Photodynamic Diagnosis System Research Articles

Variations in photodynamic diagnosis for bladder cancer due to the quality of endoscopic equipment

Background: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) has different treatment outcomes across institutions, as seen in conventional TURBT. We retrospectively compared the difference in quality between the two types of endoscopic equipment used for PDD-assisted TURBT in our institution.Methods: This study enrolled 205 consecutive patients who underwent PDD-assisted TURBT. Patients were divided into two groups according to the endoscopic equipment used for PDD-assisted TURBT: Group A using the conventionally used endoscopic system and Aladuck LS-DLED and Group S using the Storz PDD system. Cystoscopy findings of white light (WL), fluorescence light (FL), and combination (positive if either WL or FL was positive) were recorded, and diagnostic quality of PDD was compared between both groups.Results: Group A had 105 cases and 336 specimens, while Group S had 100 cases and 361 specimens, with no significant differences between patient characteristics. The tumor sensitivities of WL, FL, and combination in Group A was 71.9%, 77.1%, 90.5%, respectively, while in Group S, these were 71.5%, 92.2%, 96.1%, respectively. Group S had significantly higher sensitivity of FL and combination than Group A, as well as higher detection of carcinoma in situ lesions.Conclusion: Both endoscopic systems had improved sensitivity with PDD-assistance versus WL only, with Group S having higher sensitivity. Differences in the quality of endoscopic equipment may influence the differences in treatment results with PDD-assisted TURBT across institutions.

Significance of 5-Aminolevulinic Acid-mediated Photodynamic Diagnosis Following Standard Transurethral Resection in Non-muscle Invasive Bladder Cancer.

Transurethral resection of bladder tumors (TURBT) guided by photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) has been shown to be superior to conventional white light (WL) cystoscopy with regard to diagnostic accuracy, for non-muscle invasive bladder cancer (NMIBC); however, PDD is usually performed prior to WL TURBT. The objective of this study was to investigate the diagnostic significance of 5-ALA-mediated PDD following TUR of NMIBC. In 83 NMIBC patients, all visible tumors were completely resected under the conventional WL guidance followed by additional resection if fluorescent lesions were observed under the blue light (BL) guidance, and random biopsy was further conducted. With the BL source, 39 (47.0%) patients were judged to have fluorescent lesions. Twenty (51.3%) of the 39 patients with positive findings by PDD were diagnosed with residual cancer by additional resection, while random biopsy detected cancers in 2 (4.5%) of the 44 patients with negative findings by PDD. Accordingly, the sensitivity, specificity, positive predictive value and negative predictive value in diagnosing residual cancer by our PDD system were 90.9, 68.9, 51.3 and 95.5%, respectively. Univariate analysis showed that the presence of residual cancers shown by WL TURBT was significantly associated with the preoperative findings of urinary cytology, tumor multiplicity, pathological T stage and tumor grade, of which only the preoperative finding on urinary cytology was shown to have an independent impact on the diagnosis of residual cancer. 5-ALA-mediated PDD following standard WL TURBT could improve the diagnostic accuracy in NMIBC patients, particularly those who are positive for preoperative urinary cytology.

Photodynamic diagnosis - current tool in diagnosis of carcinoma in situ of the urinary bladder.

Photodynamic diagnosis - current tool in diagnosis of carcinoma in situ of the urinary bladder.

Photodynamic diagnosis using 5‐aminolevulinic acid during gastrectomy for gastric cancer

