Oral Administration Of 5-aminolevulinic Acid Research Articles

Comprehensive analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of bladder tumor with 5-aminolevulinic acid.

Intraoperative hypotension remains a serious adverse event of photodynamic diagnosis-assisted transurethral resection of bladder tumor with oral administration of 5-aminolevulinic acid. We conducted a re-analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of the bladder tumor with oral 5-aminolevulinic acid to ascertain its safety. A total of 407 cases who underwent transurethral resection of bladder tumors in our institution were reviewed (274 cases for the PDD group with photodynamic diagnosis and 133 for the white light (WL) group without). A classification of hypotension severity was devised to identify risk factors for clinically troublesome hypotension. The distribution of hypotension severity in each of the PDD and WL groups was compared. Additionally, the patient background and perioperative data by hypotension severity were compared only in the PDD group. More patients with moderate and severe hypotension were noted in the PDD group. The renal function was lower with increasing hypotension severity in the PDD group. More patients on general anesthesia were included in the mild and moderate hypotension group, whereas more patients on spinal anesthesia were included in the severe hypotension group. Furthermore, the frequency of side effects other than hypotension tended to increase with hypotension severity. Renal function impairment and the other adverse effects of 5-aminolevulinic acid may be risk factors for severe hypotension. Mild or moderate hypotension may be caused by general anesthesia and severe hypotension may be caused by spinal anesthesia. To elucidate specific risk factors, further case-control studies are warranted.

Tumor Models for Training of Fluorescence-Guided Brain Tumor Resection

BACKGROUND AND OBJECTIVES: Neurosurgical resection of brain tumors is a technically demanding task with a steep initial learning curve. Experience has been shown to improve surgical performance and increase the rates of resection. High-grade gliomas (HGG) are responsible for 65% of all primary malignant central nervous system tumors and are the commonest surgically treated brain tumor worldwide. There is increasing evidence that maximal safe surgical resection of HGG impacts on overall survival. The delineation of tumor tissue (and hence the extent of resection) is improved by the use of intraoperative tumor fluorescence, which is achieved by preoperative oral administration of 5-aminolevulinic acid. This however relies on the surgeon developing a skillset of operating under different light conditions for which specific training and experience are required. METHODS: We propose a novel, affordable, and highly adaptable model for recreating these surgical conditions and thus simulate fluorescence-guided HGG resection outside the operating theater for trainee neuro-oncological surgeons. We present a model incorporating plant-based polysaccharides, doped with protoporphyrin IX (PpIX), into cadaveric brains of animals. RESULTS: We show that the concentrations of polymer and PpIX can be titrated (using previously published data) to produce mechanical and fluorescence properties that model tumor tissue. We validate the simulation in a neurosurgical skills laboratory. Furthermore, we used a mini spectrometer with handheld probe to collect fluorescence signals and validate the spectroscopic signal from the PpIX. CONCLUSION: It is hoped that this model system will be useful in neurosurgical teaching and training courses and to neurosurgeons who want to try out new techniques or equipment in anatomy laboratories.

Oral 5-aminolevulinic acid administration before transurethral resection of bladder tumor induces perioperative nausea and vomiting

BackgroundThe efficacy of photodynamic diagnosis using 5-aminolevulinic acid during transurethral resection of bladder tumors has been demonstrated, albeit with limited information regarding its side effects. This study aimed to clarify the impact of oral 5-aminolevulinic acid on perioperative nausea and vomiting (NV) for the first time in a real-world clinical practice setting. MethodsPatients who underwent transurethral surgery at Kagawa University between April 2017 and March 2020 were included. Perioperative NV and antiemetic use status were prospectively assessed and compared between the patients who received oral 5-aminolevulinic acid and those who did not. Additionally, univariate and multivariate analyses were performed for predicting postoperative nausea and vomiting. ResultsOf 214 patients, 74 (34.6%) received oral 5-aminolevulinic acid preoperatively. The proportions of preoperative NV and antiemetic use in the patients who received 5-aminolevulinic acid were 9.5% and 4.1%, respectively, and higher than in those who did not (0% and 0%; P < 0.01 and P = 0.04, respectively). Postoperative NV (25.7%) and antiemetics use (8.0%) ratios in the patients who received 5-aminolevulinic acid were significantly different from those in the non-users group (3.6% and 2.1%, P < 0.01 and P < 0.01, respectively). Although no differences in risk factors were found for postoperative NV between the two groups, multivariate analyses indicated 5-aminolevulinic acid use as an independent predictive factor for postoperative NV (odds ratio, 11.5; 95% confidence interval, 3.98–33.3; P < 0.01). ConclusionsOur study clearly showed that oral administration of 5-aminolevulinic acid was associated with perioperative NV even without risk factors, highlighting the need for addressing its application.

