Hematochezia due to rectal invasion by an internal iliac artery aneurysm: A case report.

BACKGROUND: This case report presents the rare occurrence of hematochezia due to an internal iliac artery aneurysm leading to an arterioenteric fistula, expanding the differential diagnosis for gastrointestinal bleeding. It emphasizes the importance of considering vascular origins in cases of atypical hematochezia, particularly in the absence of common gastrointestinal causes, and highlights the role of imaging and multidisciplinary management in diagnosing and treating such unusual presentations. CASE SUMMARY: A 75-year-old man with a history of hypertension presented with 12 d of hematochezia, experiencing bloody stools 7-8 times per day. Initial computed tomography (CT) scans revealed an aneurysmal rupture near the right internal iliac artery with suspected hematoma development. Hemoglobin levels progressively decreased to 7 g/dL. Emergency arterial angiography and iliac artery-covered stent placement were performed, followed by balloon angioplasty. Despite initial stabilization, minor rectal bleeding and abdominal pain persisted, leading to further diagnostic colonoscopy. This identified a neoplasm and potential perforation at the proximal rectum. An exploratory laparotomy confirmed the presence of a hematoma and an aneurysm invading the rectal wall, necessitating partial rectal resection, intestinal anastomosis, and ileostomy. Postoperative recovery was successful, with no further bleeding incidents and normal follow-up CT and colonoscopy results after six months. CONCLUSION: In cases of unusual gastrointestinal bleeding, it is necessary to consider vascular causes for effective diagnosis and intervention.

The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor.

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi-modal neuroimaging analyses on a group of patients with low-grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region-of-interests and voxel-level whole-brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension.

The Dynamic Changes of Alternative Electron Flows upon Transition from Low to High Light in the Fern Cyrtomium fortune and the Gymnosperm Nageia nagi.

In photosynthetic organisms except angiosperms, an alternative electron sink that is mediated by flavodiiron proteins (FLVs) plays the major role in preventing PSI photoinhibition while cyclic electron flow (CEF) is also essential for normal growth under fluctuating light. However, the dynamic changes of FLVs and CEF has not yet been well clarified. In this study, we measured the P700 signal, chlorophyll fluorescence, and electrochromic shift spectra in the fern Cyrtomium fortune and the gymnosperm Nageia nagi. We found that both species could not build up a sufficient proton gradient (∆pH) within the first 30 s after light abruptly increased. During this period, FLVs-dependent alternative electron flow was functional to avoid PSI over-reduction. This functional time of FLVs was much longer than previously thought. By comparison, CEF was highly activated within the first 10 s after transition from low to high light, which favored energy balancing rather than the regulation of a PSI redox state. When FLVs were inactivated during steady-state photosynthesis, CEF was re-activated to favor photoprotection and to sustain photosynthesis. These results provide new insight into how FLVs and CEF interact to regulate photosynthesis in non-angiosperms.

Titanium Vacancies in TiO2 Nanofibers Enable Highly Efficient Photodriven Seawater Splitting.

Invited for the cover of this issue are Xiao-Yu Yang and co-workers at Wuhan University of Technology, Heinrich-Heine-Universität Düsseldorf, University of the Witwatersrand, and Ben-Gurion University of the Negev. The image depicts Ti vacancies in TiO2 as powerful drivers of photo- and photo-electrocatalytic seawater splitting for hydrogen production. Read the full text of the article at 10.1002/chem.202101817.

Titanium Vacancies in TiO2 Nanofibers Enable Highly Efficient Photodriven Seawater Splitting.

Photodriven seawater splitting is considered to be one of the most promising techniques for sustainable hydrogen production. However, the high salinity of seawater would deactivate catalysts and consume the photogenerated carriers. Metal vacancies in metal oxide semiconductors are critical to directed electron transfer and high salinity resistance; they are thus desirable but remain a challenge. We demonstrate a facile controllable calcination approach to synthesize TiO2 nanofibers with rich Ti vacancies with excellent photo/electro performances and long-time stability in photodriven seawater splitting, including photocatalysis and photo-electrocatalysis. Experimental measurements and theoretical calculations reveal the formation of titanium vacancies, as well as unidirectional electron trap and superior H+ adsorption ability for efficient charge transfer and resistance to corrosion by seawater. Therefore, atomic-/nanoscale characteristics and mechanism have been proposed to clarify the generation of titanium vacancies and the corresponding interfacial electron transfer.