Five-aminolevulinic acid (ALA) has received much attention recently as a new-generation photosensitive substance for photodynamic diagnosis (PDD). This study aimed to investigate the feasibility of intraoperative PDD using ALA to identify gastric cancer. Intraoperative PDD was carried out in 26 lesions of 21 patients with gastric cancer. Before surgery, 1.0 g of ALA solution was given orally through a stomach tube. After tumor resection, resected specimens were investigated by an endoscopic PDD system, and red fluorescence-positive lesions were compared with the pathological result. Red fluorescence was detected in 15 lesions of 11 patients. The sensitivity, specificity, and accuracy of PDD using ALA in detecting gastric cancer were 57.7, 100, and 66.7%, respectively. The incidence of laparoscopic surgery was significantly lower in the PDD-positive group than in PDD-negative cases (18.2% vs. 60.0%; P = 0.049), while that of intestinal type tumor was significantly higher in PDD-positive compared to PDD-negative patients (93.3% vs. 27.3%; P < 0.001). Fluorescence navigation by PDD provides good visualization and detection of gastric cancer lesions, and might be particularly useful for intestinal type gastric cancer. Thus, PDD using ALA seems to be a promising diagnostic tool for gastric cancer.

Photodynamic diagnosis of positive margin during radical prostatectomy: Preliminary experience with 5‐aminolevulinic acid

To investigate the feasibility of intraoperative photodynamic diagnosis (PDD) by 5-aminolevulinic acid (ALA) for the identification of positive surgical margins (PSM) during retropubic radical prostatectomy (RRP) in patients with prostate cancer (PCa). Intraoperative PDD was carried out in 16 patients with pathologically confirmed PCa by biopsy of the apex, or carrying >25% of probability of extraprostatic extension as defined by Japan PC Table. Before operation, 1.0 g of ALA was given orally. During open RRP, the resection margins inside the body were examined by PDD system with a fluorescence laparoscope. After their removal, 12 harvested prostates were divided and also investigated by PDD. Red fluorescent-positive lesions were biopsied and compared with the pathological result. All 16 patients were fluorescence-negative inside the body, and negative margins were pathologically confirmed during PDD. Among the 43 specimens of 12 cases obtained by biopsy under PDD, 11 specimens (25.6%) were pathologically diagnosed as malignant tissue (adenocarcinoma, 10 specimens; high grade prostatic intraepithelial neoplasia, 1 specimen) and 19 specimens (44.2%) were evaluated as positive fluorescence by PDD with a sensitivity of 81.8%, a specificity of 68.8% and a predictive accuracy of 72.1%. No side-effects were observed and the procedures were well tolerated. PDD mediated by ALA during RRP might be a feasible and safe modality for detection of surgical margins. Further prospective randomized studies with larger populations are required.

Uptake and kinetics of 5-aminolevulinic acid in oral squamous cell carcinoma

Photodynamic diagnosis (PDD) is a form of cancer detection based on the administration of an exogenous photo-activated compound that accumulates in malignant cells, followed by appropriate photo irradiation. The authors describe a spectroscopic study of 5-aminolevulinic acid (5-ALA)-generated photosensitizer protoporphyrin IX (PpIX) fluorescence in human oral squamous cell carcinoma (OSCC) cell lines to validate its clinical use. 5-ALA-induced PpIX fluorescence intensity was measured in the presence and absence of deferoxamine mesylate (DFO). Two, one and two cell lines produced poorly, moderately and well differentiated carcinomas, respectively, on transplantation in scid mice. The fluorescence intensity was high in the poorly differentiated cell lines, followed by the moderately differentiated cell line; the intensity of the well differentiated cell lines was low and not significantly different from that of normal keratinocytes in the absence of DFO. It was elevated to the level of poorly differentiated cell lines following DFO treatment. This elevation was not observed in normal keratinocytes. The results indicate that DFO enhances the photodynamic sensitivity of 5-ALA in non-responsive carcinoma cells as a result of increased cellular accumulation by inhibiting haeme biosynthesis. This PDD system can be applied clinically to the detection of OSCC irrespective of the degree of differentiation.

