Ju Hyung Moon

Prognostic Value of Glioma Cancer Stem Cell Isolation in Survival of Primary Glioblastoma Patients

Cancer stem cells (CSCs) have been reported to be critical in the initiation, maintenance, and progression of cancers. The expression of stem cell markers, such as podoplanin (PDPN), CD133, and nestin, may have been correlated with malignant progression. However, the effects of CSCs and stem cell markers on clinical outcomes in cancer patients remain unclear. In this study, we assessed the prognostic roles of glioma CSCs (gCSCs) isolation and stem cell markers in patients with primary glioblastoma (pGBM). A cohort of 39 patients with pGBM was separated into two groups, those positive or negative for gCSCs, and the correlation between gCSC and patient survival was evaluated. We observed significantly different cumulative survival (P = 0.045) when comparing patients positive for gCSCs patients and negative for gCSC. Among the patients positive for gCSCs, we observed no significant differences in survival between those whose gCSCs were each positive or negative for PDPN, CD133, or nestin. This study strongly supports the prognostic value of gCSCs isolation on the survival of patients with pGBM.

Direct suture technique of normal gland edge on the incised dura margin to repair the intraoperative cerebrospinal fluid leakage from the arachnoid recess during transsphenoidal pituitary tumor surgery.

BACKGROUND: During transsphenoidal surgery for pituitary adenomas with large suprasellar extension, cerebrospinal fluid (CSF) leakage commonly develops from a defect at the arachnoid recess between the resected dura margin and the anterior edge of a normal pituitary gland (type 1 CSF leakage). OBJECTIVE: To evaluate the usefulness of a direct suture technique of the normal gland edge on the incised dural margin to repair intraoperative CSF leakage from the arachnoid recess. METHODS: Between November 2005 and December 2012, 861 patients with pituitary adenomas were operated on with transsphenoidal surgery, and intraoperative CSF leakage was encountered in 432 patients. Type 1 CSF leakage developed in a total of 122 patients, and their defects were repaired with the direct suture technique in 51 patients, whereas a fleece-coated fibrin glue patch alone was applied onto the defect in the other 71 patients. This direct suture technique required an additional 5 to 20 minutes in most cases. RESULTS: We experienced no case of postoperative CSF rhinorrhea in the 51 patients whose defects were repaired by the direct suture technique and only 1 case of CSF rhinorrhea in 71 patients whose defects were repaired with a fleece-coated fibrin glue patch alone. There was no statistical difference in the outcome between 2 groups. Postoperative lumbar CSF drainage was not performed in any case. CONCLUSION: Our 2 different repair techniques for arachnoid recess tears are very reliable methods for managing this type of CSF leakage. The direct suture technique may be more appropriate for type 1 CSF leakage with a wider gap and more prominent CSF leakage. ABBREVIATION: TSS, transsphenoidal surgery

Long-term outcomes of concomitant chemoradiotherapy with temozolomide for newly diagnosed glioblastoma patients

Abstract The present study analyzed outcomes of surgery followed by concomitant chemoradiotherapy (CCRT) with temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM) at a single institution. Outcomes were retrospectively reviewed in 252 consecutive patients with newly diagnosed GBM who underwent surgery followed by CCRT with TMZ at the authors’ institution between 2005 and 2013. At initial operation, 126 (50.0%), 55 (21.8%), 45 (17.9%), and 26 (10.3%) patients underwent gross total resection (GTR), subtotal resection, partial resection (PR), and biopsy, respectively. Their median overall survival (OS) was 20.8 months (95% confidence interval [CI] 17.7–23.9 months) and their median progression-free survival was 12.7 months (95% CI 11.2–14.2 months). The O6-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 78 (34.1%) of the 229 patients assayed, and an isocitrate dehydrogenase 1 mutation was detected in 7 (6.6%) of the 106 patients analyzed. Univariate analyses showed that patient age, involvement of eloquent areas, involvement of the subventricular zone, presence of leptomeningeal seeding, Karnofsky Performance Status, extent of resection (EOR), MGMT promoter methylation, and presence of an oligodendroglioma component were prognostic of OS. Multivariate analysis showed that age, involvement of eloquent areas, presence of leptomeningeal seeding, EOR, and MGMT promoter methylation were significantly predictive of survival. OS in patients with GBM who undergo surgery followed by CCRT with TMZ is enhanced by complete resection. Other factors significantly prognostic of OS include that age, involvement of eloquent areas, presence of leptomeningeal seeding, and MGMT promoter methylation.

