[Basic and Advanced Techniques of Anastomosis in Deep Surgical Fields:STA-SCA Anastomosis].

This article detailly describes the subtemporal-transtentorial STA-SCA bypass technique. Through temporal base drilling, copious cerebrospinal fluid evacuation before retraction, and sufficient retraction of the temporal lobe preserving the veins of the temporal base would be primodial to obtain an appropriate surgical field. Refrection of the tentrial free edge and identification of recipient SCA posterior to the entry point of the trochlear nerve into the cavernous sinus is a micro-anatomical key. Bilateral bayonet-type needle holders and forceps should be used not to shadow the surgical corridor with one's hands.

Fractionated versus staged gamma knife radiosurgery for mid-to-large brain metastases: a propensity score-matched analysis.

PURPOSE: To compare treatment results between fractionated gamma knife radiosurgery (f-GKRS) and staged gamma knife radiosurgery (s-GKRS) for mid-to-large brain metastases (BMs). METHODS: We retrospectively analyzed data of patients with medium (4-10 mL) to large (> 10 mL) BMs who underwent s-GKRS or f-GKRS between March 2008 and September 2022. Patients were treated with (i) s-GKRS before May 2018 and (ii) f-GKRS after May 2018. Patients who underwent follow-up magnetic resonance imaging at least once were enrolled. Case-matched studies were conducted by applying propensity score matching to minimize treatment selection bias and potential confounding. Local control (LC) was set as the primary endpoint and overall survival (OS) as the secondary endpoint. RESULTS: This study included 129 patients with 136 lesions and 70 patients with 78 lesions who underwent s-GKRS and f-GKRS, respectively. Overall, 124 lesions (62 lesions in each group) were selected in the case-matched group. No differences were observed in the 6-month and 1-year cumulative incidences of LC failure between the s-GKRS and f-GKRS groups (15.6% vs. 15.9% at 6 months and 25.6% vs. 25.6% at 1 year; p = 0.617). One-year OS rates were 62.6% (95% confidence interval [CI]: 45.4-75.7%) and 73.9% (95% CI: 58.8-84.2%) in the s-GKRS and f-GKRS groups, respectively. The post-GKRS median survival time was shorter in the s-GKRS group than in the f-GKRS group (17 vs. 36 months), without significance (p = 0.202). CONCLUSIONS: This is the first study to compare f-GKRS and s-GKRS in large BMs. Fractionation is as effective as staged GKRS for treating mid-to-large BMs.

VEGFR-TKI treatment for radiation-induced brain injury after gamma knife radiosurgery for brain metastases from renal cell carcinomas.

OBJECTIVE: Antiangiogenic vascular endothelial growth factor receptor tyrosine kinase inhibitors play an essential role in systemic therapy for renal cell carcinoma. Given the anti-edematous effect of bevacizumab, an antiangiogenic antibody targeting vascular endothelial growth factor, vascular endothelial growth factor receptor tyrosine kinase inhibitors should exert therapeutic effects on radiation-induced brain injury after stereotactic radiosurgery. This preliminary study aimed to investigate the therapeutic effect of vascular endothelial growth factor receptor tyrosine kinase inhibitor against radiation-induced brain injury. METHODS: Magnetic resonance images for six patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors who were diagnosed with radiation-induced brain injury following gamma knife radiosurgery were retrospectively reviewed. RESULTS: The median brain edema volume and tumour mass volume in the pre-tyrosine kinase inhibitor period were 57.6 mL (range: 39.4-188.2) and 3.2 mL (range: 1.0-4.6), respectively. Axitinib, pazopanib (followed by cabozantinib) and sunitinib were administered in four, one and one cases, respectively. The median brain edema volume and tumour mass volume in the post-tyrosine kinase inhibitor period were 4.8 mL (range: 1.5-27.8) and 1.6 mL (range: 0.4-3.6), respectively. The median rates of reduction in brain edema volume and tumour mass volume were 90.8% (range: 51.9-97.6%) and 57.2% (range: 20.0-68.6%), respectively. The post-tyrosine kinase inhibitor values for brain edema volume (P = 0.027) and tumour mass volume (P = 0.008) were significantly lower than the pre-tyrosine kinase inhibitor values. Changes in volume were correlated with tyrosine kinase inhibitor use. CONCLUSION: This study is the first to demonstrate the therapeutic effects of vascular endothelial growth factor receptor tyrosine kinase inhibitors on radiation-induced brain injury in patients with brain metastases from renal cell carcinoma treated via gamma knife radiosurgery.

