examination. Thus, high percentage of patients present with advanced disease at the time of diagnosis. Main symptom are nutritional deficiencies, dysphagia, pressure in the epigastrium and commonly, blood loss. (Tab. 1, Fig. 1, Ref. 4.).

Endoscopy↗

Distribution and photodynamic effects of meso-tetrahydroxyphenylchlorin (mTHPC) in the pancreas and adjacent tissues in the Syrian golden hamster.

Photodynamic therapy (PDT) has the potential to destroy small tumours with safe healing of adjacent normal tissue. This study looks at the effects of PDT on the normal pancreas and adjacent tissues in hamsters using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC). Pharmacokinetic studies used fluorescence microscopy on sections of pancreas, stomach and duodenum 1 h to 6 days after mTHPC. Highest levels of sensitiser were seen in the gastric and duodenal mucosa and in the acinar pancreas after 2-4 days. For PDT, light at 652 nm was delivered by placing a 0.2 mm diameter bare-ended fibre against the tissue. An energy of 50 J was used 2 or 4 days after 0.1 or 0.3 mg kg-1 mTHPC and animals killed 1 to 7 days later. Maximum necrosis was seen 3 days after PDT with lesions up to 4 mm in pancreas, 4.5 mm in duodenum and 2.5 mm in stomach. By fractionating the light dose, the lesion size could be increased by 30%. The main complication was free or sealed duodenal perforation (avoided by shielding the duodenum). Partial, reversible bile duct obstruction was seen occasionally. There was no macroscopic damage to the bile ducts or major blood vessels. Apart from the duodenum, all lesions healed safely. In this animal model, only the duodenum was at risk of serious, irreversible damage. Treatment is likely to be safer in the much thicker human duodenum. mTHPC is a powerful photosensitiser and suitable for further study for tumours in the region of the pancreas although care is required near the duodenum.

Animals↗

Enhancement of photodynamic therapy with 5-aminolaevulinic acid-induced porphyrin photosensitisation in normal rat colon by threshold and light fractionation studies.

5-Aminolaevulinic acid (ALA)-induced prophyrin photosensitisation is an attractive option for photodynamic therapy (PDT) since skin photosensitivity is limited to 1-2 days. However, early clinical results on colon tumours using the maximum tolerated oral dose of 60 mg kg-1 showed only superficial necrosis, presumably owing to insufficient intratumoral porphyrin levels, although inadequate light dosimetry may also be a factor. We undertook experiments using ALA, 25-400 mg kg-1 intravenously, to establish the threshold doses required for a PDT effect. Laser light at 630 nm (100 mW, 10-200 J) was delivered to a single site in the colon of photosensitised normal Wistar rats at laparotomy. The animals were killed 3 days later and the area of PDT-induced necrosis measured. No lesion was seen with 25 mg kg-1. The lesion size increased with larger ALA doses and with the light dose but little benefit was seen from increasing the ALA dose above 200 mg kg-1 or the light dose above 100 J. Thus there is a fairly narrow window for optimum doses of drug and light. Further experiments showed that the PDT effect can be markedly enhanced by fractionating the light dose. A series of animals was sensitized with 200 mg kg-1 ALA and then treated with 25 J. With continuous irradiation, the lesion area was 13 mm2, but with a single interruption of 150 s the area rose to 94 mm2 with the same total energy. Results were basically similar for different intervals between fractions (10-900 s) and different numbers of fractions (2-25). This suggests that a single short interruption in the light irradiation may dramatically reduce the net light dose required to achieve extensive necrosis.

Aminolevulinic Acid↗

Photodynamic therapy for polyps in familial adenomatous polyposis--a pilot study.

Photodynamic therapy (PDT) produces localised necrosis with light after prior administration of a photosensitising drug. As PDT lesions in the gastrointestinal tract heal so well, the technique is suitable for repeated endoscopic use. In this study, PDT was used to treat large polyps (four duodenal and two colorectal) unsuitable for surgery in 6 patients with familial adenomatous polyposis (FAP). Patients were sensitised with 60 mg/kg 5-aminolaevulinic acid (ALA) orally or intravenous (i.v.) 2.0 mg/kg Photofrin. Laser treatment was performed 6 h after ALA or 48 h after Photofrin using a gold vapour laser. Necrosis was only superficial (up to 1.8 mm) using ALA but much deeper using Photofrin. The one malignant polyp (8 mm diameter in the colon) showed a complete response using Photofrin. All healed safely with no complications. Photofrin worked better, but caused cutaneous photosensitivity lasting up to 3 months. ALA cleared within 2 days, but its use is limited by the superficial effect. Better results with ALA may be obtained using higher drug doses or modified light dosimetry. Fluorescence microscopy showed no evidence of selectivity of photosensitisation between neoplastic and normal tissue. PDT is a promising treatment for inoperable polyps in patients with FAP, but further work is required to optimise the treatment conditions.

Adenoma↗