Effects of electrophotodynamic therapy in vitro on human melanoma cells--melanotic (MeWo) and amelanotic (C32).

Photodynamic therapy has been considered ineffective for melanomas because of the competition between the absorbance of melanin from the melanoma and the absorbance of photosensitizers at the photosensitizer excitation light wavelength. Melanomas show considerable heterogeneity and resistance to phototherapy. The effectiveness of photodynamic therapy could be intensified by electroporation for enhanced transport of a photosensitizer by transient pores in the membrane. In this study, photodynamic therapy combined with electroporation was tested in vitro on the human melanoma cell lines melanotic melanoma (MeWo) and amelanotic melanoma (C32). Control experiments were conducted on human keratinocytes (HaCaT). Photofrin was used as a photosensitizer. Photosensitizer distribution, cloning efficacy test, comet assay, and assessment of apoptotic proteins were performed. Melanin levels were determined before and after photodynamic therapy. The experiments indicated that electroporation effectively supports the photodynamic method. It was found that photodynamic therapy with electroporation efficiently induces apoptosis in melanotic and amelanotic melanoma cells.

Severe acute airway obstruction and respiratory failure with fibrous plug following photodynamic therapy (PDT): indication for early bronchoscopy and debridement.

INTRODUCTION: PDT is a safe procedure with most post procedural complications reported as minor. We report a case of severe acute stridor and trachea-bronchial airway obstruction with mucosal sloughing and fibrous plugs resulting in respiratory failure within three hours following PDT. To our knowledge this is the first reported case where stridor and acute respiratory failure resulted within hours following PDT treatment. CASE REPORT: A 65 year old female with previous right pneumonectomy presented with followup bronchoscopy confirming reoccurrence of carcinoma proximal and distal to the anastomosis. A standard photofrin (Porfimer sodium) was administered at 2mg/kg body weight 48 hours prior to her PDT treatment. Three hours following the procedure, patient become acutely stridurous and was subsequently intubated. Bedside bronchoscopy was performed through the endotracheal tube. During the bronchoscopy thick tracheal plugs were retrieved and slough adjacent to the treatment site was noticed which was debrided. Patient underwent 7 bronchoscopies with debridement before she was discharged. CONCLUSION: Airway obstruction (with NSCLA) is an indication as well as complication (with mucosal debris) of PDT. FDA has advised bronchoscopy at 48-72 hours post procedure, however early intervention with bronchoscopy and debridement should be considered to relieve tracheal bronchial airway obstruction and removal of accessory debris and mucosal slough.

A randomised controlled trial of ALA vs. Photofrin photodynamic therapy for high-grade dysplasia arising in Barrett's oesophagus.

Photofrin photodynamic therapy (PDT) is a licenced treatment for Barrett's oesophagus (BE) with high-grade dysplasia (HGD) but causes strictures and photosensitivity and complete reversal of dysplasia (CR-HGD) by 50 % at 5 years. 5-Aminolaevulinic acid (ALA) is an alternative treatment with non-randomised data suggesting 85 % CR-HGD and a low risk of side effects. We aimed to compare efficacy and side effect profile between the drugs. A single-centre randomised controlled trial was conducted. Presence of HGD was confirmed on three occasions by two specialist GI pathologists. Stratification was by length of BE and extent of dysplasia. Standard protocols for ALA and Photofrin-PDT were followed. Endoscopic follow-up with 2-cm four-quadrant biopsy was at 6 weeks, 4 months, and then annually. All adverse event data were collected. Sixty four patients were randomised, 34 ALA and 30 Photofrin-PDT. Median follow-up is 24 months. On intention-to-treat analysis, CR-HGD was 16/34 (47 %) with ALA-PDT and 12/30 (40 %) with Photofrin-PDT. The overall cancer incidence was 14 % (9/64). On sub-group log-rank analysis, for BE ≤ 6 cm, CR-HGD was significantly higher with ALA-PDT than Photofrin-PDT (χ(2) =5.39, p=0.02). Strictures and skin photosensitivity were significantly more common after treatment with Photofrin-PDT than ALA-PDT (33 vs. 9 % and 43 vs. 6 %, respectively, p<0.05). The rate of buried glands with either drug was significantly higher post-PDT (48 % of patients) than pre-PDT (20 %). ALA-PDT has a better risk profile than Photofrin-PDT. In patients with BE length ≤ 6 cm, preliminary results show ALA-PDT is associated with significantly higher CR-HGD. In longer segments of BE, neither PDT drug is sufficiently efficacious to warrant routine use.