The prognosis of glioblastoma: a large, multifactorial study.

OBJECTIVE: Glioblastoma is the most common and fatal primary brain tumor in adults. Even with maximal resection and a series of postoperative adjuvant treatments, the median overall survival (OS) of glioblastoma patients remains approximately 15 months. The Huashan Hospital glioma bank contains more than 2000 glioma tissue samples with long-term follow-up data; almost half of these samples are from glioblastoma patients. Several large glioma databases with long-term follow-up data have reported outcomes of glioblastoma patients from countries other than China. We investigated the prognosis of glioblastoma patients in China and compared the survival outcomes among patients from different databases. METHODS: The data for 967 glioblastoma patients who underwent surgery at Huashan Hospital and had long-term follow-up records were obtained from our glioma registry (diagnosed from 29 March 2010, through 7 June 2017). Patients were eligible for inclusion if they underwent surgical resection for newly diagnosed glioblastomas and had available data of survival and personal information. Data of 778 glioblastoma patients were collected from three separate online databases (448 patients from The Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov), 191 from REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) database (GSE108476) and 132 from data set GSE16011(Hereafter called as the French database). We compared the prognosis of glioblastoma patients from records among the different databases and the changes in survival outcomes of glioblastoma patients from Huashan Hospital over an 8-year period. RESULTS: The median OS of glioblastoma patients was 16.3 (95% CI: 15.4-17.2) months for Huashan Hospital, 13.8 (95% CI: 12.9-14.9) months for TCGA, 19.3 (95% CI: 17.0-20.0) months for the REMBRANDT database, and 9.1 months for the French database. The median OS of glioblastoma patients from Huashan Hospital improved from 15.6 (2010-2013, 95% CI: 14.4-16.6) months to 18.2 (2014-2017, 95% CI: 15.8-20.6) months over the study period (2010-2017). In addition, the prognosis of glioblastoma patients with total resection was significantly better than that of glioblastoma patients with sub-total resection or biopsy. CONCLUSIONS: Our study confirms that treatment centered around maximal surgical resection brought survival benefits to glioblastoma patients after adjusting to validated prognostic factors. In addition, an improvement in prognosis was observed among glioblastoma patients from Huashan Hospital over the course of our study. We attributed it to the adoption of a new standard of neurosurgical treatment on the basis of neurosurgical multimodal technologies. Even though the prognosis of glioblastoma patients remains poor, gradual progress is being made.

Potentially Inappropriate Medication among Older Patients Who Are Frequent Users of Outpatient Services.

Aging is accompanied by changes in organ degeneration, and susceptibility to multiple diseases, leading to the frequent occurrence of adverse drug reactions resulting from polypharmacy (PP) and potentially inappropriate medications (PIM) in older patients. This study employs a retrospective cohort design and investigates the association of PP with PIM among older patients with high rates of medical utilization. Using records from a national pharmaceutical care database, an experimental group is formed from patients meeting these criteria, who are then offered home pharmaceutical care. Correspondingly, a control group is formed by identifying older patients with regular levels of use of medical services who had been dispensed medications at community pharmacies. Multivariate logistic regression is performed to assess the association between the rate of PIM and variables, including age, gender, and PP. The study finds that experimental PP participants had a higher rate of PIM prescription (odds ratio (OR) = 5.4) than non-PP control participants (all p < 0.001). In clinical practice, additional caution is required to avoid PIMs. Patients engaged in continuously using long-term medication should take precautions in daily life to alleviate related discomforts. Pharmacists should serve as a bridge between patients and physicians to enhance their health and improve their quality of life.

Glioma surgery with awake language mapping versus generalized anesthesia: a systematic review.