In Vivo-like model of glial tumors: Creation of primary cell lines.

e14515 Background: The choice of cell source for 3D bioprinting of in vivo-like models of glial tumors is crucial and must take into account the ability to proliferation and stable metabolism. Oral administration of 5-aminolevulinic acid (5-ALA) in patients prior to surgery increases the fluorescent contrast between tumor and surrounding tissue, but the effect of contrast agents on cells in vitro is unknown. The aim of the study was obtaining viable glial tumor tissues using 5-ALA, as well as the development of a stable primary cell culture for 3D bioprinting. Methods: Tumor tissue was obtained from patients with glioblastoma during surgery under visual control using the Opmi Pentero Blue E400 microscope and 5-ALA. Material was disaggregated on a BD Machine using Medicons 50 μm (BD). Glioblastoma cells were cultured in DMEM/F12 medium with L-glutamine (Gibco) containing 10% fetal bovine serum (Biolot, Russia), 1% non-essential amino acids (NEAA, Sigma-Aldrich) and 0.5% penicillin-streptomycin (Biolot) at 37C. Glial cell lines were characterized immunohistochemically using antibodies to the glial fibrillary acidic protein (GFAP) and proliferation index (Ki-67). Microsatellite analysis was performed using three dinucleotide repeat markers D2S123, D17S250, D5S346 and five mononucleotide loci BAT25, BAT26, NR21, NR24 and NR27. Results: The positive expression of GFAP on the cell processes of the star-like shape was clearly visualized, indicating a morphological feature of glial tumors. The Ki-67 labeling index was 70%. Changes were observed at the D17S250 locus (148-148/148-152) for the glial tumor primary cells after the sixth passage. Microsatellite instability was not observed in the primary cell culture. Conclusions: The accumulation of porphyrins from 5-ALA in glial tumor cells does not prevent the in vitro creation of a cell culture from tumor tissue. Microsatellite analysis showed that the obtained glioblastoma cell lines remain stable for at least 10 passages. Material obtained during resection using 5-ALA is a reliable source of stable glial tumor cell lines.

MP72-09 INTRAOPERATIVE HYPOTENSION CAUSED BY ORAL ADMINISTRATION OF 5-AMINOLEVULINIC ACID FOR PHOTODYNAMIC DIAGNOSIS IN PATIENTS WITH BLADDER CANCER

INTRODUCTION AND OBJECTIVE:The patients in some instances experienced hypotension after the oral administration of 5-aminolevulinic acid. In this study, we analyzed the pre- and intraoperative bloo...

5-aminolevulinic acid inhibits oxidative stress and ameliorates autistic-like behaviors in prenatal valproic acid-exposed rats

