Impact of Portal Flow on the Prognosis of Children With Congenital Portosystemic Shunt: A Multicentric Observation Study in Japan.

BACKGROUND: Although congenital portosystemic shunts (CPSSs) are increasingly being recognized, the optimal treatment strategies and natural prognosis remain unclear, as individual CPSSs show different phenotypes. METHODS: The medical records of 122 patients who were diagnosed with CPSSs at 15 participating hospitals in Japan between 2000 and 2019 were collected for a retrospective analysis based on the state of portal vein (PV) visualization on imaging. RESULTS: Among the 122 patients, 75 (61.5%) showed PV on imaging. The median age at the diagnosis was 5 months. The main complications related to CPSS were hyperammonemia (85.2%), liver masses (25.4%), hepatopulmonary shunts (13.9%), and pulmonary hypertension (11.5%). The prevalence of complications was significantly higher in patients without PV visualization than in those with PV visualization (P < 0.001). Overall, 91 patients (74.6%) received treatment, including shunt closure by surgery or interventional radiology (n = 82) and liver transplantation (LT) or liver resection (n = 9). Over the past 20 years, there has been a decrease in the number of patients undergoing LT. Although most patients showed improvement or reduced progression of symptoms, liver masses and pulmonary hypertension were less likely to improve after shunt closure. Complications related to shunt closure were more likely to occur in patients without PV visualization (P = 0.001). In 25 patients (20.5%) without treatment, those without PV visualization were significantly more likely to develop complications related to CPSS than those with PV visualization (P = 0.011). CONCLUSION: Patients without PV visualization develop CPSS-related complications and, early treatment using prophylactic approaches should be considered, even if they are asymptomatic. LEVEL OF EVIDENCE: Level III.

Appendiceal atresia causing recurrent right lower quadrant pain without inflammation.

An 11-year-old girl presented with recurrent right lower quadrant (RLQ) pain. There was no evidence of inflammation and appendiceal swelling except at the initial onset. The repeated presence of a small amount of ascites at the time of abdominal pain triggered the performance of exploratory laparoscopy. Intraoperative examination revealed a non-inflamed, unswollen appendix with a cord-like atretic segment at the middle part and an appendectomy was performed. At 46 months follow-up, she remained asymptomatic. In patients with recurrent RLQ pain of unknown cause, it is necessary to consider diagnostic laparoscopy while keeping appendiceal atresia in mind as a differential diagnosis.

Evaluation of Ki-67 as prognostic factor for pediatric neuroblastoma and the possibility of molecular-targeted drugs with VEGF and PDGFR.

BACKGROUND: Neuroblastoma (NB) is a pediatric malignant solid tumor characterized as refractory cancer with poor prognosis. The Mitosis-Karyorrhexis Index (MKI) is a prognostic factor but is prone to observer bias. The usefulness of MKI with Ki-67, as a marker of malignancy, was investigated. The efficacy of molecular-targeted therapeutic agents with fewer side effects in tumors has been studied. Molecular-targeted therapy targets include vascular endothelial growth factor (VEGF), involved in tumor angiogenesis; c-Kit, receptor of Kit/stem cells involved in tumor growth, vasculature, and lymphangiogenesis; platelet-derived growth factor receptor (PDGFR); and B-Raf proto-oncogene, serine/threonine kinase (BRAF), involved in the RAS protein-mediated mitogen-activated protein kinase pathway. Therefore, expression profiles of these factors and growth inhibitory effects of molecular-targeted drugs against NB were investigated. METHODS: Ten frozen NB tissue samples collected from January 1993 to December 2017 were evaluated immunohistochemically for Ki-67 and VEGF. c-Kit, PDGFR, and BRAF expression levels were evaluated using enzyme-linked immunosorbent assays; relationships between these factors and clinicopathological parameters of NB were analyzed. RESULTS: Eight patients with NB showed no amplification of MYCN (MYCN proto-oncogene, bHLH transcription factor). There were two cases of ganglioneuroblastoma (GNB). More NB cells were positive for Ki-67 than for GNB cells. VEGF expression was observed in all NB specimens and was stronger in stage IIB and higher. No BRAF or c-Kit activity was observed; PDGFR activity was greater in NB than in GNB (P=0.02). CONCLUSIONS: Thus, Ki-67 may help evaluate NB malignancy. As the first therapy for NB prevents amplification of MYCN, agents targeting PDGFR as well as VGFG can inhibit NB cell proliferation.

