Stratification of the dysplasia and neoplasia risk using autofluorescence endoscopic surveillance of Barrett's esophagus.

BACKGROUND: This study assessed the efficacy of autofluorescence endoscopy (AFE) using the Onco-LIFE system and numerical color value (NCV) estimation in comparison to white light endoscopy (WLE) in endoscopic surveillance for identification of early dysplasia in Barrett's esophagus (BE) to aid in real-time image elucidation and minimize the overreliance on biopsy and histology. METHODS: AFE, performed simultaneously during WLE, with biopsy was performed among 24 patients with BE. None of these patients had any obvious mucosal abnormalities in WLE. A total of 376 biopsies were taken, include 325 randomly collected according to Seattle Protocol and 51 additional biopsies, taken from the sites with pathological AF and NCV. All biopsy sites were assessed in vivo using WLE, AFE and NCV and compared to histological examinations, to estimate the efficacy of these methods in dysplasia assessment in BE. RESULTS: In the case of 248 biopsies taken from sites with NCV below 1.0, two cases of unspecified dysplasia were recognized; in 14 biopsies with NCV above 2.0 in all cases the various grades of dysplasia were documented. Dysplasia was found in 42% of AFE + NCV- guided biopsy specimens, and in 7.1% of WLE-guided biopsy specimens. AFE + NCV detected high-grade dysplasia in 7 patients, 6 more than according to Seattle Protocol in WLE. The expected odds of dysplasia detection in a sample increases almost 1.9 times, if it was selected by the AFE method (p < 0.001), when compared to WLE and with accordance with Seattle Protocol guided biopsy. CONCLUSION: The above results indicate that AFE + NCV using the Onco-LIFE system leads to improved BE lesion visualization for targeted biopsy with accurate histologic correlation compared to WLE and Seattle Protocol guided biopsy alone, and can serve to minimize additional biopsies.

Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer - clinician's insight.

Vascular targeted photochemotherapy (VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer (LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory conditions. In this review, methodologic aspects of padoporfin- and padeliporfin-mediated VTP and its clinical application in focal treatment of LPCa as well as future perspective of this method were presented. Physicochemical and pharmacokinetic parameters of padoporphin and padeliporfin using as VTP photosensitizers were described, as well as methodologic question of radiation delivery and dosimetry, and oxygen monitoring in cancer tissue in context of VTP safety and efficiency of LPCa focal therapy were discussed. The results of clinical trials concerning application of padoporfin- and padeliporfin-mediated VTP in LPCa were also presented. The future of VTP is development of protocols, founded on the real-time feedback and rules-based approach to make this strategy a standard procedure in LPCa treatment. To evaluate clinical potential of this procedure, a cost-effectiveness analysis is also necessary.

Photodynamic therapy in colorectal cancer treatment--The state of the art in preclinical research.

BACKGROUND: Photodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer (CRC). This review aims to give a general overview of preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment to emphasize their potential in study of PDT mechanism, safety and efficiency to translate these results into clinical benefit in CRC treatment. MATERIALS AND METHOD: Literature on in vitro preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment with the fallowing medical subject headings search terms: colorectal cancer, photodynamic therapy, photosensitizer(s), in vitro, cell culture(s), in vivo, animal experiment(s). The articles were selected by their relevance to the topic. RESULTS: The majority of preclinical studies concerning possibility of PDT application in colon and rectal cancer is focused on phototoxic action of photosensitizers toward cultured colorectal tumor cells in vitro. The purposes of animal experiments are usually elucidation of mechanisms of observed photodynamic effects in scale of organism, estimation of PDT safety and efficiency and translation of these results into clinical benefit. CONCLUDING REMARKS: In vitro photodynamic studies and animal experiments can be useful for studies of mechanisms and efficiency of photodynamic method as a start point on PDT clinical research. The primary disadvantage of in vitro experiments is a risk of over-interpretation of their results during extrapolation to the entire CRC.

Photodynamic therapy in colorectal cancer treatment: the state of the art in clinical trials.