Two adult patients with moyamoya disease presenting with alexia with agraphia limited to kanji: can revascularization improve characteristic symptoms?

Patients with moyamoya disease (MMD) may exhibit higher brain dysfunction due to hypoperfusion, which may be ameliorated by revascularization. However, few studies have examined the relationship between cerebral perfusion and language function or the ameliorating effect of revascularization on language dysfunction. We present two cases with MMD who presented with alexia with agraphia, specifically for Japanese kanji. The patients had impaired perfusion in the left inferior temporal and lateral occipital lobes. Following superficial temporal artery-middle cerebral artery bypass, the symptoms improved dramatically. Thus, correction of hypoperfusion may be effective even in adult patients with MMD presenting with language dysfunction.

Temporo-parietal muscle pedicle flap for reconstruction of the anterior skull base after resection of recurrent olfactory groove meningioma: a technical note.

Reconstruction becomes the main issue in surgery for tumours penetrating the anterior skull base because it faces the nasal cavity. Vascularized flaps are desirable for preventing infection, but in re-opening surgery, tissue availability is limited. We report a case of recurrent olfactory groove meningioma in which the anterior skull base defect was reconstructed using a temporo-parietal muscle (TPM) pedicle flap. A 65-year-old woman presented with recurrent olfactory groove meningioma penetrating the anterior skull base. Because the frontal pericranium had been used in the initial surgery, the temporal fascia was harvested with a TPM pedicle flap from behind the initial bicoronal incision. After removal of the tumour, the pedicle flap reached the sphenoid planum easily and was sutured to the surrounding structures. The fascia lata was sutured as an inlay. The postoperative course was uneventful, and no cerebrospinal fluid leakage was observed. In re-opening surgery, a TPM pedicle flap can be an option for reconstruction of the anterior skull base.

Interfractional change of tumor volume during fractionated stereotactic radiotherapy using gamma knife for brain metastases.

PURPOSE: Fractionated stereotactic radiotherapy (FSRT) using gamma knife is useful for brain metastases. However, several uncertainties derived from fractionation pose issues for maintaining high-level accuracy. This study analyzed interfractional tumor change by performing radiological reassessment at the midterm of FSRT with ≥ 10 fractions, and the significance of replanning was evaluated. METHODS: Data of FSRT using gamma knife with ≥ 10 fractions were retrospectively collected. Interfractional volume changes in MRI at the midterm of the irradiation period were analyzed. Radiological changes after FSRT and final outcomes were also investigated. RESULTS: Overall, 114 lesions in 74 treatments from 66 patients were included, with previously irradiated lesions accounting for 46%. The median interval between planning and the interfractional MRI was 7 days. The interfractional change rates of tumor volume ranged from - 48 to + 72%. Significant interfractional enlargement was observed in 16 lesions (14%); evident regression was confirmed in 17 lesions (15%). Predictive factors for interfractional enlargement were small tumor and cystic lesion; high biologically effective dose was associated with regression. After FSRT, most lesions regressed within 6 months despite interfractional change type. The incidences of tumor control and radiation necrosis indicated no differences between interfractionally-regressed lesions and others. CONCLUSION: This is the first study to evaluate interfractional tumor change in FSRT using gamma knife with ≥ 10 fractions, indicating significant volume changes in 29% of the lesions. These preliminary results suggest that interfractional reassessment of a treatment plan in FSRT with irradiation periods exceeding a week is necessary for more adaptive treatment.

Comparison of postoperative temporalis muscle atrophy between the muscle-preserving pterional approach and the mini-pterional approach in the treatment of unruptured intracranial aneurysms.

