Is topical delta-aminolevulinic acid adequate for photodynamic therapy in Barrett's esophagus? A pilot study.

BACKGROUND AND STUDY AIMS: The methods of endoscopic ablation of metaplastic and dysplastic areas in Barrett's esophagus so far described, are not satisfactory with respect to efficacy and safety. Therefore we investigated whether photodynamic therapy (PDT) with topical delta-aminolevulinic acid (delta-ALA) leads to ablation of specialized columnar epithelium and eradication of low-grade dysplasia while not producing phototoxicity and systemic side effects. PATIENTS AND METHODS: 14 patients with histologically proven Barrett's esophagus, seven of whom had evidence of low-grade dysplasia, underwent endoscopic treatment with topical delta-ALA. Photoactivation (wavelength, 632 nm) was performed at 1.5 - 2 hours after drug administration using an argon dye laser. Patients received omeprazole 80 mg daily for 2 months; thereafter; maintenance therapy depended on reflux symptoms. Patients were endoscopically re-evaluated after 7 days, and subsequently at 3, 6, 12 and up to 48 months (mean follow up 33 months). Re-treatment with high-dose topical delta-ALA was offered to the 11 patients with remaining metaplasia and was carried out in five of them. RESULTS: Low-grade dysplasia was eradicated in all patients. One patient with no dysplasia before PDT developed a high-grade dysplasia after PDT. Complete ablation of Barrett's metaplasia was observed in 21 % of the patients after the first treatment session and in 20 % after the second treatment session. The mean reduction in the length of Barrett's metaplasia was 1.54 +/- 1.29 cm after the first PDT session and 1.02 +/- 0.80 cm after the second PDT session. Post-endoscopic pain and photosensitivity reactions were less frequent with low-dose delta-ALA PDT than with high-dose PDT (pain 15 %, 100 %, respectively; P = 0.001 by Fisher's exact test; phototoxicity, 0 %, 50 %, respectively; P = 0.021 by Fisher's exact test). CONCLUSION: Low-dose topical administration of delta-ALA provides ablation of low-grade dysplasia in the range obtained with oral delta-ALA. In addition, it is safe and well tolerated. Since, however, topical administration of delta-ALA is not able to consistently eradicate Barrett's esophagus, alternative methods will have to be developed.

Temperature distribution for combined laser hyperthermia-photodynamic therapy in the esophagus.

In recent years photodynamic laser therapy (PDT) has been tested in animal and clinical studies for treatment of esophageal cancer. In several animal experiments a synergistic effect was found by simultaneously applying PDT and hyperthermia (HT). In this paper an optical fibre system is described which can be used in the esophagus for combined PDT with a 1 W dye laser and HT with a 15 W Nd:YAG laser. A phantom was built simulating the geometry of the esophagus using cow muscle. The spatial temperature field during HT was measured versus irradiation time. The results were compared with calculations using a coupled Monte Carlo laser transport/finite difference heat transport model using the LATIS computer program. Measurements and calculations yield a realistic description of the temperature distribution during HT under various experimental conditions. The LATIS program allows the prediction of the effects of blood perfusion for in vivo situations. The results show that perfusion has considerable influence on the temperature field, reducing the effective depth in tissue for HT.

A new bronchoscopic method to measure airway size.

Bronchoscopic evaluation of stenosis is limited due to radial distortion of bronchoscopic images and the unknown distance between the endoscope and the stenotic area. The purpose of this study was the development and validation of a method for measuring cross-sectional areas in large airways. Distance measurements were performed using a laser probe inserted into the working channel of a bronchoscope. The laser probe was positioned to the locus of interest in the airway, a ring of light (helium/neon) projected on to the luminal wall and the images acquired using an electronic bronchoscope. The images taken were distortion-corrected by means of a computer program. The method was validated by simulating airways using tubes of known diameter. Additionally, distortion-corrected bronchoscopic images were compared with distortion-free videoscopic image analysis of tracheal slices taken from pigs. In the case of the plastic tubes, Pearson's correlation coefficient (r) as well as the intraclass correlation coefficient (ICC) were slightly higher (r=0.99, p<0.01, ICC=0.97) than the correlation of cross-sectional areas between bronchoscopic and videoscopic images of tracheal slices (r=0.88, p<0.01, ICC=0.87). This concept allows accurate and reproducible determination of cross-sectional areas in large airways.

Photodynamic therapy of nonresectable cholangiocarcinoma.

