[Ablative treatment of rectosigmoidal precanceroses and early cancer]. / Ablatívna liecba rektosigmoideálnych prekanceróz a vcasných karcinómov.

Endoscopic mucosal resection and piece meal polypectomy are methods of choice in broad based unifocal rectosigmoideal lesions. Thermal ablative modalities are indicated for flat adenomas, lateral spreading tumors and as an adjunct therapeutic modality for incomplete polypectomy. Photodynamic therapy using ALA photosensitiser is effective in the treatment of multifocal lesions either alone or in a combination with thermal ablative techniques. At present "tailored suite" combination of these techniques for each patient according the character of the lesion is considered to be the most effective treatment for rectosigmoideal praecancerous lesions and early cancer.

Endoscopic treatment of praecancerous colorectal lesions and early colorectal cancer.

Endoscopic mucosal resection or piece meal polypectomy are the methods of choice for the treatment of unifocal visualized lesion. Thermal ablative techniques are indicated for flat adenomas as a adjunct therapy after an imcomplete EMR or piece meal polypectomy. Photodynamic therapy using ALA photosensitisation is effective in the treatment of multifocal lesions and also in combination with EMR or thermal ablative techniques. At present, the "tailored suite" combination of these techniques for each patient, according to the character of the lesions, is considered to be the most effective treatment of precancerous lesions and early colorectal cancer (Tab. 1, Fig. 2, Ref. 16). Full Text (Free, PDF) www.bmj.sk.

Infectious embolisation to the central nervous system from endocarditis: analyses of 99 cases.

Within a cohort of 606 cases of infective endocarditis, 263 were complicated and 99 embolizing, of them 32 to the central nervous system (CNS). Significant predictors of CNS embolisation were inappropriate therapy (p<0.01) and enterococcal etiology (p<0.01). Mortality in patients with CNS emboli was 65% what was significantly higher than in cases without embolisation - 15% (p<0.01).

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.

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.).

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.).

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.).

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.).

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.).

Photodynamic therapy for gastrointestinal tumors using three photosensitizers--ALA induced PPIX, Photofrin and MTHPC. A pilot study.

Photodynamic therapy (PDT) produces localized necrosis with light after prior administration of a photosensitizing drug. As PDT lesions in the gastrointestinal tract heal well, the technique is suitable for repeated endoscopic use. In this study we used PDT to treat benign and malignant gastrointestinal tumors in esophagus, duodenum and rectum in 22 patients, who refused or were not suitable for surgery. Patients were sensitized with 0.15 mg/kg of body weight with mesotetrahydroxyphenylchlorin i.v. m-THPc (2 patients), with 2.0 mg/kg Photofrin i.v. (4 patients) or 60 mg/kg 5-aminolevulinic acid orally ALA (which is converted in vivo to active derivate protoporphyrin IX-PRIX) in fractionated doses (16 patients). Laser treatment was performed 2 days after Photofrin, 2 and 4 days after mTHPc and 4 hours after ALA, using a metal vapour laser (628 nm, 50-150 J/cm2 for ALA and Photofrin, 650 nm and 10-15 J/cm2 for mTHPc). Using ALA, the necrosis was only superficial (up to 1.8 mm depth). Four patients treated with Photofrin showed deeper necrosis, in one case of 8 mm colon cancer complete response, in three cases 1-1.5 cm adenomatous polyps involving the ampulla Vateri 50% longer term reduction in size-seen endoscopically. Two patients with rectal villous adenomas treated with mTHPc showed 60-80% reduction in size (observed endoscopically) within few days after PDT, with better effects for treatment carried out 4 rather than 2 days after the sensitization. In all patients the healing was without any complications. Photofrin and mTHPc work better, but cause cutaneous photosensitivity lasting 12 and 5 weeks, respectively. Better results with ALA are possible when using higher drug doses or modified light dosimetry. PDT is a promising treatment for small localized tumors in patients unsuitable for surgery, but further work is required to optimize the treatment conditions.

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.

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.

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.

Sensitization and photodynamic therapy (PDT) of gastrointestinal tumors with 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX). A pilot study.

5-Aminolaevulinic acid (ALA) is a promising agent for photodynamic therapy (PDT) sensitization as it can be given orally and only causes skin photosensitivity for 1-2 days. In fluorescence and photodynamic studies 26 patients with benign and malignant gastrointestinal tumors were given 30-60 mg ALA orally (single or divided doses) and biopsies were taken of tumor and normal tissue at 1-24 hours for fluorescence microscopy. With 30 mg/kg, highest protoporphyrin IX (PPIX) levels were seen in esophagus, duodenum and less in colon, but without tumor selectivity. Better tumor selectivity was seen in colon after 60 mg/kg (5:1). Six patients had transient rises in transaminases and five mild nausea. Sixteen patients were later treated (after further ALA) with red light (628 nm, bare or diffuser fibre, 50-100 J at 50 mW at each site). All but two showed subsequent necrosis, but only 0.5-1.5 mm of depth. PDT with ALA is simple, safe and promising for tumors in the gastrointestinal tract. Modification of treatment parameters may make it suitable for larger lesions.

Endoscopic ND:YAG laser treatment of rectosigmoidal cancer.

Over a period of 7 years 126 patients with rectosigmoid carcinoma considered unsuitable for surgery underwent endoscopic Nd:YAG laser treatment for palliation of symptoms and tumor eradication, if feasible. Altogether 72 (59%) of the lesions had distal margins less than 7 cm from the anus and 32 (23%) above the peritoneal reflection. In 14 patients with tumor less than 3 cm in diameter, symptomatic improvement was achieved in all. In the remaining 112 patients with larger tumors (81 greater than 3/4 circumferential, mean length 5.5 cm) symptomatic improvement was achieved with repeated treatments (average 3.7) in 58 (71%). All treatment failures occurred in patients with extensive tumors (17 initial, 12 late). Bowel perforation did not occur and there was no treatment related mortality. The average stay in hospital for all laser patients was 9 days (32% of patients were outpatient attendance). These results suggest that laser therapy may be the palliative treatment of choice in patients with rectosigmoid carcinoma unsuitable for surgery.

Palliative treatment of esophagogastric cancer by laser photocoagulation.

Over a 7-year period 158 nonsurgical patients with an advanced esophageal cancer were treated by palliation. The initial success rate was 79% and the complications rate was 2.3%. Average improvement duration was 136 days. Tumors were mostly situated in lower and middle part of oesophagus.

[Treatment of digestive tract tumors using the Nd-YAG laser]. / Liecba nádorov tráviaceho traktu Nd YAG laserom.

The authors submit an account of contemporary possibilities of the application of laser in the endoscopic treatment of some gastrointestinal diseases. They give an account of their own experience with the use of Nd YAG laser, particularly in the treatment of oesophageal tumours, stenotizing tumours of the rectum and with removal of broad-based polyps. Good results were achieved in endophytic types of oesophageal tumours, especially those localized in the middle part and with a length up to 10 cm, and also in recanalisation of stenotizing tumours of the rectum. The laser therapy in these cases was palliative. Curative laser therapy was applied in destruction of broad-based polyps and the results were satisfactory.