Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non–small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC. Materials and Methods: This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling. Results: A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS. Conclusion NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.

OBJECTIVE: Bilateral cavernous sinus dural arteriovenous fistula (CSdAVF) is very rare, even in Asian countries. The research intended to present clinical and radiologic outcomes of treating such fistulas through endovascular embolization. MATERIALS AND METHODS: Data was obtained from 220 consecutive patients, with CSdAVF, who were treated from January 2004 to December 2015. Bilateral CSdAVF was identified in 17 patients (7.7%). The clinical and radiologic outcomes of the fistulas were assessed with an emphasis on the technical aspects of treatment. RESULTS: At the time of treatment, 7 and 10 patients presented with bilateral and unilateral symptoms, respectively. In the former cases, 4 patients had progressed from unilateral to bilateral symptoms. Bilateral fistulas were treated with a single-stage transvenous embolization (TVE) in 15 patients, via bilateral inferior petrosal sinuses (IPS) (n = 9) and unilateral IPS (n = 6). In the other 2 patients with one-sided dominance of shunting, only dominant fistula was treated. Two untreated lesions were found on follow-up to have spontaneously resolved after treatment of the dominant contralateral fistula. Of the 34 CSdAVF lesions, complete occlusion was achieved in 32 lesions after TVE. Seven patients (41.2%) developed worsening of cranial nerve palsy after TVE. During the follow-up period, 4 patients obtained complete recovery, whereas the other 3 remained with deficits. CONCLUSION: With adjustments of endovascular procedures to accommodate distinct anatomical configurations, endovascular treatment for bilateral CSdAVF can achieve excellent angiographic occlusion results. However, aggravation of symptoms after TVE may occur frequently in bilateral CSdAVF. In the patients with one-sided dominance of shunt, treatment of only dominant fistula might be an alternative option.
Arteriovenous Fistula ; Asian Continental Ancestry Group ; Cavernous Sinus* ; Central Nervous System Vascular Malformations* ; Cranial Nerve Diseases ; Endovascular Procedures ; Fistula ; Follow-Up Studies* ; Humans

BACKGROUND/AIMS: Needle-knife precut fistulotomy (NK-F) is a well-known freehand technique for difficult biliary cannulation (DBC). Another approach involves the use of Iso-Tome®, a modified precutting device with an insulated needle tip to prevent direct thermal injury. This comparative study aimed to evaluate the efficacy of the Iso-Tome® precut (IT-P) compared to that of NK-F for DBC. METHODS: Patients with a naive papilla who underwent early IT-P or NK-F for DBC were enrolled. DBC was defined as failure to achieve selective biliary access by wire-guided cannulation despite 5 minutes of attempted cannulation, ≥5 papillary contacts, or a hook-nose-shaped papilla. The primary endpoint was the primary technical success rate, which was based on a noninferiority model. RESULTS: A total of 239 DBC cases were enrolled. The primary technical success rates were 74.7% (89/119) in the IT-P group and 91.6% (110/120) in the NK-F group (lower limit of 90% confidence interval, −0.23; p=0.927 for a noninferiority margin of 10%). The total technical success rates were 87.4% and 95.0%, respectively (p=0.038). The mean precutting times for successful biliary access were 11.2 minutes for IT-P and 7.3 minutes for NK-F (p < 0.01). The procedure-related adverse event rates were 9.2% for IT-P and 5.8% for NK-F (p=0.318). The rates of post-endoscopic retrograde cholangiopancreatography pancreatitis were 4.2% and 2.5%, respectively (p=0.499). CONCLUSIONS: IT-P failed to exhibit noninferiority compared with NK-F regarding the primary technical success rate of DBC, but there was no difference in the frequency of adverse events.
Catheterization* ; Humans ; Needles ; Pancreatitis

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status. MATERIALS AND METHODS: Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D). RESULTS: Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities. CONCLUSION: Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.
Arm ; Carcinoma, Non-Small-Cell Lung* ; Chemoradiotherapy* ; Cisplatin* ; Erlotinib Hydrochloride* ; Humans ; Neoplasm Metastasis ; Pathology, Molecular ; Receptor, Epidermal Growth Factor

