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IntroductionComplete macroscopic cytoreduction represents the most important prognostic parameter for overall survival in ovarian cancer. This dogma remains tenacious despite significant improvements in adjuvant systemic treatment. Hence, optimization of surgical therapy is an overarching goal to improve patients’ outcomes. In this context, intraoperative tumor-specific imaging might facilitate optimized cytoreduction. In neurosurgery, intraoperative 5-aminolevulinic acid (5-ALA) guided imaging is applied in clinical routine to assess surgical resection margins. Here, we report the case of a patient with ovarian cancer in whom intraoperative 5-ALA tumor visualization led to optimized complete cytoreduction.ObjectiveIntraoperative administration of 5-ALA led to improved complete cytoreduction by identification and resection of additional ovarian cancer tumor manifestations.CaseThe 39-year-old patient, Jehovah`s witness, presented to our department with a left sided ovarian mass, suspicious of ovarian cancer, based on clinical examination, sonographic suspicious features and a CA12-5 elevation. The patient’s medical history and family history was unremarkable. Preoperative CT imaging of the thorax and abdomen showed no pathology besides the adnexal mass. Surgery was performed by a midline laparotomy with hysterectomy, bilateral adnexectomy, pelvic peritonectomy, omentectomy, ureterolysis, diaphragm stripping, adhesiolysis and the collection of peritoneal and rectal samples. Intraoperative 5-ALA imaging using a dedicated excitation and detection loupe system (Reveal, DVI) led to tumor detection at the diaphragm, the omentum and the rectum that was not detectable by palpation and visualization using white light. The pathology results revealed that the 5-ALA positive samples (diaphragm, rectum and omentum) obtained by intraoperative 5-ALA were positive for ovarian cancer.ConclusionIntraoperative administration of 5-ALA represents a promising approach to improve complete cytoreduction in ovarian cancer surgery thereby improving clinical outcomes. Hence, further research and clinical trials are required to investigate the potential of intraoperative 5-ALA imaging in ovarian cancer debulking surgery and its impact on long-term clinical outcomes.

The poor prognosis of patients with esophageal cancer leads to the constant search for new ways of treatment of this disease. One of the methods used in high-grade dysplasia, superficial invasive carcinoma, and sometimes palliative care is photodynamic therapy (PDT). This method has come a long way from the first experimental studies to registration in the treatment of esophageal cancer and is constantly being improved and refined. This review describes esophageal cancer, current treatment methods, the introduction to PDT, the photosensitizers (PSs) used in esophageal carcinoma PDT, PDT in squamous cell carcinoma (SCC) of the esophagus, and PDT in invasive adenocarcinoma of the esophagus. For this review, research and review articles from PubMed and Web of Science databases were used. The keywords used were "photodynamic therapy in esophageal cancer" in the years 2000-2020. The total number of papers returned was 1,000. After the review was divided into topic blocks and the searched publications were analyzed, 117 articles were selected. [ABSTRACT FROM AUTHOR]

The poor prognosis of patients with esophageal cancer leads to the constant search for new ways of treatment of this disease. One of the methods used in high-grade dysplasia, superficial invasive carcinoma, and sometimes palliative care is photodynamic therapy (PDT). This method has come a long way from the first experimental studies to registration in the treatment of esophageal cancer and is constantly being improved and refined. This review describes esophageal cancer, current treatment methods, the introduction to PDT, the photosensitizers (PSs) used in esophageal carcinoma PDT, PDT in squamous cell carcinoma (SCC) of the esophagus, and PDT in invasive adenocarcinoma of the esophagus. For this review, research and review articles from PubMed and Web of Science databases were used. The keywords used were “photodynamic therapy in esophageal cancer” in the years 2000–2020. The total number of papers returned was 1,000. After the review was divided into topic blocks and the searched publications were analyzed, 117 articles were selected.

Background: Achieving maximal functionally safe resection of gliomas located withintheeloquent speechareas is challenging, andthereis alackof literatureonthe combined use of 5-aminolevulinic acid (5-ALA) guidance and awake craniotomy. Objective: The aim of this study was to describe our experience with the simultaneous use of 5-ALA fluorescence and awake speech mapping in patients with left frontal gliomas located within the vicinity of eloquent speech areas. Materials and Methods: A prospectively collected database of patients was reviewed. 5-ALA was administered at a dose of 20 mg/kg 2 h prior to operation, and an operating microscope in BLUE400 mode was used to visualize fluorescence. All patients underwent surgery using the "asleep-awake-asleep" protocol with monopolar and bipolar electrical stimulation to identify the proximity of eloquent cortex and white matter tracts and to guide safe limits of resection along with fluorescence guidance. Speech function was assessed by a trained neuropsychologist before, during, and after surgery. Results: In 28 patients operated with cortical mapping and 5-ALA guidance (12 Grade 4, 6 Grade 3, and 10 Grade 2 gliomas), Broca's area was identified in 23 cases and Wernicke's area was identified in 5 cases. Fluorescence was present in 14 cases. Six tumors had residual fluorescence due to the positive speech mapping in the tumor bed. Transient aphasia developed in 14 patients, and permanent aphasia developed in 4 patients. In 6 patients operated with cortical and subcortical speech mapping and 5-ALA guidance (4 Grade 4, 1 Grade 3, and 1 Grade 2 gliomas), cortical speech areas were mapped in 5 patients and subcortical tracts were encountered in all cases. In all cases, resection was stopped despite the presence of residual fluorescence due to speech mapping findings. Transient aphasia developed in 6 patients and permanent aphasia developed in 4 patients. In patients with Grade 2-3 gliomas, targeted biopsy of focal fluorescence areas led to upgrading the grade and thus more accurate diagnosis. Conclusion: 5-ALA guidance during awake speech mapping is useful in augmenting the extent of resection for infiltrative high-grade gliomas and identifying foci of anaplasia in non-enhancing gliomas, while maintaining safe limits of functional resection based on speech mapping. Positive 5-ALA fluorescence in diffuse Grade 2 gliomas may be predictive of a more aggressive disease course. [ABSTRACT FROM AUTHOR]

