π-Conjugation effects on excited-state intermolecular proton-transfer reactions of anthracene-urea derivatives in the presence of acetate anions.

This study investigated emissive urea compounds with an anthryl moiety on one side and a substituent group (biphenyl, naphthyl, benzyl, or cyclohexyl) on the other side across from the urea group. This was performed to determine the contribution of π-conjugation on a substituent group to excited-state intermolecular proton-transfer (ESPT) reactions in the presence of acetate anions. Fluorescence lifetime measurements revealed that the rate constant of the ESPT reaction from the normal form to the tautomer form increased with the length of the π-conjugation. Considering that there were a few differences among the wavelengths of the fluorescence maxima for the anthracene-urea derivatives in the presence of acetate anions, we observed that the extension of π-conjugation promoted tautomer formation. This maintained the energy levels of the normal and tautomer forms in the excited state. Furthermore, an anthracene-urea derivative without π-conjugation did not undergo a reverse ESPT reaction, implying that π-conjugation is considerably involved in the reverse ESPT reaction from the tautomer form to the normal form.

Koopmans' Theorem-Compliant Long-Range Corrected (KTLC) Density Functional Mediated by Black-Box Optimization and Data-Driven Prediction for Organic Molecules.

Density functional theory (DFT) is a significant computational tool that has substantially influenced chemistry, physics, and materials science. DFT necessitates parametrized approximation for determining an expected value. Hence, to predict the properties of a given molecule using DFT, appropriate parameters of the functional should be set for each molecule. Herein, we optimize the parameters of range-separated functionals (LC-BLYP and CAM-B3LYP) via Bayesian optimization (BO) to satisfy Koopmans' theorem. Our results demonstrate the effectiveness of the BO in optimizing functional parameters. Particularly, Koopmans' theorem-compliant LC-BLYP (KTLC-BLYP) shows results comparable to the experimental UV-absorption values. Furthermore, we prepared an optimized parameter dataset of KTLC-BLYP for over 3000 molecules through BO for satisfying Koopmans' theorem. We have developed a machine learning model on this dataset to predict the parameters of the LC-BLYP functional for a given molecule. The prediction model automatically predicts the appropriate parameters for a given molecule and calculates the corresponding values. The approach in this paper would be useful to develop new functionals and to update the previously developed functionals.

Pancreaticoduodenal Artery Aneurysm Rupture Presenting as Duodenal Obstruction Successfully Treated with Early Transcatheter Arterial Embolization: A Case Report of Suspected Segmental Arterial Mediolysis.

Visceral aneurysms are a rare but important form of abdominal vascular disease. Rupture of the aneurysms leads to serious symptoms, such as acute abdomen or abdominal bleeding. However, duodenal obstruction due to arterial rupture of an aneurysm is very rare. We herein report a 50-year-old woman with suspected segmental arterial mediolysis (SAM) who was first diagnosed with acute abdomen and duodenal obstruction. Rupture of a pancreaticoduodenal artery aneurysm was confirmed, and she was treated with transcatheter arterial embolization. In cases of acute abdomen, SAM is a rare but important possibility to consider as a differential diagnosis.

The optimal management of ruptured basilar artery dissecting aneurysms: a case series and scoping review.

The natural history of ruptured basilar artery dissecting aneurysms (BADAs) remains unclear compared to that of ruptured vertebral artery dissecting aneurysms (VADAs). In this study, we investigated the natural history and optimal management of ruptured BADAs. We identified 17 patients with ruptured BADA among 4586 patients with aneurysmal subarachnoid hemorrhage (SAH) treated in seven participating hospitals. A scoping literature review was undertaken to investigate prognostic factors. Six patients among the profiled patients (35.3%) died, all with poor SAH grades (World Federation of Neurological Societies Grade IV and V). Rebleeding after admission was observed in three patients (17.6%) with poor SAH grades. Aggressive treatment and conservative management were initiated in seven and ten patients, respectively. Patients with good SAH grades had significantly higher favorable treatment outcomes than those with poor grades (83.3% vs. 9.1%, P = 0.005). Moreover, based on a scoping review of 158 cases with ruptured BADA, including the patients from our series, approximately 90% of patients with good SAH grades had favorable outcomes. A good SAH grade and no rebleeding after admission were favorable prognostic factors (P < 0.0001 and P = 0.002, respectively). The rebleeding rates were 20.2%, 13.3%, and 6.3% for dilated, pearl and string, and stenotic lesions, respectively. We concluded that the natural history of isolated ruptured BADAs may be better than that of VADAs. Although definitive treatment, if possible, is undoubtedly important, conservative management with careful radiological follow-up for morphological changes might be a viable option for patients in good clinical condition and with non-dilated lesions.