OBJECTIVE: Stents are widely used in coil embolization of intracranial aneurysms, but on occasion, a microcatheter must traverse a stented segment of artery (so-called trans-cell technique) to select an aneurysm, or double stenting may necessary. In such situations, microguidewire passage and microcatheter delivery through a tortuous stented parent artery may pose a technical challenge. Described herein is a microguidewire looping technique to facilitate endovascular navigation in these circumstances. METHODS: To apply this technique, the microguidewire tip is looped before entering the stented parent artery and then advanced distally past the stented segment, with the loop intact. Rounding of the tip prevents interference from stent struts during passage. A microcatheter is subsequently passed into the stented artery for positioning near the neck of aneurysm, with microguidewire assistance. The aneurysm is then selected, steering the microcatheter tip (via inner microguidewire) into the dome. RESULTS: This technique proved successful during coil embolization of nine saccular intracranial aneurysms (internal carotid artery [ICA], 6; middle cerebral artery, 2; basilar tip, 1), performing eight trans-cell deliveries and one additional stenting. Selective endovascular embolization was enabled in all patients, resulting in excellent clinical and radiologic outcomes, with no morbidity or mortality directly attributable to microguidewire looping. CONCLUSION: Microguidewire looping is a reasonable alternative if passage through a stented artery is not feasible by traditional means, especially at paraclinoid ICA sites.
Aneurysm ; Arteries* ; Carotid Arteries ; Embolization, Therapeutic ; Humans ; Intracranial Aneurysm* ; Middle Cerebral Artery ; Mortality ; Neck ; Parents* ; Stents*

OBJECTIVE: Outcomes of stent-assisted coil embolization (SACE) have not been well established in the setting of vertebrobasilar dissecting aneurysms (VBDAs) due to the low percentage of cases that need treatment and the array of available therapeutic options. Herein, we presented clinical and radiographic results of SACE in patients with VBDAs. MATERIALS AND METHODS: A total of 47 patients (M:F, 30:17; mean age ± SD, 53.7 ± 12.6 years), with a VBDA who underwent SACE between 2008 and 2014 at two institutions were evaluated retrospectively. Medical records and radiologic data were analyzed to assess the outcome of SACE procedures. Cox proportional hazards regression analysis was conducted to determine the factors that were associated with aneurysmal recanalization after SACE. RESULTS: Stent-assisted coil embolization technically succeeded in all patients. Three cerebellar infarctions occurred on postembolization day 1, week 2, and month 2, but no other procedure-related complications developed. Immediately following SACE, 25 aneurysms (53.2%) showed no contrast filling into the aneurysmal sac. During a mean follow-up of 20.2 months, 37 lesions (78.7%) appeared completely occluded, whereas 10 lesions showed recanalization, 5 of which required additional embolization. Overall recanalization rate was 12.64% per lesion-year, and mean postoperative time to recanalization was 18 months (range, 3-36 months). In multivariable analysis, major branch involvement (hazard ratio [HR]: 7.28; p = 0.013) and the presence of residual sac filling (HR: 8.49, p = 0.044) were identified as statistically significant independent predictors of recanalization. No bleeding was encountered in follow-up monitoring. CONCLUSION: Stent-assisted coil embolization appears feasible and safe for treatment of VBDAs. Long-term results were acceptable in a majority of patients studied, despite a relatively high rate of incomplete occlusion immediately after SACE. Major branch involvement and coiled aneurysms with residual sac filling may predispose to recanalization.
Aneurysm ; Aneurysm, Dissecting* ; Embolization, Therapeutic* ; Follow-Up Studies ; Hemorrhage ; Humans ; Infarction ; Medical Records ; Retrospective Studies ; Stents

OBJECTIVE: The dual microcatheter technique is common practice for coil embolization of a wide-necked aneurysm, due to safety and efficacy. However, technical limitations of some complex configurations may necessitate additional microcatheters to bolster coil stability, compact the coil, or for protection. Described herein is a triple microcatheter technique for endovascular management of wide-necked intracranial aneurysms. MATERIALS AND METHODS: Data accruing prospectively between January 2006 and October 2014 on simultaneously executed triple microcatheter coil embolization procedures done in 38 saccular aneurysms were reviewed. Clinical and morphological outcomes were assessed, with emphasis on technical aspects of treatment. RESULTS: The triple microcatheter technique was successfully applied to all 38 saccular aneurysms, involving the posterior communicating artery (n = 13), the middle cerebral artery (n = 10), the basilar tip (n = 7), the anterior cerebral artery (n = 5), and the internal carotid artery (n = 3). Stent protection was added in four patients and balloon remodeling in one. Dual microcatheters (n = 24) were usually deployed to deliver the coil within sacs of aneurysms, with the additional microcatheter used for protection. Otherwise, triple microcatheters were deployed for coil delivery (n = 11) or coils were delivered via a single microcatheter, with dual microcatheters deployed for protection (n = 3). Successful occlusion of aneurysms was achieved in 89.5% of cases, with no procedure-related morbidity or mortality. Stable occlusion was maintained in 72.2% (26/36) of the aneurysms at the final follow-up (mean interval, 30.2 +/- 22.7 months). CONCLUSION: The outcomes of this limited study suggest that the triple microcatheter technique may be an effective and safe therapeutic option for wide-necked aneurysms, using technical strategies tailored to complex angio-anatomic configurations.
Aged ; Angiography ; Carotid Arteries/radiography ; Embolization, Therapeutic ; Female ; Humans ; Intracranial Aneurysm/*therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Retrospective Studies ; *Stents