Safety and long term efficacy of porfimer sodium photodynamic therapy in locally advanced biliary tract carcinoma.

BACKGROUND: In patients with unresectable cholangiocarcinoma, photodynamic therapy (PDT) with porfimer sodium promotes biliary drainage and may improve survival and quality of life. AIM: To prospectively evaluate the safety and efficacy of PDT in patients with locally advanced biliary tract carcinoma. METHODS: Eligible patients had unresectable, histologically confirmed disease, a Karnofsky performance status of ≥30% and life expectancy >12 weeks. Patients received 2mg/kg i.v. of porfimer sodium, followed by endobiliary laser activation and stent replacement 48 h later. Patients were assessed clinically and radiologically before treatment and on day 28, and followed up thereafter at three-monthly intervals until death. RESULTS: 36 patients were entered over an 18 months period: 14 males, 22 females, with a median age of 65 (30-79)yr and performance status of 80 (50-100). PDT was technically successful in all cases and was generally well tolerated; there was no grade 4 toxicity and no treatment-associated mortality. The median survival was 12 (1-84) months. CONCLUSIONS: Porfimer sodium PDT can be delivered safely to patients with biliary tract cancer and is suitable for testing in phase III studies (UKCRN ID 1218).

Expression of complement and pentraxin proteins in acute phase response elicited by tumor photodynamic therapy: the engagement of adrenal hormones.

Treatment of solid tumors by photodynamic therapy (PDT) was recently shown to trigger a strong acute phase response. Using the mouse Lewis lung carcinoma (LLC) model, the present study examined complement and pentraxin proteins as PDT-induced acute phase reactants. The results show a distinct pattern of changes in the expression of genes encoding these proteins in the tumor, as well as host liver and spleen, following PDT mediated by photosensitizer Photofrin™. These changes were influenced by glucocorticoid hormones, as evidenced by transcriptional activation of glucocorticoid receptor and the upregulation of gene encoding this receptor. The expression of gene for glucocorticoid-induced zipper (GILZ) protein, whose activity is particularly susceptible to glucocorticoid regulation, was also changed in PDT-treated tumors. A direct demonstration that tumor PDT induces glucocorticoid hormone upregulation is provided by documenting elevated levels of serum corticosterone in mice bearing PDT-treated LLC tumors. Tumor response to PDT was negatively affected by blocking glucocorticoid receptor activity, which suggests that glucocorticoid hormones have a positive impact on the therapeutic outcome with this therapy.

The pharmacokinetics and safety of porfimer after repeated administration 30-45 days apart to patients undergoing photodynamic therapy.

BACKGROUND: Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus. AIM: To assess the pharmacokinetics as well as the safety profiles of porfimer after a first and a second dose administered 30-45 days apart in patients undergoing photodynamic therapy. METHODS: Nineteen patients (16 with cholangiocarcinoma) were enrolled. Porfimer sodium was administered by i.v. injection over 3-5 min. Blood samples were collected prior to starting i.v. drug injection and postdose at different time points after the first and second administrations. RESULTS: Porfimer exposure values after the second administration were statistically higher than those observed after the first administration, suggesting a slight accumulation of porfimer following repeated administration. The apparent mean elimination half-life of porfimer increased from 410 h after the first administration to 725 h after the second administration. The safety profiles of porfimer after a first and a second administration were similar and did not raise additional concern. Eight patients experienced nine serious adverse events. Only photosensitivity was deemed study-drug related. CONCLUSION: Porfimer appears to display a safe and tolerable profile when used in patients requiring a second photodynamic therapy within 45 days.

The role of photodynamic therapy in the esophagus.

Photodynamic therapy (PDT) is a drug and device therapy using photosensitizer drugs activated by laser light for mucosal ablation. Porfimer sodium PDT has been used extensively with proven long-term efficacy and durability for the ablation of Barrett esophagus and high-grade dysplasia. and early esophageal adenocarcinoma. However, continued use is hampered by an associated stricture risk and prolonged photosensitivity (4-6 weeks). Promising single-center European studies using other forms of PDT, such as aminolevulinic acid PDT, have not been replicated elsewhere, limiting the widespread use of other forms of PDT. Future use of PDT in esophageal disease depends on the development of improved dosimetry and patient selection to optimize treatment outcomes, while minimizing adverse events and complications.

Influence of intra-articular neutrophils on the effects of photodynamic therapy for murine MRSA arthritis.