Awake craniotomy with language mapping is being increasingly applied to avoid postoperative language dysfunctions worldwide. However, the effectiveness and reliability of this technique remain unclear due to the paucity of studies comparing the awake craniotomy with general anesthesia. To determine the benefit of awake craniotomy for language, motor, and neurological functions, as well as other clinical outcomes, we searched Medline, Embase, the Cochrane Library, and the Chinese Biomedical Literature Database up to December 2019. Gray literatures were also searched. We included randomized and non-randomized controlled studies comparing awake craniotomy versus general anesthetic resection and reporting the language and neurological outcomes. Ten studies with 833 patients were included in the meta-analysis. The pooled risk ratio (RR) suggested no significant differences in language and neurological outcomes between general anesthesia group and awake craniotomy group without electrical stimulation. Awake craniotomy with electrical stimulation, however, was associated with improved late language and neurological outcomes (≥ 3 months) versus general anesthesia with pooled RR of 0.44 (95% CI = 0.20-0.96) and 0.49 (95% CI = 0.30-0.79), respectively. Awake craniotomy with electrical stimulation was also associated with better extent of resection with the pooled RR of 0.81 (95%CI = 0.71-0.92) and shorter hospital stay duration with the pooled weighted mean difference (WMD) of - 1.14 (95%CI = - 1.80 to - 0.48). This meta-analysis suggested that the application of awake craniotomy with electrical stimulation during glioma resection is associated with lower risks of long-term neurological and language deficits and higher extent of tumor resection, as well as shorter hospital stay duration.

Comparing two airway management strategies for moderately sedated patients undergoing awake craniotomy: A single-blinded randomized controlled trial.

BACKGROUND: In the monitored anesthesia care (MAC) setting for awake craniotomy (AC), maintaining airway patency in sedated patients remains challenging. This randomized controlled trial aimed to compare the validity of the below-epiglottis transnasal tube insertion (the tip of the tube placed between the epiglottis and vocal cords) and the nasopharyngeal airway (simulated by the above-epiglottis transnasal tube with the tip of the tube placed between the epiglottis and the free edge of the soft palate) with respect to maintaining upper airway patency for moderately sedated patients undergoing AC. METHODS: Sixty patients scheduled for elective AC were randomized to receive below-epiglottis (n = 30) or above-epiglottis (n = 30) transnasal tube insertion before surgery. Moderate sedation was maintained in the pre- and post-awake phases. The primary outcome was the upper airway obstruction (UAO) remission rate (relieved obstructions after tube insertion/the total number of obstructions before tube insertion). RESULTS: The UAO remission rate was higher in the below-epiglottis group [100% (12/12) vs 45% (5/11); P = .005]. The tidal volume values monitored through the tube were greater in the below-epiglottis group during the pre-awake phase (P < .001). End-tidal carbon dioxide (EtCO2 ) monitored through the tube was higher in the below-epiglottis group at bone flap removal (P < .001). During the awake phase, patients' ability to speak was not impeded. No patient had serious complications related to the tube. CONCLUSION: The below-epiglottis tube insertion is a more effective method to maintain upper airway patency than the nasopharyngeal airway for moderately sedated patients undergoing AC.

Personalized Multimodal Demarcation of Peritumoral Tissue in Glioma.

PURPOSE: Gliomas are life-threatening brain tumors, and the extent of surgical resection is one of the strongest influences on survival rate. However, the proper distinction of infiltrated tissue remains elusive. The aim of this study was to use multimodal analyses to demarcate peritumoral tissue (PT) from tumoral (TT) and healthy tissue (HT). METHODS: A total of 40 patients with histologically confirmed glioma were recruited. We analyzed resting-state functional magnetic resonance imaging (rs-fMRI) using the voxel-based mean blood-oxygen-level-dependent (BOLD) signal and the corresponding structural MRI (s-MRI) alongside RNA sequencing, whole-exome sequencing, and histology results of biopsy samples obtained from PT, HT, and TT. RESULTS: We demarcated a functionally defined PT area where the mean BOLD signal gradually decreased near the edge of the tumor and extended beyond the TT borders (as defined by s-MRI), which was confirmed on a case-by-case basis. Correspondingly, genetic analyses showed a gene expression pattern and mutational landscape of the PT that were distinct from that seen in HT and TT. The genetic characterization of PT relative to HT and TT converged with the MRI-defined PT zones. This was confirmed in three individual cases after additional histologic analysis. A wider PT was associated with a longer progression-free survival, which suggests PT might act as an intermediate area between TT and HT. CONCLUSION: Combined multimodal imaging and genetic analyses can allow for an objective demarcation of the PT in glioma and a robust classification of the degree of infiltration of the PT. These findings could help improve both neurosurgical resection and radio-oncologic therapy.

Scale-Free Analysis of Intraoperative ECoG During Awake Craniotomy for Glioma.

