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Photo Dynamic Therapy

Photodynamic therapy (PDT), matured as a feasible medical technology in the 1980s at several institutions throughout the world, is used to eradicate premalignant and early-stage cancer and reduce the tumour size in end-stage cancers[1] involving three key components: a photosensitizer, light, and tissue oxygen.

Treatment of internal organs may be achieved through the use of endoscopes and fiber optic catheters to deliver light, and intravenously-administered photosensitizers. A great deal of research and clinical study is now underway to determine optimal combinations of photosensitizers, light sources, and treatment parameters for a wide variety of different cancers. It is currently being tested as a treatment for severe acne.[2][3][4]

In photo Dynamic Therapy, dyes or medications that absorb light are absorbed by tumours, then exposed to specific wave lenghts of light. Light photons are absorbed by the pigment of the dye, which becomes chemically reactive and causes the cancer cells to die.

Professor Campbell was trained in Photo Dynamic Therapy in 2003 when the Chancellor of Swinburne University funded two trips to Germany and Ireland where he was trained by the Russian Scientists who completed the original research of the Radachlorin photosensitiser

Russian original research

Russian 5 year clinical experience

PDT and vaccine synergism

We cite the following peer reviewed references but first let us consider the significance of peer review.
Pragmatically, peer review refers to the work done during the screening of submitted manuscripts and funding applica-tions. This process encourages authors to meet the accepted standards of their discipline and prevents the dissemina-tion of irrelevant findings, unwarranted claims, unaccepted interpretations, and personal views. Publications that have not undergone peer review are likely to be regarded with suspicion by scholars and professionals.
So we have revisited PubMed, at the National Library of Medicine, Bethesda Maryland USA and mainly cited human research (in vivo) rather than laboratory research (in vitro) where the benefits of therapy are stated in conventional terms. This highlights therapies which are scientific, properly substantiated and capable of benefiting many cancer patients.
It is indeed alright to collaborate with healers from other backgrounds and traditions, especially when the greater goal of the best outcome for the patients is achieved, rather than protecting the sanctity and exclusiveness of the MD Club.
Wisneski L MD, The Scientific Basis of Integrative Medicine, CRC Press 2005.

Photo Dynamic Therapy (PDT) in Australia
PDT has been used by Prof. Andrew Kaye, the James Stewart Professor of Surgery, at the Royal Melbourne Hospital, over the past 17 years using lasers to selectively kill brain cancer while not harming adjacent normal brain. A special laser is used to produce light that will activate the sensitiser chemical within the cancer cell. This produces a local toxic reaction that kills the cancer cell while not harming the adjacent brain.
Clinically over 200 patients have been treated with Haematoporphyrin Derivative (HpD) which is the largest study of this type of the therapy in the world of brain tumours. The results of the trial show that the therapy is well tolerated and the median life expectancy with primary malignant glioma is extended from nine months using conventional therapies of surgery and radiotherapy to 26 months using surgery, PDT and radiotherapy. Nearly 25% of patients have survived more than 5 years.

Dr Miyatake in his 2009 article using Photo Dynamic Therapy for brain tumours says he uses 5-aminolevulinic acid (5-ALA) for photodynamic diagnosis in the removal of malignant gliomas (brain tumour). 5-ALA is converted to pro-toporphyrin IX (PpIX) in the body and emits red fluorescence, with the excitation of blue-violet light. As PpIX prefer-entially accumulates in tumour tissue in comparison with normal tissue, this red fluorescence becomes a good hall-mark for discrimination between normal and tumour tissues, especially in malignant gliomas, which have infiltrative characteristics. In this paper he discusses high quality international research on 5-ALA guided surgery for malignant gliomas.