Antitumor effect of polyphyllin D on liver metastases of neuroblastoma.

PURPOSE: We previously reported that polyphyllin D, a main component of the traditional Chinese medicinal herb Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aims of this investigation was to examine the presence or absence of in vivo anti-metastasis effects of polyphyllin D were to establish a liver metastasis model of neuroblastoma and to evaluate the anti-metastasis effects of polyphyllin D. METHODS: Subcutaneous and intraperitoneal tumors, and metastasis models were established in immune-deficient BALB/c nude and BALB/c Rag-2/Jak3 double-deficient (BRJ) mice using the human neuroblastoma cell lines IMR-32, LA-N-2, or NB-69. For evaluating polyphyllin D activity, we used a mouse model of liver metastasis with the IMR-32 cells line injected through the tail vein. We analyzed the livers number and area of liver tumors in of the phosphate buffer solution- and polyphyllin D-treated groups. RESULTS: Liver metastasis and intraperitoneal dissemination models were successfully established in immune-deficient BRJ mice using the three human neuroblastoma cell lines. In the liver metastasis, the model of IMR-32 cells, we found that polyphyllin D suppressed both the number and total area of metastatic foci the average number of metastatic foci, average focus areas, and number of cleaved caspase-3-positive cells were significantly lower in the polyphyllin D group (p = 0.016, 0.020, 0.043, respectively). CONCLUSIONS: We developed a mouse models of neuroblastoma metastasis and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma liver metastases.

Urgent intraoperative endovascular stent placement to resolve acute hepatic or portal venous obstruction during liver surgery: a case series.

BACKGROUND: Acute obstruction of the hepatic vein (HV) or the portal vein (PV), particularly when it occurs during liver surgery, is potentially fatal unless repaired swiftly. As surgical interventions for this problem are technically demanding and potentially unsuccessful, other treatment options are needed. CASE PRESENTATION: We report two cases of acute, surgically uncorrectable HV or PV obstruction during liver resection or living donor liver transplantation (LDLT), which was successfully treated with urgent intraoperative placement of endovascular stents using interventional radiology (IVR). In Case 1, a patient with colonic liver metastases underwent a non-anatomic partial hepatectomy of the segments 4 and 8 with middle hepatic vein (MHV) resection. Additionally, the patient underwent an extended right posterior sectionectomy with right hepatic vein (RHV) resection for tumors involving RHV. Reconstruction of the MHV was needed to avoid HV congestion of the anterior section of the liver. The MHV was firstly reconstructed by an end-to-end anastomosis between the MHV and RHV resected stumps. However, the reconstruction failed to retain the HV outflow and the anterior section became congested. Serial trials of surgical revisions including re-anastomosis, vein graft interposition and vein graft patch-plasty on the anastomotic wall failed to recover the HV outflow. In Case 2, a pediatric patient with biliary atresia underwent an LDLT and developed an intractable PV obstruction during surgery. Re-anastomosis with vein graft interposition failed to restore the PV flow and elongated warm ischemic time became critical. In both cases, the misalignment in HV or PV reconstruction was likely to have caused flow obstruction, and various types of surgical interventions failed to recover the venous flow. In both cases, an urgent IVR-directed placement of self-expandable metallic stents (SEMS) restored the HV or PV perfusion quickly and effectively, and saved the patients from developing critical conditions. Furthermore, in Cases 1 and 2, the SEMS placed were patent for a sufficient period of time (32 and 44 months, respectively). CONCLUSIONS: The IVR-directed, urgent, intraoperative endovascular stenting is a safe and efficient treatment tool that serves to resolve the potentially fatal acute HV or PV obstruction that occurs in the middle of liver surgery.

Arctigenin induces apoptosis in human hepatoblastoma cells.

