Precision of preoperative diagnosis in patients with brain tumor - A prospective study based on "top three list" of differential diagnosis for 1061 patients.

BACKGROUND: Accurate diagnosis of brain tumor is crucial for adequate surgical strategy. Our institution follows a comprehensive preoperative evaluation based on clinical and imaging information. METHODS: To assess the precision of preoperative diagnosis, we compared the "top three list" of differential diagnosis (the first, second, and third diagnoses according to the WHO 2007 classification including grading) of 1061 brain tumors, prospectively and consecutively registered in preoperative case conferences from 2010 to the end of 2017, with postoperative pathology reports. RESULTS: The correct diagnosis rate (sensitivity) of the first diagnosis was 75.8% in total. The sensitivity of the first diagnosis was high (84-94%) in hypothalamic-pituitary and extra-axial tumors, 67-75% in intra-axial tumors, and relatively low (29-42%) in intraventricular and pineal region tumors. Among major three intra-axial tumors, the sensitivity was highest in brain metastasis: 83.8% followed by malignant lymphoma: 81.4% and glioblastoma multiforme: 73.1%. Sensitivity was generally low (≦60%) in other gliomas. These sensitivities generally improved when the second and third diagnoses were included; 86.3% in total. Positive predictive value (PPV) was 76.9% in total. All the three preoperative diagnoses were incorrect in 3.4% (36/1061) of cases even when broader brain tumor classification was applied. CONCLUSION: Our institutional experience on precision of preoperative diagnosis appeared around 75% of sensitivity and PPV for brain tumor. Sensitivity improved by 10% when the second and third diagnoses were included. Neurosurgeons should be aware of these features of precision in preoperative differential diagnosis of a brain tumor for better surgical strategy and to adequately inform the patients.

Cytotoxic effect of selected wild orchids on two different human cancer cell lines.

Majority of the orchid species are used in the traditional medicines for the treatment of several diseases. They are the sources of polysaccharides, phenanthrenes, bibenzyl derivatives, revesteral, stilbenoids and polyphenol compounds. This study explored the cytotoxic activity of seven wild orchid species and identification of medicinally active compounds. The extracts of orchid species were screened for cytotoxic effect on the human cervical cancer cells (HeLa) and human glioblastoma cells (U251) using an MTT assay. The medicinally active compounds of high cytotoxic extracts were identified by GC-MS resulting in many stilbenoids and phenolic derivatives. The extract of Dendrobium transparens (DTs) and Vanda cristata (VCw) showed high cytotoxic effect towards the HeLa and U251 cell lines (IC50 of DTs: 382.14 µg/ml and 75.84 µg/ml respectively and IC50 of VCw: 317.23 µg/ml and 163.66 µg/ml respectively). This study concludes that they could be used as cancer therapeutics.

A case of developing obstructive hydrocephalus following aqueductal stenosis caused by developmental venous anomalies.

Developmental venous anomalies (DVAs), previously also known as venous angiomas, are variations of normal trans-medullary veins draining from white and gray matter. DVAs are usually asymptomatic and mostly discovered incidentally on brain imaging. However, some studies have reported symptomatic cases associated with DVAs. In this report, we report an extremely rare case of a 14-month-old boy with obstructive hydrocephalus following aqueductal stenosis caused by developmental venous anomalies. At the age of 14 months, his head circumference exceeded + 2SD significantly. Brain magnetic resonance imaging (MRI) showed triventriculomegaly and dilated collector vein coursing through the Sylvian aqueduct, causing aqueductal stenosis. Endoscopic third ventriculostomy (ETV) was successfully performed. During the procedure, a dilated collector vein was confirmed obstructing the Sylvian aqueduct. Postoperative cine MRI showed good flow signal through the opening and improvement of hydrocephalus was noted. Obstructive hydrocephalus following aqueductal stenosis caused by DVAs is very rare; nonetheless, it can be considered as a causal differential diagnosis for hydrocephalus. Whether ETV should be chosen, as the technique for diversion of cerebrospinal fluid (CSF) flow, remains controversial. This case report showed that ETV was effective and safe.

Sellar Xanthogranuloma: A Quest Based on Nine Cases Assessed with an Anterior Pituitary Provocation Test.