Dr Zheng Huang in his 2006 review article says Photodynamic therapy(PDT) is a unique treatment modality in which a systemically or locally administered photosensitizer is activated locally by irradiating the lesion site with light of a suitable wavelength and power through a specially designed light applicator.
PDT offers various treatment options in cancer management and has been used for localized superficial or endolu-minal malignant and premalignant conditions. Its application has also been recently expanded to solid tumours.
The non-invasive or minimally invasive nature of PDT also offers great promise in some non-malignant conditions.
Photo dynamic diagnostics using fluorescent markers provide an innovative, non-invasive and safer imaging technol-ogy. Dr Huang covers the use of PDT in Dermatological (Skin) Disease, Ophthalmic (Eye) Disease, Head and Neck Cancer, Brain tumours, Pulmonary (Lung) and Pleural Mesothelial Cancer, Cardiovascular Diseas, Gastroenterologi-cal Cancer, Urological Disease and Gynaecological Cancer.
He provides 129 peer reviewed articles in this review article.

Dr Martijn in his review article in 2006 says Photo Dynamic Therapy is increasingly being recognized as an attrac-tive, alternative treatment modality for superficial cancer. Efficacy is high for small superficial tumours, and, except for temporary skin photosensitization, there are no long term side effects if appropriate protocols are followed. Heal-ing occurs with little or no scarring and the procedute can be repeated without cumulative toxicity. The data show that, when properly used, PDT is an effective alternative treatment in oncology. He provides 118 references in this review article.
Dr Allen Oseroff in his 2005 paper has described the treatment of diffuse basal cell carcinomas and basaloid follicular hamartomas in nevoid basal cell carcinoma syndrome by wide area 5-Aminolevulinic acid Photo Dynamic Therapy.
Results: Morbidity was minimal, with selective phototoxicity and rapid healing. After 4-7 sessions, with individual areas receiving 1 to3 treatments, the patients had 85% to 98% overall clearance and excellent cosmetic outcomes with-out scarring. Responses were durable up to 6 years. This study demonstrates the success of treating widespread skin cancers in 3 children at the highly regarded Roswell Park Cancer Institute.

Dr Paoli in his 2006 paper described the treatment of ten patients with penile intraepithelial neoplasia (cancer) with Photo Dynamic Therapy. Lesions responded in 7 out of 10 patients. No patient developed invasive penile cancer with a mean follow up of 46.5 months.

Dr Pech in his 2005 paper described long term results of PDT with 5-aminolevulinic acid for superficial Barretts can-cer and high-grade intraepithelial neoplasia. The excellent long-term results of PDT with ALA in patients with HGIN or mucosal cancer might offer PDT with ALA as an alternative to surgical oesophagectomy (removal of the oesopha-gus) and endoscopic resection, especially in cases with multifocal Barrett‘s neoplasia(cancer).

The Victorian Cosmetic Institute at Templestowe and Berwick use Photo Dynamic Therapy to treat pre cancerous skin lesions, some non-melanoma cancerous skin lesions and psoriasis.

CDC Clinics in Armidale Victoria use Photo Dynamic Therapy to treat skin cancers. They claim an 80% success rate for skin cancers.

Conclusions regarding Photo Dynamic Therapy
There are 6753 articles on PubMed regarding Photo Dynamic Therapy and Cancer.
As can be seen in the articles I have cited on previous pages clinical treatment and further research is wide spread including the 17 years experience at The Royal Melbourne Hospital.

Technol Cancer Res Treat. 2005 Jun;4(3):283-93.
A review of progress in clinical photodynamic therapy.
Huang Z.

HealthONE Alliance, 899 Logan Street, Suite 203, Denver, CO 80203, USA. zheng_huang@msn.com
Abstract
Photodynamic therapy (PDT) has received increased attention since the regulatory approvals have been granted to several photosensitizing drugs and light applicators worldwide. Much progress has been seen in basic sciences and clinical photodynamics in recent years. This review will focus on new developments of clinical investigation and discuss the usefulness of various forms of PDT techniques for curative or palliative treatment of malignant and non-malignant diseases.