Tumor Mesenchymal Stem-Like Cell as a Prognostic Marker in Primary Glioblastoma

The isolation from brain tumors of tumor mesenchymal stem-like cells (tMSLCs) suggests that these cells play a role in creating a microenvironment for tumor initiation and progression. The clinical characteristics of patients with primary glioblastoma (pGBM) positive for tMSLCs have not been determined. This study analyzed samples from 82 patients with pGBM who had undergone tumor removal, pathological diagnosis, and isolation of tMSLC from April 2009 to October 2014. Survival, extent of resection, molecular markers, and tMSLC culture results were statistically evaluated. Median overall survival was 18.6 months, 15.0 months in tMSLC-positive patients and 29.5 months in tMSLC-negative patients (P = 0.014). Multivariate cox regression model showed isolation of tMSLC (OR = 2.5, 95% CI = 1.1~5.6, P = 0.021) showed poor outcome while larger extent of resection (OR = 0.5, 95% CI = 0.2~0.8, P = 0.011) has association with better outcome. The presence of tMSLCs isolated from the specimen of pGBM is associated with the survival of patient.

Snare technique for the remodeling of the redundant arachnoid pouch to prevent cerebrospinal fluid rhinorrhea and hematoma collection during transsphenoidal surgery for suprasellar-extended pituitary tumors

OBJECTIVE Transsphenoidal surgery (TSS) is considered a most effective treatment for pituitary tumors with huge suprasellar extension. However, the chance of developing CSF leakage is relatively high, because tearing of the arachnoid membrane is common and there could be multiple tear points during the dissection of suprasellar tumors from the overlying arachnoid membrane. If there are multiple leaking points in the arachnoid membrane packing methods such as using fat or multilayered fascia graft may not be sufficient to seal off the leaking points. Moreover, the packing material may not provide sufficient tamponade to stop bleeding, and thus generates postoperative hematoma formation in the tumor resection cavity. To prevent these complications, the authors have developed a new technique for remodeling the redundant arachnoid pouch (the so-called snare technique) to reconstruct the diaphragm, seal off the CSF leak points completely, and reduce the dead space in the tumor resection cavity. METHODS In 9 patients with huge macroadenomas (> 2.5 cm in diameter) with suprasellar extension, the snare technique was used to remodel the arachnoid pouch after tumor removal via standard TSS between July 2009 and August 2014. Complications were investigated, including postoperative CSF rhinorrhea, postoperative hematoma collection, and visual compromise. RESULTS During the resection of the tumor, CSF leakage was encountered in 8 cases, all of which were sealed off using the snare technique. In 1 case without intraoperative CSF leakage, the snare technique was also applied after intentional puncturing of the arachnoid membrane to reduce the volume and tension of the arachnoid pouch. None of the 9 patients experienced postoperative CSF rhinorrhea. Lumbar CSF drainage was not required in any case. Magnetic resonance imaging studies performed 24 hours after surgery revealed a remarkable reduction in the height of the diaphragm in all cases. Visual deficits improved in all patients immediately after surgery. CONCLUSIONS Remodeling of the arachnoid pouch using the snare technique is simple and effective for completely sealing off the CSF leak point and preventing hematoma collection in the tumor resection cavity after TSS for huge pituitary tumors with suprasellar extension.

Solitary fibrous tumor/hemangiopericytoma: treatment results based on the 2016 WHO classification

OBJECTIVESolitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a new combined entity for which a soft-tissue-type grading system, ranging from grades I to III, has been introduced in the 2016 WHO classification of tumors of the CNS. The results of the treatment of this new disease entity require evaluation.METHODSThe authors retrospectively reevaluated the pathological findings and medical records of patients with SFT/HPC. This study included 60 patients (27 men and 33 women, median age 42.5 years, range 13-69 years) treated at Severance Hospital between February 1981 and February 2016. Four, 40, and 16 patients were categorized as having SFT/HPC grades I, II, and III, respectively. Among these patients, SFTs diagnosed in 7 patients were regraded as grades I (n = 4), II (n = 2), and III (n = 1).RESULTSThe median overall survival (OS) was 73.2 months (range 1.4-275.7 months), and the progression-free survival (PFS) after the first operation was 53.8 months (range 1.4-217.7 months). Six patients (10%) showed extracranial metastasis during a median period of 103.7 months (range 31.9-182.3 months). Nineteen patients (31.7%) presented with tumor recurrences. The patients in the grade III group had shorter PFS and OS, as well as a shorter period to extracranial metastasis, compared with patients in the grade II group. In the grade II group, patients who underwent gross-total resection showed longer PFS than those who underwent subtotal resection; however, there was no difference in OS. Patients who underwent adjuvant radiation therapy (RT) after surgery had longer PFS compared with that of patients who did not undergo adjuvant RT.CONCLUSIONSThe SFT/HPC grade I group showed a relatively benign course compared with those of the other groups. The grade III group presented a course with a more aggressive nature than that of the grade II group. In the grade II group, the extent of resection and adjuvant RT was significantly associated with longer PFS. The long-term follow-up and periodic systemic evaluation are mandatory to detect systemic metastasis.

