CyberKnife Radiosurgery for Spinal Intramedullary Arteriovenous Malformations: A Single-Center Experience.

BACKGROUND: Intramedullary spinal arteriovenous malformation (ISAVM, glomus type) is a type of spinal cord arteriovenous malformation, which is a rare disease known often to have a complex vascular supply interfering with that of the spinal cord, and is in complex anatomical relations with cord structures and nerve roots. Though microsurgical and endovascular treatment has mainly been the standard options, in high-risk cases with these treatments, stereotactic radiotherapy (SRT) might be the option of choice. METHODS: We retrospectively reviewed 10 consecutive patients with ISAVM who received SRT using CyberKnife at the Japanese Red Cross Medical Center (Tokyo, Japan) from January 2011 to March 2022. RESULTS: No case in this series suffered from hemorrhage after applying SRT. One case experienced neurological impairment 10 years after SRT, which we attributed to venous congestion due to the remaining lesion. No case of radiation myelopathy was observed in this series. In one case, the nidus volume reduction and loss of flow voids were obvious, though improvement in the neurological outcome was not apparent. No radiological changes were observed in the other 9 patients. CONCLUSIONS: Even in lesions without radiological changes, no hemorrhagic events were observed for an average period of 4 years. SRT may be a feasible option in treating ISAVM, especially for lesions in which microsurgical resection and endovascular treatment are inapplicable. To ascertain the safety and efficacy of this approach, further studies with more patients and longer follow-up is required.

Metastatic Spinal Tumor from Benign Pleomorphic Adenoma: Case Report and Literature Review.

PURPOSE: Pleomorphic adenomas tend to arise in the salivary glands. They are rare and histologically benign but can result in distant metastasis, and their characteristics need further investigation. We report a case of locally recurring benign primary palatal pleomorphic adenoma that resulted in spinal metastases and review the relevant literature. CASE REPORT: A 58-year-old woman had undergone surgery for a palatal pleomorphic adenoma 22 years earlier and 6 subsequent operations for local recurrences. During follow-up, metastases to multiple organs, including the spine, were diagnosed and 4 CyberKnife treatments were performed. She suffered right flank pain and slight paralysis of the right leg; radiological findings showed a growing metastatic spinal tumor. She underwent removal of a thoracic vertebral tumor and posterolateral fusion. Postoperatively, her symptoms improved. Histopathological analysis indicated a pleomorphic adenoma and no evidence of malignancy. Although there was no local recurrence, 23 months after surgery, a fifth CyberKnife procedure was performed for a growing salivary gland tumor and she is currently being followed up. CONCLUSION: We described a rare case of benign pleomorphic adenoma that metastasized to the spine. Long-term follow-up for recurrence and metastasis is required for patients with benign pleomorphic adenoma.

Highly Radiosensitive Diffuse Large B-cell Lymphoma of the Skull Treated With Low-Dose CyberKnife Radiotherapy: A Case Report.

Diffuse large B-cell lymphoma (DLBCL) of the skull is rare, and there are no reports of treatment using CyberKnife (CK). Here, we report the case of a patient with skull DLBCL treated with low-dose CK radiotherapy (CKR), resulting in effective local control. The patient was a 75-year-old man who was initially diagnosed with multiple skull metastases (frontal, occipital, right orbital bones) from renal pelvic cancer. We initially created a CKR treatment plan for the frontal bone lesion with a marginal dose of 35 Gy and a maximum of 64.8 Gy in five fractions every other day. Because the frontal bone lesion shrank rapidly from the start of the treatment, we completed CKR with a marginal dose of 21 Gy and a maximum of 38.9 Gy in three fractions over five days. At six weeks after CKR, the MRI showed complete resolution of not only the frontal bone lesion but also the occipital and orbital bone lesions that we did not directly target for irradiation. The maximum doses irradiated to the occipital and orbital bone lesions were 0.31 Gy and 0.34 Gy. Because of the marked shrinkage of the skull lesions, we suspected that the patient had a radiosensitive neoplastic disease. FDG-PET/CT revealed multiple lymph nodes and bone metastases. The patient underwent a scrotal biopsy, and the histologic diagnosis was DLBCL. The patient subsequently received chemotherapy for DLBCL. Ten months after CKR and six months after the start of chemotherapy for DLBCL, the patient died due to gastrointestinal bleeding. The skull lesions were well-controlled locally without adverse events due to CKR until the end of the life. Our present case suggests the importance of diagnosis and the effectiveness of low-dose CKR in the skull DLBCL.