PMID: 15896084 [PubMed - indexed for MEDLINE]PMCID: PMC1317568Free PMC Article

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A review of clinical photo dynamic therapy

Brain Nerve. 2009 Jul;61(7):835-42.
[Intraoperative photo-dynamic diagnosis of brain tumors].
[Article in Japanese]

Miyatake S, Kajimoto Y, Kuroiwa T.

Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
Abstract
Conventionary, we use 5-aminolevulinic acid (5-ALA) for photo-dynamic diagnosis in the removal of malignant gliomas. 5-ALA is converted to protoporphyrin IX (PpIX) in the body and emits red fluorescence, with the excitation of blue-violet light. As PpIX preferentially accumulates in the tumor tissue in comparison with normal tissue, this red fluorescence becomes a good hallmark for discrimination between normal and tumor tissues, especially in malignant gliomas, which have infiltrative characteristics. Approximately 80% to 90% of the malignant gliomas show this red fluorescence in surgery as mentioned above, while only a limited number of metastatic brain tumor cases do. In the surgery for metastatic brain tumor and lesionectomy for radiation necrosis and neurodegenerative disease, white matter around the lesion showed vague fluorescence, which also provided us with a hallmark in the surgery. Additionally, in meningioma, some tumors showed the red fluorescence, which is especially helpful in the removal of the infiltrative portion in the bone and normal parenchyma. In this paper, we also discuss high quality international reserch on 5-ALA-guided surgery for malignant gliomas. The most important point in 5-ALA-guided microsurgery is the use of good equipment that can provide sufficient operative fields even under fluorescence mode.

PMID: 19618861 [PubMed - indexed for MEDLINE]

Oncologist. 2006 Oct;11(9):1034-44.

Photodynamic therapy in oncology.
Triesscheijn M, Baas P, Schellens JH, Stewart FA.

Division of Experimental Therapy (H6), The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Abstract
Photodynamic therapy (PDT) is increasingly being recognized as an attractive, alternative treatment modality for superficial cancer. Treatment consists of two relatively simple procedures: the administration of a photosensitive drug and illumination of the tumor to activate the drug. Efficacy is high for small superficial tumors and, except for temporary skin photosensitization, there are no long-term side effects if appropriate protocols are followed. Healing occurs with little or no scarring and the procedure can be repeated without cumulative toxicity. Considering the efficacy and lack of long-term toxicity of PDT, and the fact that the first treatment of cancer with PDT was done more than 100 years ago, one might expect that this treatment had already become an established therapy. However, PDT is currently offered in only a few selected centers, although it is slowly gaining acceptance as an alternative to conventional cancer therapies. Here, we show the developmental steps PDT underwent and summarize the current clinical applications. The data show that, when properly used, PDT is an effective alternative treatment option in oncology.

PMID: 17030646 [PubMed - indexed for MEDLINE]Free Article

http://theoncologist.alphamedpress.org/cgi/content/full/11/9/1034

Brain Nerve. 2009 Jul;61(7):835-42.
[Intraoperative photo-dynamic diagnosis of brain tumors].
[Article in Japanese]

Miyatake S, Kajimoto Y, Kuroiwa T.

PMID: 19618861 [PubMed - indexed for MEDLINE]

World J Surg. 2008 Aug;32(8):1763-7.
Image-guided liver mapping using fluorescence navigation system with indocyanine green for anatomical hepatic resection.
Aoki T, Yasuda D, Shimizu Y, Odaira M, Niiya T, Kusano T, Mitamura K, Hayashi K, Murai N, Koizumi T, Kato H, Enami Y, Miwa M, Kusano M.

Department of General and Gastroenterological Surgery, School of Medicine, Showa University, Tokyo, Japan. takejp@wb4.so-net.ne.jp
Abstract
BACKGROUND: In malignant hepatic neoplasm, anatomic resection could improve survival and limit complications from hepatectomy. Our purpose was to develop an intraoperative method for identifying segment and subsegment of the liver with high-sensitivity near-infrared fluorescence imaging.