BACKGROUND: Electrocorticography (ECoG) has been utilized in many epilepsy cases however, the use of this technique for evaluating electrophysiological changes within tumoral zones is spare. Nonetheless, epileptic activities seem to arise from the neocortex surrounding the gliomas suggesting a link between epileptogenesis and glioma cell infiltration in the peritumoral area. The purpose of this study was to implement novel scale-free measures to assess how cortical physiology is altered by the presence of an invasive brain tumor. METHODS: Twelve patients undergoing an awake craniotomy for resection of a supratentorial glioma were included. ECoG data over the main tumor and the exposed surroundings was acquired intra-operatively just prior to tumor resection. Six of the patients presented with seizures and had data acquired both in the awake and anesthetic state. The corresponding anatomical location of each electrode in relation to the macroscopically-detectable tumor was recorded using the neuronavigation system based on structural anatomical images obtained pre-operatively. The electrodes were classified into tumoral, healthy or peritumoral based on the macroscopically detectable tumoral tissue from the pre-operative structural MRI. RESULTS: The electrodes overlying the tumoral tissue revealed higher power law exponent (PLE) values across tumoral area compared to the surrounding tissues. The difference between the awake and anesthetic states was significant in the tumoral and healthy tissue (p < 0.05) but not in the peritumoral tissue. The absence of a significant PLE reduction in the peritumoral tissue from the anesthetic to the awake state could be considered as an index of the presence or absence of infiltration of tumor cells into the peritumoral tissue. CONCLUSIONS: The current study portrays for the first time distinct power law exponent features in the tumoral tissue, which could provide a potential novel electrophysiological marker in the future. The distinct features seen in the peritumoral tissue of gliomas seem to indicate the area where both the onset of epileptiform activity and the tumor infiltration take place.

Analysis of the clinical characteristics and refraction state in premature infants: a 10-year retrospective analysis.

AIM: To report the visual outcomes and refractive status in premature infants with and without retinopathy of prematurity (ROP) who were or not treated. METHODS: The clinical records of all premature infants with or without ROP and with or without treatment between 2007 and 2017 were retrospectively reviewed. Basic demographic data, serial changes in ROP incidence, treatment and outcomes, and the refractive states were analyzed. Correlations among myopia and astigmatism progression, birth weight, gestational age, and treatment methods were also analyzed. RESULTS: A total of 562 screened premature infants (all Chinese, 1124 eyes), were recruited with a 378:184 male-to-female ratio. Birth weight did not directly influence ROP incidence. The overall ROP incidence was 16.55% (93/562 cases). The incidences in boys and girls were 16.14% (33/378 cases) and 17.39% (32/184 cases), respectively, and this difference was not significant. However, all infants with serious ROP (stage IV and V) were male. Myopia combined with astigmatism was common in premature infants with and without ROP (30.99%, 172/555 cases), and myopic refraction (including myopia and myopia combined with astigmatism) was more common in premature infants with ROP (48.84%, 42/86 cases). In the >8.00 diopter group, there were significantly more ROP infants than without ROP. Myopic refraction (including myopia and myopia combined with astigmatism) was most common in infants with ROP after treatment (63.63%, 7/11 cases). CONCLUSION: The refractive state is different between premature infants and mature infants. Those treated for ROP had a higher chance of developing myopia, astigmatism, and higher diopter.

How much is enough-Can resting state fMRI provide a demarcation for neurosurgical resection in glioma?

This study represents a systematic review of the insights provided by resting state functional MRI (rs-fMRI) use in the glioma population. Following PRISMA guidelines, 45 studies were included in the review and were classified in glioma-related neuronal changes (n=28) and eloquent area localization (n=17). Despite the heterogeneous nature of the studies, there is considerable evidence of diffuse functional reorganization occurring in the setting of gliomas with local and interhemispheric functional connectivity alterations involving different functional networks. The studies showed evidence of decreased long distance functional connectivity and increased global local efficiency occurring in the setting of gliomas. The tumour grade seems to correlate with distinct functional connectivity changes. Overall, there is a potential clinical utility of rs-fMRI for identifying the functional brain network disruptions occurring in the setting of gliomas. Further studies utilizing standardized analytical methods are required to elucidate the mechanism through which gliomas induce global changes in brain connectivity.

Unforgettable Ups and Downs of Acupuncture Anesthesia in China.