BACKGROUND: Xanthogranuloma is a chronic inflammatory mass characterized by cholesterol crystal deposition, which is rarely seen in the sellar region. The objective of this study is to identify the clinical features and cause of sellar xanthogranulomas. METHODS: We retrospectively analyzed manifestation, radiographic, and endocrinologic presentation in 9 patients (7 women and 2 men) whom we had previously treated. RESULTS: The patients were between 26 and 73 years of age (median, 56 years). The chief symptoms were visual symptoms in 3, polyuria in 3, headache in 4, and tiredness in 4 patients. Perimetry found visual field deficit in 6 patients. Anterior pituitary provocation tests disclosed impairment of ≥1 hormone in all patients: growth hormone in 8 patients and adrenocorticotropic hormone-cortisol axis in 8 patients. The lesions were suprasellar in 2 patients, intrasellar in 2 patients, and intrasuprasellar region in 5 patients. Three of the lesions were solid and 6 were single cystic to multicystic. Very low intensity area on T2-weighted magnetic resonance imaging was observed in 4 lesions. Postcontrast study performed in 7 lesions showed enhancement in solid parts or cyst walls. Surgical decompression improved visual disturbance in half of the patients but rarely improved hormonal deficits. Follow-up (median, 47 months) found no recurrence of the lesion. In addition to these 9 cases, we found 2 xanthogranulomatous lesions pathologically associated with ciliated epithelia, which also presented with severe hypopituitarism. CONCLUSIONS: Xanthogranuloma seems to be the last stage of the chronic inflammation affecting Rathke cleft cyst or craniopharyngioma presenting with severe anterior pituitary insufficiency.

Deep Sylvian Meningioma without Dural Attachment - A Case Report.

Deep Sylvian meningiomas are rare, accounting for 0.3-0.4% of all meningiomas, and mostly present in young adults and children. We report on a 32-year-old man who presented with headache but had no neurological deficits. Computed tomography of brain revealed a 24 × 19 × 21 mm3 mass lesion in the right Sylvian fissure with calcification. Magnetic resonance imaging showed that the lesion was isointense on T1- and T2-weighted images (WI), with homogenous enhancement on post-gadolinium T1WI. The lesion was surgically removed via right fronto-temporal craniotomy. The tumor was located in deep Sylvian fissure and had no dural attachment. Histopathological examination of the lesion revealed both meningothelial and fibroblastic features, thereby suggesting the diagnosis of transitional meningioma (WHO grade I), with Ki-67 labeling index of 6.9%. Thus, meningioma should be considered as a differential diagnosis of enhancing mass lesions in the Sylvian fissure even in the absence of dural tail sign, especially in young adults and children.

Microvascular Decompression in Patients Aged 30 Years or Younger.

OBJECTIVE: The aim of this study was to identify the etiology of hemifacial spasm (HFS) and trigeminal neuralgia (TN) in patients aged 30 years or younger and to examine the efficacy of microvascular decompression (MVD). PATIENTS AND METHODS: Between 1996 and 2012, 228 HFS and 190 TN patients underwent MVD at Atsuchi Neurosurgical Hospital. Of these, 7 patients were 30 years of age or younger at the time of treatment (HFS: n = 6, TN: n = 1). Assessments were based on their medical history and on magnetic resonance imaging, magnetic resonance angiography, surgical, and follow-up findings. RESULTS: The age of the 6 HFS patients ranged from 23 to 30 years (mean 27.8 ± 1.8 [standard deviation] years) at the time of surgery; the earliest symptom onset was in an 11-year-old boy. We noted vascular variations in 5 patients, a duplicate posterior inferior cerebellar artery in 2 patients, a short basilar artery in 1 patient, and an aberrant arterial course in 2 patients. At the latest follow-up, 1-69 months after MVD, 5 of the HFS patients were asymptomatic and the 6th had mild residual symptoms. A 23-year-old TN female underwent straightening of the trigeminal nerve by separation of a thickened arachnoid membrane from the nerve and dislocation of a small branch of the superior cerebellar artery from the distal end of the root exit zone. While she continued to experience occasional facial pain 48 months after the operation, she required no medication because surgery yielded significant pain amelioration. CONCLUSION: Although the pathogenesis of early-onset HFS and TN remains unclear, our findings suggest that vascular variations may be related to the etiology of vascular compression symptoms in patients with HFS or TN. MVD was useful for the treatment of neurovascular compression symptoms in young patients.