BACKGROUND: Photodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer. This review aims to give a general overview of the PDT application to colorectal cancer in the field of clinical trials to emphasize its curative, and insufficiently exploited potential. MATERIALS AND METHODS: Literature on PDT for colorectal cancer with the following medical subject headings search terms: colorectal cancer, photodynamic therapy, clinical trials was reviewed. The articles were selected by their relevance to the topic. RESULTS: There are many positive and promising trial results from I to II/III phase for the use of PDT in colorectal cancer both in less advanced tumors as well as in the palliative therapy of advanced lesions. CONCLUDING REMARKS: PDT seems to be a safe and a feasible treatment option for colorectal cancer. Theoretical assumptions confirmed by many results of preclinical studies taking into consideration an increasing number of analyzed clinical trials, should lead to the development of optimized standards by using PDT in colorectal cancer treatment.

ALA-mediated photodynamic effect on apoptosis induction and secretion of macrophage migration inhibitory factor (MIF) and of monocyte chemotactic protein (MCP-1) by colon cancer cells in normoxia and in hypoxia-like conditions in vitro.

BACKGROUND: Photodynamic therapy (PDT) reveals immune modulatory effect. The aim of the study was to evaluate the influence of 5-aminolevulinic acid (ALA) mediated photodynamic effect on secretory activity (MIF, MCP-1) of colon cancer cells in vitro both in normoxia and in hypoxia-like conditions. METHODS: Two colon cancer cell lines differing in malignancy potential: SW480 (lower grade) and SW620 (higher grade) were used. MCP-1 and MIF concentrations in supernatants of cells cultures after pretreatment with ALA at concentrations of 500, 1000 and 1500µM and irradiation with incoherent light (λ=600-720nm) at fluences of 10, 30 and 60J/cm(2), using Bio-Plex ProTM Assay kit and Bio-Plex Suspension Array System apparatus, were measured. RESULTS: The SW620 cells were more susceptible to ALA-mediated phototoxic effect than SW480 one, however this effect may be partly abolished in hypoxia-like condition. In the case of SW480 cell line, no influence of hypoxia-like conditions on cell susceptibility to ALA-mediated photodynamic effect was found. The MIF concentration increased, contrary to MCP-1 one which decreased after ALA-mediated photodynamic action in both cell lines. No difference between cytokines concentration in supernatant from cells cultures in normoxia or hypoxia-like conditions was observed. CONCLUSIONS: Detected reduction in MCP-1 secretion appears to be advantage because of tumor's growth limiting but an increase in the secretion of MIF, which is responsible for stimulation of tumor cells proliferation, is an unfavorable effect. These results may be explained by the fact that the used cancer cell lines differ from each other in cancer stage.

Photodynamic therapy in treatment of cutaneous and choroidal melanoma.

Melanoma is a malignant, the most aggressive and dreaded skin cancer. This form of cancer arises from melanocytes and may grow rapidly and metastasize. Melanoma predominantly occurs in skin, but could also be found in the mouth, iris and retina of the eye. Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. It is highly resistant to traditional chemotherapy and radiotherapy, although modern biological therapies are showing some promise. Photodynamic therapy (PDT), as a novel effective modality of the treatment of skin cancers, opens up new possibilities in melanoma treatment also. Many experimental photodynamic therapy studies were performed. The results of many experiments indicate that that photodynamic therapy may be a promising tool for adjuvant treatment in advanced melanoma.

The role of fluorescence diagnosis in clinical practice.

Fluorescence diagnosis is a fast, easy, noninvasive, selective, and sensitive diagnostic tool for estimation of treatment results in oncology. In clinical practice the use of photodynamic diagnosis is focused on five targets: detection for prevention of malignant transformation precancerous changes, detection of neoplasmatic tissue in the early stages for fast removal, prevention of expansion and detection of recurrence of the cancer, monitoring therapy, and the possibility of excluding neoplasmatic disease. In this article, selected applications of fluorescence diagnosis at the Center for Laser Diagnostics and Therapy in Bytom, Poland, for each of these targets are presented.

Clinical evaluation of twenty cases of heterotopic gastric mucosa of upper esophagus during five-year observation, using gastroscopy in combination with histopathological and microbiological analysis of biopsies.