This study aimed to compare the muscle-preserving pterional approach (modified classic pterional approach, mCP) and the mini-pterional approach (mPA) with respect to postoperative temporalis muscle atrophy.From November 2013 to April 2020, 78 patients with unruptured intracranial aneurysm of the anterior circulation underwent surgery using mCP or mPA in our institution. Patients' background characteristics, postoperative complications, and temporalis muscle volume (MV) rates (operative side/healthy side) were retrospectively investigated. In 64 patients (n = 31, mCP group; n = 33, mPA group), excluding 14 patients with missing imaging data from 6 to 24 months after surgery, associations between the MV rate and clinical variables were assessed. A multiple regression model was used to examine the association between the MV rate and the surgical method, which is a predictor of postoperative atrophy.The mCP group had a significantly higher mean MV rate than the mPA group (0.955 ± 0.040 and 0.915 ± 0.070, respectively; p = 0.008). Based on the results of the univariate analysis, a multiple regression model was established using sex, age, follow-up period, and the presence of diabetes in addition to the surgical method. Patients who underwent mCP had a higher MV rate than those who underwent mPA (t value = 2.33, p = 0.023).The present result suggested that mCP has a preventive effect on postoperative temporalis muscle atrophy. However, further studies are needed in order to prove that mCP is also effective in terms of postoperative aesthetic and functional outcomes.

Fractionated Gamma Knife radiosurgery after cyst aspiration for large cystic brain metastases: case series and literature review.

Tumor cyst aspiration followed by Gamma Knife radiosurgery (GKRS) for large cystic brain metastases is a reasonable and effective management strategy. However, even with aspiration, the target lesion tends to exceed the dimensions of an ideal target for stereotactic radiosurgery. In this case, the local tumor control rate and the risk of complication might be a critical challenge. This study is aimed to investigate whether fractionated GKRS (f-GKRS) could solve these problems. Between May 2018 and April 2021, eight consecutive patients with nine lesions were treated with f-GKRS in five or ten sessions after cyst aspiration. The aspiration was repeated as needed throughout the treatment course to maintain the cyst size and shape. The patient characteristics, radiologic tumor response, and clinical course were reviewed using medical records. The mean follow-up duration was 10.2 (2-28) months. The mean pre-GKRS volume and maximum diameter were 16.7 (5-55.8) mL and 39.0 (31-79) mm, respectively. The mean tumor volume reduction achieved by aspiration was 55.4%. The tumor volume decreased for all lesions, and symptoms were alleviated in all patients. The median overall survival was 10.0 months, and the estimated 1-year survival rate was 41.7% (95% CI: 10.9-70.8%). The local tumor control rate was 100%. No irradiation-related adverse events were observed. f-GKRS for aspirated cystic brain metastasis is a safe, effective, and less invasive management option for large cystic brain metastases.

How do I: Venous reconstruction of accidentally injured superficial sylvian vein during the clipping of an unruptured cerebral aneurysm.

BACKGROUND: The transsylvian approach is a versatile treatment method for aneurysms of the anterior circulatory system. Studies have shown that sylvian veins run in various patterns, suggesting the need for dissection between veins to obtain appropriate surgical corridor. In case of inadvertent sylvian vein injury, serious complications such as venous congestion may occur. METHOD: We herein describe the "side-to-side anastomosis reconstruction technique" of the resected superficial sylvian vein. CONCLUSION: This technique can be effective for the reconstruction of other cortical veins, and indocyanine green videoangiography was effective in determining the indications for venous reconstruction.

Superficial temporal artery lengthening technique to prevent postoperative wound complications in direct revascularization to the anterior cerebral artery for Moyamoya disease.

BACKGROUND: Neurocognitive dysfunctions or psychomotor symptoms of Moyamoya disease may improve after direct revascularization to the anterior cerebral artery (ACA). However, long-distance harvest of the frontal branch of the superficial temporal artery (STA) is needed to reach the cortical ACA, frequently resulting in postoperative wound complications. To solve this problem, we devised a novel method (STA lengthening technique). In this study, we compared the STA lengthening technique and the conventional method regarding postoperative wound complications. METHODS: Twenty-five patients who underwent STA-ACA direct bypass from December 2016 to October 2021 were retrospectively reviewed, and postoperative wound complications were recorded. Magnetic resonance angiography was performed to evaluate the patency of the bypass to the ACA and postoperative development of collaterals to the skin flap. RESULTS: Thirty-eight hemispheres (new method [n = 12] vs. conventional method [n = 26]) were treated. Wound complications occurred in 12 surgeries (46%) of the conventional method, and none (0%) of the new method. The anastomosis with the cortical ACA was patent in all surgeries. Postoperative development of collaterals to the skin flap was confirmed after all surgeries (100%) in the new method, whereas after only five surgeries (20%) in the conventional method. CONCLUSION: The STA lengthening technique can enable to preserve the collateral circulation to the skin flap postoperatively, resulting in good wound healing.