Autism spectrum disorders (ASDs) constitute a neurodevelopmental disorder characterized by social deficits, repetitive behaviors, and learning disability. Oxidative stress and mitochondrial dysfunction are associated with ASD brain pathology. Here, we used oxidative stress in prenatal valproic acid (VPA)-exposed rats as an ASD model. After maternal VPA exposure (600 mg/kg, p.o.) on embryonic day (E) 12.5, temporal analyses of oxidative stress in the brain using an anti-4-hydroxy-2-nonenal antibody revealed that oxidative stress was increased in the hippocampus after birth. This was accompanied by aberrant enzymatic activity in the mitochondrial electron transport chain and reduced adenosine triphosphate (ATP) levels in the hippocampus. VPA-exposed rats exhibited impaired spatial reference and object recognition memory alongside impaired social behaviors and repetitive behaviors. ASD-like behaviors including learning and memory were rescued by chronic oral administration of 5-aminolevulinic acid (5-ALA; 30 mg/kg/day) and intranasal administration of oxytocin (OXT; 12 μg/kg/day), a neuropeptide that improves social behavior in ASD patients. 5-ALA but not OXT treatment ameliorated oxidative stress and mitochondrial dysfunction in the hippocampus of VPA-exposed rats. Fewer parvalbumin-positive interneurons were observed in VPA-exposed rats. Both 5-ALA and OXT treatments augmented the number of parvalbumin-positive interneurons. Collectively, our results indicate that oral 5-ALA administration ameliorated oxidative stress and mitochondrial dysfunction, suggesting that 5-ALA administration improves ASD-like neuropathology and behaviors via mechanisms different to those of OXT.

Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron

Heme oxygenase-1 (HO-1) is a major anti-inflammatory enzyme and a key regulator that induces immune tolerance through affecting the differentiation of dendritic cells. The aim of this study is to determine whether the combination of 5-aminolevulinic acid (ALA) and iron induces HO-1 expression in healthy human peripheral blood mononuclear cells (PBMC).The study was an open labeled, non-randomized, non-placebo-controlled trial using healthy male adults and consisted of three parts. Study A aimed to find the peak HO-1 expression at 0, 1, 2, 3, 4, 6, 8, 12, 16, and 24 h after administration. Study B aimed to examine HO-1 dose dependency at 150, 300, and 600 mg of ALA and the need for iron supplementation. Study C aimed to investigate HO-1 changes during a three-day, repetitive administration of ALA and iron.The combination of ALA 600 mg and sodium ferrous citrate (SFC) 942 mg upregulated HO-1 in PBMC at 8 h after administration while sole administration of ALA or SFC was unable to induce HO-1. HO-1 in blood myeloid and plasmacytoid dendritic cells was also upregulated with ALA+SFC. Clear dose dependency of ALA+SFC was not detected, and a slight tendency towards a cumulative effect of HO-1 after three-day, repetitive administration was observed.ALA, which is already approved for use in several countries as a diagnosis agent for cancer, has the potential to become a novel therapeutic drug for diseases stemming from unwanted immune response such as autoimmune diseases and the rejection response following organ transplantation.

The clinical trial on the safety and effectiveness of the photodynamic diagnosis of non-muscle-invasive bladder cancer using fluorescent light-guided cystoscopy after oral administration of 5-aminolevulinic acid (5-ALA)

ObjectiveTo examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy. MethodsThe study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0g/50mL) was performed 180–240min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source. ResultsRegarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20mg/kg/body. ConclusionsALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20mg/kg/body in the present study.

Fluorescence-guided resection with 5-aminolevulinic acid of meningeal sarcoma in a child.

The usefulness of fluorescence-guided resection with 5-aminolevulinic acid for malignant brain gliomas was demonstrated by Stummer. However, there are several articles in the literature showing the usefulness of the technique for other types of tumors, including benign tumors, such as ependymomas or meningiomas. Meningeal sarcomas are rare, highly aggressive malignant tumors, predominately affecting the pediatric population and have a poor prognosis in spite of treatment. Surgical treatment thereof should consist of the most complete resection possible. In this article, we present the case of a seven-year-old boy who received surgical treatment for a left frontal tumor after oral administration of 5-aminolevulinic acid (5-ALA); the definitive histological diagnosis of which was meningeal sarcoma. The technique was useful for achieving a complete resection, as the lesion emitted intense fluorescence, and after resection of the lesion with the usual technique, intraoperative fluorescent spots were observed in the resection bed that were also tumor. Imaging tests performed 5years after surgery ruled out recurrence of the tumor. To our knowledge, this is the first case published in the literature of meningeal sarcoma in a child in which intraoperative fluorescence with 5-ALA was used to achieve a complete resection.