PURPOSE: Arctigenin has been shown to have anti-tumor effects in various types of cancers. This study was conducted to verify these effects in the human-derived hepatoblastoma cell line, HUH-6 clone 5 (hereinafter, HUH-6). METHODS: Arctigenin was added to cultured HUH-6 cells, and cellular activity was evaluated by MTS assay. To determine the relationship between reduced cellular activity and apoptosis, we measured the activities of caspase 3/7, 8, and 9 and conducted flow cytometry with Annexin V/PI staining. RESULTS: The MTS assay revealed that cellular activity decreased after arctigenin treatment in a concentration-dependent manner (IC50 = 4 µM). To investigate apoptosis induction, activity assays of caspase 3/7, 8, and 9 were performed. While caspase 3/7 and 8 exhibited high activity, caspase 9 showed no activity. Thus, apoptosis induction may have involved the action of tumor necrosis factor receptor 1 (TNFR1). Flow cytometry conducted with Annexin V/PI staining revealed the occurrence of early apoptosis. CONCLUSION: We found that arctigenin has anti-tumor effects in HUH-6 cells in a concentration-dependent manner. Arctigenin may have exerted its anti-tumor effect by inducing apoptosis via TNFR1, which recruits Complex IIa to activate caspase 8 and 3/7. These results may be useful for developing therapeutic agents for hepatoblastoma.

Tailored Predictive Formulas for Glomerular Filtration Rate for Early Detection of Deteriorating Renal Function After Pediatric Living-Donor Liver Transplant.

OBJECTIVES: In pediatric patients, renal dysfunction after living-donor liver transplant is a major issue that is difficult to evaluate. Recently, predictive equations for Japanese children have been introduced. MATERIALS AND METHODS: We conducted a retrospective study by prospectively collecting data on 26 patients under 16 years old who underwent living-donor liver transplant between June 2004 and March 2015. Serum creatinine and cystatin C levels were measured. Paired t tests and Bland-Altman plots were used to compare the following formulas for estimated glomerular filtration rate: the Schwartz formula and 3 formulas that were matched with Japanese children (polynomial, simple, and cystatin C formulas). RESULTS: Average estimated glomerular filtrations rates (in mL/min/1.73 m2) were 143.46, 122.90, 121.58, and 123.31 using the Schwartz, polynomial, simple, and cystatin C formulas, respectively. The estimated glomerular filtrations rate for biliary atresia was 141.53 ± 31.37 versus 109.95 ± 19.52 for other diseases, with significant differences only noted with the cystatin C formula. The formulas tailored for Japanese children showed significantly lower estimated glomerular filtrations rates than those obtained using the Schwartz formula (P < .01). CONCLUSIONS: The use of formulas for measuring estimated glomerular filtrations rates that are based on race may allow early detection of deteriorating renal function.

Omphalocele and Gastroschisis in Newborns: Over 16 Years of Experience from a Single Clinic.

Infants born with potentially life-threatening conditions of omphalocele and gastroschisis may require long-term hospitalization. We aimed to compare the outcomes of these two conditions occurring over a 16-year period (2001-16). It is a retrospective study of 19 newborns undergoing surgery for these two abdominal wall defects (8 patients with omphalocele and 11 cases of gastroschisis). The average birth weights for the newborns with omphaloceles and gastroschisis were 2554.5 g and 2248.6 g respectively. Associated anomalies included trisomy 18, Beckwith-Wiedemann syndrome, congenital heart disease, Meckel's diverticulum, inguinal hernias, renal deformities, limb deformities, cryptorchidism, body stalk anomalies, and closed gastroschisis. The average hospital stay for the newborns with omphaloceles and gastroschisis were 42.6 days 50.2 days respectively. The time to the start of postoperative nutritional supplementation for the newborns with omphaloceles and gastroschisis were 4.3 days for the infants with omphaloceles and 7.3 days for respectively. The survival rates for the newborns with omphaloceles and gastroschisis were similar, 87.5% and 81.8% respectively. Survival rates in omphalocele correlated negatively with associated anomalies. In gastroschisis cases, strict care is necessary when intestinal dilation is observed via fetal sonography.

Polyphyllin D, a steroidal saponin in Paris polyphylla, induces apoptosis and necroptosis cell death of neuroblastoma cells.

PURPOSE: Neuroblastoma is a refractory pediatric malignant solid tumor. The previous studies demonstrated that Polyphyllin D, the main constituent of Paris polyphylla, a traditional Chinese medicine, exerts an anti-tumor effect on many tumors. However, its effects against neuroblastomas are unclear. METHODS: We examined the anti-tumor effect of polyphyllin D in human neuroblastoma using IMR-32 and LA-N-2 cells, which exhibit MYCN gene amplification, and NB-69 cells, which do not exhibit MYCN gene amplification. RESULTS: All cell lines showed reduced cell viability in response to polyphyllin D treatment. No caspase-3/-7, -8, and -9 activity was observed in IMR-32 and LA-N-2 cells treated with polyphyllin D. In contrast, activation of caspase-3/-7, and -8 activity was observed in NB-69 cells. When polyphyllin D and specific inhibitors of RIPK3 involved in necroptosis were added to IMR-32 and LA-N-2 cell lines, polyphyllin D-induced cell death was inhibited. CONCLUSION: Together, this indicates that the underlying mechanism of polyphyllin D-induced cell death in NB-69 cells is apoptosis, whereas the cell death of IMR-32 and LA-N-2 cells occurs by necroptosis. We continue research on this topic and look forward the discovery of a new therapeutic agent for neuroblastoma.