Very delayed discontinuation of telescoped Pipeline embolization devices: a case report.

BACKGROUND: Flow diversion with the Pipeline embolization device (PED) is a widely accepted treatment modality for aneurysm occlusion. Previous reports have shown no recanalization of aneurysms on long-term follow-up once total occlusion has been achieved. CASE DESCRIPTION: We report on a 63-year-old male who had a large internal carotid artery cavernous segment aneurysm. Treatment with PED resulted in complete occlusion of the aneurysm. However, follow-up angiography at four years revealed recurrence of the aneurysm due to disconnection of the two PEDs placed in telescoping fashion. CONCLUSION: Herein, we present the clinico-radiological features and discuss the possible mechanisms resulting in the recanalization of aneurysms treated with flow diversion.

Changes in quality of life in patients with acromegaly after surgical remission - A prospective study using SF-36 questionnaire.

Patients with acromegaly have a compromised quality of life (QOL). Modern surgical techniques have improved the surgical cure rate. However, there are no prospective studies reporting postoperative changes in QOL among patients cured solely by surgery. The aim of the present study was to determine the effect of surgery on QOL using the 36-item short form health survey (SF-36) questionnaire. SF-36 scores comprise 3 components: the physical component summary (PCS), the mental component summary (MCS) and role-social component summary (RCS). Included in this prospective cohort were 41 patients with acromegaly who underwent surgery alone and achieved postoperative normalization of insulin-like growth factor-1. All participants completed the SF-36 preoperatively and 1 year postoperatively. Preoperatively, RCS and 4 subscale scores (role physical, social functioning, role emotional, mental health) were below the set standards for the normal population. Postoperatively, the PCS and RCS scores did not change significantly, but the MCS score improved significantly (from 48.1 ± 11.3 to 51.7 ± 8.9, p=0.03). Further we compared the QOL of 26 patients whose nadir GH level was < 0.4 µg/L during postoperative oral glucose tolerance testing (complete remission group) with that of 15 patients whose nadir GH level was ≥ 0.4 µg/L (partial remission group). There were no significant differences between these groups in terms of PCS, MCS, RCS, or any subscale scores. In conclusion, surgical remission mostly improved the participants' mental condition. There was no difference in QOL between patients who achieved the new remission criteria and those who did not.

Treatable glomerular hyperfiltration in patients with active acromegaly.

OBJECTIVE: The glomerular filtration rate (GFR) is increased in patients with active acromegaly. The aim of this study is to elucidate whether renal function deteriorates in patients with acromegaly and whether this deterioration is reversible after surgical remission. DESIGN/METHODS: A case-control study of 48 acromegalic patients who were surgically cured (cases) and 48 patients with nonfunctioning pituitary adenomas (NFomas, controls) was conducted. We performed clinical and biochemical examinations before surgery and 3months post-surgery. The GFR of each patient was estimated (estimated GFR, eGFR) using their serum creatinine, age, sex, and body surface area, and postoperative changes in the eGFR were assessed. RESULTS: The preoperative eGFR was significantly higher in patients with acromegaly than in those with NFoma (99.8 vs 75.1mL/min respectively, P<0.01). In acromegalic patients, surgical remission was accompanied by a significant decline in the eGFR (from 99.8 to 86.2mL/min, P<0.01). Conversely, in patients with NFoma, the postoperative eGFR did not change significantly (from 75.1 to 81.9mL/min, P=0.12). Among the acromegalic patients, the postoperative decreases in the eGFR were more prominent in patients with a preoperatively high or normal vs low eGFR. CONCLUSIONS: Our data demonstrated a significant post-surgical eGFR decrease in patients with acromegaly, but not in patients with NFomas. This change in the eGFR was reversible in acromegalic patients with a high/normal preoperative eGFR, but not in those with a low preoperative eGFR. This suggests that the reversible pathophysiological change in some patients is functional but not organic.

A Novel Bilateral Approach for Suprasellar Arachnoid Cysts: A Case Report.