AIM OF THE STUDY: Heterotopic gastric mucosa of the upper esophagus (HGMUE) may be connected with disorders of the upper gastrointestinal tract, exacerbated by Helicobacter pylori. Furthermore, HGMUE may be the origin of malignant progression to cervical esophageal carcinoma. MATERIAL AND METHODS: In this work, 20 patients with diagnosed heterotopic gastric mucosa of the upper esophagus (HGMUE) were subjected to 5-year follow-up to determine the extent and structure of histopathological changes within HGMUEs, as well as HGMUE dysplasia and metaplasia, and risk of their malignant transformation. As a diagnostic tool to describe localization, form, size and surface feature of HGMUEs, endoscopy was used. At the same time, the biopsies were collected for histopathological and microbiological analysis. RESULTS: In examined patients, HGMUEs were associated with inflammation, chronic gastritis, hiatus hernia, duodenal bulb erosion and ulcer and infection of H. pylori. Intestinal metaplasia and low grade dysplasia were also indicated. During 5 years of observation, both the clinical and histopathological image of diagnosed HGMUEs was stable. The patients with detected presence of H. pylori were treated with triple or quadruple therapy. These results show that HGMUEs may be associated with severe complications in the gastrointestinal tract, such as infection by H. pylori, hiatus hernia or duodenal ulcer. Although dysplasias and metaplasias found in diagnosed HGMUEs were not very numerous and relatively stable both clinically and histopathologically, at the present stage of the study we cannot exclude the possibility of HGMUE malignant transformation.

Autofluorescence endoscopy with "real-time" digital image processing in differential diagnostics of selected benign and malignant lesions in the oesophagus.

BACKGROUND: Oesophageal papilloma and Barrett's oesophagus are benign lesions known as risk factors of carcinoma in the oesophagus. Therefore, it is important to diagnose these early changes before neoplastic transformation. METHOD: Autofluorescence endoscopy is a fast and non-invasive method of imaging of tissues based on the natural fluorescence of endogenous fluorophores. The aim of this study was to prove the diagnostic utility of autofluorescence endoscopy with digital image processing in histological diagnosis of endoscopic findings in the upper digestive tract, primarily in the imaging of oesophageal papilloma. RESULTS: During the retrospective analysis of about 200 endoscopic procedures in the upper digestive tract, 67 cases of benign, precancerous or cancerous changes were found. White light endoscopy (WLE) image, single-channel (red or green) autofluorescence images, as well as green and red fluorescence intensities in two modal fluorescence image and red-to-green (R/G) ratio (Numerical Colour Value, NCV) were correlated with histopathologic results. The NCV analysis in autofluorescence imaging (AFI) showed increased R/G ratio in cancerous changes in 96% vs. 85% in WLE. Simultaneous analysis with digital image processing allowed us to diagnose suspicious tissue as cancerous in all of cases. Barrett's metaplasia was confirmed in 90% vs. 79% (AFI vs. WLE), and 98% in imaging with digital image processing. In benign lesions, WLE allowed us to exclude tissue as malignant in 85%. Using autofluorescence endoscopy R/G ratio was increased in only 10% of benign changes causing the picture to be interpreted as suspicious, but when both methods were used together, 97.5% were cases excluded as malignancies. Mean R/G ratios were estimated to be 2.5 in cancers, 1.25 in Barrett's metaplasia and 0.75 in benign changes and were statistically significant (p=0.04). CONCLUSION: Autofluorescence imaging is a sensitive method to diagnose precancerous and cancerous early stages of the diseases located in oesophagus. Especially in two-modal imaging including white light endoscopy, autofluorescence imaging with digital image processing seems to be a useful modality of early diagnostics. Also in observation of papilloma changes, it facilitates differentiation between neoplastic and benign lesions and more accurate estimation of the risk of potential malignancy.

Targeted photodynamic therapy--a promising strategy of tumor treatment.

Targeted therapy is a new promising therapeutic strategy, created to overcome growing problems of contemporary medicine, such as drug toxicity and drug resistance. An emerging modality of this approach is targeted photodynamic therapy (TPDT) with the main aim of improving delivery of photosensitizer to cancer tissue and at the same time enhancing specificity and efficiency of PDT. Depending on the mechanism of targeting, we can divide the strategies of TPDT into "passive", "active" and "activatable", where in the latter case the photosensitizer is activated only in the target tissue. In this review, contemporary strategies of TPDT are described, including new innovative concepts, such as targeting assisted by peptides and aptamers, multifunctional nanoplatforms with navigation by magnetic field or "photodynamic molecular beacons" activatable by enzymes and nucleic acid. The imperative of introducing a new paradigm of PDT, focused on the concepts of heterogeneity and dynamic state of tumor, is also called for.