c-Jun N-terminal kinase activation by oxidative stress suppresses retinoid signaling through proteasomal degradation of retinoic acid receptor α protein in hepatic cells.

We previously reported that impaired retinoid signaling causes hepatocellular carcinoma (HCC) through oxidative stress. However, the interaction between oxidative stress and retinoid signaling has not been fully understood. To address this issue, the effects of hydrogen peroxide on the transcriptional activity of RAR/RXR heterodimers, RARα and RXRα proteins and intracellular signaling pathways were examined. The transcriptional activity of RAR/RXR examined by the DR5-tk-Luc reporter assay was significantly suppressed. The RARα protein level began to decrease at 6 h after treatment and declined thereafter. However, RARα mRNA were not changed. Activation of extracellular regulated kinases (ERK), p38, c-Jun N-terminal kinase (JNK) and Akt was observed after treatment of hydrogen peroxide. SP600125, an inhibitor of JNK, reversed the RARα protein level reduced by hydrogen peroxide. Anisomycin, an activator of JNK, reduced RARα protein. Transfection of wild-type JNK-constitutive actively expressing plasmid, but not kinase-negative JNK-expressing plasmid caused reduction of RARα protein. Proteasomal degradation of RARα was observed after anisomycin treatment; however, the mutant RARα, of which phosphorylation sites are replaced with alanines, was not degradated. In hepatitis C virus (HCV)-related human liver tissues, phospho-JNK and RARα reciprocally expressed with the progression of liver disease. Finally, the staining of 8-OHdG and thioredoxin was increased with the disease progression. These data indicate that JNK activation by oxidative stress suppresses retinoid signaling through proteasomal degradation of RARα, suggesting that a vicious cycle between aberrant retinoid signaling and oxidative stress accelerates hepatocarcinogenesis.

Disrupted plasma membrane localization of equilibrative nucleoside transporter 2 in the chemoresistance of human pancreatic cells to gemcitabine (dFdCyd).

Although the nucleoside pyrimidine analogue gemcitabine is the most effective single agent in the palliation of advanced pancreatic cancer, cellular resistance to gemcitabine treatment is a major problem in the clinical scene. To clarify the molecular mechanisms responsible for chemoresistance to gemcitabine, mRNA expression of the key enzymes including cytidine deaminase (CDA), deoxycytidine kinase (dCK), 5'-nucleotidase (NT5), equilibrative nucleoside transporter 1 and 2 (ENT1 and ENT2), dCMP deaminase (dCMPK), ribonucleotide reductase M1 and M2 (RRM1 and RRM2), thymidylate synthase (TS) and CTP synthase (CTPS) was examined. The interacellular uptake of gemcitabine was greatly impaired in the chemoresistant cell lines due to dysfunction of ENT1 and ENT2. Protein expression of ENT1 and ENT2 and their protein coding sequences were not altered. Immunohistochemical and western blot analyses revealed that localization of ENT2 on the plasma membrane was disrupted. These data suggest that the disrupted localization of ENT2 is one of causes of the impaired uptake of gemcitabine, resulting in a gain of chemoresistance to gemcitabine.

Boost radiosurgery for treatment of brain metastases after surgical resections.

