Currently, Q-switched lasers (ruby, alexandrite, and Nd:YAG) are mainly used in the treatment of Nevus of Ota as well as ectopic Mongolian spots, and their efficacy is clear. However, complications such as pigmentation and depigmentation are problematic. In recent years, picosecond lasers have emerged and are expected to reduce the risk of complications. At our clinic, picosecond YAG laser with 339 ps pulse width is used for the treatment of Nevus of Ota and ectopic Mongolian spots. Good results (50–74% improvement) were obtained in both Nevus of Ota and ectopic Mongolian spots, especially in infants, but there were some cases of poor efficacy (0–24% improvement) in adults. Complications were milder and less frequent than with Q-switched laser treatment. However, even in the same patient, differences in treatment efficacy were observed, which may be due to differences in the thickness of the affected skin and the practitioner. Further studies are needed to determine which patients are suitable for picosecond lasers and the optimal fluence settings.

We monitored 19 patients with malignant brain tumors, who received photodynamic therapy (PDT). Among them, 17 patients had gliomas, which included 13 Grade IV tumors (eight first-onset and five recurrent) and four Grade III tumors (one first-onset and three recurrent) based on the WHO2016 classification. Nine cases were subjected to carmustine wafer implantation together with PDT. While some patients displayed reasonable local control, nine cases (six Grade IV and three Grade III tumors) exhibited recurrence. One patient died of postoperative intracranial hemorrhage, although the causal link to the treatment was uncertain. The median progression-free survival of newly-diagnosed glioblastoma patients was found to be 15 months, with a 6-month progression-free survival rate of 51%. Analysis of surgical videos suggests that local control may be enhanced in regions with sufficient PDT. However, preventing recurrence and dissemination in remote sites appeared to be challenging. Therefore, wide-area laser irradiation and careful monitoring are essential for optimal treatment outcomes.

We assessed demographics, progression free survival (PFS), overall survival (OS), and adverse effects of photodynamic therapy (PDT) for malignant brain tumors at the Department of Neurosurgery, Niigata University from July 2018 to June 2021. Median PFS was 14 months and median OS was not reached in 9 newly-diagnosed glioblastoma patients undergoing PDT during initial surgery. Death was observed in only one patient who showed early, distant recurrence. Main adverse effects, all transient, included photosensitivity in 1 case, reversible FLAIR hyperintensity in 3 cases, and depressive state in 5 cases. Depressive state due to long light shielding times were observed and effort to reduce shielding times should be made. We share our initial PDT experience by introducing specific cases, and also our preclinical experiments for near-infrared photoimmunotherapy (NIR-PIT), which we consider to be the next-generation, intraoperative treatment for malignant brain tumors. NIR-PIT targets cancer cell-specific surface antigens, and treating with near-infrared light destroys the cell membrane of tumor cells. We succeeded in treating glioblastoma cell lines by NIR-PIT, using an antibody against the specific surface antigen X.

We assessed irradiation techniques, complications, recurrence times, and patterns of recurrence regarding photodynamic therapy (PDT) for malignant glioma. The subjects were 106 patients with malignant glioma diagnosed by imaging, who were treated with PDT. Major complications were only observed in 1 patient who developed nail burn, and 2 patients were suspected of having heat injury in the cerebral cortex. The median progression-free survival was approximately 12 months. Local recurrence occurred in 50 patients, and distant recurrence or dissemination occurred in 27 patients. These results indicate that the control of PDT-resistant tumor cells is important for the prevention of the recurrence of malignant glioma.

The effect of photodynamic therapy (PDT) on newly diagnosed glioblastoma patients was retrospectively evaluated. PDT significantly prevented the tumor progression from the lateral wall of the resection cavity, but did not prevent recurrence from the bottom of the cavity. The incidence of adverse events after craniotomy was similar regardless of PDT. PDT was safe, and prevented recurrence from the lateral wall of the resection cavity, resulted in prolonged maintenance of PS, and improved survival of patients.

Some reports have shown that photodynamic therapy (PDT) with talaporfin sodium for primary malignant brain tumors is safe, but its efficacy remains unclear. Therefore, we discussed the issues based on a review of the outcomes of PDT in our institution. Forty-one PDT sessions were performed in 36 patients with primary malignant brain tumors. The median PFS of 5 patients with newly diagnosed glioblastoma and 19 patients with recurrent glioblastoma was 31.6 and 5.8 months, respectively. The median OS of those was 50.8 and 15.7 months, respectively. The adverse event associated with PDT was asymptomatic increased brain edema, but no skin adverse events were observed. For newly diagnosed glioblastoma, long-term local control was observed in patients who underwent PDT after total resection. In recurrent glioblastoma, long-term local control was achieved in one patient with postoperative wound infection. These results suggest that PDT can be safely administered and may be effective with adequate total resection. A randomized controlled trials needs to be conducted to evaluate the efficacy of PDT in patients with newly diagnosed glioblastoma that have been totally resected.

Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5ALA) and photodynamic therapy (PDT) using talaporfin sodium for high grade glioma (PDD) have been widely used in Japan, contributing to extent of resection and improved median survival. Both techniques use photosensitizers and laser light of specific wavelengths. Photosensitivity is a well-known adverse event, but there are few reports of other adverse events in the department of neurosurgery. We experienced a case of marked hypotension after taking 5ALA, which delayed the start of surgery. We also experienced a case of depression during light shielding after PDT. We report our experience and discuss adverse events associated with 5ALA and talapofin sodium and their countermeasures.

Delirium is defined as an acute and reversible disorder of consciousness caused by physical or environmental stress and is present in 10–15% of postoperative patients. Subsyndromal delirium is considered to be intermediate between delirium and the normal state. Photodynamic therapy (PDT) is one of the treatment modalities for recurrent localized esophageal cancer after chemoradiotherapy. Light shielding is required for approximately 2 weeks after PDT, which may induce abnormal sleep-wake rhythms and promote delirium. However, postoperative delirium in PDT has not been reported previously. In this study, we aimed to clarify the frequency of delirium in esophageal PDT and the effect of light shielding on the occurrence of delirium. We compared the frequency of delirium and subsyndromal delirium with respect to endoscopic submucosal dissection (ESD), an endoscopic treatment with the same degree of invasiveness as PDT, using medical records. Patients treated at our hospital and who underwent PDT with talaporfin sodium over a 2-year period from April 2019 were included in the PDT group, and esophageal ESD over a 6-month period from November 2015 in the ESD group. Delirium was defined as a psychiatrist’s diagnosis, obvious disturbing behavior, or self-removal of intravenous infusions; subsyndromal delirium was defined as drug use indicated during nocturnal restlessness. There were 61 and 54 patients in the PDT and ESD groups, respectively. Delirium occurred in 3 (4.9%)/1 (1.9%) patients in the PDT/ESD group, and subsyndromal delirium occurred in 13 (21.3%)/10 (18.5%) patients in the PDT/ESD group, with no significant difference between the groups. The median of the first drug administration day was 2/0.5 days (POD) in the PDT/ESD group and the median of the medication administration frequency was 3/1.5 times in the PDT/ESD group, indicating that the PDT group tend to receive drugs later and use them for a relatively long time compared to the ESD group. The incidence of delirium in PDT was lower than that of postoperative delirium in general. There was no significant increase in the occurrence of delirium that could be attributed to light shading.

Photodynamic therapy (PDT) is gaining attention as a salvage therapy for recurrent esophageal cancer after chemoradiotherapy (CRT). The incidence of post-PDT scar stenosis, one of the associated adverse events, is relatively high. It occurs in about 30% of the patients in our hospital and requires attention because it significantly reduces the patient’s quality of life. In most cases, endoscopic balloon dilatation (EBD) is successful in improving stenosis. However, refractory or severe stenosis is possible in patients undergoing extensive laser irradiation or multiple PDT for recurrent esophageal cancer, and the endoscopic balloon dilation alone may not be sufficient to sustain the opening of the stenosis. Radial incision and cutting (RIC) have been proposed as a new stenosis-reversal technique for such cases. RIC is highly satisfactory for patients because it reliably removes scar tissue and dramatically improves the passage. However, the restenosis rate after RIC is high, and the need for repeated prophylactic balloon dilatations and steroid administration has been reported. In this case report, we describe a case of pinhole-like stenosis that was difficult to treat with balloon dilation or RIC alone. In these cases, we also report the effective treatment approach implemented with a combination of incision using a needle knife, EBD, and RIC. this treatment resulted in a good improvement in quality of life.