Although there have been some reports about the cytotoxic effects of photodynamic therapy (PDT) on multidrug-resistant bacteria, there have been few reports in which favorable results of PDT on a local infection site are described. This study aimed to verify the hypothesis that the low efficacy of PDT on a local infection site is due to the cytotoxic effect of PDT on leukocytes. PDT using Photofrin exerted significant cytotoxicity for cultured methicillin-resistant Staphylococcus aureus (MRSA). Nevertheless, this therapeutic modality was not effective for a murine MRSA arthritis model. Approximately 30% of intra-articular leukocytes, mainly neutrophils, died immediately after PDT, and a further decrease in the number of intra-articular leukocytes and atrophy of the synovial tissue were seen 24 h after PDT. Isolated peripheral neutrophils showed significant affinity for Photofrin and showed significant morphological damage, resulting in cell death, when they were subject to PDT using Photofrin. These results indicate that intra-articular neutrophils have an influence on the effects of PDT for MRSA arthritis.

Drug-induced photosensitivity.

(1) Photosensitivity reactions are cutaneous disorders due to exposure to ultraviolet (UV) radiation of natural or artificial origin. They occur or are more prevalent on unprotected skin. The main clinical manifestations are burns, eczema-like rash, urticaria, pigmentation, or onycholysis; (2) Many drugs increase cutaneous sensitivity to UV, sometimes for therapeutic purposes, but it is generally an unwanted effect.

Nonoperable patients with superficial esophageal cancer treated by photodynamic therapy after chemoradiotherapy have more severe complications than patients treated in primary intent.

INTRODUCTION: Photodynamic therapy (PDT) is a therapeutic option in patients with a superficial esophageal cancer. Recently, PDT was shown to be effective as a salvage therapy for a local recurrence after chemoradiotherapy (CRT). AIM: To compare retrospectively the results and the complications rate of PDT between consecutive patients treated in primary intent for a superficial esophageal cancer versus patients treated by PDT for a local recurrence after CRT. METHODS: Between 1999 and 2007 in a single center, 40 consecutive patients were treated by PDT for a superficial esophageal cancer, 25 (group 1) in primary intent and 15 (group 2) for a local recurrence after CRT. Two days after intravenous (IV) Photofrin (2 mg/kg), the phototherapy was performed with a dye laser. The treatment response and severe complications, defined as perforation and stricture requiring endoscopic dilation, were compared between the two groups. RESULTS: The patient and tumor characteristics were not different between the two groups. In group 1, 19 out of 25 patients (76%) were successfully treated versus 8 out of 15 patients (53%) in group 2 (P= 0.17). Severe complications occurred more frequently in patients with a prior CRT (8%vs 46.7%, P= 0.008) and included two perforations and five strictures requiring endoscopic dilation, while only two strictures occurred in group 1. A prior CRT was an independent risk factor of severe complications (odds ratio [OR] 8.05; 95% confidence interval [CI]1.22-43.0). CONCLUSIONS: Severe complications were significantly more frequent in patients treated after a prior CRT. PDT as a salvage therapy in patients with a local recurrence after CRT for esophageal cancer tended to be less efficient than in first-line treatment.

[External radiotherapy and photodynamic therapy for esophageal carcinoma: a dangerous association?]. / Radiothérapie externe et photothérapie dynamique des cancers de l'oesophage: une association dangereuse ?

A 60-year-old man presented an oesophageal transmural necrosis fistulised in the trachea following curative photodynamic therapy (PDT) for a superficial recurrence of an oesophageal carcinoma, initially treated by radiochemotherapy. Two stents, a tracheal and an oesophageal one, were placed. Eight months later the patient is in complete remission with only mild swallowing problems. This complication, although unusual, has already been described by other teams with the association of radiochemotherapy and PDT. The present case study suggests that illumination dose should be lowered in this indication.

Patient predictors of esophageal stricture development after photodynamic therapy.