Hypofractionated Stereotactic Radiotherapy with CyberKnife for Large Arteriovenous Malformations and Arteriovenous Malformations Located in Eloquent Areas.

Literature has yet to establish an appropriate treatment strategy for large arteriovenous malformations (AVMs) and AVMs located in eloquent areas. In this study, the treatment outcomes of hypofractionated stereotactic radiotherapy (HSRT) with CyberKnife (CK) for large AVMs and AVMs in eloquent areas were evaluated. This study retrospectively evaluated 38 consecutive patients with AVMs treated with HSRT in the Japanese Red Cross Medical Center between August 2010 and July 2015. Obliteration rates and hemorrhage rates at 3- and 5-years of follow-up were calculated. Factors for hemorrhage and obliteration were analyzed with logistic regression analysis. Fourteen (36.8%) patients had a history of hemorrhage. Twenty (52.6%) AVMs were larger than 10 mL, and 34 (89.5%) AVMs were located in eloquent areas. The majority of the AVMs (84.2%) were classified into high grades (grades 3, 4, and 5) using the Spetzler-Martin grading scale. The median modified radiosurgery-based AVM score was 2.05, and the median Virginia Radiosurgery AVM Score was 3. The mean marginal dose was 24.5 ± 2.5 Gy. Twenty-three and 15 patients received three- and five-fraction stereotactic radiotherapy, respectively. At 3 and 5 years posttreatment, two (2.0%/year) and six (6.7%/year) patients had hemorrhage with obliteration rates of 15.2% and 16.7%, respectively. AVM localization in eloquent areas was a risk factor for obliteration failure. This study revealed that HSRT with CK for large AVMs and AVMs located in eloquent areas contributed to hemorrhage risk reduction and obliteration, at least in the early stages.

The Treatment Outcome of CyberKnife-Based Stereotactic Radiotherapy for Intracranial and Extracranial Nonvestibular Schwannomas: A Single-Center Experience.

BACKGROUND: Data on the outcomes of CyberKnife-based hypofractionated stereotactic radiosurgery (hSRS) for intracranial and extracranial nonvestibular schwannomas (nVSs) are not sufficient. METHODS: Patients who underwent hSRS for nVSs between 2010 and 2019 were retrospectively reviewed. RESULTS: A total of 39 patients with 39 nVSs were identified. The mean age was 53 (±18) years, and 20 patients (51%) were women. Twenty-five patients (64%) had previous surgeries. Seventeen patients (44%) had nVSs extending outside the cranium. The mean prescribed dose covering 95% of the planning target volume was 22 Gy (±3.7 Gy), the mean fractionation was 4 (±2), and the mean target volume was 13 cm3 (±16 cm3). The radiological tumor control rate was 100% during the mean follow-up period of 67 months (±37 months). Thirty-seven patients (95%) were clinically stable during the mean follow-up period of 72 months (±35 months). Nine patients (23%) suffered from transient adverse radiation effects (AREs), including transient tumor expansion, and 2 (5%) suffered from permanent AREs. CONCLUSIONS: We summarized the treatment outcomes of hSRS for nVSs. Although all patients achieved radiological tumor control, the risk of either transient or permanent ARE was high. Therefore, it is necessary to monitor patients for clinical deterioration due to AREs.

Nivolumab and stereotactic radiation therapy for the treatment of patients with Stage IV non-small-cell lung cancer.

BACKGROUND: Radiation therapy might modify the cancer immune environment to enhance the antitumor effect of immune checkpoint inhibitors. We performed a feasibility study of nivolumab following stereotactic radiation therapy for chemotherapy pretreated advanced non-small-cell lung cancer. PATIENTS AND METHODS: Pretreated advanced/recurrent non-small-cell lung cancer patients received stereotactic radiation therapy to one of the disease sites. Nivolumab at a dose of 3 mg/kg was given within 2 weeks after the completion of stereotactic radiation therapy and continued every 2 weeks thereafter until disease progression or unacceptable toxicities. The primary endpoint was the occurrence rate of Grade 3 pneumonitis (within 12 weeks) or other non-hematological toxicity (within 8 weeks). RESULTS: From September 2016 to September 2017, six patients were enrolled. Five received stereotactic radiation therapy to their primary lesions. All patients received nivolumab on the following day after stereotactic radiation therapy completion. Grade 3 pneumonitis occurred in one patient, but no other serious adverse events were reported for the other patients. One complete response and two partial responses were achieved. Four patients had measurable lesions outside the irradiated area, of whom three patients responded to the treatment. The initial progression sites were mainly outside the irradiated field, including one brain metastasis. CONCLUSIONS: Nivolumab therapy immediately following stereotactic radiation therapy was well tolerated. This sequential combination warrants further study.

