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aminolevulinic acid, glioma

Koji Omoto, Ryosuke Matsuda, Ichiro Nakagawa, Yasushi Motoyama, Hiroyuki Nakase
Background: 5-aminolevulinic acid (5-ALA)-guided surgery is one of the gold standard perioperative modalities for maximum resection of malignant gliomas. However, it should be noted that 5-ALA fluorescence does not definitively indicate the presence of malignant tumor cells. Case Description: We report a rare case of false-positive lesion mimicking glioblastoma multiforme (GBM) under 5-ALA-guided surgery. A 44-year-old woman presented with persistent headache and flickering in her eyes...
2018: Surgical Neurology International
Michael Schwake, Andrei Nemes, Jana Dondrop, Juliane Schroeteler, Stephanie Schipmann, Volker Senner, Walter Stummer, Christian Ewelt
BACKGROUND: Light irradiation (635 nm) of cells containing protoporphyrin IX (PPIX) after 5- aminolevulinic acid (5-ALA) pretreatment causes cell death via different pathways including apoptosis and necrosis, as previously demonstrated for malignant glioma cells. OBJECTIVE: To elucidate whether various malignant pediatric brain tumors, which have been shown to accumulate PPIX, would also be susceptible to photodynamic therapy (PDT). METHODS: Medulloblastoma (DAOY, UW228), pNET (PFSK-1), and rhabdoid tumor (BT16) cell lines were incubated with 5-ALA in variable concentrations for 4 h...
March 12, 2018: Neurosurgery
Albert W Girotti
One of the advantages of PDT is that it can often circumvent tumor resistance to chemotherapeutic agents such as cisplatin and doxorubicin. However, pre-existing and acquired resistance to PDT has also been demonstrated. One type of resistance, which involves nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS/NOS2) in tumor cells, was discovered in the author's laboratory. When subjected to a 5-aminolevulinic acid (ALA)-based photodynamic challenge, several cancer lines, including breast, prostate, and glioma, underwent intrinsic apoptosis that could be substantially enhanced by iNOS enzymatic inhibitors or a NO scavenger, implying iNOS/NO-mediated resistance...
March 5, 2018: Lasers in Surgery and Medicine
Kazuhide Shimizu, Masayuki Nitta, Takashi Komori, Takashi Maruyama, Takayuki Yasuda, Yu Fujii, Ken Masamune, Takakazu Kawamata, Taketoshi Maehara, Yoshihiro Muragaki
Objective: The goal of this study was to demonstrate the feasibility of intraoperative photodynamic diagnosis (PDD) of malignant glioma using the fluorescence from talaporfin sodium (TS), which is used simultaneously for photodynamic therapy (PDT). Methods: Patients with suspected primary malignant glioma who were eligible for surgical removal of the tumor and PDT with TS were enrolled in this prospective study. Tissue samples were obtained from the contrast-enhanced (CE) region and from the surrounding non-contrast-enhanced (NCE) marginal tissue at the boundary between the tumor and normal tissue...
2018: Frontiers in Neurology
Rosario Maugeri, Alessandro Villa, Mariangela Pino, Alessia Imperato, Giuseppe Roberto Giammalva, Gabriele Costantino, Francesca Graziano, Carlo Gulì, Francesco Meli, Natale Francaviglia, Domenico Gerardo Iacopino
High-grade gliomas (HGGs) are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first step of multimodal therapy is an accepted goal in malignant glioma surgery. Gross total resection has an important role in improving overall survival (OS) and progression-free survival (PFS), but identification of tumor borders is particularly difficult in HGGS. For this reason, imaging adjuncts, such as 5-aminolevulinic acid (5-ALA) or fluorescein sodium (FS) have been proposed as superior strategies for better defining the limits of surgical resection for HGG...
February 7, 2018: Brain Sciences
Seigo Kimura, Toshihiko Kuroiwa, Naokado Ikeda, Naosuke Nonoguchi, Shinji Kawabata, Yoshinaga Kajimoto, Toshihisa Ishikawa
BACKGROUND: Oral 5-aminolevulinic acid (ALA) induces biosynthesis/accumulation of the natural photo-sensitizer protoporphyrin IX (PpIX) in cancer cells. ALA is used widely in photodynamic diagnosis (PDD) and therapy (PDT) during malignant glioma surgery, but few studies have examined the effects of photodynamics plus ALA on normal brain tissue in vivo. We investigated the effects of ALA-mediated PDD and PDT on normal brain tissue. METHODS: We established a rat model in which the brain surface was irradiated through the skull by light-emitting diode (635 nm) after ALA administration...