Access to a novel near-infrared photodynamic therapy through the combined use of 5-aminolevulinic acid and lanthanide nanoparticles

There have been considerable efforts to develop photodynamic therapy (PDT) for cancer, in which photoirradiation of a sensitizer delivered near cancer cells results in the conversion of oxygen into active species, causing cell destruction. Aiming at the best cancer selectivity, one PDT method employed protoporphyrin IX (PPIX), which selectively accumulated in cancer cells after oral administration of 5-aminolevulinic acid (ALA). The drawback, however, is that blue incident lights are required to excite PPIX, resulting in low tissue penetrability, and therefore limiting its application to surface cancers. To overcome the low penetrability of the incident light, we employed a light energy upconverter, lanthanide nanoparticle (LNP), which, upon irradiation with highly penetrative near-infrared (NIR) radiation, emits visible light within the Q-band region of PPIX absorbance allowing its sensitization. To discover the optimum conditions for the LNP-assisted PDT, the cytotoxicity and PPIX-sensitizability of LNPs were first studied. Then, the LNP-assisted PDT was validated using the MKN45 cell line: cells were pretreated with ALA and LNP, irradiated with a 975-nm diode laser, and subjected to MTT assay to measure cell viability. The singlet oxygen generation on NIR-irradiation of the PPIX-LNP mixture was proved, indicating that the emission from LNP could excite the PPIX sensitizer. An intermittent NIR-irradiation for 32 min of MKN45, pretreated with LNP (1mg/mL) and ALA (2mM), caused 87% cell destruction. The potential applicability of the NIR-irradiation PDT with ALA- and LNP-pretreated cancer cells was demonstrated.

Effect of Oral Administration of 5-Aminolevulinic Acid in Japanese Eel Anguilla japonica

Effect of Oral Administration of 5-Aminolevulinic Acid in Japanese Eel Anguilla japonica

Oral 5‐aminolevulinic acid in simultaneous photodynamic diagnosis of upper and lower urinary tract transitional cell carcinoma – a prospective audit

What's known on the subject? and What does the study add? The idea of using photosensitizing agents to enhance visualization of cancer tissue dates back to 1900. 5-Aminolevulinic acid (5-ALA) was first suggested for photodynamic diagnosis (PDD) of transitional cell cancer (TCC) of the bladder in 1992. Since then, PDD with intravesical application of 5-ALA or its ester hexaminolevulinate (Hexvix) has proven to be superior over standard white-light cystoscopy in detection of carcinoma in situ and dysplasia as well as enhancing margins of TCC. PDD of upper urinary tract TCC is under-studied because of trouble with delivery of the photosensitizer. Fluorescence after oral 5-ALA was initially reported in 1956. Oral 5-ALA for photodynamic therapy was suggested for upper urinary tract TCC in 1998 and for refractory non-muscle invasive bladder cancer in 2001. A study in 2012 on oral and intravesical application of 5-ALA for bladder PDD showed no difference in diagnostic accuracy for each modality. To our knowledge our series is the first report on use of oral 5-ALA for PDD in detection of upper urinary tract tumours. We published our initial results in 2010. We think that our recent audit is quite encouraging. PDD ureterorenoscopy resulted in detection of additional urothelial tumours that could have been missed by the conventional white-light endoscopy. We suggest that this technique should be used in large multicentre trials to replicate our results. • To evaluate the diagnostic accuracy of photodynamic diagnostic ureterorenoscopy after oral administration of 5-aminolevulinic acid (5-ALA) for upper urinary tract urothelial cancers. • In this audit, twenty-six patients underwent thirty-nine procedures (cystoscopy/ureterorenoscopy) following oral administration of 5-ALA for photodynamic diagnosis (PDD). • Twenty mg/kg body weight of 5-ALA was given orally 3-4 hours prior to the planned endoscopic visualisation. • Following standard white light cystoscopy and ureterorenoscopy, photodynamic diagnostic endoscopy was performed using D-light system (Olympus PDD cystoscope and 7.5Fr KARL STORZ PDD Flex-X ureterorenoscope) to detect fluorescence. • Biopsies were carried out from all suspicious areas, noting if lesions were detected under white or blue light or both. • A total of sixty-two biopsies were performed for suspicious urothelial lesions (35 bladder, 26 ureter/renal pelvis and 1 from prostatic urethra). • Of the 35 bladder biopsies, 11 lesions were seen under both white and blue light and 91% of these were malignant. • While 24 (68.5%) biopsies were taken from lesions seen only under blue light and 45.8% of these were malignant. • Similarly, of the 26 ureteric/renal pelvicalyceal biopsies, 11 were concurrent in both white and blue light and 100% of these were malignant. • While 10 (38.5%) lesions were seen only under blue light and 70% of these were malignant. • Photodynamic diagnosis using oral 5-ALA is safe and feasible with additional advantages of detecting lesions not visualised with conventional white light endoscopy. • This may translate into more complete treatment thereby decreasing subsequent recurrences and possibly progression of the upper urinary tract urothelial cancers.

