Postoperative Airway Management after Anterior Cervical Spine Surgery: Retrospective Neurosurgical Multicenter Study.

Airway complications that occur after anterior cervical spine surgery pose a life-threatening risk, which encompasses complications including prolonged intubation, unplanned reintubation, and/or necessity of tracheostomy. The present study aimed to identify the surgical risks associated with postoperative airway complications in neurosurgical training institutes. A retrospective, multicenter, observational review of data from 365 patients, who underwent anterior cervical spine surgery between 2018 and 2022, at three such institutes was carried out. Postoperative airway complication was defined as either the need for prolonged intubation on the day of surgery or the need for unplanned reintubation. The perioperative medical information was obtained from their medical records. The average age of the cohort was over 60 years, with males comprising approximately 70%. Almost all surgeries predominantly involved anterior cervical discectomy and fusion or anterior cervical corpectomy and fusion, with most surgeries occurring at the level of C5/6. In total, 363 of 365 patients (99.5%) were extubated immediately after surgery, and the remaining two patients were kept under intubation because of the risk of airway complications. Of the 363 patients who underwent extubation immediately after surgery, two (0.55%) required reintubation because of postoperative airway complications. Patients who experienced airway complications were notably older and exhibited a significantly lower body mass index. The results of this study suggested that older and frailer individuals are at an elevated risk for postoperative airway complications, with immediate postoperative extubation generally being safe but requiring careful judgment in specific cases.

The Safety of Spine Surgery in the Late-Stage Elderly of 75 Years of Age or Older: A Retrospective Multicenter Study.

OBJECTIVE: The objective of this study was to verify that spine surgery for late-stage elderly (LSE) (age 65-74 years) is as safe as that for early-stage elderly (ESE) (age 65-74 years). METHODS: This retrospective multicenter study included elderly patients aged ≥65 years who underwent spine surgery between 2018 and 2021. The medical information for individual patients was obtained from medical records. Activities of daily living (ADL) were estimated using a 5-grade scale based on the Eastern Cooperative Oncology Group performance status. Good outcome was defined as ADL grade 0 or 1 at discharge; poor outcome was defined as ADL grade 2 to 4 at discharge. The postoperative complications were listed with reference to the Common Terminology Criteria for Adverse Events v5.0. RESULTS: There were 311 patients in the ESE group and 395 patients in the LSE group. Reoperation during hospitalization was significantly higher in the LSE group (4.6%) than in the ESE group (1.6%). The total number of days of hospitalization was significantly longer in the LSE group than in the ESE group. However, there was no significant difference in the postoperative complications or ADL at discharge between the 2 groups. In the statistical analysis, preoperative American Society of Anesthesiologists physical status class 3-6, underlying heart or renal disease, and cervical or thoracic spine level of surgical procedures were significantly associated with poor ADL outcomes at discharge. CONCLUSIONS: Spine surgery even for LSE can be safely done, if perioperative risk factors are appropriately managed.

Ablation efficacy of 5-aminolevulinic acid-mediated photodynamic therapy on human glioma stem cells.

BACKGROUND: Cancer cells with stem cell-like features are generally more resistant to chemotherapy and radiotherapy than differentiated tumor cells. Thus, these cells tend to increase the propensity for tumor recurrence and metastasis. This study investigated the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in destructing glioma stem cells (GSCs), including the mesenchymal subtype (MES-GSCs) demonstrated to have the lowest radio- and chemosensitivity. METHODS: Five high-grade glioma (HGG) GSC lines and derived differentiated glioma cell (DGC) lines were examined for protoporphyrin-IX (PpIX) expression using fluorescence-activated cell sorting (FACS) and then assessed for ALA-PDT sensitivity using cell viability assays. MES-GSCs surviving ALA-PDT were then isolated and evaluated for stem cell and mesenchymal marker expression levels (CD44, ALDH1A3, KLF4, nestin) by qRT-PCR. The ability of these surviving cells to form tumors was then examined using colony forming and by xenograft tumor assays in athymic mice. Finally, the relationship between PpIX expression level (high versus low) and ALA-PDT sensitivity was examined by FACS and colony forming assays. RESULTS: ALA-PDT was effective against all GSC lines including MES-GSCs. MES-GSC lines exhibited higher PpIX expression than derived DGCs. Surviving MES-GSCs demonstrated lower stem cell marker expression and tumor forming potential than naive MES-GSCs. Higher PpIX production capacity by MES-GSCs was associated with greater colony forming ability, and ALA-PDT was more effective against MES-GSCs with greater PpIX accumulation. CONCLUSION: ALA-PDT may be clinically effective against HGG by targeting GSCs, including MES-GSCs.

The effect of hypoxia on photodynamic therapy with 5-aminolevulinic acid in malignant gliomas.