METHODS: The subjects were 35 patients with hepatic malignant liver disease who received hepatectomy in 2006. The segments of liver method of identification that used infrared observation camera system termed Photo Dynamic Eye-2 (PDE-2) with indocianine green (ICG) for the patient with malignant liver tumor (hepatocellular carcinoma: 13 cases; metastatic liver cancer: 18 cases; intrahepatic cholangio carcinoma: 4 cases) were performed before liver resection.

RESULTS: Although greenish stain of the liver surface after the injection of ICG via portal vein is not visible clearly without infrared observation camera system PDE-2, 1 minute after injection of ICG with fluorescent using infrared observation camera system PDE-2, demarcation of liver segment and subsegment was clearly detected. Ten minutes after injection of ICG with fluorescent using infrared observation camera system PDE-2, fluorescence of liver subsegment remained. Stained subsegment and segment of liver were identifiable in 33 (94.3%) of the 35 patients. There were no complications or side-effects related to the injection of patent blue dye.

CONCLUSION: We demonstrated here that near-infrared fluorescence imaging system is a novel and reliable intraoperative technique to identify hepatic segment and subsegment for anatomical hepatic resection.

PMID: 18543027 [PubMed - indexed for MEDLINE]

J Clin Neurosci. 1999 May;6(3):227-32.
Modulation of light delivery in photodynamic therapy of brain tumours.
Tudge SH, Kaye AH, Hill JS.

Neuroscience Research Laboratory, Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Australia.
Abstract
This study was performed to determine whether modulation of light delivery could improve tumour kill in photodynamic therapy (PDT) of brain tumours, as optimal dosimetry has not been fully established. One hundred and sixty-five adult Wistar rats were treated, of which 70 had an implanted C6 cerebral glioma. Haematoporphyrin derivative (HpD) was injected at doses between 0 and 20 mg/kg, 24 h prior to irradiation with 630 nm laser light. The total energy dose was varied from 0 to 1200 J/cm(2), with fluence rates of 625, 3125 or 9375 mW/cm(2). In some studies, the light delivered at 3125 mW/cm(2) was divided into 10 fractions of approximately 13 s, with refractory intervals of 60 s. The most striking finding was that HpD was much more potent than previously reported. All doses greater than 1.0 mg/kg resulted in normal brain damage with light doses above 50 J/cm(2). However, at 1.0 mg/kg, significant normal injury was not apparent until 1200 J/cm(2). Failure of drug-light dose reciprocity indicated that photobleaching occurred, protecting normal tissue. Selective tumour kill was observed to 2.2. mm depth (SE +/- 0.44 mm). Using lower power or fractionated light did not improve tumour kill and normal tissue injury occured with fluence rates of 9375 mW/cm(2). In conclusion, the doses of HpD currently used in clinical brain tumour trials may be too high to achieve selective tumour kill. Higher light fluence rates allowed shorter intraoperative irradiation times with no loss of efficacy. Photodynamic therapy continues to demonstrate potential as an effective treatment for local control of cerebral lesions.

PMID: 18639156 [PubMed - in process]

J Clin Neurosci. 2006 Jul;13(6):615-25. Epub 2006 Mar 22.
Photodynamic therapy of cerebral glioma--a review Part I--a biological basis.
Stylli SS, Kaye AH.

Department of Neurosurgery, 5th Floor Clinical Sciences Building, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria 3052, Australia. stanley.stylli@mh.org.au
Abstract
Photodynamic therapy (PDT) has been investigated extensively in the laboratory for decades, and for over 25 years in the clinical environment, establishing it as a useful adjuvant to standard treatments for many cancers. A combination of both photochemical and photobiological processes occur that lead to the eventual selective destruction of the tumour cells. It is a potentially valuable adjuvant therapy that can be used in conjunction with other conventional therapies for the treatment of cerebral glioma. PDT has undergone extensive laboratory studies and clinical trials with a variety of photosensitizers (PS) and tumour models of cerebral glioma. Many environmental and genetically based factors influence the outcome of the PDT response. The biological basis of PDT is discussed with reference to laboratory and preclinical studies.