Currently, photodynamic therapy (PDT) involves a 2-week light-shading period to prevent photosensitivity. However, in some cases, patients metabolize drugs more quickly, making a 2-week light-shielding period redundant. Furthermore, the current photosensitivity test is invasive, weather-dependent, and qualitative in its evaluation. To overcome these limitations, the authors aim to develop a new photosensitivity test and light-shielding management approach by quantifying the photosensitivity response through image analysis and combining it with a fluorescence-based monitoring system and a mathematical model to estimate drug metabolism. This paper outlines the current state of photosensitivity testing, quantification methods, and monitoring devices we developed. Three color spaces, namely RGB, CIELAB, and HSV, were used for evaluation in this study. Among them, the CIELAB color space is the most effective for the quantitative assessment of redness due to photosensitivity reactions. The realization of these quantitative assessments of photosensitivity risk is expected to produce benefits in both improving patient quality of life and reducing healthcare costs.

We summarized photodynamic diagnosis (PDD) utilizing 5-aminolevulinic acid (5-ALA) in the field of domestic Neurosurgery/Neuro-Oncology, focusing on its introduction and evolution since 2000s. Beginning with the significance consideration of glioma surgery, the usefulness of 5-ALA-PDD is described as one of the surgical modality in multimodal era in Neurosurgery. After ranging and scrutinizing systematic reviews and meta-analyses recently reported, the points of discussion were addressed.

Fluorescent-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) for malignant brain tumors has been mainly performed with microscopes equipped with emission light source and filter for observation. Recently, endoscope, surgical loupe, and exoscope for 5-ALA-FGS were commercially available, and their usefulness was suggested. Commonly, fluorescence evaluation was based on surgical microscopes accumulated over many years; thus, the fluorescence with these novel fluorescence observational systems should be considered different. Additionally, operators should well understand the cons of the introduction of these novel systems.

This study elucidated the relationship between the findings of photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) and tumor control in 41 patients undergoing resection of newly diagnosed glioblastoma. All patients underwent maximal resection of contrast-enhanced lesions by PDD using 5-ALA. Intraoperative PDD findings, postoperative lesions with contrast-enhanced residuals, and recurrence sites were analyzed. Residual fluorescent lesion was correlated with the total resection of contrast-enhanced lesion seen in magnetic resonance images. In addition, recurrent disease tended to develop within the lesions with residual fluorescence after resection under white light or blue light. These findings suggested that tumor evaluation using PDD with 5-ALA may aid in the determination of the extent of resection in enhanced lesion and in the prediction of sites for intensification of local treatment.

Fluorescence-guided surgery using 5-aminolevulinic acid (ALA) is safe and has high tumor selectivity. It has been widely used in glioma surgery. 5-ALA is converted into protoporphyrin IX (PpIX) via the heme synthesis pathway. As PpIX is a photosensitizer, 5-ALA is available as a live marker in fluorescence-guided surgery. Therefore, the condition of the excited light affects the fluorescence of 5-ALA-induced PpIX during the surgery. In some cases, non-neoplastic lesions showed the fluorescence of 5-ALA-induced PpIX. In this review, we discussed the current situation and the issues related to 5-ALA fluorescence-guided neurosurgery.

The usefulness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) for brain tumors has already been recognized, and in Japan, the preoperative administration of 5-ALA formulation for malignant gliomas was approved by insurance in 2013 with the intent to improve the removal rate. We have performed 5-ALA-PDD for various brain tumors for many years and have used quantitative evaluation of fluorescence intensity by spectral analysis (measurement with a fluorometer) in addition to the conventional subjective evaluation of fluorescence strength by the surgeon (three-step evaluation by the naked eye). In this paper, we first describe the fluorescence intensity of 5-ALA exposure in brain tumors other than gliomas. Second, we identify the characteristics and usefulness of 5-ALA-PDD in metastatic brain tumors, which are increasing among brain tumors. Finally, we introduce navigation-guided needle biopsy, which has been previously performed, including the use of auxiliary light sources. Although the mechanism of 5-ALA-induced fluorescence in brain tumors is still unclear, we will review our data to further develop 5-ALA-PDD in clinical practice.

There are few reports on the fluorescence intensity of photodynamic diagnosis (PDD) with talaporfin sodium (TS) and microscopic visibility at the time of excision. Therefore, we retrospectively examined the relationship between the fluorescence intensity of tumor-specific fluorescence and clinical characteristics of recurrent malignant gliomas. Two of the seven patients who underwent PDD with TS were strongly fluorescent, four had weak fluorescence, and one had no fluorescence. Tumor fluorescence was difficult to distinguish from surrounding tissue in the weakly fluorescent cases. In this study, we found that PDD with TS clearly confirmed tumor-specific fluorescence in strongly fluorescent-positive cases. However, it is difficult to use PDD with TS as well as 5ALA to improve the extent of resection in recurrent malignant gliomas surgery. Further research is needed to enhance the tumor specific fluorescence.