Efficacy and safety of stereotactic body radiotherapy using CyberKnife in Stage I primary lung tumor.

BACKGROUND: CyberKnife® (CK) is a new, advanced radiotherapy technique. This study aimed to evaluate its efficacy and toxicity in Japanese patients with early-stage primary lung tumor who were medically unfit and inoperable. METHODS: This retrospective study investigated patients who received CK treatment for medically inoperable Stage І primary lung tumor at the Japanese Red Cross Medical Center between June 2011 and September 2016. Each patient received a total of 36-48 Gy (median, 43 Gy) administered by CK in 4-5 fractions. RESULTS: Totally, 40 patients (T1a, n = 19; T1b, n = 15; T2a, n = 6) were included. Their median age was 86 (range, 56-95) years. Tracking required the use of fiducial markers in 28 patients and the Xsight Spine Tracking System in 12. The median follow-up was 14.5 (range, 1-51) months. Local recurrence occurred in seven (17.5%) patients. The local progression-free survival rates at 1 and 2 years were 83.9% and 74.0%, respectively. Distant recurrence occurred in regional lymph nodes (n = 5), the lung outside the radiation field (n = 3), and the bone (n = 1). Seven patients died. Overall survival rates at 1 and 2 years were 93.6% and 73.1%, respectively. Radiation pneumonitis was identified in 28 (70%) patients (Grade 1, n = 25; Grade 2, n = 2; Grade 5, n = 1). CONCLUSIONS: CK showed good local control with limited toxicity and could be an alternative treatment modality in medically inoperable patients with Stage І primary lung tumor.

Long-term results of hypofractionated stereotactic radiotherapy with CyberKnife for growth hormone-secreting pituitary adenoma: evaluation by the Cortina consensus.

The aim of the present study was to evaluate the safety and feasibility of hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for growth hormone-secreting pituitary adenoma (GH-PA). Fifty-two patients with GH-PA were treated with hypofractionated SRT between September 2001 and October 2012. Eight patients had clinically silent GH-PA and 44 were symptomatic. Only 1 patient was inoperable. The other patients had recurrent or postoperative residual tumors on MRI. All patients had received pharmacotherapy prior to SRT with a somatostatin analog, dopamine agonist, and/or GH receptor antagonist. The marginal doses were 17.4-26.8 Gy for the 3-fraction schedule and 20.0-32.0 Gy for the 5-fraction schedule. Endocrinological remission was assessed by the Cortina consensus criteria 2010 (random GH <1 ng/ml or nadir GH after an oral glucose tolerance test <0.4 ng/ml and normalization of age- and sex-adjusted insulin-like growth factor-1). The median follow-up period was 60 months (range 27-137). The 5-year overall survival, local control, and disease-free survival rates were 100, 100, and 96 %, respectively. Nine patients (5 clinically silent and 4 symptomatic patients) satisfied the Cortina criteria without receiving further pharmacotherapy, whereas the remaining 43 patients did not. No post-SRT grade 2 or higher visual disorder occurred. Symptomatic post-SRT hypopituitarism was observed in 1 patient. CyberKnife hypofractionated SRT is safe and effective when judged by imaging findings for GH-PA. However, it may be difficult to satisfy the Cortina consensus criteria in most symptomatic patients with SRT alone. Further investigations of optimal treatments are warranted.

Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma.

AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher's exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral bleeding and another patient had an esophageal ulcer after treatment. CONCLUSION: The Cyberknife can be safely administered to patients with advanced or terminal stage HCC. High AFP levels were associated with worse survival, but a higher radiation dose improved the survival.