BACKGROUND: Glioblastoma (GBM) is a high-grade, poor prognosis tumor that is resistant to standard treatment. The presence of a small number of glioma stem cells (GSCs) surviving in the harsh microenvironment is responsible for their refractoriness. This study aimed to investigate the effect of a hypoxic environment on the sensitivity of GSCs to photodynamic therapy with 5-aminolevulinic acid (ALA-PDT). MATERIALS AND METHODS: Six human GSC lines, Mesenchymal types HGG13, HGG30, HGG1123, and Proneural types HGG146, HGG157, HGG528, were divided into two groups: normoxia (O2 21%)-cultured cells (Normoxia-GSCs), and hypoxia (O2 5%)-cultured cells (Hypoxia-GSCs). To compare the effects of different oxygen partial pressures on photoporphyrin Ⅸ (PpⅨ) biosynthetic activity, PpⅨ biosynthetic enzyme and transporter expression levels were examined by qRT-PCR; the intracellular PpⅨ concentration was determined using flow cytometry. Additionally, the sensitivity of these two groups of cells to ALA-PDT was evaluated in vitro. RESULTS: Hypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert PpⅨ to heme, compared with Normoxia-GSCs. Flow cytometry revealed that the accumulation of PpⅨ in Hypoxia-GSCs reduced upon incubation with ALA. However, Hypoxia-GSCs showed less reduction in sensitivity to ALA-PDT than Normoxia-GSCs. CONCLUSION: Hypoxia-GSCs had lower intracellular PpⅨ accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA-PDT was reduced less, despite accumulating lower concentrations of PpⅨ. ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.

5-Aminolevulinic acid-mediated photodynamic therapy can target human glioma stem-like cells refractory to antineoplastic agents.

BACKGROUND: Glioblastoma (GBM) is a highly malignant lethal brain cancer. Accumulated evidence suggests that elevated resistance of GBM to both chemo- and radio-therapy is, at least in part, due to the presence of a small population of glioma stem cells (GSC). In the present study, we aimed to determine the sensitivity of GSCs to 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT). METHODS: For this purpose, we established GSC-enriched cell cultures (termed glioma stem-like cells or GSLCs) from A172 human GBM cell line. Under our cultivation conditions, GSLCs formed floating spheroid clusters that contained increased population of CD133/Sox2 expressing cells. Firstly, to compare the activity of protoporphyrin IX (PpIX) biosynthesis in the GSLCs and the parental A172 glioma cells, we examined the expression levels of biosynthesis enzymes and transporters for PpIX using qRT-PCR, and investigated the intracellular levels of PpIX with use of flow cytometry analysis. Then, we evaluated the sensitivity of these cells to ALA-PDT in vitro. Finally, to confirm the therapeutic impact of ALA-PDT on GSLCs with more clinically relevant model, we performed the same experiment using three different patient-derived glioma sphere lines, which cultivated them either in stem cell media or under differentiation conditions in the presence of serum. RESULTS AND CONCLUSION: GSLCs expressed higher mRNA levels of PpIX biosynthesis enzymes and its transporters PEPT1/2 and ABCB6, when compared to the parental A172 glioma cells. Consistently, flow cytometry analysis revealed that upon incubation with ALA, GSLCs accumulate a higher level of PpIX. Finally, we showed that GSLCs were more sensitive to ALA-PDT than the original A172 cells, and confirmed that all patient-derived glioma sphere lines also showed significantly increased sensitivity to ALA-PDT if cultivated under the pro-stem cell condition. Our data indicate that ALA-PDT has potential as a novel clinically useful treatment that might eliminate GBM stem cells that are highly resistant to current chemo- and radio-therapy.

Experimental study to understand nonspecific protoporphyrin IX fluorescence in brain tissues near tumors after 5-aminolevulinic acid administration.

OBJECTIVE: (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA), which appears in various tumors including malignant gliomas, is a good navigator for tumor resection. However, some non-neoplastic tissue also shows a weak PpIX fluorescence. The origin of non-neoplastic PpIX is still unknown, and three hypotheses on its origins can be proposed: tumor cell-derived PpIX followed by dispersal via bulk flow, direct PpIX production by normal brain or gliotic brain tissue, or PpIX produced in other organs leaking from the tumor vessels. We investigated the possibility of these three origins experimentally. METHODS: In vitro, we exposed various cultured glioma and meningioma cell lines to different conditions of 5-ALA. After this, the degree of fluorescence of the culture medium and cells was each quantitatively measured and analyzed by means of photometrical assay. We administered 5-ALA directly into the normal brains of rats by using convection-enhanced delivery technique, and we also administered 5-ALA or PpIX systemically after blood-brain barrier (BBB) disruption. RESULTS: As a result of our in vitro study using cell lines, we found fluorescence of extracellular PpIX in the culture medium. As a result of rat study, we found PpIX fluorescence of the extracted normal brain after systemic administration of 5-ALA with BBB disruption. However, no PpIX fluorescence was observed when we administered PpIX. CONCLUSIONS: It was demonstrated that PpIX was quickly excreted by tumor cells out to the extracellular space, and that even normal brain tissue can produce PpIX in the presence of 5-ALA.