BACKGROUND & AIMS: Successful treatment in nonresectable Bismuth type III and IV cholangiocarcinoma is seldom achieved. The aim of this study was to evaluate the effect of photodynamic therapy on cholestasis, quality of life, and survival in these patients. METHODS: Nine patients with advanced nonresectable cholangiocarcinomas Bismuth type III and IV, who showed no sufficient drainage (bilirubin decrease <50%) after endoscopic stent insertion, underwent photodynamic therapy. Two days after intravenous application of a hematoporphyrin derivate, intraluminal photoactivation was performed cholangioscopically. Serum bilirubin, quality of life, and survival time were assessed in two monthly intervals after photodynamic therapy. RESULTS: After photodynamic therapy, bilirubin serum levels declined from 318 +/- 72 to 103 +/- 35 micromol/L (P = 0.0039) with no significant increase during the two monthly follow-ups. Quality of life indices improved dramatically and remained stable (e.g., Karnofsky index from 32.2% +/- 8.13% to 68.9% +/- 6.1%; P = 0.0078). Thirty-day mortality was 0%, and median survival time was 439 days. CONCLUSIONS: This study provides clear evidence that photodynamic therapy is effective in restoring biliary drainage and improving quality of life in patients with nonresectable disseminated cholangiocarcinomas Bismuth type III and IV. Compared with published data, survival time seems to be prolonged.

Nd:YAG laser and tracheobronchial metallic stents: an experimental in vitro study.

STUDY DESIGN/MATERIALS AND METHODS: The aim of this experimental study was to investigate the effect of Nd:YAG laser on metallic tracheobronchial stents, because Nd:YAG laser could be used for resection of tumourous tissue growing through stent meshes (Strecker-, Palmaz-, Wallstent). STUDY DESIGN/MATERIALS AND METHODS: An in vitro worst-case-model was used to investigate the effects of different types of laser application on metallic stents: non-contact application, and contact application with bare fibres and with hemispherical sapphires. RESULTS: In the non-contact method and with bare fibres stent destruction occurred at power settings exceeding 10 W, whereas in the contact method with hemispherical sapphires power settings of 20 W were possible without stent damage.

Beneficial effect of combined glucose-insulin-potassium and mechanical support in acute myocardial ischaemia.

The influence of glucose-insulin-potassium infusion in combination with a mechanical assist device (intraaortic balloon pumping, IABP) on the levels of high energy phosphates in the canine heart after coronary artery ligation was compared with the effect of a separate application of these measures to protect the acute ischaemic myocardium. The combined method normalized the tissue content of creatine phosphate in the nonischaemic tissue contrary to the application of the mechanical or pharmacological assistance alone. In the ischaemic cardiac tissue only the combination of both methods reduced the loss of creatine phosphate, ATP and the sum of adenine nucleotides. With the balloon pumping a reduction in lactate accumulation was achieved, which, however, was significantly lower than that obtained by the combination of heart protective measures: IABP plus glucose-insulin-potassium.

[Animal experiment comparison of the therapeutic efficacy of tumor excision with a scalpel or with a CO2 laser in subcutaneously implanted Lewis lung cancer]. / Tierexperimenteller Vergleich der therapeutischen Effektivität einer Tumorexzision mittels Skalpell oder CO2-Laser am subkutan implantierten Lewis-lung-Karsinom.

An animal experimental study was carried out in order to compare the therapeutical value of two different surgical methods for excising the subcutaneous implanted Lewis lung carcinoma - tumor excision with scalpel or with carbon dioxide laser. The radicalism of operation methods, the survival time, and the tumor local recurrences were performed. The therapeutic effectivity of tumor excision with the carbon dioxide laser is more favourable than the scalpel method.

[Improved protection of the myocardium with a combination of intra-aortic balloon counter-pulsation and aimed substrate administration in acute myocardial infarct--a comparative study]. / Verbesserter Myokardschutz durch Kombination der intraartalen Ballongegenpulsation mit gezielter Substratzufuhr bei akuter Myokardischämie--eine vergleichende Untersuchung.

In comparative studies in 36 mongrel dogs it was tried to find out how far intraaortic balloon pumping (IABP) applied solely and in combination with glucose-insulin-potassium (GIK) might influence the degree of acute myocardial ischemia. The ischemia lasted 3 hours. After 60 min myocardial ischemia IABP, the isolated GIK infusion, or the combination of IABP plus GIK were used. The directed GIK application into the aortic root was carried out by electronic triggering during the diastolic augmentation via a precoronary catheter. In the ischemic and in the non-ischemic myocardium of the left ventricle, ATP, creatine phosphate, and lactate were determined. Electronmicroscopical studies were carried out qualitatively as well as quantitatively. The isolated use of IABP suggested no protection of the energy-rich phosphates. The most significant morphological changes were found when exclusively the coronary ligature was applied and when only IABP was used, respectively. The best protective effect was achieved by our technique of the triggered GIK infusion via the precoronary catheter in combination with IABP. The ATP value (n mol/mg w.w.) in the ischemic area was 3.06 and in the non-ischemic one 4.96 in comparison to 1.96 and 3.99, respectively, in the control group. The creatine phosphate (n mol/mg w.w.) was 4.18 in the ischemic and 9.38 in the non-ischemic area in contrast to 2.36 and 6.99, respectively, in the control group. The technique of the triggered drug supply in combination with IABP offers the following advantages: --additive summation of IABP and substrate supply directed to the myocardium --high drug concentration in the myocardium --smaller drug load of the whole organism --clinical use of instable substances.