BACKGROUND & AIMS: The most common significant adverse event after photodynamic therapy (PDT) with porfimer sodium is esophageal stricture formation. This study assessed whether pretreatment variables, including prior endoscopic therapy for Barrett's esophagus, are associated with post-PDT stricturing. METHODS: Data from all patients who had undergone PDT with porfimer sodium for Barrett's esophagus with high-grade dysplasia, intramucosal carcinoma, or T1 cancer at our institution since 1997 were reviewed. RESULTS: One hundred sixteen patients underwent 160 courses of PDT. The incidence of stricture formation after index PDT was 16% (19/116). For all PDT courses, the overall incidence of stricture was 23% (37/160). Stricture rate was significantly higher after a second PDT course compared with index PDT (43% vs 16%, P = .0007). There was no association between post-PDT stricture development and age, gender, body mass index, or prior endoscopic mucosal resection. Patients who developed a stricture had a longer length of Barrett's esophagus before treatment than those who did not develop a stricture (7.7 vs 5.7 cm for index PDT only, P = .025; 7.4 vs 5.7 cm for all PDT courses, P = .007). Length of Barrett's esophagus, multiple PDT courses, and presence of intramucosal carcinoma on pretreatment pathology were independent predictors of post-PDT stricture in a stepwise logistic regression analysis controlling for treatment variables, including treatment length. CONCLUSIONS: An increased risk of stricture development was seen after multiple courses of PDT. An association between post-PDT stricture and length of Barrett's esophagus but not treatment length was also found. Endoscopic mucosal resection did not appear to influence the likelihood of stricture development after porfimer sodium-based PDT.

Cranial neuropathies after intracranial Photofrin-photodynamic therapy for malignant supratentorial gliomas-a report on 3 cases.

BACKGROUND: In an RCT of PDT in the treatment of malignant gliomas, 3 patients developed cranial neuropathies after photoillumination. We are aware of no previous reports on cranial neuropathy after intracranial PDT. METHODS: In a cohort of 80 patients, there were 41 men and 39 women; 47 were newly diagnosed and 33 had recurrent tumors. All patients underwent surgical tumor extirpation. There were 77 malignant gliomas, 2 meningiomas, and 1 metastatic tumor. The tumor locations were as follows: 39 frontal, 25 temporal, 12 parietal, and 4 occipital. Of the 25 patients with temporal lobe tumors, 18 received PDT. RESULTS: Three of the 18 patients with temporal lobe tumors developed cranial neuropathies after PDT. The floor of the middle fossa received photoillumination in all 3 patients. This complication was not seen in any other patient with tumors in the frontal, parietal, or occipital regions, or patients with temporal lobe tumors who did not receive PDT. The first patient developed seventh nerve paresis and hypoesthesia in fifth nerve distribution, which resolved only partially. The second patient developed a seventh nerve paresis that resolved completely. The third patient developed transient neuralgic pain in the trigeminal nerve distribution. CONCLUSIONS: Cranial neuropathies could be the result of photoillumination of fifth and seventh cranial nerves during PDT of the temporal fossa. We recommend shielding of the middle fossa floor during PDT.

The application of photodynamic therapy in the head and neck.

UNLABELLED: Photodynamic therapy (PDT) is considered to be a minimally invasive treatment modality which shows great promise in premalignant and malignant conditions of the head and neck. This therapy can be applied before or after any of the conventional treatment modalities (ie surgery, radiotherapy or chemotherapy) and the treatment can be repeated as much as is needed at the same site. PDT uses photosensitizing drugs that are activated by exposure to light of a specific wavelength. Illumination of the suspected premalignant or malignant site by light at the activating wavelength results in cellular destruction by a non-free radical oxidative process. Most photosensitizers are administered systemically, although some can be applied topically in the treatment of skin cancer. Recent developments in photosensitizers and light delivery systems have substantially reduced treatment times and residual photosensitivity, while increasing the achievable depth of necrosis. Compared with standard approaches, PDT can achieve equivalent or greater efficacy in the treatment of premalignant and malignant lesions in the head and neck, with greatly reduced morbidity and disfigurement. The technique is simple, can commonly be carried out in outpatient clinics, and is highly acceptable to patients. It can be repeated to debulk large tumours progressively, and it can also be applied through interstitial light delivery to large solid tumours. CLINICAL RELEVANCE: Photodynamic therapy is now shown to achieve equivalent or greater efficacy than standard treatment of premalignant and malignant lesions in the head and neck, with greatly reduced morbidity and disfigurement.

Subclinical photodynamic therapy treatment modifies the brain microenvironment and promotes glioma growth.