February 4, 2018: Photodiagnosis and Photodynamic Therapy
Evgenii Belykh, Eric J Miller, Danying Hu, Nikolay L Martirosyan, Eric C Woolf, Adrienne C Scheck, Vadim A Byvaltsev, Peter Nakaji, Leonard Y Nelson, Eric J Seibel, Mark C Preul
OBJECTIVE: Fluorescence-guided surgery with protoporphyrin IX (PpIX) as a photodiagnostic marker is gaining acceptance for resection of malignant gliomas. Current wide-field imaging technologies do not have sufficient sensitivity to detect low PpIX concentrations. We evaluated a scanning fiber endoscope (SFE) for detection of PpIX fluorescence in gliomas and compared it with an operating microscope (OPMI) equipped with fluorescence module and a benchtop confocal laser scanning microscope (CLSM)...
January 31, 2018: World Neurosurgery
Michael D Jenkinson, Damiano Giuseppe Barone, Andrew Bryant, Luke Vale, Helen Bulbeck, Theresa A Lawrie, Michael G Hart, Colin Watts
BACKGROUND: Extent of resection is considered to be a prognostic factor in neuro-oncology. Intraoperative imaging technologies are designed to help achieve this goal. It is not clear whether any of these sometimes very expensive tools (or their combination) should be recommended as standard care for people with brain tumours. We set out to determine if intraoperative imaging technology offers any advantage in terms of extent of resection over standard surgery and if any one technology was more effective than another...
January 22, 2018: Cochrane Database of Systematic Reviews
Satoshi Suehiro, Takanori Ohnishi, Daisuke Yamashita, Shohei Kohno, Akihiro Inoue, Masahiro Nishikawa, Shiro Ohue, Junya Tanaka, Takeharu Kunieda
OBJECTIVE High invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA-mediated SDT (5-ALA-SDT). METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells...
January 19, 2018: Journal of Neurosurgery
Adam B Pippin, Ronald J Voll, Yuancheng Li, Hui Wu, Hui Mao, Mark M Goodman
The endogenous amino acid, 5-aminolevulinic acid (5-ALA), has received significant attention as an imaging agent, including ongoing clinical trials for image-guided tumor resection due to its selective uptake and subsequent accumulation of the fluorescent protoporphyrin IX in tumor cells. Based on the widely reported selectivity of 5-ALA, a new positron emission tomography imaging probe was developed by reacting methyl 5-bromolevulinate with [ 13 N] ammonia. The radiotracer, [ 13 N] 5-ALA, was produced in high radiochemical yield (65%) in 10 min and could be purified using only solid phase cartridges...
December 14, 2017: ACS Medicinal Chemistry Letters
James L Ross, Lee A D Cooper, Jun Kong, David Gutman, Merete Williams, Carol Tucker-Burden, Myles R McCrary, Alexandros Bouras, Milota Kaluzova, William D Dunn, Duc Duong, Constantinos G Hadjipanayis, Daniel J Brat
Glioblastoma (GBM) contains diverse microenvironments with uneven distributions of oncogenic alterations and signaling networks. The diffusely infiltrative properties of GBM result in residual tumor at neurosurgical resection margins, representing the source of relapse in nearly all cases and suggesting that therapeutic efforts should be focused there. To identify signaling networks and potential druggable targets across tumor microenvironments (TMEs), we utilized 5-ALA fluorescence-guided neurosurgical resection and sampling, followed by proteomic analysis of specific TMEs...
November 15, 2017: Scientific Reports
Yijing Xie, Maria Thom, Michael Ebner, Victoria Wykes, Adrien Desjardins, Anna Miserocchi, Sebastien Ourselin, Andrew W McEvoy, Tom Vercauteren
In high-grade glioma surgery, tumor resection is often guided by intraoperative fluorescence imaging. 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) provides fluorescent contrast between normal brain tissue and glioma tissue, thus achieving improved tumor delineation and prolonged patient survival compared with conventional white-light-guided resection. However, commercially available fluorescence imaging systems rely solely on visual assessment of fluorescence patterns by the surgeon, which makes the resection more subjective than necessary...
November 2017: Journal of Biomedical Optics
William Sage, Mathew Guilfoyle, Catriona Luney, Adam Young, Rohitashwa Sinha, Donatella Sgubin, Joseph H McAbee, Ruichong Ma, Sarah Jefferies, Rajesh Jena, Fiona Harris, Kieren Allinson, Tomasz Matys, Wendi Qian, Thomas Santarius, Stephen Price, Colin Watts
Grade IV glioma is the most common and aggressive primary brain tumour. Gross total resection with 5-aminolevulinic acid (5-ALA) guided surgery combined with local chemotherapy (carmustine wafers) is an attractive treatment strategy in these patients. No previous studies have examined the benefit carmustine wafers in a treatment programme of 5-ALA guided resection followed by a temozolomide-based chemoradiotherapy protocol. The objective of this study was to examine the benefit of carmustine wafers on survival in patients undergoing 5-ALA guided resection...