Factor analysis of error in oxidation potential calculation: A machine learning study.

The conductor-like polarizable continuum model (C-PCM), which is a low-cost solvation model, cannot treat characteristic interactions between the solvent and substructure(s) of the solute. Moreover, the error in a charged system is significant. Using machine learning, we clarified that the systematic error of the oxidation potential calculated by the G3B3/C-PCM was correlated with the molecular size of a solute. The G3B3/C-PCM overestimated the Gibbs oxidation energy by averaging 6.94 kcal/mol. According to the performance of related methods reported in previous studies, this error is mainly due to the solvation energy of the charged solute. Additionally, we succeeded in reducing the error to 2.27 kcal/mol (32%)-3.2 kcal/mol (40%) by correction based on the substructure information of the solute. To modify the C-PCM, effects that correlate with the molecular size of the solute in the charged system should be incorporated.

Quantification of Global DNA Hydroxymethylation Level Using UHRF2 SRA-Luciferase Based on Bioluminescence Resonance Energy Transfer.

5-Methylcytosine (5mC) plays an important role in the regulation of gene expression. Ten-eleven translocation (TET) continuously oxidizes 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). High levels of 5hmC are found in the brain and embryonic stem cells, while global hydroxymethylation levels are reduced in several cancer cells. Moreover, alterations in hydroxymethylation levels occur in neurological diseases, such as Alzheimer's disease and Parkinson's disease. In this study, a convenient sensing method for the determination of global hydroxymethylation levels was developed. A bioluminescence resonance energy transfer (BRET) assay for global methylation level determination has been previously reported. In the assay, BOBO-3 DNA intercalating dye is excited by the bioluminescence of methyl-CpG-binding domain-fused firefly luciferase (MBD-Fluc); that is, the BRET signal depends on the content of methylated CpG on genomic DNA. To develop a hydroxymethylation level sensing method, SET- and RING-associated (SRA) domain of ubiquitin-like with PHD and RING finger domains 2 (UHRF2)-fused Fluc (UHRF2 SRA-Fluc) was prepared. UHRF2 SRA is known to bind to both hydroxymethylated and methylated CpG sites; thus, MBD was utilized to mask the methylated CpG on genomic DNA. We demonstrated that the BRET signal between UHRF2 SRA-Fluc and BOBO-3 depends on the global hydroxymethylation level in the presence of MBD (R2 = 0.99, and relative standard deviation < 2.3%). The limit of detection for hydroxymethylated genomic DNA was 0.75 ng µL-1. In this assay, the global hydroxymethylation level was quantified within 40 min in a single tube, indicating that the assay would be utilized not only for clinical diagnostics but also for the elucidation of 5hmC functions.

Spontaneous regression of a rectal tonsil presenting as a large submucosal tumor.

Rectal tonsils are localized hyperplastic lymphoid tissues in the rectum, and the initial endoscopic findings are consistent with those for neoplastic lesions. However, rectal tonsils are benign entities, and the diagnosis should be made cautiously. A 70-year-old man presented with pain on defecation with rectal bleeding. Colonoscopy revealed a 3-cm protruding mass in the rectum with mucosal erosion, but no malignant features were observed on forceps biopsy. Endoscopic ultrasonography (EUS) showed that the lesion was a hypoechoic mass without blood flow. Fine needle aspiration under EUS revealed no malignant components, although the size of the lesion had shrunk, and symptoms, such as blood-stained stool, tenesmus, and discomfort during defecation, had resolved. A second forceps biopsy showed intermediate-sized lymphocytes without lymphoepithelial lesions. Based on immunostaining, the lesion was diagnosed as a rectal tonsil. Rectal tonsils occur due to localized proliferation of reactive lymphoid follicles in the submucosa or muscularis mucosa. However, endoscopic diagnosis is difficult since less invasive treatment is performed for neoplastic lesions of the rectum to preserve the function of the anal sphincter. Diagnosis and treatment of small lesions might be possible by endoscopic resection; however, for relatively large lesions, formulating a diagnosis based only on biopsy specimens becomes even more difficult. Therefore, repeated biopsies might be helpful for the diagnosis of rectal tonsils and for excluding other neoplasms.

[A Case of Effective Chemoradiotherapy for the Treatment of Distant Recurrence of Squamous Cell Carcinoma in the Anal Canal].