PMID: 16554159 [PubMed - indexed for MEDLINE]

J Clin Neurosci. 2006 Aug;13(7):709-17. Epub 2006 Mar 29.
Photodynamic therapy of cerebral glioma - a review. Part II - clinical studies.
Stylli SS, Kaye AH.

Department of Neurosurgery, Department of Surgery, 5th Floor Clinical Sciences Building, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria 3052, Australia. stanley.stylli@mh.org.au
Abstract
Photodynamic therapy (PDT) is a binary treatment modality that has been used to treat malignant brain tumours for 25 years. The treatment involves the selective uptake of a photosensitizer (PS) by the tumour cells followed by irradiation of the tumour with light of the appropriate wavelength to excite and activate the PS resulting in selective tumour destruction and is a potentially valuable adjunct to surgical excision and other conventional therapies. PDT has undergone extensive laboratory studies and clinical trials with a variety of PS and tumour models. These are discussed with reference mainly to clinical studies involving the PDT of brain tumours.

PMID: 16567094 [PubMed - indexed for MEDLINE]

J Clin Laser Med Surg. 1996 Oct;14(5):251-61.
Photodynamic therapy of brain tumors.
Popovic EA, Kaye AH, Hill JS.

Department of Neurosurgery, Melbourne Neuroscience Centre, Royal Melbourne Hospital, Victoria, Australia.
Abstract
Photodynamic therapy (PDT) for the treatment of a variety of brain tumors, particularly gliomas, has been extensively investigated in laboratory studies and has been studied in clinical trials. The main advantage of PDT lies in its ability to select out tumor cells that are infiltrating brain parenchyma and that are responsible for local tumor recurrence, the major therapeutic dilemma in the treatment of gliomas. PDT has been shown to be safe clinically but adequate trials have yet to be undertaken to prove its efficacy and much work remains to be done to optimize treatment. The laboratory studies and clinical trials involving PDT in the treatment of cerebral tumors, particularly the commonest brain tumors, gliomas, are discussed.

PMID: 9612191 [PubMed - indexed for MEDLINE]

Semin Surg Oncol. 1995 Sep-Oct;11(5):335-45.
Photodynamic therapy of brain tumors.
Popovic EA, Kaye AH, Hill JS.

Department of Neurosurgery, Melbourne Neuroscience Centre, Royal Melbourne Hospital, Victoria, Australia.
Abstract
Photodynamic therapy (PDT) is a binary treatment modality suitable for various malignant tumors including brain. It involves the selective uptake of a photosensitizer into tumor followed by intraoperative irradiation of the tumor with light of an appropriate wavelength to cause activation of the sensitizer and subsequent selective tumor destruction. PDT has been extensively investigated in laboratory studies and has been used in clinical trials to treat a variety of brain tumors, particularly gliomas. The main advantage of PDT lies in its ability to select out infiltrating tumor cells that are responsible for local tumor recurrence. The therapy has been shown to be safe clinically but adequate trials have yet to be undertaken to prove its efficacy and much work remains to be done to optimize treatment. The biological basis, laboratory studies, and clinical trials involving PDT in the treatment of cerebral tumors are discussed.

PMID: 7569555 [PubMed - indexed for MEDLINE]

Ann Acad Med Singapore. 1993 May;22(3 Suppl):470-81.
Photodynamic therapy of brain tumours.
Kaye AH, Hill JS.