Postoperative Gamma Knife Radiosurgery for Cavernous Sinus–Invading Growth Hormone–Secreting Pituitary Adenomas

OBJECTIVE We aimed to determine the long-term effects of Gamma knife radiosurgery (GKS) on remnants in the cavernous sinus (CS) after transsphenoidal surgery (TSS) for acromegaly and to identify its possible adverse effects. METHODS Thirty patients who had remnant tumors only inside the CS after TSS and who consequently underwent GKS were included. They were followed for a median period of 47 months after GKS with regular hormonal and radiologic examinations. RESULTS The mean tumor volume and margin dose irradiated by GKS was 3.7 cm3 and 26.2 Gy, respectively. Radiologic tumor control was identified in all patients, and no tumor regrowth or recurrent tumors were identified. For 14 patients who achieved endocrinologic remission, the median duration from GKS until remission was 35 months. The actuarial rates of remission at 2, 5, and 10 years were 7.1%, 43.6%, and 65.6%, respectively. The degree of decrease in the nadir GH level in the OGTT at 6 months after GKS was a statistically significant predictor of remission. Newly developed hypopituitarism frequently developed in a time-dependent manner. Radiation necrosis developed in 4 patients with relatively large remnant volumes. CONCLUSIONS GKS is an effective adjuvant treatment option for remnant tumors inside the CS after TSS. Maximal surgical resection, leaving minimal volume of remnants only inside the CS, allows the safe and sufficient delivery of a radiation dose to tumors, thereby increasing the possibility of remission. However, the risk of new hypopituitarism and radiation necrosis should be considered when tumors inside the CS are treated with GKS.

Age- and Sex-Specific Differences as Predictors of Surgical Remission Among Patients With Acromegaly

Context Sex and age are factors conferring resistance to medical treatment in patients with acromegaly. However, their impact on outcomes of transsphenoidal-selective adenomectomy (TSA) has not been evaluated. Objective To analyze age- and sex-related differences concerning surgical outcomes of growth hormone (GH)-secreting pituitary adenomas. Design Retrospective. Setting Single-center tertiary hospital. Participants Patients with acromegaly (n = 463) who underwent TSA between January 2000 and July 2014. Intervention TSA. Main Outcome Measurements Tumor characteristics and surgical outcomes. Results Sex differences existed in the baseline insulinlike growth factor-1 levels and the mean tumor size. Overall, surgical remission rates were 89.7% and 76.5% in male and female patients, respectively (P < 0.001). Total tumor tissue resection was performed in 92.6% and 85.8% of male and female participants, respectively (P = 0.021). Premenopausal women had a higher proportion of pituitary adenoma with cavernous sinus invasion than did men aged <50 years (35.3% vs 21.7%, P = 0.007). In immediate postoperative, 75-g oral glucose tolerance tests, fewer premenopausal women reached <1 ng/dL nadir GH levels than did men aged <50 years (59.9% vs 87.7%, P < 0.001). Surgical results were similar in both sexes among older patients (≥50 years). However, premenopausal women had significantly lower long-term remission rates than did men aged <50 years (69.3% vs 88.0%, P < 0.001). Conclusion Premenopausal women with acromegaly tend to have larger tumors, more aggressive tumor types, and lower remission rates than do men. However, further studies on the clinical implications are needed.

Spontaneous Acute Subdural Hemorrhage in a Patient with a Tick Borne Bunyavirus-Induced Severe Fever with Thrombocytopenia Syndrome

We report the first case of severe fever with thrombocytopenia syndrome (SFTS) and a spontaneous acute subdural hematoma (SDH) in Korea. A 79-year-old male presented with fever and thrombocytopenia. On the third day of hospitalization, his mental changed from drowsy to semi-coma. Brain computed tomography indicated an acute subdural hemorrhage on the right convexity. He was given early decompressive craniectomy, but did not survive. Real-time reverse transcription polymerase chain reaction analysis of a blood sample indicated the presence of SFTS virus (SFTSV). This is the first reported case with intracranial hemorrhage and SFTS. This case report describes our treatment of a patient with acute SDH and an infection from a tick-borne species of Bunyaviridae.

Primary Diffuse Leptomeningeal Gliosarcomatosis

Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare condition with a fatal outcome, characterized by diffuse infiltration of the leptomeninges by neoplastic glial cells without evidence of primary tumor in the brain or spinal cord parenchyma. In particular, PDLG histologically diagnosed as gliosarcoma is extremely rare, with only 2 cases reported to date. We report a case of primary diffuse leptomeningeal gliosarcomatosis. A 68-year-old man presented with fever, chilling, headache, and a brief episode of mental deterioration. Initial T1-weighted post-contrast brain magnetic resonance imaging (MRI) showed diffuse leptomeningeal enhancement without a definite intraparenchymal lesion. Based on clinical and imaging findings, antiviral treatment was initiated. Despite the treatment, the patients neurologic symptoms and mental status progressively deteriorated and follow-up MRI showed rapid progression of the disease. A meningeal biopsy revealed gliosarcoma and was conclusive for the diagnosis of primary diffuse leptomeningeal gliosarcomatosis. We suggest the inclusion of PDLG in the potential differential diagnosis of patients who present with nonspecific neurologic symptoms in the presence of leptomeningeal involvement on MRI.