A 75-year-old woman diagnosed with squamous cell carcinoma of the anal canal was treated using chemoradiotherapy and revealed a complete response to the tumor. After 6 months of treatment, swollen para-aortic lymph nodes were found to develop. The patient received the same regimen of chemoradiotherapy again, resulting in lymph node disappearance. However, 2 months later, PET-CT revealed accumulation of FDG in the axillary and cervical lymph nodes. Chemoradiotherapy was performed for the third time. Swollen lymph nodes were found to disappear. After 12 months, para-aortic, axillary, and cervical lymph nodes developed, following which she received BSC; subsequently, she died after 38 months of the carcinoma diagnosis.

Best Motor Response Predicts Favorable Outcome for "True" WFNS Grade V Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The universal application of ultra-early surgery for World Federation of Neurological Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage (aSAH) patients may lead to the increased implementation of unnecessary treatment. Therefore, this study aimed to refine the patient selection process for timely definitive treatment. METHODS: From January 2011 to March 2020, a total of 517 aSAH patients were treated at our institution. Among these, 177 aSAH patients with WFNS grade V on admission were identified from our database. Patients with improved grades in response to the initial supportive treatment, with clinical or radiological signs of herniation, and with irreversible signs of brain damage such as bilaterally dilated pupils and global ischemia on follow-up CT scan were excluded. The outcome of definitive treatment for 54 patients without herniation who remained with WFNS grade V after the initial supportive treatment were analyzed to seek any factor for a favorable outcome (modified Rankin scale 0-2). RESULTS: Among 54 patients, 19 (35.2%) had a favorable outcome after a definitive treatment. Multivariate logistic regression analysis showed that the best motor response (BMR) 4 on Glasgow Coma Scale was significantly associated with favorable outcomes (odds ratio, 3.76; 95% confidence interval, 1.09-13.0, p = 0.03). The positive predictive value of BMR 4 was 48.3%. CONCLUSIONS: Albeit being simple, BMR 4 may facilitate the prompt aggressive treatment for patients with WFNS grade V including those with "true" grade V who do not have any clinical and radiological signs of herniation.

Risk factors of meralgia paresthetica after prone position surgery: Possible influence of operating position, laminectomy level, and preoperative thoracic kyphosis.

Obesity and a prolonged surgical duration are reported risk factors for meralgia paresthetica (MP) after prone position surgery; however, this fails to explain why MP seldom occurs after prone position craniotomy. We reviewed the incidence of MP after spinal surgery and craniotomy in the prone position and investigated whether unidentified factors are involved in the mechanism of postoperative MP. Between January 2014 and March 2020, we performed 556 prone position surgeries. We excluded patients aged ≤16 years and those who were comatose or who required redo-surgery, and reviewed 446 eligible patients (124 who underwent craniotomies and 322 who underwent posterior spinal surgeries). Postoperative MP occurred in 46 (10.3%) patients with a higher incidence after spinal surgery than after craniotomy (13.7% vs. 1.6%, p < 0.001). Among the 322 patients who received posterior spinal surgery, thoracic and lumbar laminectomies were associated with a higher incidence of MP than cervical laminectomy. Analyses limited to those patients who received thoracic and lumbar laminectomies revealed that the preoperative thoracic kyphosis (TK) angle was significantly greater in patients with MP than in those without MP (average TK angle, 38.9° vs. 23.1°; p < 0.001), and that the preoperative lumbar lordosis angle did not significantly differ between the two groups. Apart from the known predisposing factors, we found that thoracolumbar-sacral laminectomy in patients with a greater TK angle is also a risk factor for MP after prone position surgery.

Unique Photophysical Properties of 1,8-Naphthalimide Derivatives: Generation of Semi-stable Radical Anion Species by Photo-Induced Electron Transfer from a Carboxy Group.