BACKGROUND: We evaluated results of resection surgery followed by boost radiosurgery for the treatment of brain metastases. METHODS: We treated 21 patients (13 male, 8 female) with surgical resection (subtotal or total) followed by boost radiosurgery. The mean patient age was 61 years (range, 41-80 years); supratentorial lesions were treated in 12 patients, and posterior fossa lesions were treated in 9 patients. The most common primary cancers were lung (24%) and colon (24%). Fifty-three percent of patients had brain metastases only, whereas 47% had extracranial metastases. The radiosurgery dose plan was designed to radiate the operative cavity; the mean treatment volume (50% isodose) was 10.7 mL (range, 3.4-23.3 mL), and the mean marginal dose was 17 Gy (range, 13-20 Gy). RESULTS: Local control was achieved in 16 (76%) patients. However, new intracranial lesions developed in 10 patients, and meningeal carcinomatosis occurred in 5 patients. Local tumor recurrence occurred more often for patients treated with lower radiotherapy doses (<18 vs > or =18 Gy, P = .03), and meningeal carcinomatosis occurred more often in patients with posterior fossa lesions (P = 0.05). Gamma knife radiosurgery was performed in 13 patients, and whole-brain radiation was performed in 2 patients. No patients experienced symptomatic radiation injury, and the median survival time was 20 months. CONCLUSIONS: Although boost radiosurgery is less invasive and reduces morbidity, the radiosurgical dose must be higher than 18 Gy for the treatment to be most effective. Treatment of lesions of the posterior fossa must be considered carefully because of the higher frequency of meningeal carcinomatosis. Also, we recommend that the surgeons who operate on the metastatic tumors must try to decrease the resected cavity volume and to prevent cerebrospinal fluid dissemination at the operation for posterior fossa lesions.

[The surgical treatment of non-functioning pituitary adenomas in the ninth decade].

There are no reports of surgical treatment for non-functioning pituitary adenomas in the 9th decade of life, and it is thought that these patients often select conservative treatment and observation, because of their worry about deterioration of their general condition due to invasive surgery and because hypopituitarism and other medical problems are often present. However, it is also true that there is necessity for considering surgical treatment for the pituitary adenomas even in the 9th decade when there is a complaint of visual disturbance. We carried out the palliative surgical removal of three non-functioning pituitary adenomas with visual disturbance in the 9th decade and report these surgical treatments and outcomes. The improvement of visual disturbance was obtained in all three cases. The only perioperative complication was pneumothorax caused by barotrauma. The palliative transsphenoidal surgical removal of non-functioning pituitary adenomas for the purpose of improvement of visual disturbance is a safe procedure in the 9th decade of life.

Surgery after radiosurgery for acoustic neuromas: surgical strategy and histological findings.

OBJECTIVE: To retrospectively review the authors' experience with surgical resections after failed radiosurgery for acoustic neuromas. METHODS: The study group consisted of six patients with acoustic neuromas. The median age was 61 years (range, 18-72 yr). The median marginal radiation dose was 11 Gy (range, 10-12.5 Gy). The median interval between radiosurgery and surgical resection was 28 months (range, 4-74 mo). The operative indications were cerebellar ataxia and symptoms associated with increased intracranial pressure. The median follow-up period was 36 months (range, 11-72 mo) after surgical resection. RESULTS: The tumors were subtotally removed (> or = 80%) in four patients and partially removed (< 80%) in the other two patients. Three patients had intratumoral bleeding. Preexisting facial nerve palsy improved in two patients and deteriorated in one patient, and one patient experienced new facial palsy. No other new neurological deficits emerged after surgery. Histological features were typical of acoustic schwannoma, and some tumors were associated with foamy macrophages, myxoid degeneration, and necrosis attributed to radiation effects. At follow-up, the residual tumor was decreased in five patients and increased in one patient with an expanding intratumoral hematoma. CONCLUSION: Surgical resection after radiosurgery is indicated in the presence of such symptoms as cerebellar ataxia and increased intracranial pressure. It must be carefully considered because of the natural regression of transient tumor swelling over time. Surgical resection should be limited to subtotal removal for functional preservation. In patients with tumor enlargement several years after radiosurgery, the possibility of chronic intratumoral bleeding resulting from delayed radiation injury must be considered.

[The usefulness of adjuvant therapy using gamma knife radiosurgery for the recurrent or residual nonfunctioning pituitary adenomas].