Radiologically suspected low-grade gliomas (LGG) represent a special challenge for the neurosurgeon during surgery due to their histopathological heterogeneity and indefinite tumor margin. Therefore, new techniques are required to overcome these current surgical drawbacks. Intraoperative visualization of brain tumors with assistance of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence is one of the major advancements in the neurosurgical field in the last decades. Initially, this technique was exclusively applied for fluorescence-guided surgery of high-grade glioma (HGG). In the last years, the use of 5-ALA was also extended to other indications such as radiologically suspected LGG. Here, we discuss the current role of 5-ALA for intraoperative visualization of focal malignant transformation within suspected LGG. Furthermore, we discuss the current limitations of the 5-ALA technology in pure LGG which usually cannot be visualized by visible fluorescence. Finally, we introduce new approaches based on fluorescence technology for improved detection of pure LGG tissue such as spectroscopic PpIX quantification fluorescence lifetime imaging of PpIX and confocal microscopy to optimize surgery.

Radiologically suspected low-grade gliomas (LGG) represent a special challenge for the neurosurgeon during surgery due to their histopathological heterogeneity and indefinite tumor margin. Therefore, new techniques are required to overcome these current surgical drawbacks. Intraoperative visualization of brain tumors with assistance of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence is one of the major advancements in the neurosurgical field in the last decades. Initially, this technique was exclusively applied for fluorescence-guided surgery of high-grade glioma (HGG). In the last years, the use of 5-ALA was also extended to other indications such as radiologically suspected LGG. Here, we discuss the current role of 5-ALA for intraoperative visualization of focal malignant transformation within suspected LGG. Furthermore, we discuss the current limitations of the 5-ALA technology in pure LGG which usually cannot be visualized by visible fluorescence. Finally, we introduce new approaches based on fluorescence technology for improved detection of pure LGG tissue such as spectroscopic PpIX quantification fluorescence lifetime imaging of PpIX and confocal microscopy to optimize surgery. [ABSTRACT FROM AUTHOR]

Fluorescence, fluorescein, CNS tumors, gliomas, PNST, 5-ALA, ICG, confocal endomicroscopy They found a dense and homogenous fluorescence in all extramedullary tumors and in 73.3% of intramedullary tumors, while 13.3% of intramedullary tumors presented lower and more heterogeneous fluorescence. Keywords: CNS tumors; gliomas; PNST; fluorescence; 5-ALA; fluorescein; ICG; confocal endomicroscopy EN CNS tumors gliomas PNST fluorescence 5-ALA fluorescein ICG confocal endomicroscopy 1 3 3 02/10/22 20220207 NES 220207 This Research Topic " I Intraoperative Fluorescence Imaging and Diagnosis in Central and Peripheral Nervous System Tumors: Established Applications and Future Perspectives i " consists of 13 articles contributed by 100 authors in the field of Neurosurgery, Neuropathology, Neuro-oncology, Medical Physics, and Biophotonics. [Extracted from the article]

Background: Previous studies showed that confocal laser endomicroscopy (CLE) images of brain tumors acquired by a first-generation (Gen1) CLE system using fluorescein sodium (FNa) contrast yielded a diagnostic accuracy similar to frozen surgical sections and histologic analysis. We investigated performance improvements of a second-generation (Gen2) CLE system designed specifically for neurosurgical use.Methods: Rodent glioma models were used for in vivo and rapid ex vivo CLE imaging. FNa and 5-aminolevulinic acid were used as contrast agents. Gen1 and Gen2 CLE images were compared to distinguish cytoarchitectural features of tumor mass and margin and surrounding and normal brain regions. We assessed imaging parameters (gain, laser power, brightness, scanning speed, imaging depth, and Z-stack [3D image acquisition]) and evaluated optimal values for better neurosurgical imaging performance with Gen2.Results: Efficacy of Gen1 and Gen2 was similar in identifying normal brain tissue, vasculature, and tumor cells in masses or at margins. Gen2 had smaller field of view, but higher image resolution, and sharper, clearer images. Other advantages of the Gen2 were auto-brightness correction, user interface, image metadata handling, and image transfer. CLE imaging with FNa allowed identification of nuclear and cytoplasmic contours in tumor cells. Injection of higher dosages of FNa (20 and 40 mg/kg vs. 0.1–8 mg/kg) resulted in better image clarity and structural identification. When used with 5-aminolevulinic acid, CLE was not able to detect individual glioma cells labeled with protoporphyrin IX, but overall fluorescence intensity was higher (p < 0.01) than in the normal hemisphere. Gen2 Z-stack imaging allowed a unique 3D image volume presentation through the focal depth.Conclusion: Compared with Gen1, advantages of Gen2 CLE included a more responsive and intuitive user interface, collection of metadata with each image, automatic Z-stack imaging, sharper images, and a sterile sheath. Shortcomings of Gen2 were a slightly slower maximal imaging speed and smaller field of view. Optimal Gen2 imaging parameters to visualize brain tumor cytoarchitecture with FNa as a fluorescent contrast were defined to aid further neurosurgical clinical in vivo and rapid ex vivo use. Further validation of the Gen2 CLE for microscopic visualization and diagnosis of brain tumors is ongoing.