Department of Neurosurgery, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Abstract
Photodynamic therapy is a binary treatment combining the selective uptake of a photosensitizer into a tumour followed by irradiation of the tumour with light of the appropriate wavelength to cause activation of the sensitizer as selective tumour kill. Photodynamic therapy has been extensively investigated in laboratory studies in the treatment of cerebral tumours and has been utilised in clinical trials to treat a variety of tumours including cerebral glioma. The clinical trials have usually used PDT as an adjuvant therapy following tumour resection but studies are being undertaken to use the treatment in combination with stereotactic techniques. The photosensitizer haematoporphyrin derivative (HpD) has been shown to be selectively localised into all grades of glioma with a direct correlation between the grade of glioma and HpD level in the tumour. The levels were highest in the glioblastoma multiforme (mean uptake of 5.9 micrograms HpD/g tumour wet weight) and lower in the intermediate grade anaplastic astrocytoma (2.4 micrograms/g) and low grade astrocytoma (1.6 micrograms/g). Uptake into normal brain tissue taken from HpD sensitized patients was 0.2 microgram/g. HpD was also localised into the brain adjacent to the tumour region.

PMID: 8215203 [PubMed - indexed for MEDLINE]

J Clin Oncol. 2001 Jan 15;19(2):519-24.
Phase I and pharmacokinetic study of photodynamic therapy for high-grade gliomas using a novel boronated porphyrin.
Rosenthal MA, Kavar B, Hill JS, Morgan DJ, Nation RL, Stylli SS, Basser RL, Uren S, Geldard H, Green MD, Kahl SB, Kaye AH.

Centre for Developmental Cancer Therapeutics, Parkville, Australia. mark.rosenthal@ludwig.edu.au
Abstract
PURPOSE: To determine the recommended dose, toxicity profile, and pharmacokinetics of a novel boronated porphyrin (BOPP) for photodynamic therapy (PDT) of intracranial tumors.

PATIENTS AND METHODS: BOPP was administered alone in increasing doses (0.25, 0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg) preoperatively in patients with intracranial tumors undergoing postresection PDT until dose-limiting toxicity (DLT) was observed.

RESULTS: Twenty-nine assessable patients with intracranial tumors received BOPP intravenously 24 hours before surgery. The recommended dose was 4 mg/kg. Dose escalation was limited by thrombocytopenia. The most common nonhematologic toxicity was skin photosensitivity. Pharmacokinetic parameters showed increased area under the plasma concentration-time curve and maximum concentration with increased dose. Tumor BOPP concentrations also increased with increased dose.

CONCLUSION: BOPP at a dose of 4 mg/kg was well tolerated. DLT was thrombocytopenia, and photosensitivity was the only other toxicity of note. The efficacy of PDT using BOPP requires further exploration.

PMID: 11208846 [PubMed - indexed for MEDLINE]

Arch Dermatol. 2005 Jan;141(1):60-7.
Treatment of diffuse basal cell carcinomas and basaloid follicular hamartomas in nevoid basal cell carcinoma syndrome by wide-area 5-aminolevulinic acid photodynamic therapy.
Oseroff AR, Shieh S, Frawley NP, Cheney R, Blumenson LE, Pivnick EK, Bellnier DA.

Department of Dermatology, Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, NY 14263, USA. allan.oseroff@roswellpark.org
Abstract
OBJECTIVE: To report the use of wide-area 5-aminolevulinic acid photodynamic therapy to treat numerous basal cell carcinomas (BCCs) and basaloid follicular hamartomas (BFHs).

DESIGN: Report of cases.

SETTING: Roswell Park Cancer Institute. Patients Three children with BCCs and BFHs involving 12% to 25% of their body surface areas. Interventions Twenty percent 5-aminolevulinic acid was applied to up to 22% of the body surface for 24 hours under occlusion. A dye laser and a lamp illuminated fields up to 7 cm and 16 cm in diameter, respectively; up to 36 fields were treated per session.

MAIN OUTCOME MEASURES: Morbidity, patient response, and light dose-photodynamic therapy response relationship and durability.