Fluorescence diagnosis of lymph node metastasis of lung cancer in a mouse model

Fluorescence diagnosis of lymph node metastasis of non-small cell lung cancer has not been reported previously. This study was conducted to evaluate the feasibility of fluorescence detection using 5-aminolevulinic acid and mono-L-aspartyl chlorine e6 for lymph node metastasis in a lung cancer mouse model. Human lung cancer cell line Ma44-3, which forms metastatic lymph nodes in the mediastinum, was injected into the left lungs of 6 severe combined immunodeficiency disease mice. Two weeks after implantation, 2 groups of 3 mice received oral administration of 5-aminolevulinic acid (100 mg/kg) or intraperitoneal administration of mono-L-aspartyl chlorine e6 (5 mg/kg). Both lungs and mediastinal organs were removed en-bloc and illuminated with blue light (405 nm) to evaluate the detectability of lung tumors and metastatic lymph nodes in the mediastinum. These organs were evaluated histopathologically. Clear red fluorescence was observed in the lung tumors of all mice. Metastatic lymph nodes had formed in 5 of 6 mice and were detected by fluorescent detection in all 5 mice even though one of the lymph nodes was invisible macroscopically under white light. In conclusion, fluorescence diagnosis of lymph node metastasis is possible in a mouse model. The successful result with small lymph node metastasis suggests the possibility of clinical application.

Surgical Outcomes of Fluorescence-Guided Laparoscopic Partial Nephrectomy Using 5-Aminolevulinic Acid-Induced Protoporphyrin IX

To evaluate the clinical performance of photodynamic diagnostic (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) for assessment of tumor type and surgical margins in laparoscopic nephron-sparing surgery. This is a prospective, non-randomized single-center study. A total of 77 patients with a renal mass < 4 cm diameter underwent laparoscopic partial nephrectomy (LPN). For photosensitization, 1.5 g 5-ALA was administered orally 4 h prior to surgery. During the operation, the resection site and the outer tumor border were inspected under excitation light for characteristic red fluorescence. The results of PDD were matched up to the histological findings. Mean operative time was 94.1 min with a mean warm-ischemia time of 23 min. Fifty-eight of 61 (95.1%) renal cell carcinomas showed a positive response when exposed to excitation light. In 16 cases (21%), final pathology revealed a nonmalignant lesion. However, characteristic fluorescence was also detected in 1 angiomyolipoma of 16 nonmalignant lesions. False-negative rate was 3/61 (4.9%) and false-positive rate was 1/77 (1.3%), with these data corresponding to a sensitivity of 95% and a specificity of 94%. Further, PDD with 5-ALA was able to predict the type of the lesion with an accuracy of 94% and with a positive predictive value of 98%. Furthermore, PDD with 5-ALA also identified both cases with positive resection margins, which were confirmed on histological examinations. No side effects of systemic 5-ALA administration were observed. PDD after systemic administration of 5-ALA is a reliable tool to assess the type and the resection status of a suspected renal tumor during laparoscopic nephron-sparing surgery.