[Emergency oncology cases for whom stereotactic radiotherapy by cyberknife proved effective for cerebellar metastasis of lung cancer].

BACKGROUND: Cerebellar metastasis sometimes causes symptoms such as ataxia and dizziness, or hydrocephalus by compression of the fourth ventricle, making emergency treatment necessary. We report two cases for whom we performed emergency stereotactic radiotherapy, and whose tumors decreased and symptoms improved. Case 1: A 58-year-old male was diagnosed with small cell lung cancer in December 2008, and received chemotherapy and conventional radiotherapy at another hospital. He developed difficulty in walking and experienced nausea from March 2010 on. Because neoplastic lesions had been found in the cerebellar vermis on computed tomography(CT)scan, he was referred to our hospital. We urgently performed stereotactic radiotherapy by CyberKnife, and his symptoms then improved. As a chest CT scan revealed a mass lesion in his right upper lobe, the diagnosis of recurrent small cell lung cancer was made, and we performed chemotherapy sequentially. Case 2: A 73-year-old female experienced severe headache and dizziness and noticed difficulty in walking in July 2010. Because neoplastic lesions had been found in the left cerebellar hemisphere on CT scan at another hospital, she was referred to our hospital. Chest X-ray films showed a mass lesion in the left middle lung field and cytologic examination of sputum showed squamous cell carcinoma. We urgently performed stereotactic radiotherapy by CyberKnife, and her symptoms then improved. Therefore, we performed chemotherapy sequentially. CONCLUSION: Stereotactic radiotherapy by CyberKnife is less invasive, and is one good treatment option in the event of an emergency.

Single and hypofractionated stereotactic radiotherapy with CyberKnife for craniopharyngioma.

Craniopharyngiomas are slow-growing tumors found in the suprasellar region, with especially high incidence in Japanese children. Due to the location, proximity and adhesiveness of the tumor to adjacent critical structures, these tumors remain a significant clinical challenge. The purpose of this study was to evaluate the clinical outcome of single and hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for craniopharyngioma. Forty-three patients (21 men and 22 women; median age 44 years; range 3-85 years) were treated at two institutions. Three cases were treated in a single fraction to a marginal dose of 13-16 Gy. The other 40 cases were treated in 2-5 fractions to a marginal dose of 13-25 Gy. Tumor volumes ranged from 0.09 to 20.8 cm(3) (median 2.0 cm(3)). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period was 40 months (range 12-92 months). The 3-year overall survival and local control rates were 100 and 85%, respectively. In-field cyst enlargement was observed in 9 patients. These tumors had significantly larger volumes (mean 6.9 cm(3); 95% confidence interval, CI, 2.8-10.9 cm(3)) than the 34 controlled tumors (2.9 cm(3); CI 1.5-4.3 cm(3)) (P = 0.02). Out-field tumor regrowth was observed in 4 patients. No radiation-induced symptomatic visual disorder or brain necrosis was observed. Hypopituitarism was observed in only 1 patient. Single and hypofractionated SRT using CyberKnife produced high tumor control rates with minimal complications. Hypofractionated SRT may be useful for protecting the visual nerve and neuroendocrine function, especially for tumors located near the optic pathways and for large tumors.

[Treatment of spontaneous spinal epidural hematoma].

OBJECTIVE: Spontaneous spinal epidural hematoma (SSEH) is rare. There was not enough information about diagnosis and treatment of SSEH, although they require emergency surgery and some surgeons may hesitate to use alternative treatments. We report our six cases SSEH and discuss treatment of SSEH from the literature. MATERIALS AND METHODS: We encountered six cases of SSEH. They were 4 female and 2 male cases and age ranged from 61 to 75 years (averaging 67.3 years). The SSEH were located in the cervical (n=3), cervicothoracic (n=3) regions. In 4 cases, there were hematomas at the right side of the spinal epidural space, and 2 cases were at the left side. RESULTS: All cases experienced severe neck or shoulder pain. In five cases, hemiparesis was noted. Cervical MRI showed that epidural hematoma had compressed the spinal cord posterolateraly. In all cases, cervical CT scans also revealed epidural hematoma, too. Five cases were operated on by removal of the hematoma with hemilaminectomy and one case was operated on with laminectomy because of severe paresis. The mean time since the start of the operation was 11 hours (ranging from 7 to 20 hours). Only one case who had only severe pain without paresis was treated conservatively. All except two patients completely recovered neurologically. The two cases continued to have sensory disturbance. CONCLUSIONS: We successfully treated 6 cases of SSEH. MRI is useful for diagnosis of SSEH, and CT scan can also diagnose it as in our cases. Cases with severe neurological deficit would be considered as needing surgical treatment at an appropriate time and the cases without neurological deficit should be kept under observation until surgery becomes necessary.