The development of anion sensors for selective detection of a specific anion is a crucial research topic. We previously reported a selective photo-induced colorimetric reaction of 1-methyl-3-(N-(1,8-naphthalimidyl)ethyl)imidazolium (MNEI) having a cationic receptor in the presence of molecules having multiple carboxy groups, such as succinate, citrate, and polyacrylate. However, the mechanism underlying this reaction was not clarified. Here, we investigate the photo-induced colorimetric reaction of N-[2-(trimethylammonium)ethyl]-1,8-naphthalimide (TENI), which has a different cationic receptor from MNEI and undergoes the photo-induced colorimetric reaction, and its analogues to clarify the reaction mechanism. The TENI analogues having substituents on the naphthalene ring provide important evidence, suggesting that the colorimetric chemical species were radical anions generated via photo-induced electron transfer from carboxylate to the naphthalimide derivative. The generation of the naphthalimide-based radical anion is verified by 1H NMR and cyclic voltammetry analyses, and photo-reduction of methylene blue is mediated by TENI. In addition, the role of the cationic receptor for the photo-induced colorimetric reaction is investigated with TENI analogues having different hydrophilic groups instead of the trimethylammonium group. Interestingly, the photo-induced colorimetric reaction is observed in a nonionic analogue having a polyethylene glycol group, indicating that the colorimetric reaction does not require a cationic receptor. On the other hand, we reveal that the trimethylammonium group stabilizes the radical anion species. These generation and stabilization phenomena of naphthalimide-based radical anion species will contribute to the development of sophisticated detection systems specific for carboxylate.

Trigeminal neuralgia caused by an arachnoid cyst in Meckel's cave: A case report and literature review.

BACKGROUND: We present a rare case of trigeminal neuralgia (TN) caused by an arachnoid cyst (AC) in Meckel's cave (MC). CASE DESCRIPTION: A 35-year-old man presented with facial pain in the left maxillary and mandibular regions. Since the initial magnetic resonance (MR) imaging showed no apparent offending vessels or tumors, the patient was diagnosed with idiopathic TN, for which carbamazepine was initially effective. When his pain worsened, he was referred to our hospital. A slightly asymmetric shape of MC and distorted course of the trigeminal nerve was confirmed on the initial and repeat MR images. His pain was characterized as electric-shock-like pain, which was triggered by touching the face. Under the tentative diagnosis of an AC confined to MC compressing the trigeminal nerve, the exploration of MC through suboccipital craniotomy was performed. Intraoperatively, the AC was identified in the rostral portion of MC. The indentation of the trigeminal nerve was also observed at the orifice of MC, indicating severe compression by the AC. The wall of the AC was fenestrated. The patient's pain was relieved immediately after surgery. Postoperative MR images showed that the course of the trigeminal nerve was straightened. Although our literature review found five similar cases, the size of the AC was the smallest in our case. CONCLUSION: Although it is rare, the AC confined to MC can cause TN. The findings of this study emphasize the importance of evaluating subtle radiological findings of compression on the trigeminal nerve in cases of TN seemingly without neurovascular compression.

Carotid endarterectomy restores decreased vision due to chronic ocular ischemia.

BACKGROUND: The therapeutic effect of carotid endarterectomy (CEA) on visual disturbance caused by chronic ocular ischemia due to carotid artery stenosis has not been validated. This prospective observational study aims to investigate whether CEA is associated with an increase in ocular blood flow (OBF) and postoperative visual improvement. METHODS: In total, 41 patients with carotid artery stenosis treated by CEA between March 2015 and September 2018 were enrolled in this study. OBF was evaluated by laser speckle flowgraphy, which can measure the mean blur ratio (MBR) which is well correlated to the absolute retinal blood flow. Visual acuity was assessed before and after CEA by subjective improvement and objective visual assessment using CSV-1000, an instrument used to test contrast sensitivity. RESULTS: OBF increased after CEA on the operated side (mean MBR 33.5 vs 38.2, p < 0.001) but not on the non-operated side (mean MBR 37.8 vs 37.5, p = 0.50). After CEA, 23 patients (56.1%) reported subjective visual improvement on the operated side. The mean CSV-1000 score among the patients with increased OBF after CEA (5.44 vs 5.88, p = 0.04) but not among those without increased OBF (5.48 vs 5.95, p = 0.09). The mean CSV-1000 scores increased significantly after CEA in 18 patients with decreased vision and decreased OBF (4.51 vs 5.37, p < 0.001), but not in the 23 patients without those (6.19 vs 6.31, p = 0.6). CONCLUSION: CEA may successfully reverse visual dysfunction caused by chronic ocular ischemia due to carotid artery stenosis by increasing OBF.

Masked malignant phenotype with a benign appearance: beat-up copy number profile may be the key for hemangioblastoma dissemination.