The endoscopic method is used to treat suprasellar arachnoid cysts (SACs) but it is sometimes difficult to make sufficiently sized fenestrations. Creating a larger fenestration on the cyst wall is preferable to prevent closure of the stoma. In this paper, we report a novel endoscopic approach for SAC treatment in which we use bilateral burr holes to achieve a more extensive cyst fenestration. A 7-year-old girl was referred to our hospital because of incidentally detected hydrocephalus by computed tomography scans. Physical examination did not show any signs of intracranial hypertension, but a digital impression of her skull on X-ray implied chronic intracranial hypertension. Magnetic resonance imaging (MRI) revealed enlargement of both lateral ventricles and a cystic mass occupying the third ventricle. We performed cyst wall fenestration using a bilateral approach in which we created two burr holes to introduce a flexible endoscope and a rigid endoscope. The cyst wall was held by forceps with the flexible endoscope, and resection of the cyst wall was achieved by using a pair of scissors with the rigid endoscope. There were no postoperative complications, and MRI performed 1 year after treatment showed disappearance of the superior part of the cyst wall.

Effect of Revascularization on Headache Associated with Moyamoya Disease in Pediatric Patients.

Episodic headache is common in childhood moyamoya disease (MMD). The onset, mechanism, cause of headache and the effect of revascularization surgery on headache are not yet clear. We studied 10 cases of children (7 boys and 3 girls) younger than 18 years who underwent revascularization for MMD between 2009 and 2013. We evaluated frequency of headache and cerebral blood flow changes by single photon emission computed tomography brain imaging with [I123]-labeled iofetamine (IMP-SPECT) before and after surgery. Patients' ages ranged from 0 to 15 years at onset and 2 to 17 years at the time of surgery, mean age being 6.7 and 8.0 years respectively. 9 of 10 patients presented with ischemic symptoms and 8 had headache. 5 patients underwent indirect bypass and 5 underwent combined direct and indirect bypass. Cerebral blood flow improvement was obtained in 14 of the 15 cerebral hemispheres revascularized. The mean follow-up duration was 32.9 months. All the patients had good outcomes with improvement of ischemic neurological deficits. Headache improved in 7 (87.5%) of 8 patients. Headache in pediatric moyamoya disease is associated with change in cerebral hemodynamics. Revascularization including combined direct bypass and indirect techniques may be required to reduce headache in patients with MMD.

Choroid Plexus Tumors: Experience of 10 Cases with Special References to Adult Cases.

Choroid plexus tumors (CPTs) are rare intraventricular neoplasms accounting for about 0.3-0.6% of all intracranial tumors. This retrospective study on CPTs presents clinico-pathological features and management strategies based on a 20-year single-institutional experience. This series included 10 consecutive patients with pathologically proven CPTs; 5 choroid plexus papillomas (CPPs), 3 atypical CPPs (ACPPs), and 2 choroid plexus carcinomas (CPCs). Their clinical, radiological, and histopathological features as well as management including follow-up studies were reviewed. The patients included five males and five females, aging from 0 years to 61 years with median of 28 years. The affected site was lateral ventricle in two adults and fourth ventricle in eight patients; four children and four adults. The most common symptoms were gait disturbance and memory disturbance. All the patients underwent craniotomy with total, subtotal, and partial removals achieved in 50%, 40%, and 10% of the patients, respectively. The occurrence of the high grade subtypes was 50% in both the adult and pediatric groups. The Ki-67/MIB-1 index increased across the three histological subtypes, from CPP to ACPP and then to CPC. Adjuvant therapy was administered in three patients. The two patients (one adult and one child) with CPC died of whole central nervous system dissemination. At a median of 62-month follow-up, the other eight patients were alive, with only one patient having recurrence and reoperation. The results demonstrate that gross total resection is usually curative for CPP and ACPP, and adjuvant chemoradiotherapy would be required for CPC and incompletely resected ACPP.

Third ventricular atypical meningioma which recurred with further malignant progression.