Clinical evaluation of bioadhesive hydrogels for topical delivery of hexylaminolevulinate to Barrett's esophagus

Fluorescence diagnosis following oral administration of 5-aminolevulinic acid (5-ALA) has shown to enable the sensitive visualization of intestinal metaplasia, dysplasia and early carcinoma in Barrett's esophagus. Once being established, this technique will be a potential alternative to today's standard diagnosis, i.e. four-quadrant random biopsies which are taken every 1–2 cm of the esophagus for histopathological analysis. In order to further improve this methodology, topical application of lipophilic 5-ALA esters to the esophagus could be advantageous in terms of fluorescence contrast and fluorescence intensity in the target tissue, adverse side effects, as well as application time. Therefore, the aim of this study was to develop a bioadhesive formulation loaded with hexylaminolevulinate (HAL) targeting the esophageal lining. In the present study, different mucoadhesive gels including poloxamer 407, cross-linked polyacrylic acid, hydroxypropylmethylcellulose, sodium carboxymethylcellulose and chitosan have been evaluated with respect to bioadhesion to the esophagus using an ex vivo rat model and a clinical study on healthy volunteers. In order to visualize the mucoadhesive properties of the formulations, a blue dye was incorporated as contrast agent. Chitosan has shown the best esophageal adhesion both in vitro and in vivo. Furthermore, using the in vitro release profiles from chitosan loaded with 40 mM of HAL, one can estimate that after a residence time of 10 min on the esophageal wall, the amount of HAL delivered to the epithelium will be sufficient to perform fluorescence diagnosis of Barrett's esophagus following swallowing of this formulation.

Long Term Results of PDT for Early Neoplasia in Barrett's Esophagus

Objectives: Photodynamic therapy (PDT) has proved to be save and effective in patients with early neoplasia in Barrett's esophagus. Although there are several reports on PDT in these patients, long term results are still lacking. Methods: Between January 1997 and January 2003, 680 patients with early neoplasia in Barrett's esophagus were referred for local endoscopic therapy. 66 patients (mean age 61.4 ± 10.2 years) with high grade intraepithelial neoplasia (HGIN) (group A; n = 35) and early adenocarcinoma (group B; n = 31) were treated by PDT. Protoporphyrin IX induced by oral administration of 5-aminolevulinic acid was used as photosensitizer. Results: A total of 82 ALA-PDT were performed. 34 of the 35 patients in group A (97%) and all patients in group B (100%) achieved a complete response during a mean follow-up period of 41.7 ± 18.4 months. One local recurrence was observed in group A, and 10 in group B. 7 patients died during follow-up, but no death was tumor-related. No major complications were observed. The calculated 6-year survival was 97% in group A and 75% in group B. Conclusions: The long term results show excellent survival rates in patients with early neoplasia in Barrett's esophagus treated by ALA-PDT.

Photodynamic therapy with 5-aminolevulinic acid is not effective in bile duct cancer

Background: The results of preliminary studies of photodynamic therapy (PDT) for palliation of patients with bile duct cancer with hematoporphyrin derivative have been good. Rapid elimination of a photosensitizer could potentially shorten the time requirement for shielding from light. This would enhance the benefit of this form of palliative treatment. Therefore the feasibility of PDT was investigated for nonresectable bile duct cancer by using 5-aminolevulinic acid. Methods: Four patients with nonresectable bile duct cancer underwent cholangiography, cholangioscopy, and intraductal US before PDT. Light activation was performed 5 to 7 hours after oral administration of 5-aminolevulinic acid. All patients had an endoprosthesis placed in the bile duct after PDT. Results: Cholangioscopy 72 hours after PDT revealed superficial fibrinoid necrosis. However, 4 weeks after PDT there was no significant reduction in bile duct stenoses. Two patients had infectious complications develop, but phototoxicity was not observed. Conclusions: Although superficial tumor necrosis was evident, PDT with 5-aminolevulinic acid failed to significantly reduce malignant bile duct obstruction. Therefore 5-aminolevulinic acid-PDT cannot be recommended for the palliative treatment of bile duct cancer.