Dissemination of histologically benign hemangioblastoma is rare; approximately 30 cases have previously been reported, and all cases occurred several months to years after surgical resection. Herein, we report a case of hemangioblastoma in which leptomeningeal dissemination occurred 2 years after hypofractionated radiation therapy (39 Gy/13 fractions). The tumor was treated primarily with radiation without surgical resection. Biopsy of the disseminated lesion confirmed histological diagnosis as histologically benign hemangioblastoma. Ki67 index was not remarkably elevated for hemangioblastomas. In addition, the methylation class determined by the methylation profiling classifier developed by the German Cancer Research Center (DKFZ)/University Hospital Heidelberg/German Consortium for Translational Cancer Research was consistent with that of common hemangioblastomas. However, genetic analyses showed significant gains and losses throughout the whole genome, indicating that highly aberrant copy number profiles may be the key to elucidating this rare but life-threatening clinical entity. Accumulation of more detailed case reports based on the comparison of specimens obtained before and after surgery or radiation is necessary to better understand the pathophysiology of the dissemination phenotype of hemangioblastoma.

A Prospective Randomized Study on the Preventive Effect of Japanese Herbal Kampo Medicine Goreisan for Recurrence of Chronic Subdural Hematoma.

Although the recurrence of chronic subdural hematoma (CSDH) after surgical treatment significantly affects the patients' quality of life, the recurrence rate has not improved in decades. Goreisan, a Japanese herbal Kampo medicine, promotes the hydragogue effect and has been empirically used in the treatment of CSDH in Japan. We conducted a prospective randomized study to investigate whether Goreisan treatment decreases the recurrence rate of CSDH. Between March 2013 and December 2018, a total of 224 patients who underwent initial burr hole surgery for CSDH were randomly assigned to receive Goreisan for 3 months (Group G) or no medication (Group N). The primary endpoint was symptomatic recurrence within 3 months postoperatively, and the secondary endpoint was complications, including the adverse effects of Goreisan. Of 224 randomized patients, 208 were included in the final analysis (104 in Group G and 104 in Group N). The overall recurrence rate was 9.1% (19/208). The recurrence rate of Group G was lower than that of Group N (5.8% vs 12.5%, P = 0.09), but the difference was not statistically significant. However, a significant preventive effect of Goreisan was found in 145 patients with high-risk computed tomography (CT) features, namely, homogeneous and separated types (5.6% vs 17.6%, P = 0.04). Although the present study did not prove the beneficial effect of Goreisan treatment, it suggested the importance of selecting patients with an increased risk of recurrence. A subset of patients whose hematoma showed homogeneous and separated patterns on CT image might benefit from Goreisan treatment.

Extirpation of a Ruptured Anterior Spinal Artery Aneurysm Accompanied by Dural Arteriovenous Fistula at the Craniovertebral Junction via a Posterolateral Approach: The Management of Extradural Venous Congestion.

Objective This study was aimed to discuss how to control extradural venous congestion with an increased pressure in cases of arteriovenous shunt disease of the craniovertebral junction. Design The study is presented through an operative video. Results A 77-year-old patient with subarachnoid hemorrhage had a dural arteriovenous fistula located at the C1-C2 level. Left vertebral angiography showed a fistula between the left C2 radiculomeningeal muscular artery and perivertebral plexus. Furthermore, right vertebral angiography showed a ruptured aneurysm at the aberrant branch of the anterior spinal artery originating from the contralateral vertebral artery (VA), possibly formed because of the concurrently increased pressure of the perimedullary veins. Aneurysm extirpation was planned through a posterolateral approach. To reduce venous bleeding during the approach, preoperative embolization of the radiculomeningeal muscular artery was performed. During surgery, the suboccipital triangle was exposed following layer-by-layer dissection of the suboccipital muscles ( Figs. 1 and 2 ). Subperiosteal dissection of the paravertebral plexus surrounding the VA around the C1 lamina was effective to avoid venous bleeding. A bloodless operative field was achieved, and key anatomical structures, such as the C2 nerve root, feeder, and V3 portion of the left VA, were clearly identified. With a sufficient amount of lateral exposure, the ruptured anterior spinal artery aneurysm was successfully extirpated with bipolar coagulation. The patient was discharged with no neurologic deficit. Fig. 1 ( A ) The initial CT scan showing the subarachnoid hemorrhage. ( B ) Left vertebral angiogram demonstrating a dural arteriovenous fistula at the craniovertebral junction. ( C ) Right vertebral angiogram showing an aneurysm (arrow) arising at the aberrant branch of the anterior spinal artery. ( D ) The postoperative angiogram demonstrating the extirpation of the aneurysm (arrowhead). Fig. 2 ( A ) Intraoperative photograph showing the subperiosteal dissection technique to protect the vertebral artery and minimize the bleeding from the paravertebral plexus. ( B ) The sufficient posterolateral exposure was obtained with minimal bleeding. C1, C1 lamina; C2, C2 lamina; Occ, occipital bone. Conclusion Controlling extradural venous congestion is essential to obtain a clear operative field in cases of arteriovenous shunt disease at the craniovertebral junction. The link to the video can be found at: https://youtu.be/fCT69WtAQbo .