Traumatic pseudoaneurysm resulting from avulsion of the falcine branch of an azygos anterior cerebral artery: a case report.

Traumatic anterior cerebral artery (ACA) aneurysms are extremely rare. Traumatic anterior ACA aneurysms are thought to develop when the ACA at the pericallosal segment travel adjacent to immobile falx cerebri. As the majority of aneurysms are pseudoaneurysms, direct neck clipping is usually not possible, and it is often necessary to carry out direct or endovascular trapping in conjunction with proficient bypass techniques. The authors describe the first reported case of a traumatic ACA pseudoaneurysm resulting from avulsion of the falcine branch of an azygos ACA. In this case, the lacerated aneurysm wall was successfully sutured, without the need for a bypass. Neurosurgeons should be aware that avulsion of the falcine branch arising from the ACA can occur, and that this may cause a traumatic aneurysm on the distal ACA. Furthermore, direct suturing of a lacerated arterial wall should be considered a treatment option for this type of traumatic intracranial aneurysm.

The efficacy of temporary clamping of V3 with a suboccipital far-lateral approach in microvascular decompression for Hemifacial spasm associated with the vertebral artery.

Hemifacial spasm (HFS) is often caused by compression of the vertebral artery (VA) directly or indirectly as a result of other intervening vessels, so VA-associated HFS is difficult to treat. Recently, we have achieved good surgical outcomes using a far lateral approach and temporary clamping of V3 for VA-associated HFS. Herein, we present our method with an accompanying surgical video. From April 2018 to March 2019, 5 patients with VA-associated HFS underwent surgery, and pre-and postoperative symptoms and postoperative complications were evaluated. In the procedure, the suboccipital muscles were dissected and reflected layer by layer, and the extracranial VA (V3) was secured within the suboccipital triangle. A lateral suboccipital craniotomy followed by far lateral drilling was made to widen the surgical field from the caudolateral side. After reducing the VA flow pressure by temporary clamping of V3, the VA was transposed using a Teflon sling via two triangular space above and below the lower cranial nerves (LCNs). Causative vessels included direct VA compression in two cases and intervening vessels in three cases. The symptoms disappeared in four cases and improved satisfactorily in one case. One patient had mild hearing loss (approximately 10 dB) and hoarseness, but both improved 9 months after surgery. There was no postoperative cerebrospinal fluid leakage in any cases. A wide surgical field via the far lateral approach and the temporary clamping of V3 contributed to thorough observation of the REZ and safe and complete VA transposition.

Revascularization to the ACA: effectiveness and variation of the STA-RAG-A3 bonnet bypass.

BACKGROUND: The effectiveness of bypass surgery in patients with atherothrombotic ischemia in the anterior cerebral artery (ACA) domain remains unclear. In this study, three cases with ischemia in the ACA territory underwent revascularization surgery using superficial temporal artery (STA)-radial artery graft (RAG)-A3 (pericallosal artery) bonnet bypass. Herein, we discuss the effectiveness and variations of this approach. METHODS: Among 182 consecutive patients with atherothrombotic ischemic stroke admitted to the NTT Medical Center, Tokyo, from April 2017 to May 2021, three patients with hemodynamic insufficiency in the extensive ACA territory beyond the recent infarct area were treated using STA-RAG-A3 bonnet bypass. RESULTS: One patient with bilateral severe cerebral blood flow (CBF) deficiency required additional A3-A3 and STA-middle cerebral artery single bypass in conjunction with STA-RAG-A3 bypass. There were no complications associated with the surgical procedure. The patients' hemodynamic study results and neurocognitive performances improved dramatically after surgery. CONCLUSION: Our results suggest the efficacy of STA-RAG-A3 bypass for atherothrombotic ACA ischemia. However, because the number of cases was too small to generalize our results, more cases and thorough pre- and postoperative hemodynamic studies are necessary to prove the validity of the approach.

The impact of EGFR-TKI use on clinical outcomes of lung adenocarcinoma patients with brain metastases after Gamma Knife radiosurgery: a propensity score-matched analysis based on extended JLGK0901 dataset (JLGK0901-EGFR-TKI).