RESULTS: Morbidity was minimal, with selective phototoxicity and rapid healing. After 4 to 7 sessions, with individual areas receiving 1 to 3 treatments, the patients had 85% to 98% overall clearance and excellent cosmetic outcomes without scarring. For laser treatments, a sigmoidal light dose-response relationship predicted more than 85% initial response rates for light doses 150 J/cm(2) or more. Responses were durable up to 6 years. Conclusion 5-Aminolevulinic acid photodynamic therapy is safe, well tolerated, and effective for extensive areas of diffuse BCCs and BFHs and appears to be the treatment of choice in children.

PMID: 15655143 [PubMed - indexed for MEDLINE]

Acta Derm Venereol. 2006;86(5):418-21.
Penile intraepithelial neoplasia: results of photodynamic therapy.
Paoli J, Ternesten Bratel A, Löwhagen GB, Stenquist B, Forslund O, Wennberg AM.

Department of Dermatology and Venereology, Sahlgrenska University Hospital, SE-41345 Göteborg, Sweden. john.paoli@vgregion.se
Abstract
Failure of response to treatment or recurrent disease is often noted in patients with penile intraepithelial neoplasia. Photodynamic therapy has recently been added to the list of treatment modalities used for this diagnosis. Our primary objective was to study the results of photodynamic therapy in the treatment of penile intraepithelial neoplasia in men over the age of 40 years. Ten patients aged 42-82 years with histopathologically confirmed lesions were studied. Lesions initially responded to photo-dynamic therapy in 7 out of 10 patients. Four of these patients presented no recurrences during a mean follow-up of 35 months, and were completely cleared after 2-8 treatments (mean 4.5 treatments). Three patients presented recurrences after treatment. No patient developed invasive penile cancer (mean follow-up 46.5 months). Photodynamic therapy is an alternative in the treatment of penile intraepithelial neoplasia, although prospective randomized trials are required to provide therapeutic guidelines.

PMID: 16955186 [PubMed - indexed for MEDLINE]Free Article

Gastrointest Endosc. 2005 Jul;62(1):24-30.
Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett's cancer and high-grade intraepithelial neoplasia.
Pech O, Gossner L, May A, Rabenstein T, Vieth M, Stolte M, Berres M, Ell C.

Department of Medicine II, HSK Wiesbaden, Teaching Hospital of the University of Mainz, Germay.
Abstract
BACKGROUND: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has proven to be safe and effective in patients with early neoplasia in Barrett's esophagus. However, long-term results in patients with high-grade intraepithelial neoplasia (HGIN) or with early cancer are still lacking.

METHODS: The aim of the study was to evaluate the efficacy of ALA-PDT and the survival of patients with early Barrett's neoplasia. ALA-PDT was carried out in 66 patients. Protoporphyrin IX induced by oral administration of ALA (60 mg/kg body weight orally applied 4-6 hours before PDT) was used as the photosensitizer. Acid suppression was maintained in all patients.

RESULTS: Between September 1996 and September 2002, 667 patients with early neoplasia in Barrett's esophagus were referred for local endoscopic therapy. A total of 558 patients fulfilled the criteria for local endoscopic therapy, and 66 patients (mean [standard deviation] age 61.4 [10.2] years) with HGIN (group A; n = 35) and early adenocarcinoma (group B; n = 31) were treated by PDT. A total of 82 ALA-PDT were performed. A total of 34 of the 35 patients in group A (97%) and all patients in group B (100%) achieved a complete response during a median follow-up period of 37 months (interquartile range 23-55) (not significant). One local recurrence was observed in group A and 10 in group B (p < 0.005). Seven patients died during follow-up; but, all deaths were not tumor related. No major complications were observed. Disease-free survival in patients with HGIN was 89%, and, in patients with mucosal cancer, it was 68%. The calculated 5-year survival was 97% in group A and 80% in group B, but there occurred no death related to Barrett's neoplasia.

CONCLUSIONS: The excellent long-term results of PDT with ALA in patients with HGIN or mucosal cancer might offer PDT with ALA as an alternative to surgical esophagectomy and endoscopic resection, especially in cases with multifocal Barrett's neoplasia.