OBJECTIVE: Described herein is a microcatheter looping technique to facilitate aneurysm selection in paraclinoid aneurysms, which remains to be technically challenging due to the inherent complexity of regional anatomy. MATERIALS AND METHODS: This retrospective study was approved by our Institutional Review Board, and informed consent was waived. Microcatheter looping method was employed in 59 patients with paraclinoid aneurysms between January 2012 and December 2013. In the described technique, construction of a microcatheter loop, which is steam-shaped or pre-shaped, based on the direction of aneurysms, is mandatory. The looped tip of microcatheter was advanced into distal internal carotid artery and positioned atop the target aneurysm. By steering the loop (via inner microguidewire) into the dome of aneurysm and easing tension on the microcatheter, the aneurysm was selected. Clinical and morphologic outcomes were assessed with emphasis on technical aspects of the treatment. RESULTS: Through this looping technique, a total of 59 paraclinoid aneurysms were successfully treated. After aneurysm selection as described, single microcatheter technique (n = 25) was most commonly used to facilitate coiling, followed by balloon protection (n = 21), stent protection (n = 7), multiple microcatheters (n = 3), and stent/balloon combination (n = 3). Satisfactory aneurysmal occlusion was achieved through coil embolization in 44 lesions (74.6%). During follow-up of 53 patients (mean interval, 10.9 +/- 5.9 months), only one instance (1.9%) of major recanalization was observed. There were no complications related to microcatheter looping. CONCLUSION: This microcatheter looping method facilitates safe and effective positioning of microcatheter into domes of paraclinoid aneurysms during coil embolization when other traditional microcatheter selection methods otherwise fail.
Adult ; Carotid Artery, Internal/radiography/*surgery ; Catheterization/methods ; Cerebral Angiography/methods ; Embolization, Therapeutic/*methods ; Female ; Humans ; Intracranial Aneurysm/*therapy ; Male ; Middle Aged ; Retrospective Studies ; Stents

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). METHODS: The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study. RESULTS: The incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414). CONCLUSION: Montelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment.
Body Weight ; Bronchopulmonary Dysplasia* ; Drug-Related Side Effects and Adverse Reactions ; Gestational Age ; Health Resorts ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Leukotriene Antagonists ; Pharmacokinetics ; Prospective Studies ; Sodium* ; Steroids ; Ventilation

OBJECTIVE: Spontaneous cerebellar hemorrhage (SCH) is less common than supratentorial intracerebral hemorrhage. This study investigated the treatment of SCH and the relation between its clinical and radiological manifestation and outcome. MATERIALS AND METHODS: We presented a SCH management protocol in our institute and analyzed the clinical and radiological findings in 41 SCH patients. The outcomes of each method (surgery and conservative treatment) were compared among patients with initial Glasgow Coma Scale (GCS) score of 9-13 and hematoma volume greater than 10 mL. RESULTS: Two (4.9%), 16 (39%), and 23 (56.1%) patients had an initial GCS score of 3-8, with 3-8, 9-13, and 14-15, respectively. Initial GCS score showed significant correlation with Glasgow Outcome Scale (GOS) score (p = 0.005). The mean largest hematoma diameter was 3.2 +/- 1.5 cm, and the mean volume was 11.0 +/- 11.5 mL. Both of them showed significant inverse correlation with GOS score (p < 0.001). Among patients with an initial GCS score of 9-13 and hematoma volumes greater than 10 mL, 3 (50%) had good outcome and 3 (50%) had poor outcome in the surgical, and all of those in the conservative treatment group had poor outcomes. The outcome distribution differed significantly in the surgical and conservative groups (p = 0.030). CONCLUSION: Initial GCS score and largest hematoma diameter and volume on brain computed tomography are important determinants of outcome in SCH patients. The surgery group showed better outcome than the conservative treatment group among those with an intermediate neurological status and large hematomas.
Brain ; Cerebellum ; Cerebral Hemorrhage ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Hematoma ; Hemorrhage* ; Humans