PURPOSE: Recent advances in targeted therapy have prolonged overall survival (OS) for patients with lung cancer. The impact of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) on brain metastases (BM) treated with stereotactic radiosurgery (SRS) has not, however, been fully elucidated. We investigated the influence of post-SRS EGFR-TKI use on the efficacy and toxicity of SRS for BM from lung adenocarcinoma. METHODS: We used the updated dataset of the Japanese Leksell Gamma Knife (JLGK) 0901 study, which proved the efficacy of Gamma Knife SRS in patients with BM. Propensity score matching (PSM) analysis was employed to determine the impact of concurrent or post-SRS EGFR-TKI use on OS, neurological death, intracranial disease recurrence and SRS-related adverse events. RESULTS: Among 1194 patients registered in the JLGK0901 study, 608 eligible lung adenocarcinoma patients were identified and 238 (39%) had received EGFR-TKI concurrently or during the post-SRS clinical course. After PSM, there were 200 patient pairs with/without post-SRS EGFR-TKI use. EGFR-TKI use was associated with longer OS (median 25.5 vs. 11.0 months, HR 0.60, 95% CI 0.48-0.75, p < 0.001), although the long-term OS curves eventually crossed. Distant intracranial recurrence was more likely in patients receiving EGFR-TKI (HR 1.45, 95% CI 1.12-1.89, p = 0.005). Neurological death, local recurrence and SRS-related adverse event rates did not differ significantly between the two groups. CONCLUSIONS: Although patients receiving EGFR-TKI concurrently or after SRS had significantly longer OS, the local treatment efficacy and toxicity of SRS did not differ between patients with/without EGFR-TKI use.

Stereotactic radiosurgery in elderly patients with brain metastases: comparison with non-elderly patients using database of a multi-institutional prospective observational study (JLGK0901-Elderly).

PURPOSE: Stereotactic radiosurgery (SRS) has been increasingly used for elderly patients with brain metastases (BMs). However, no studies based on a large sample size have been reported. To compare SRS treatment results between elderly and non-elderly patients, we performed a subset study of elderly patients using our prospectively-accumulated multi-institution study database (JLGK0901 Study, Lancet Oncol 15:387-395, 2014). METHODS: During the 2009-2011 period, 1194 eligible patients undergoing gamma knife SRS alone for newly diagnosed BMs were enrolled in this study from 23 gamma knife facilities in Japan. Observation was discontinued at the end of 2013. The 1194 patients were divided into the two age groups, 693 elderly ( ≥ 65 years) and 501 non-elderly ( < 65 years) patients. Our study protocol neither set an upper age limit nor required dose de-escalation. RESULTS: Median post-SRS survival time was significantly shorter in the elderly than in the non-elderly patient group (10.3 vs 14.3 months, HR 1.380, 95% CI 1.218-1.563, p < 0.0001). However, regarding all secondary endpoints including neurological death, neurological deterioration, SRS-related complications, leukoencephalopathy, local recurrence, newly-developed tumors, meningeal dissemination, salvage SRS, whole brain radiotherapy and surgery and decreased mini-mental state examination scores, the elderly patient group was not inferior to the non-elderly patient group. In the 693 elderly patients, there was no post-SRS median survival time difference between those with 5-10 versus 2-4 tumors (10.8 vs 8.9 months, HR 0.936, 95% CI 0.744-1.167, p = 0.5601). CONCLUSIONS: We conclude that elderly BM patients are not unfavorable candidates for SRS alone treatment.

Induration at Injection or Infusion Site May Reduce Bioavailability of Parenteral Phenobarbital Administration.

BACKGROUND: Phenobarbital is well tolerated and effective for controlling agitation or preventing convulsion at the end of life. No information is available concerning parenteral bioavailability of phenobarbital when induration develops at the injection or infusion site. We investigated whether induration at injection or infusion site is related to phenobarbital bioavailability via parenteral routes of continuous subcutaneous infusion and intermittent subcutaneous or intramuscular injection. METHODS: A retrospective analysis was conducted on the medical data obtained from 18 patients who received chronic subcutaneous or intramuscular injections of phenobarbital for the prevention of convulsions and underwent plasma concentration monitoring of the drug. Patients whose concomitant medications were altered during the observation periods were excluded from the analysis. Comparisons were performed for concentration/dose (C/D) ratios obtained from patients with induration at injection or infusion sites (induration group, n = 6) and those without induration (noninduration group, n = 12). P < 0.05 was considered statistically significant. RESULTS: The induration group showed significantly reduced C/D ratio compared with the noninduration group [median (range): 0.131 (0.114-0.334) versus 0.219 (0.180-0.322) d/L, P < 0.05). Assuming that systemic clearance was constant in our patients, changes in the C/D ratio would have contributed to 40% (median) reduction in bioavailability of the drug from the injection or infusion site. CONCLUSIONS: Our data suggest that absolute bioavailability of phenobarbital may be reduced when induration develops at the injection or infusion site in patients treated parenterally by continuous subcutaneous infusion or intramuscular injection.

Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study.

BACKGROUND: We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. METHODS: This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint; however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. FINDINGS: We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). INTERPRETATION: Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. FUNDING: Japan Brain Foundation.

Salvage pemetrexed for brain metastases from ALK-positive lung cancer after Gamma Knife radiosurgery: illustrative case.

BACKGROUND: Systemic therapy for cancer treatment has improved, and therapeutic options for intracranial lesions are increasing. Combinations of treatment modalities are required in certain difficult cases. Gamma Knife radiosurgery (GKS) is effective for the treatment of brain metastases, especially for lesions that are inoperable because of their anatomical or functional location. OBSERVATIONS: The authors report a case of brain metastases in anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma initially treated with GKS followed by the combination of repeat GKS and ALK tyrosine kinase inhibitors (ALK-TKIs) for tumor recurrence. During the clinical course, acquired resistance to ALK-TKIs due to the long exposure period was suspected. After a great deal of thought and discussion with the oncologist responsible for the treatment of the pulmonary lesions, the authors successfully controlled the lesion for the next 17 months by salvage pemetrexed administration. LESSONS: This is the first report on the effectiveness of pemetrexed for recurrent brain metastasis from ALK-positive lung adenocarcinoma resistant to both radiosurgery and ALK inhibitors. Salvage pemetrexed showed a favorable therapeutic effect in this specific case.

Spontaneous Regression of an Unruptured Arteriovenous Malformation Due to Drainer Vein Thrombosis in a Patient with Protein S Deficiency: A Case Report and Literature Review.

Spontaneous regression of an arteriovenous malformation (AVM) is a rare condition observed in 0.3%-1.3% of patients with AVMs and is most likely caused by hemorrhagic events. The regression of an unruptured AVM is rarer than that of a ruptured AVM. Moreover, due to its low frequency of occurrence, the etiology and natural course of spontaneous regression of an AVM is still unclear. This is the first report presenting a case of a spontaneous regression of an unruptured AVM caused by a gradual drainer vein thrombosis that was suspected to result from hypercoagulability due to protein S deficiency.

Comparing Fractionated and Single-Fraction Gamma Knife Radiosurgery for Brain Metastases From Non-Small-Cell Lung Cancer With a Focus on Driver Alterations.

Background As the overall survival in non-small-cell lung cancer has increased, safer, long-term treatments for brain metastases are increasingly needed. This study aimed to analyze the outcomes of fractionated and single-fraction gamma knife radiosurgery for brain metastases from non-small-cell lung cancer, focusing on driver alteration status. Methodology Patients who underwent gamma knife radiosurgery as their first local treatment for brain metastases from non-small-cell lung cancer between May 2018 and December 2021 at our institution were retrospectively enrolled. Results Among the 98 patients (287 lesions), 45 (130 lesions) harbored driver alterations, including epidermal growth factor receptor mutations in 35 patients and anaplastic lymphoma kinase or ROS1 rearrangement in 10 patients. Overall, 64 and 34 patients underwent single-fraction and fractionated radiosurgery (3-15 fractions), respectively. Large tumor size was a risk factor for recurrence, while fractionated radiosurgery (subdistribution hazard ratio (sHR) = 16.47; confidence interval (CI) = 3.58-75.77; p < 0.001) and small tumor size (sHR = 1.15; CI = 1.04-1.28; p = 0.008) independently protected against radiation necrosis. In the case-matched analyses, the cumulative radiation necrosis rates were significantly lower in the fractionated group than in the single-fraction group among all lesions (p = 0.017) and among those with driver alterations (p = 0.046), whereas no significant difference was confirmed among wild-type lesions (p = 0.382). Conclusions Fractionated gamma knife radiosurgery may be an alternative therapeutic approach for reducing the risk of radiation necrosis, particularly for patients with driver alterations, even when the tumors are small. Further research is necessary to determine the optimal indications for fractionated gamma knife radiosurgery and fractionation methods.