[CyberKnife radiosurgery--present status and future prospect].

The CyberKnife Robotic Radiosurgery System is a non-invasive alternative to surgery for the treatment of both cancerous and non-cancerous tumors anywhere in the body, including the prostate, lung, brain, spine, liver, pancreas, and kidney. The treatment, which involves the delivery of high doses of radiation to tumors with extreme accuracy, offers new hope to patients who have inoperable or surgically complex tumors or who may prefer a nonsurgical option. To date, more than 95,000 patients have been treated and more than 207 systems have been installed worldwide. The CyberKnife System is a one-of-a-kind device because of the following reasons. First, the CyberKnife System uses image guidance software to track and continually adjust treatment for any patient or tumor movement. This advantage places the system far ahead of other similar treatments. It allows patients to breathe normally and relax comfortably during treatment. Second, some forms of radiosurgery require rigid head frames that are screwed into the patient's skull in order to minimize any head movement. The CyberKnife System does not require such extreme procedures to maintain the head position; instead, it relies on the sophisticated tracking software, allowing for a much more comfortable and noninvasive treatment. Third, unlike some radiosurgery systems, which can only treat tumors in the head, the CyberKnife System has unlimited reach to treat a broad range of tumors throughout the body, including the prostate, lung, brain, spine, liver, pancreas, and kidney. Finally, the CyberKnife System's treatment accuracy is unrivaled. Its ability to treat tumors with supreme accuracy is noncomparable to that of other radiation therapy and radiosurgery systems. The CyberKnife System can essentially "paint" the tumor with radiation, allowing it to precisely deliver treatment to the tumor alone, sparing surrounding healthy tissue.

[CyberKnife treatment for parasellar tumors].

Microscopic and endoscopic techniques requiring superior skills are required for the examination of parasellar tumors. However, the parasellar region is surgically inaccessible, and complete excision of parasellar tumors remains a challenge. CyberKnife (CK) enables frameless radiosurgery and provides chronological and spatial freedom. We have previously treated parasellar tumors with stereotactic radiotherapy (SRT). Here, we evaluated the feasibility of CK surgery for parasellar tumors. Between June 2000 and August 2010, we conducted CK surgery for 4,500 patients. This study included 246 patients with pituitary adenoma (PA); 78, craniopharyngioma (CP); 38, parasellar meningioma (PM); and 6, metastatic pituitary tumor (M). The tumor volume ranged from 0.3 to 107 mL (median: 4.8 mL), and the patients were treated with 1-5 sessions of SRT. The treatment results were analyzed with a follow-up period of more than a year (range, 12-120 months; median: 35 months). The control rate of PA, CP, PM, and M was 96.6%, 79.0%, 100%, and 100%, respectively. Treatment failure in the case of CP was related to tumor volume. One PA patient had visual deterioration, and another had new hypopituitarism. One M patient showed visual loss 12 months after the CK treatment, which was related to the treatment dose. Thus, CK was found to be feasible for parasellar tumors, although its safety and efficacy must be observed in long-term follow up.

Stromal cell-derived factor-1 expression in pituitary adenoma tissues and upregulation in hypoxia.

The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is known to have a homing effect, recruiting endothelial progenitor cells (EPCs) from the bone marrow to ischemic foci. In this study, we investigated whether SDF-1 is triggered by hypoxia and might be a major driving force for tumor angiogenesis in pituitary adenomas. SDF-1 and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from 59 cases with pituitary adenomas. In vitro secretion of SDF-1 by the AtT20 mouse pituitary adenoma cell line under hypoxic conditions was quantitatively analyzed by ELISA, and SDF-1 mRNA levels were determined by real-time RT-PCR. Double-fluorescence immunohistochemistry showed that increases in MVD were significantly correlated with increased SDF-1 grade (P < 0.0001), and, concomitantly, the expression of SDF-1 was significantly greater in macroadenomas (P = 0.0203). SDF-1 secretion was inversely related to oxygen levels, with more severe degrees of hypoxia inducing greater levels of SDF-1 secretion. Real-time RT-PCR demonstrated that the SDF-1 mRNA level in AtT20 cells was significantly increased at 1% oxygen (logarithmic mean value = 1.55 +/- 0.56) compared with that at 21% oxygen. The current study strongly suggests that SDF-1 is a crucial angiogenic factor in pituitary adenomas, where it acts as a homing agent to mediate the mobilization of CD34-positive endothelial progenitor cells to the tumor parenchyma under hypoxic conditions.