PMID: 15990815 [PubMed - indexed for MEDLINE]

Gastroenterology. 1998 Mar;114(3):448-55.
Photodynamic ablation of high-grade dysplasia and early cancer in Barrett's esophagus by means of 5-aminolevulinic acid.
Gossner L, Stolte M, Sroka R, Rick K, May A, Hahn EG, Ell C.

Department of Medicine II, Klinikum der Landeshauptstadt Wiesbaden, Germany.
Comment in:

Gastroenterology. 1998 Mar;114(3):604-6.
Abstract
BACKGROUND & AIMS: The first therapeutic experiences with the conventional photosensitizer dihematoporphyrinester in the treatment of Barrett's esophagus show the curative potential of photodynamic therapy (PDT). The aim of this study was to test 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX, a photosensitizer with a high mucosa specificity without phototoxic side effects on the skin, as a new form of PDT.

METHODS: Thirty-two patients (mean age, 68.5 years) with histologically proven high-grade dysplasia (n = 10) and mucosal cancer (n = 22) in Barrett's esophagus were treated. Four to 6 hours after oral ingestion of 5-ALA (dose, 60 mg/kg body wt), irradiation was conducted with a dye laser system (635 nm) with a light dose of 150 J/cm2. The patients received 20-80 mg omeprazole daily after PDT.

RESULTS: High-grade dysplasia was eradicated in all patients (10 of 10), and mucosal cancer was eliminated in 17 of 22 patients (77%) at a mean follow-up of 9.9 months (range, 1-30 months). All tumors < or = 2 mm in thickness were completely ablated (17 of 17). The method-related mortality and morbidity was 0%.

CONCLUSIONS: Severe dysplasia and thin (< or = 2 mm) mucosal cancer of Barrett's esophagus can be completely ablated. PDT might offer a minimally invasive treatment modality as an alternative to esophagectomy.

PMID: 9496934 [PubMed - indexed for MEDLINE]

Gastrointest Endosc Clin N Am. 2000 Jul;10(3):421-37.
Barrett's esophagus: treatment with 5-aminolevulinic acid photodynamic therapy.
Barr H.

Department of Surgery, Cranfield Postgraduate Medical School (Gloucester), Gloucestershire Royal Hospital, United Kingdom.
Abstract
Barrett's esophagus has been identified as the premalignant precursor of esophageal adenocarcinoma. The eradication of metaplastic or dysplastic columnar-lined (Barrett's) esophagus may prevent progression to esophageal adenocarcinoma. 5-Aminolevulinic acid photodynamic therapy is a simple method for the mucosal ablation of the abnormal segment. Areas of metaplastic epithelium may remain buried after treatment and continued surveillance is necessary. Repeated treatments often are necessary but are very well tolerated with few complications.

PMID: 10899256 [PubMed - indexed for MEDLINE]

Gastroenterol Nurs. 2005 Sep-Oct;28(5):413-9; quiz 420-1.
An educational tool for photodynamic therapy of Barrett esophagus with high-grade dysplasia: from screening through follow-up.
Phan M, Dyke S, Whittaker MA, Simmerman A, Abrams S, Panjehpour M, Overholt BF.

Center of Excellence for PDT of Barrett Esophagus, Thompson Cancer Survival Center, Knoxville, Tennessee 37916, USA. mphan@covhlth.com
Abstract
Photodynamic therapy using a centering balloon was recently approved by the Food and Drug Administration for ablation of Barrett esophagus with high-grade dysplasia. This article is an educational tool for the photodynamic therapy team, addressing four important steps involved with photodynamic therapy: screening for potential patients, patient education, treatment using the centering balloon, and follow-up after treatment. Each step ensures proper care for the patient requiring photodynamic therapy.

PMID: 16234638 [PubMed - indexed for MEDLINE]

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