November 14, 2017: Journal of Neuro-oncology
Zahra Jamali, Sedigheh Marjaneh Hejazi, Seyed Mohsen Ebrahimi, Hemen Moradi-Sardareh, Maliheh Paknejad
Photodynamic therapy (PDT) has received high attention in cancer treatment due to its minimal side effects, specific cancer-targeting, non-invasion and low cost. It utilizes a specific group of anti-cancer drugs called photosensitizers (PS), which can be only activated under a certain wavelength light illumination and kills cancer cells. To screen the potential of PS and setup of PDT treatment protocol, it is essential to assess the PDT efficacy in vitro. In this study, a light-emitting diode- (LED-) based illumination system at two wavelengths (red & blue) with homogeneous and stable irradiation, and constant temperature conditions in 96-well plates was provided...
November 7, 2017: Photodiagnosis and Photodynamic Therapy
Sadao Kaneko, Muftah S Eljamel
Surgery plays an important role in the management of high-grade gliomas (HGG) and imparts significant tumor-free and overall survival advantages. However HGG margins are often invisible, making their gross total resection (GTR) a difficult task. Hence intraoperative technology such as intraoperative fluorescence was a revolutionary discovery. A critical literature review revealed fluorescence improved the GTR of HGG from 36% using standard surgery to 74.5 and 84.4% using aminolevulinic acid (ALA) or fluorescein (FLCN), respectively...
November 2017: Future Oncology
Syed O Mahboob, Muftah Eljamel
Surgery is paramount in glioma management and extent of resection is an independent significant prognostic factor. However, these tumors are often invisible intraoperatively. Hence imaging plays an important role in surgical guidance. A critical literature review, using MEDLINE/PubMed service was carried out. It demonstrated a gross total resection (GTR) with neuronavigation (NNS) of 31-36%, adding 5-aminolevulinic acid or fluorescein fluorescence, or intraoperative ultrasound or MRI improved GTR to 69.1, 84...
November 2017: Future Oncology
Jan Coburger, Arya Nabavi, Ralph König, Christian Rainer Wirtz, Andrej Pala
OBJECTIVES: In glioma surgery, intraoperative imaging is regarded highly valuable to improve extent of resection. Current distribution of intraoperative imaging techniques is largely unknown. Further, controversy exists which method might be most beneficial. PATIENTS AND METHODS: We performed a web-based survey among members of the European Association of Neurological Surgeons(EANS) from April to May 2017. Our questionnaire included intraoperative MRI(iMRI), 5-aminolevulinic acid(5-ALA), intraoperative ultrasound(iUS),Na-Fluorescein and intraoperative CT(iCT)...
December 2017: Clinical Neurology and Neurosurgery
R Yagi, S Kawabata, N Ikeda, N Nonoguchi, M Furuse, Y Katayama, Y Kajimoto, T Kuroiwa
BACKGROUND: Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is a promising real-time navigation method in the surgical resection of malignant gliomas. In order to determine whether this method is applicable to metastatic brain tumors, we evaluated the usefulness of intraoperative fluorescence patterns and histopathological features in patients with metastatic brain tumors. METHODS: We retrospectively reviewed the cases of 16 patients with metastatic brain tumors who underwent intraoperative 5-ALA fluorescence-guided resection...
September 29, 2017: World Journal of Surgical Oncology
Jan F Cornelius, Lennert Eismann, Lara Ebbert, Brigitte Senger, Athanasios K Petridis, Marcel Alexander Kamp, Rüdiger V Sorg, Hans Jakob Steiger
BACKGROUND: Chordomas are very rare tumors of the skull base and the sacrum. They show infiltrating and destructive growth and are known to be chemo- and radio-resistant. After surgical resection, the recurrence rate is high and overall survival limited. As current adjuvant treatments are ineffective, new treatment concepts are urgently needed. 5-aminolevulinic acid-based photodynamic therapy (5-ALA based PDT) showed promising results for malignant gliomas. However, it is unknown so far, whether chordomas accumulate protoporphyrin IX (PPIX) after application of 5-ALA and whether they are sensitive to subsequent 5-ALA based PDT...
December 2017: Photodiagnosis and Photodynamic Therapy
Fumitaka Matsuda, Naokado Ikeda, Yoshinaga Kajimoto, Naosuke Nonoguchi, Koji Takeuchi, Masao Fukumura, Shinji Kawabata, Motomasa Furuse, Tetsuo Sugano, Taku Sato, Kiyoshi Saito, Toshihiko Kuroiwa
BACKGROUND: Fluorescence image guided surgery (FIGS) with 5-aminolevulinic acid for malignant gliomas improves surgical outcome. One of the problems during FIGS is photobleaching under surgical microscopic white light. A solid laser-based white light source for neurosurgery that we developed does not include light with a wavelength of around 405nm, which is strongly absorbed by protoporphyrin IX. In the present study, we examined the efficacy of this light source to prevent the photobleaching of protoporphyrin IX-induced fluorescence...
December 2017: Photodiagnosis and Photodynamic Therapy
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