Meningiomas in the third ventricle are rare, with only very few cases reported in the literature. We report a case of primary third ventricular anaplastic meningioma in a 49-year-old man who presented with progressive weakness of the left limbs and headache. Magnetic resonance imaging revealed a tumor which seemed to arise from the right thalamus and extending into third ventricle. The tumor was heterogeneously enhanced with gadolinium. It was totally removed by right transventricular-subchoroidal approach. The lesion was intraoperatively found to be whitish hard and embedded in right thalamus, but had attachment to choroid plexus near foramen Monroi with narrow interface. The histological diagnosis was atypical meningioma, WHO Grade II. Lesion recurred 20 months later and was resected via the same approach, which turned out to be papillary meningioma, WHO Grade III. The patient had second recurrence 23 months after second surgery which was operated and the final diagnosis was anaplastic meningioma (WHO Grade III). Literature review showed meningioma of the third ventricle is quite exceptional and more than half of the cases were aggressive subtypes (Grade II or III).

Solitary Cranial Langerhans Cell Histiocytosis: Two case reports.

Langerhans cell histiocytosis (LCH) is a proliferation of Langerhans cells intermixed with inflammatory cells, in particular eosinophils, that may manifest as a unisystem (unifocal or multifocal) or multisystem disease. We describe the clinical and histologic spectrum of LCH of the orbit and skull in our two cases. Both cases had unifocal erosive skull lesions with a history of trauma. Typical histologic features included numerous histiocytes with varying degrees of giant cell formation and scattered eosinophilic granulocytes. The presence of Langerhans cells was confirmed by CD1a and S100 immunohistochemistry. LCH has an excellent prognosis when treated with surgical resection, steroids and radiotherapy or chemotherapy. One of our patients is disease free at 7 year follow-up and one patient had regression of lesion on follow-up.

Cardiopulmonary Resuscitation-induced Thoracic Vertebral Fracture: A Case Report.

Thoracic vertebral fractures are very unusual complications of cardiopulmonary resuscitation (CPR). A 78-year-old man developed cardiac arrest after aspirating and conventional CPR was performed. After recovery, the patient had complete paraplegia (Frankel grade A). Magnetic resonance image of spine showed a dislocation fracture with hematoma at T6 thoracic level. Computed tomography scan of chest revealed the fracture of sternum. After the patient's condition became stable with subsequent medical treatment, posterior decompression and pedicle screw fixation was performed. The patient had uneventful postoperative course with continued rehabilitation. Thus, this report emphasizes that care should be taken especially in elderly patients with fragile bone to recognize such rare complication of chest compression; however, adequate compressions to ensure circulation should be maintained.

Thyroid storm induced by TSH-secreting pituitary adenoma: a case report.

Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon tumors of the anterior pituitary gland. Patients with TSHomas may present with hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year-old woman. Preoperatively she had symptoms of excessive sweating and palpitation. Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 µ U/mL, fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a pituitary tumor with maximum diameter of 13 mm that was extirpated through transsphenoidal route. After operation the patient was stuporous and thyroid storm occurred presenting with hyperthermia, hypertension, and tachycardia. It was well managed with nicardipine, midazolam, steroids, and potassium iodide. Immunohistochemical staining of tumor specimen was positive for TSH and growth hormone (GH). One year after operation, fT3 and fT4 levels were still high. As her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection therapy was started, which normalized thyroid hormone levels. This is the second reported case with thyroid storm due to TSHoma and emphasizes the importance of strategies with interdisciplinary cooperation for prevention of such emergency conditions.

C-type natriuretic peptide modulates permeability of the blood-brain barrier.

C-type natriuretic peptide (CNP) is abundant in brain and is reported to exert autocrine function in vascular cells, but its effect on blood-brain barrier (BBB) permeability has not been clarified yet. Here, we examined this effect. Transendothelial electrical resistance (TEER) of in vitro BBB model, composed of bovine brain microvascular endothelial cells and astrocytes, was significantly dose dependently decreased by CNP (1, 10, and 100 nmol/L). C-type natriuretic peptide treatment reduced both the messenger RNA (mRNA) and protein expressions of tight junction (TJ) protein zonula occludens-1 (ZO-1). The effects on TEER, mRNA, and protein expressions of ZO-1 were mimicked by cyclic GMP (cGMP) analog 8-bromo-cGMP (1 µmol/L) and reversed by protein kinase G (PKG) inhibitor Rp-8-CPT-cGMPS (100 µmol/L), thus implying the role of PKG and cGMP signaling in BBB function. Transcription factor JunD knockdown by small interfering RNA resulted in no change of permeability by CNP. In vivo study of mouse brain by fluorimetric analysis with intravenous administration of sodium fluorescein (40 mg/kg) also showed a significant increase in BBB permeability by CNP (10 nmol/kg, intravenously). These findings suggest that CNP modulates the BBB permeability by altering ZO-1 expression.