Clinical experience with 5-aminolevulinic acid and photodynamic therapy for refractory superficial bladder cancer.

We determined whether photodynamic therapy after the oral administration of 5-aminolevulinic acid in patients with superficial bladder cancer that cannot be controlled by transurethral resection and intravesical bacillus Calmette-Guerin (BCG) immunotherapy would preserve the bladder, while stopping tumor progression. Side effects of treatment were also assessed. We performed photodynamic therapy after the oral administration of 5-aminolevulinic acid in 24 patients with rapidly recurring, multifocal, BCG refractory superficial pTa-pT1 transitional cell carcinoma of the bladder and carcinoma in situ. At a median followup of 36 months (range 12 to 51) 3 of the 5 patients with carcinoma in situ and 4 of the 19 with papillary tumors were free of recurrence. Three patients were rendered disease-free by repeat photodynamic therapy with 5-aminolevulinic acid and 3 underwent cystectomy. Tumor progression was stopped in 20 of our 24 cases. Immediately after the oral administration of 5-aminolevulinic acid hypotension and tachycardia occurred in 19 and 10 patients, respectively, with previously known severe cardiovascular disease. No phototoxic skin reaction or decreased bladder capacity was observed. These initial clinical results suggest that photodynamic therapy with orally administered 5-aminolevulinic acid is effective as an organ preserving procedure for treating superficial bladder cancer even in patients with bacillus Calmette-Guerin refractory carcinoma. One should be aware of hemodynamic instability after the oral administration of 5-aminolevulinic acid, particularly in patients with cardiovascular co-morbidity.

CLINICAL EXPERIENCE WITH 5-AMINOLEVULINIC ACID AND PHOTODYNAMIC THERAPY FOR REFRACTORY SUPERFICIAL BLADDER CANCER

Purpose: We determined whether photodynamic therapy after the oral administration of 5-aminolevulinic acid in patients with superficial bladder cancer that cannot be controlled by transurethral resection and intravesical bacillus Calmette-Guerin (BCG) immunotherapy would preserve the bladder, while stopping tumor progression. Side effects of treatment were also assessed.Materials and Methods: We performed photodynamic therapy after the oral administration of 5-aminolevulinic acid in 24 patients with rapidly recurring, multifocal, BCG refractory superficial pTa-pT1 transitional cell carcinoma of the bladder and carcinoma in situ.Results: At a median followup of 36 months (range 12 to 51) 3 of the 5 patients with carcinoma in situ and 4 of the 19 with papillary tumors were free of recurrence. Three patients were rendered disease-free by repeat photodynamic therapy with 5-aminolevulinic acid and 3 underwent cystectomy. Tumor progression was stopped in 20 of our 24 cases. Immediately after the oral administra...

Assessment of 5-aminolevulinic acid–induced porphyrin fluorescence in patients with peritoneal endometriosis

Objective: The purpose of this study was to examine the diagnostic potential for patients with endometriosis of porphyrin fluorescence after oral administration of 5-aminolevulinic acid. Study Design: Fifteen women referred for laparoscopy because of suspected endometriosis received 1 or 10 mg/kg 5-aminolevulinic acid orally. After 1.5 to 6 hours endoscopic fluorescence spectral analysis and video inspection were performed. Results: With 10 mg/kg 5-aminolevulinic acid and application intervals of >3 hours we observed a significantly higher porphyrin fluorescence in active peritoneal endometriosis than in adjacent normal peritoneum. Pigmented and nodular endometriosis showed weak to negative fluorescence. A strong fluorescence of the fimbrial mucosa was seen. A 1-mg/kg dose of 5-aminolevulinic acid was insufficient for fluorescence diagnosis. No side effects were recorded. Conclusion: Porphyrin fluorescence after oral administration of 5-aminolevulinic acid may be beneficial in diagnosis of peritoneal endometriosis. The strong fluorescence of fimbrial mucosa may limit the applicability of this technique in young women, however, because phototoxic damage cannot be excluded at present. (Am J Obstet Gynecol 2000;183:52-7.)