Photodynamic therapy (PDT) has been clinically investigated as an adjuvant local therapy for brain tumors. Therapeutic interventions intended to promote tumor cell death can also promote changes in the tumor microenvironment that could favor tumor growth. We have previously shown that PDT can activate pro-angiogenic factors in the normal rodent brain. This study seeks to further elucidate the effects of subtherapeutic doses of Photofrin-PDT on normal brain and to establish a mouse model for studying glioma progression in an environment modified by oxidative stress. Photofrin was administered to nude mice, and a defined intracranial area was illuminated with laser to deliver an optical dose equivalent to 80 J/cm(2). Three and 7 days after PDT, mice were sacrificed and brains were fixed and analyzed by immunohistochemistry. PDT treatment resulted in transient increase in cell proliferation, associated with a robust activation of astrocytes and microglia in the treated region, without causing substantial cell death. To test how this modified environment would affect glioma growth, human glioblastoma U87 cells were implanted in the PDT-treated hemisphere or in the control brain subjected to sham surgery. Significantly larger tumors were observed after 3 weeks in the PDT treated brains relative to control treatment. Our results indicate that subclinical Photofrin-PDT locally alters the brain homeostasis without inflicting significant disruption to the tissue architecture, providing a model to study the effects of the microenvironment on glioma growth, with implications for the optimization of the clinical use of PDT for brain tumors.

Predictors of stricture formation after photodynamic therapy for high-grade dysplasia in Barrett's esophagus.

BACKGROUND: Stricture formation is the leading cause of long-term morbidity after photodynamic therapy (PDT). Risk factors for stricture formation have not been studied. OBJECTIVE: To assess risk factors for stricture formation in patients undergoing PDT for Barrett's esophagus with high-grade dysplasia (HGD). DESIGN: Retrospective cohort study. SETTING: Barrett's Unit, Mayo Clinic, Rochester, Minnesota. METHODS: Records of patients undergoing PDT for HGD were reviewed. Patients underwent PDT by using either bare cylindrical diffusing fibers (2.5-5.0 cm in length) or balloon diffusers with 5- to 7-cm windows. Univariate and multivariate logistic regression analyses were performed to assess risk factors for stricture formation. MAIN OUTCOME MEASUREMENT: Esophageal stricture formation. RESULTS: Thirty-five of 131 patients (27%) developed strictures. On multivariate analysis, statistically significant predictors of stricture formation were the following: EMR before PDT was odds ratio (OR) 2.7, 95% confidence interval (CI) 1.13-6.59; a prior history of esophageal stricture was OR 2.7, 95% CI 1.15-6.47; and the number of PDT applications was OR 2.2, 95% CI 1.22-4.12. The OR for stricture formation in patients when centering balloons were used was 0.41, 95% CI 0.11-1.46, P = .168, indicating that centering balloons did not significantly decrease the risk of stricture formation. LIMITATIONS: Retrospective single-center study; small proportion of patients treated with centering balloons. CONCLUSIONS: Risk factors for development of strictures after PDT included history of a prior esophageal stricture, performance of EMR before PDT, and more than 1 PDT application in 1 treatment session. The use of centering balloons was not associated with a statistically significant reduction in the risk of stricture formation.

Feasibility of photofrin II as a radiosensitizing agent in solid tumors--preliminary results.

BACKGROUND: Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in in vitro and in vivo tumor models. We aimed to investigate the feasibility of a clinical application of Photofrin II. MATERIAL AND METHODS: 12 patients were included in the study (7 unresectable solid tumors of the pelvic region, 3 malignant gliomas, 1 recurrent oropharyngeal cancer, 1 recurrent adenocarcinoma of the sphenoid sinus). The dose of ionizing irradiation was 30-50.4 Gy; a boost irradiation of 14 Gy was added for the pelvic region. All patients were intravenously injected with 1 mg/kg Photofrin II 24 h prior to the commencement of radiotherapy. Magnetic resonance imaging (MRI) controls and in some cases positron emission tomography (PET) were performed in short intervals. The mean follow-up was 12.9 months. RESULTS: No major adverse events were noted. Minor adverse events consisted of mild diarrhea, nausea and skin reactions. A complete remission was observed in 4/12 patients. A reduction in local tumor volume of >45% was achieved in 4/12 patients. Stable disease was observed in 4/12 patients. 1 patient showed local disease progression after 5 months. CONCLUSION: The early follow- up results are encouraging regarding the feasibility of the application of Photofrin II as a radiosensitizing agent.

Changes in esophageal motility after porfimer sodium photodynamic therapy for Barrett's dysplasia and mucosal carcinoma.