Geometric survey on magnetic resonance imaging of growth hormone producing pituitary adenoma.

Apart from the radiologic features regarding size and invasiveness, we had noticed some differences in morphology among types of pituitary adenomas. We conducted this study to verify the differences in radiologic morphology between growth hormone producing pituitary adenomas (GHoma) and nonfunctioning pituitary adenomas (NFoma). Pre-surgical magnetic resonance images (MRIs) were assessed in 50 cases of GHoma and 50 cases of NFoma. Geometric parameters on MRI were set in accordance with sellar anatomy. Intensity of T1-weighted image was not different between the two groups, but hypo-intensity of T2-weighted image was more frequently seen in GHoma. Predominant inferior extension of tumor was seen mostly in GHoma (88 vs. 38%). Extension of the tumor to the superior compartment of cavernous sinus was more frequent in NFoma. Pituitary gland was generally located superior to GHoma and postero-superior to NFoma. Growth characteristics of pituitary adenoma were confirmed to differ between GHoma and NFoma.

The assessment of relationship between the skull base development and the severity of frontal plagiocephaly after bilateral fronto-orbital advancement in the early life.

PURPOSE: The deformation of the skull base in patients with unilateral frontal plagiocephaly (UFP) is well known, but the mechanism is not still clear. We analyzed the skull base in the patients with UFP who underwent fronto-orbital advancement (FOA) in the early life during the last decade. METHODS: We assessed the treatment results and outcome of FOA performed in six patients, four girls and two boys younger than 2 years, in the last decade. Also, the basal cranium's angles were measured by 3D reconstruction images on computed tomography (CT) scan. RESULTS: The mean patients' age at FOAs was 11 months. Two cases were classified as grade 2A, two cases as grade 2B, and two cases as grade 3 (the classification of Di Rocco and Velardi). The ethmoidal axis was deviated a mean of 8.2° to the affected side. The mean angle between the petrosal pyramids and the midline (anterior-petrosal-sagittal angle, APSA) was 75.3° on the affected side and 66.2° on the normal side. The mean difference of APSA was 9.2°. On the follow-up CT images 5 years after surgery, the deviations of the ethmoidal axis clearly decreased, 5.7°, but the differences of APSA did not change, 8.8°. CONCLUSIONS: The midline distortion of anterior skull base should be considered to be spontaneously corrected during the follow-up periods in patients with all types of UFP who underwent FOA, unlike posterior skull base in the patients with grades 2B and 3 classification.

Effect of thrombin concentration on the adhesion strength and clinical application of fibrin glue-soaked sponge.

Fibrin glue-soaked gelatin sponge (FGGS) has been used for tissue sealing in neurosurgical practice, but too rapid clotting of fibrin glue occasionally prevents good fixation of FGGS. Dilution of thrombin may provide adequate manipulation time between mixing fibrinogen and thrombin on gelatin sponge and application into the tissue defects. The present study characterized the effect of thrombin dilution on the adhesion strength of FGGS and retrospectively assessed the clinical usage of the dilution for filling dead space or sealing arachnoid defect in 255 cases who underwent transsphenoidal surgery for the last 66 months. FGGS was prepared using three different concentrations of thrombin: 250 (standard), 50 (1:5 dilution), and 25 (1:10 dilution) units/ml, and incubated for three different periods (5, 20, and 60 seconds). FGGSs were applied over two adjacently positioned porcine skins placed on two metallic plates. The adhesion strength was evaluated by measuring maximum tensile strength during pulling out the sliding plate at a constant rate of displacement. The maximum adhesion strength was greater for FGGS with 1:10 diluted thrombin solution than for FGGS prepared with higher concentrations (p < 0.05). Adhesion strength did not decay for 20 seconds after the mixture. Only four of 255 cases (1.6%) required second reconstruction of sella floor due to the cerebrospinal fluid leakage. FGGS prepared with diluted thrombin solution can provide adequate adhesion strength for clinical use.