Intracerebral hemorrhage caused by a neoplastic aneurysm from pleomorphic lung carcinoma.

A 61-year-old man presented with an extremely rare neoplastic cerebral aneurysm caused by brain metastasis from pleomorphic lung carcinoma manifesting as intracerebral hematoma and sudden onset of semicoma. Computed tomography demonstrated huge intracerebral hemorrhage in the left cerebral hemisphere, which had collapsed into the lateral ventricle. Cerebral angiography disclosed a fusiform aneurysm in the periphery of the left middle cerebral artery (approximately 2 mm diameter). Resection of the aneurysm and removal of the hematoma were performed. Histological examination revealed that the aneurysm walls were invaded by pleomorphic carcinoma. The present case indicates that neoplastic cerebral aneurysm may be the cause of intracerebral hemorrhage in patients with pleomorphic lung carcinoma.

Regulation of cell invasion and signalling pathways in the pituitary adenoma cell line, HP-75, by reversion-inducing cysteine-rich protein with kazal motifs (RECK).

Degradation and remodelling of the extracellular matrix has been investigated, with the main focus on the balance between matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP). Recent reports disclose the presence of a novel MMP-inhibiting cell membrane-anchored glycoprotein designated 'reversion-inducing cysteine-rich protein with Kazal motifs' (RECK). Our main aim in this study was to elucidate the role of RECK in cell invasion of pituitary adenomas and its contribution to signal transduction. The function of RECK in cell invasion was investigated by comparing data obtained from full-length RECK clone transfection and gene silencing with RECK mRNA-targeting siRNA. RECK expression was confirmed using real-time RT-PCR and Western blotting. Levels of matrix metalloproteinases (MMP-2 and -9) and TIMP-1 were measured by zymography and reverse zymography, respectively. Cell invasion was examined with a 3-D invasion assay. The signal cascade was investigated by cDNA microarray analysis. As expected, expression of RECK was elevated upon cDNA transfection, and diminished using siRNA. We observed elevation of MMP-2 and -9 expression and consequent 3-D cell invasion in cells under-expressing RECK. However, TIMP expression was not affected by RECK. Analysis with cDNA microarray revealed that RECK additionally upregulates growth hormone-releasing hormone receptor (GHRHR) and latrophilin 2 at the transcriptional level. Our findings collectively suggest that RECK regulates the cell signalling pathway, playing a critical neuroendocrinological role in the pituitary adenoma cell line.

Cervical ligamentum flavum ossification. Two case reports.

A 58-year-old woman (Case 1) presented with disturbance of fine movement and gait. Magnetic resonance (MR) imaging and computed tomography (CT) demonstrated bilateral ossified ligamentum flava at the C3-4 and C4-5 levels and severe cervical canal stenosis. She underwent posterior decompression and despite strong adhesion to the dura mater, the ossified ligamentum flavum was removed without inducing liquorrhea. Her neurological symptoms improved postoperatively. A 63-year-old man (Case 2) was admitted with disturbance of fine movement and gait that had developed gradually. MR imaging and postmyelography CT demonstrated cervical canal stenosis via the ossified posterior longitudinal ligament at the C4-6 levels and ossified ligamentum flavum on the right at the C4-5 levels. He underwent right posterior decompression of C4-5. After right hemilaminectomy of C4-5, the ligamentum flavum was exposed. Neither the ligamentum flavum nor the ossification had adhered to the dura mater, so complete removal was successful and he recovered completely from his neurological symptoms. Diffuse-type ossified ligamentum flavum had adhesion to the dura mater, as in our Case 1, whereas focal-type ossified ligamentum flavum did not, as in our Case 2. This information is useful for treatment planning.