Esophageal dysmotility is common in patients with Barrett's esophagus. Previously we have reported deterioration of esophageal motility after photodynamic therapy (PDT) in a heterogeneous group of patients with esophageal carcinoma. This prospective study in consecutive patients describes changes in motility noted after endoscopic ablation. Forty-seven patients referred to our institution for endoscopic ablation for Barrett's high grade dysplasia or mucosal carcinoma between August 2001 and May 2003 were prospectively evaluated with esophageal manometry before and after porfimer sodium PDT. Six patients did not complete the study. Manometry results were classified as normal, diffuse esophageal spasm, ineffective esophageal motility, or aperistalsis. Abnormal esophageal motility was found in 14 of 47 (30%) patients at study entry ([diffuse esophageal spasm] DES-3, [ineffective esophageal motility] IEM-7, Aperistalsis-4). After PDT, 11 of 41 patients with paired studies experienced a change in manometric diagnosis. Three patients had an improvement in motility, seven a worsening and one changed diagnosis, but did not particularly worsen or improve. No patient developed new aperistalsis. Therefore, abnormal motility was present in 19 of 41 (46%) patients after PDT (DES-2, IEM-14, Aperistalsis-3). There was a statistically significant (P = 0.016) relationship with longer segment Barrett's esophagus and deterioration of function. Baseline abnormalities in motility can occur in patients with Barrett's high-grade dysplasia or mucosal carcinoma. Changes in esophageal function also may occur following photodynamic therapy, but usually are not clinically significant. Worsening in function was more likely to occur in patients with longer segment Barrett's esophagus.

A phase II trial of intraperitoneal photodynamic therapy for patients with peritoneal carcinomatosis and sarcomatosis.

PURPOSE: A previous phase I trial of i.p. photodynamic therapy established the maximally tolerated dose of Photofrin (Axcan Pharma, Birmingham, AL)-mediated photodynamic therapy and showed encouraging efficacy. The primary objectives of this phase II study were to determine the efficacy and toxicities of i.p. photodynamic therapy in patients with peritoneal carcinomatosis and sarcomatosis. EXPERIMENTAL DESIGN: Patients received Photofrin 2.5 mg/kg i.v. 48 hours before debulking surgery. Intraoperative laser light was delivered to the peritoneal surfaces of the abdomen and pelvis. The outcomes of interest were (a) complete response, (b) failure-free survival time, and (c) overall survival time. Photosensitizer levels in tumor and normal tissues were measured. RESULTS: One hundred patients were enrolled into one of three strata (33 ovarian, 37 gastrointestinal, and 30 sarcoma). Twenty-nine patients did not receive light treatment. All 100 patients had progressed by the time of statistical analysis. The median failure-free survival and overall survival by strata were ovarian, 2.1 and 20.1 months; gastrointestinal cancers, 1.8 and 11.1 months; sarcoma, 3.7 and 21.9 months. Substantial fluid shifts were observed postoperatively, and the major toxicities were related to volume overload. Two patients died in the immediate postoperative period from bleeding, sepsis, adult respiratory distress syndrome, and cardiac ischemia. CONCLUSIONS: Intraperitoneal Photofrin-mediated photodynamic therapy is feasible but does not lead to significant objective complete responses or long-term tumor control. Heterogeneity in photosensitizer uptake and tumor oxygenation, lack of tumor specificity for photosensitizer uptake, and the heterogeneity in tissue optical properties may account for the lack of efficacy observed.

Porfimer: new drug. Endobrachyesophagus: encouraging preliminary results.

(1) Patients with endobrachyesophagus (Barrett's oesophagus) and high-grade dysplasia are at high risk of developing adenocarcinoma within 3 to 7 years. Esophagectomy carries a risk of major morbidity and mortality. Local treatments (photocoagulation and endoscopic mucosectomy) are currently under evaluation. (2) Marketing authorisation has been granted for a photodynamic treatment based on intravenous porfimer injection and laser illumination of the lesion. (3) In a randomised trial comparing porfimer photodynamic therapy plus omeprazole with omeprazole alone, 208 patients were monitored for at least 2 years. There was no difference in mortality between the groups. Thirteen percent of patients on combination treatment developed adenocarcinoma (stage not specified), compared to 29% of patients treated with omeprazole alone (p = 0.006). Nearly half the patients had symptoms of photosensitization, and 38% had oesophageal contraction requiring at least 1 dilation session. (4) In practice, despite some encouraging results, we do not know if photodynamic therapy based on porfimer reduces the long-term risk of recurrence, invasive carcinoma, or major surgery. However, there is a risk of serious adverse effects. Porfimer photodynamic therapy needs to be compared with other endoscopic interventions.