We evaluated the treatment results of nonfunctioning pituitary adenomas in the era of radiosurgery. Between January 1994 and December 2003, we operated on 44 patients with nonfunctioning pituitary adenomas. 43 patients were operated on by transsphenoidal surgery and one patient was operated on by the transcranial approach. Total removal was able to be achieved in 13 patients (30%). Gamma knife radiosurgery was performed for residual tumor in 26 patients and for recurrence in 2 patients. The mean tumor diameter at the gamma knife radiosurgery was 18.2 mm (7.9 to 26.3 mm). The treatment dose was a mean of 12.3 Gy (8 to 16 Gy) to the tumor margin. The mean follow-up period after radiosurgery was 36.4 months. Tumor growth control was able to be achieved in 26 patients (93%). Two patients (7%) required adrenal and thyroid hormonal replacement during the follow-up period after radiosurgery due to radiation-induced endocrinopathy. None of the patients suffered from new cranial nerve deficits. This included optic neuropathy. Surgical resection using transsphenoidal surgery and subsequent gamma knife radiosurgery for residual and recurrent tumor proved to have a highly effective tumor growth control rate, and maintained the quality of life in patients with nonfunctioning pituitary adenomas.

A brainstem cavernoma demonstrating a dramatic, spontaneous decrease in size during follow-up: case report and review of the literature.

BACKGROUND: Many reports have demonstrated a worse prognosis for patients whose cavernomas were subtotally removed than for those whose cavernomas were not surgically treated. Therefore, it is better not to touch the cavernoma if a surgeon is not prepared to totally remove it. This report describes a large brainstem cavernoma showing a spontaneous, dramatic reduction in size after removal of only the biopsy specimen of the lesion. CASE DESCRIPTION: A 42-year-old woman experienced facial numbness, diplopia, and ataxia. A magnetic resonance (MR) study revealed a pontine cavernoma with hemorrhage. Two weeks later, recurrence of the patient's symptoms and consciousness disturbance were noted. An MR study revealed massive hemorrhage from the cavernoma with a ventricle dilatation. An operation on the lesion was conducted 3 months after the initial hemorrhage. However, the operation was aborted when an exploration of the lesion showed a tight adhesion between the lesion and the pons. Removal of only a biopsy specimen and evacuation of the suckable hematoma were done. No neurologic recovery and no decrease in the size of the cavernoma were detected postoperatively. Her family did not wish for further treatments. She was in a bedridden state with severe brainstem dysfunction when she was transferred to a local hospital. Sixteen months after the surgery, her consciousness was clear, and MR imaging confirmed a marked reduction in the size of the cavernoma. CONCLUSION: A dramatic, spontaneous decrease in size does occur even in the case of a large brainstem cavernoma showing hemorrhages. Conservative therapy may be one of the treatment options for the symptomatic brainstem cavernoma.

Regrowth and fatal rerupture despite proximal occlusion after coil embolization of a ruptured large basilar bifurcation aneurysm--case report.

A 40-year-old man suffered chronic progressive symptoms of brainstem compression after undergoing endosaccular coil placement in a ruptured large basilar bifurcation aneurysm. Radiographical examinations showed coil compaction and regrowth of the aneurysmal mass with perifocal mesencephalic edema. The symptoms did not resolve even after additional clip occlusion of the upper basilar artery and the patient died of rerupture. At present, direct surgical clipping using a skull base technique with or without hypothermic circulatory arrest or upper basilar artery occlusion with or without bypass surgery may be a better choice as an initial treatment for giant or large basilar bifurcation aneurysm with a wide neck.

[The treatment for asymptomatic meningiomas in the era of radiosurgery].

We evaluated the treatment results in asymptomatic meningiomas in the era of radiosurgery. We encountered 56 patients with asymptomatic meningiomas from January, 1994 to December, 2001. There were 16 male patients and 40 female patients. The most common location was the cerebral convexity. We performed gamma knife radiosurgery for three patients after diagnosis of cavernous sinus meningiomas. The other patients were followed-up after diagnosis for a mean follow-up period of 30.8 months (5 months to 8 years). Tumor growth was verified in 25 patients (43%) and two patients (3.7%) suffered neurological deficits. Among the tumor growth patients, operative resection was performed in six patients (11%) and gamma knife radiosurgery was performed in four patients (7.5%). The other patients were placed under observation. We decided the treatment strategy paying attention to the tumor location, tumor growth speed, tumor size and operative difficulty. The tumor growth rate was 0.1 cm/year among the patients with tumor growth. It was 0.72 cm/year (0.02 to 1.54 cm/year) in the operative group, 0.3 cm/year (0.04 to 0.76 cm/year) in the gamma knife radiosurgery group and 0.08 cm/year (0.01 to 0.76 cm/year) in the observed group. One patient suffered procedure-related deterioration of paresis after operation. The treatment of asymptomatic meningiomas must be decided depending on their natural history and locations. We recommend early radiosurgery for cavernous sinus meningiomas.