Low-power fluorescence microscopy of 5-ALA-induced PpIX has emerged as a valuable intraoperative imaging technology for improving the resection of malignant gliomas. However, current fluorescence imaging tools are not highly sensitive nor quantitative, which limits their effectiveness for optimizing operative decisions near the surgical margins of gliomas, in particular non-enhancing low-grade gliomas. Intraoperative high-resolution optical-sectioning microscopy can potentially serve as a valuable complement to low-power fluorescence microscopy by providing reproducible quantification of tumor parameters at the infiltrative margins of diffuse gliomas. In this forward-looking perspective article, we provide a brief discussion of recent technical advancements, pilot clinical studies, and our vision of the future adoption of handheld optical-sectioning microscopy at the final stages of glioma surgeries to enhance the extent of resection. We list a number of challenges for clinical acceptance, as well as potential strategies to overcome such obstacles for the surgical implementation of these in vivo microscopy techniques.

Low-power fluorescence microscopy of 5-ALA-induced PpIX has emerged as a valuable intraoperative imaging technology for improving the resection of malignant gliomas. However, current fluorescence imaging tools are not highly sensitive nor quantitative, which limits their effectiveness for optimizing operative decisions near the surgical margins of gliomas, in particular non-enhancing low-grade gliomas. Intraoperative high-resolution optical-sectioning microscopy can potentially serve as a valuable complement to low-power fluorescence microscopy by providing reproducible quantification of tumor parameters at the infiltrative margins of diffuse gliomas. In this forward-looking perspective article, we provide a brief discussion of recent technical advancements, pilot clinical studies, and our vision of the future adoption of handheld optical-sectioning microscopy at the final stages of glioma surgeries to enhance the extent of resection. We list a number of challenges for clinical acceptance, as well as potential strategies to overcome such obstacles for the surgical implementation of these in vivo microscopy techniques. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed that confocal laser endomicroscopy (CLE) images of brain tumors acquired by a first-generation (Gen1) CLE system using fluorescein sodium (FNa) contrast yielded a diagnostic accuracy similar to frozen surgical sections and histologic analysis. We investigated performance improvements of a second-generation (Gen2) CLE system designed specifically for neurosurgical use. Methods: Rodent glioma models were used for in vivo and rapid ex vivo CLE imaging. FNa and 5-aminolevulinic acid were used as contrast agents. Gen1 and Gen2 CLE images were compared to distinguish cytoarchitectural features of tumor mass and margin and surrounding and normal brain regions. We assessed imaging parameters (gain, laser power, brightness, scanning speed, imaging depth, and Z-stack [3D image acquisition]) and evaluated optimal values for better neurosurgical imaging performance with Gen2. Results: Efficacy of Gen1 and Gen2 was similar in identifying normal brain tissue, vasculature, and tumor cells in masses or at margins. Gen2 had smaller field of view, but higher image resolution, and sharper, clearer images. Other advantages of the Gen2 were auto-brightness correction, user interface, image metadata handling, and image transfer. CLE imaging with FNa allowed identification of nuclear and cytoplasmic contours in tumor cells. Injection of higher dosages of FNa (20 and 40 mg/kg vs. 0.1–8 mg/kg) resulted in better image clarity and structural identification. When used with 5-aminolevulinic acid, CLE was not able to detect individual glioma cells labeled with protoporphyrin IX, but overall fluorescence intensity was higher (p < 0.01) than in the normal hemisphere. Gen2 Z-stack imaging allowed a unique 3D image volume presentation through the focal depth. Conclusion: Compared with Gen1, advantages of Gen2 CLE included a more responsive and intuitive user interface, collection of metadata with each image, automatic Z-stack imaging, sharper images, and a sterile sheath. Shortcomings of Gen2 were a slightly slower maximal imaging speed and smaller field of view. Optimal Gen2 imaging parameters to visualize brain tumor cytoarchitecture with FNa as a fluorescent contrast were defined to aid further neurosurgical clinical in vivo and rapid ex vivo use. Further validation of the Gen2 CLE for microscopic visualization and diagnosis of brain tumors is ongoing. [ABSTRACT FROM AUTHOR]