BACKGROUND: Acupuncture anesthesia originated from the pain relief and pain prevention theory in acupuncture and moxibustion. This technique is a new exploration of anesthesiology and an original achievement of China, representing a landmark combination of Traditional Chinese Medicine and Western medicine. OBJECTIVES: The aim of this historical vignette to introduce acupuncture anesthesia with its meaningful history, especially the use in neurosurgery to the public. DESIGN: This historical vignette introduced the development, mechanism research, awake craniotomy, in order to analyze the utility of acupuncture anesthesia, its global impact, the current situation and future of acupuncture anesthesia. CONCLUSION: Acupuncture anesthesia was initiated in 1958, and, reflecting the historical background of China after the 1960s, the use of this technique spread widely throughout the country. Reaching other countries after 1971, acupuncture anesthesia had a significant influence, drawing attention from medical academia worldwide. Thus, acupuncture anesthesia has made a special contribution to the medical science of modern China.

Lubiprostone Is Effective in the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy and safety of lubiprostone in the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). PATIENTS AND METHODS: We performed a literature search of the MEDLINE, Cochrane, Google Scholar, and ClinicalTrials.gov databases (from January 1, 2005, through January 31, 2015). Relevant studies meeting the inclusion criteria were manually searched by 2 independent reviewers. Efficacy outcomes evaluated at 1 week, 1 month, and 3 months of intervention were weekly frequency of spontaneous bowel movements, severity of constipation, consistency of stools, degree of abdominal pain/discomfort, degree of straining, and abdominal bloating. RESULTS: Of 246 studies identified, data from 9 trials comprising 1468 patients (63.6%) in the lubiprostone group and 841 (36.4%) in the placebo group were analyzed. We found that lubiprostone treatment significantly improved the severity of constipation, stool consistency, abdominal pain, degree of straining, and abdominal bloating at 1 week (P≤.03) and 1 month (P≤.004), except for abdominal pain at 1 month, which was similar to that when treated with placebo (P=.21). At 3 months, except for abdominal bloating (P=.03), there was no difference between lubiprostone and placebo groups in all other outcomes (P≥.05). Adverse effects such as nausea, vomiting, and diarrhea were common (incidence rate, 2.4%-75%); however, the incidence of serious adverse effects was low (<5%) and was mostly unrelated to lubiprostone treatment. CONCLUSION: Lubiprostone is a safe and efficacious drug for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation, with limited adverse effects in 3 months of follow-up.

Contribution of combined intraoperative electrophysiological investigation with 3-T intraoperative MRI for awake cerebral glioma surgery: comprehensive review of the clinical implications and radiological outcomes.

OBJECTIVE: This study aimed to assess the clinical efficiency of combined awake craniotomy with 3-T intraoperative MRI (iMRI)-guided resection of gliomas adjacent to eloquent cortex performed at a single center. It also sought to explore the contribution of iMRI to surgeons' learning process of maximal safe resection of gliomas. METHODS: All patients who underwent an awake craniotomy and iMRI for resection of eloquent area glioma during the 53 months between January 2011 and June 2015 were included. The cases were analyzed for short- and long-term neurological outcome, progression-free survival (PFS), overall survival (OS), and extent of resection (EOR). The learning curve was assessed after dividing the cohort into Group A (first 27 months) and Group B (last 26 months). Statistical analyses included univariate logistic regression analysis on clinical and radiological variables. Kaplan-Meier and Cox regression models were used for further analysis of OS and PFS. A p value < 0.05 was considered statistically significant. RESULTS: One hundred six patients were included in the study. Over an average follow-up period of 24.8 months, short- and long-term worsening of the neurological function was noted in 48 (46.2%) and 9 (8.7%) cases, respectively. The median and mean EOR were 100% and 92%, respectively, and complete radiographic resection was achieved in 64 (60.4%) patients. The rate of gross-total resection (GTR) in the patients with low-grade glioma (89.06% ± 19.6%) was significantly lower than that in patients with high-grade glioma (96.4% ± 9.1%) (p = 0.026). Thirty (28.3%) patients underwent further resection after initial iMRI scanning, with a 10.1% increase of the mean EOR. Multivariate Cox proportional hazards modeling demonstrated that the final EOR was a significant predictor of PFS (HR 0.225, 95% CI 0.070-0.723, p = 0.012). For patients with high-grade glioma, the GTR (p = 0.033), the presence of short-term motor deficit (p = 0.027), and the WHO grade (p = 0.005) were independent prognostic factors of OS. Performing further resection after the iMRI (p = 0.083) and achieving GTR (p = 0.05) demonstrated a PFS benefit trend for the patients affected by a low-grade glioma. Over time, the rate of performing further resection after an iMRI decreased by 26.1% (p = 0.005). A nonsignificant decrease in the rate of short-term (p = 0.101) and long-term (p = 0.132) neurological deficits was equally noted. CONCLUSIONS: Combined awake craniotomy and iMRI is a safe and efficient technique allowing maximal safe resection of eloquent area gliomas with possible subsequent OS and PFS benefits. Although there is a learning curve for applying this technique, it can also improve the surgeon's ability in eloquent glioma surgery.