Prevention of Thromboembolic Infarction After Surgery for Traumatic Cervical Fracture with Vertebral Artery Occlusion by Preoperative Endovascular Coil Embolization.

BACKGROUND: Vertebral artery injuries (VAIs) caused by cervical trauma include irregularities with narrowing of the arterial wall, dissection, pseudoaneurysm formation, occlusion, and transection. Although recent guidelines have recommended anticoagulant or antiplatelet therapy to prevent subsequent stroke in patients with traumatic VAIs, regardless of the type of vascular injury, the clinical role of endovascular surgery in the treatment of traumatic VAIs remains to be elucidated. METHODS: We retrospectively evaluated the treatment outcomes of 23 patients with cervical fracture and vertebral artery occlusion (VAO) who had required cervical surgery in the acute stage. RESULTS: No patient received antiplatelet or anticoagulant therapy, because the VAs had already become occluded. After cervical surgery, 5 of the 23 patients developed radiologically confirmed thromboembolic stroke after cervical surgery. None of these 5 patients with postoperative infarction had undergone preoperative VA embolization. Univariate analysis revealed that only the implementation of preoperative VA embolization was associated with the prevention of postoperative infarction (P = 0.004). Factors such as age, reduction, level of VAO, and diabetes mellitus did not correlate with increased risk. CONCLUSIONS: The clinical role of endovascular surgery for traumatic VAI has not been previously established; however, a more specific selection of patients according to the VAI type might be necessary. Our data have indicated that preoperative embolization of the occluded VA significantly reduces the risk of postoperative infarction in a specific cohort of patients with traumatic VAI (i.e., patients with post-traumatic VAO who require cervical surgery).

A Large Carcinosarcoma of the Gallbladder Accompanied by Pancreaticobiliary Maljunction: A Case with a Six-year Survival.

Pancreatobiliary maljunction (PBM) is a rare congenital malformation, often associated with adenocarcinoma. However, PBM accompanying gallbladder carcinosarcoma has rarely been reported. A 72-year-old woman was referred to our hospital, complaining of abdominal pain. Computed tomography showed a polypoid mass in the gallbladder. Endoscopic retrograde cholangiopancreatography showed PBM, and aspirated bile demonstrated elevated levels of pancreatic-type amylase (26,780 U/L) and cancer cells. Extended cholecystectomy was performed. Histologically, the tumor had adenocarcinoma, squamous cell carcinoma and sarcoma components. Despite the large tumor size (84 mm) and intra-vessel cancer permeations, this patient has been healthy for 73 months since the surgery.

Intraoperative quantification of meningioma cell proliferation potential using rapid flow cytometry reveals intratumoral heterogeneity.

BACKGROUND: Standard sampling methods to evaluate the proliferative ability of meningioma have not been established. METHODS: This prospective study was conducted to evaluate the effectiveness of intraoperative rapid flow cytometry (iFC) using raw samples for the quantitative assessment of proliferative ability in meningioma cells and to investigate intratumoral heterogeneity. Proliferation index (PI) was defined as the ratio of aneuploid cells with an abnormal number of chromosomes to the total cells. RESULTS: From 50 patients, 118 specimens were analyzed. There was a statistically significant correlation between the postoperative MIB-1 labeling index (LI) and PI (R = 0.59, P < 0.0001). A higher PI was correlated with a higher annual growth rate (AGR, cm3 /y) (R = 0.50, P = 0.0002, 26 patients). AGR showed a correlation with the intratumoral distribution of PI. PI was the highest at the center or the peripheral section of the tumor in tumors with high AGR, whereas it was highest at the dural attachment in tumors with low AGR (P = 0.039, n = 20). Pial feeders were more frequently observed when PI was high in the center or in the peripheral section (P = 0.006, n = 37). CONCLUSIONS: Rapid iFC may thus become a substitute for MIB-1 LI. Intratumoral heterogeneity of cellular proliferative potential exists in meningiomas and is related to tumor biological characteristics such as AGR and development of pial feeders. This observation underscores the importance of standardization in the sampling method to accurately estimate the risk of meningioma recurrence.