Intraoperative Photodynamic Evaluation of Surgical Margins During Endoscopic Extraperitoneal Radical Prostatectomy with the Use of 5-Aminolevulinic Acid

Today there are no established techniques to image positive surgical margins (PSM) intraoperatively in endoscopic extraperitoneal radical prostatectomy (EERPE). The intention of this study was to describe the specific technique of photodynamic diagnosis (PDD) in patients undergoing EERPE and report on the potential to detect PSM under PDD. Twenty-four patients with clinically organ-confined prostate cancer received 5-aminolevulinic acid 20 mg/kg body weight orally 3 hours prior to nonnerve-sparing EERPE. An endoscopic PDD system (Karl Storz, Tuttlingen, Germany) including a Tricam PDD 3-chip camera head linked with a straight 10-mm telescope and a D-light C system was used. During EERPE, visualization of the surgical margins was performed by means of both white light and PDD at specific steps during standardized prostatectomy in all patients. Positive PDD areas on the prostate specimen were marked with white ink and consequently processed in pathology. In white light endoscopy, no suspicion of a PSM was raised. Six out of the eight PSM were detected by PDD. In two cases, areas of positive PDD findings were free of prostate cancer and two PSM were not detected by PDD ( one bladder neck, one lateral). The overall sensitivity and specificity were 75% and 88.2%, respectively. Laparoscopy offers an appropriate setting for the use of PDD in prostate cancer to visualize possible PSM. Although imaging of PSM by PDD is promising with the technique being feasible and safe, larger series are needed to prove the reproducibility of our results.

Photodynamic therapy for lung cancers based on novel photodynamic diagnosis using talaporfin sodium (NPe6) and autofluorescence bronchoscopy

We had previously developed the possibility of use of a photodynamic diagnosis (PDD) system using a tumor-selective photosensitizer and laser irradiation for the early detection and photodynamic therapy (PDT) for centrally located early lung cancers. Recently, we established the autofluorescence diagnosis system integrated into a videoendoscope (SAFE-3000) as a very useful technique for the early diagnosis of lung cancer. Twenty-nine patients (38 lesions) with centrally located early lung cancer received PDD and PDT using the second-generation photosensitizer, talaporfin sodium (NPe6). Just before the PDT, we defined the tumor margin accurately using the novel PDD system SAFE-3000 with NPe6 and a diode laser (408nm). Red fluorescence emitted from the tumor by excitation of the photosensitizer by the diode laser (408nm) from SAFE-3000 allowed accurate determination of the tumor margin just before the PDT. The complete remission (CR) rate following NPe6-PDT in the cases with early lung cancer was 92.1% (35/38 lesions). We also confirmed the loss of red fluorescence from the tumors immediately after the PDT using SAFE-3000. We confirmed that all the NPe6 in the tumor had been excited and photobleached by the laser irradiation (664nm) and that no additional laser irradiation was needed for curative treatment. This novel PDD system using SAFE-3000 and NPe6 improved the quality and efficacy of PDT and avoided misjudgement of the dose of the photosensitizer or laser irradiation in PDT. PDT using NPe6 will become a standard option of treatments for centrally located early lung cancer.

Videoscopic fluorescence diagnosis of peritoneal and thoracic metastases from human hepatoblastoma in nude rats

Various medical disciplines are employing photodynamic diagnosis (PDD) when searching for malignancies. It is still unknown whether pediatric solid tumors such as hepatoblastoma are susceptible to this technique as well. Human hepatoblastoma cells were injected into the abdomen or right thoracic cavity of nude rats. Tumor growth was allowed for 7 weeks. Then, photosensitization was induced by peritoneal lavage with 5-aminolevulinic acid (ALA). Applying the Storz PDD system and one 4-mm scope, all animals were investigated by videoscopic white light diagnosis (WD) and PDD. Suspicious lesions were marked and analyzed by spectrometry and histology. Positive fluorescence was documented for every tumor seen by WD in the abdomen or right thoracic cavity. Spectrometry of lesions showed a 6.34-fold increased fluorescence intensity. Histology revealed hepatoblastoma in all specimens. Human hepatoblastoma can be detected by PDD in a rat model. Considering the clinical success of this method in other specialties, our findings indicate that further investigations to evaluate the benefit of PDD for children with hepatoblastoma should be performed.