Intraoperative Multi-Information-Guided Resection of Dominant-Sided Insular Gliomas in a 3-T Intraoperative Magnetic Resonance Imaging Integrated Neurosurgical Suite.

OBJECTIVE: To evaluate the clinical application of 3-T intraoperative magnetic resonance imaging (iMRI), awake craniotomy, multimodal functional mapping, and intraoperative neurophysiologic monitoring (IONM) for resection of dominant-sided insular gliomas. METHODS: From March 2011 to June 2013, 30 gliomas involving the dominant insular lobe were resected in the IMRIS 3.0-T iMRI integrated neurosurgical suite. For 20 patients, awake craniotomy with cortical electrical stimulation mapping was performed to locate the language areas. For 10 patients who were not suitable for awake surgery, general anesthesia and functional navigation were performed. Diffusion tensor imaging tractography-based navigation, continuous motor evoked potential monitoring, and subcortical electrical stimulation mapping were applied to localize and monitor the motor pathway in all cases. iMRI was used to assess the extent of resection. The results of intraoperative imaging, IONM, and the surgical consequences were analyzed. RESULTS: Intraoperative imaging revealed residual tumor in 26 cases and led to further resection in 9 cases. As a result, the median extent of resection was increased from 90% to 93% (P = 0.008) in all cases, and from 88% to 92% (P = 0.018) in low-grade gliomas. The use of iMRI also resulted in an increase in the percentage of gross and near total resection from 53% to 77% (P = 0.016). The rates of permanent language and motor deficits resulting from tumor removal were 11% and 7.1%, respectively. CONCLUSIONS: The combination of iMRI, awake craniotomy, multimodal brain mapping, and IONM tailored for each patient permits the maximal safe resection of dominant-sided insular glioma.

Microfluidics for rapid detection of isocitrate dehydrogenase 1 mutation for intraoperative application.

OBJECT Conventional methods for isocitrate dehydrogenase 1 (IDH1) detection, such as DNA sequencing and immunohistochemistry, are time- and labor-consuming and cannot be applied for intraoperative analysis. To develop a new approach for rapid analysis of IDH1 mutation from tiny tumor samples, this study used microfluidics as a method for IDH1 mutation detection. METHODS Forty-seven glioma tumor samples were used; IDH1 mutation status was investigated by immunohistochemistry and DNA sequencing. The microfluidic device was fabricated from polydimethylsiloxane following standard soft lithography. The immunoanalysis was conducted in the microfluidic chip. Fluorescence images of the on-chip microcolumn taken by the charge-coupled device camera were collected as the analytical results readout. Fluorescence signals were analyzed by NIS-Elements software to gather detailed information about the IDH1 concentration in the tissue samples. RESULTS DNA sequencing identified IDH1 R132H mutation in 33 of 47 tumor samples. The fluorescence signal for IDH1-mutant samples was 5.49 ± 1.87 compared with 3.90 ± 1.33 for wild type (p = 0.005). Thus, microfluidics was capable of distinguishing IDH1-mutant tumor samples from wild-type samples. When the cutoff value was 4.11, the sensitivity of microfluidics was 87.9% and the specificity was 64.3%. CONCLUSIONS This new approach was capable of analyzing IDH1 mutation status of tiny tissue samples within 30 minutes using intraoperative microsampling. This approach might also be applied for rapid pathological diagnosis of diffuse gliomas, thus guiding personalized resection.

Metabolic approach for tumor delineation in glioma surgery: 3D MR spectroscopy image-guided resection.

OBJECT The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy ((1)H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D (1)H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection. METHODS Choline (Cho)-N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D (1)H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection. RESULTS Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional (1)H-MRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up. CONCLUSIONS This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D (1)H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.