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Button battery ingestion requires emergency endoscopic removal since severe complications, such as esophageal perforation, can develop within 4 hours of the ingestion. Given that guardians do not witness the children’s foreign body ingestion 40% of the time, physicians can only guess what was swallowed based on plain radiography. We report a case of a 45-month-old-boy who visited the emergency department after swallowing an unknown foreign body and whose radiographs showed “circle-within-a-circle appearance” on the anteroposterior view and “step-off appearance” on the lateral view, suggesting button battery ingestion. We conducted emergency endoscopic removal, and found stacked coins mimicking a button battery on the radiographs. The coins were pushed into the stomach and came out through defecation 3 weeks later without further complications. Distinguishing between stacked coins and a button battery through radiography may help avoid unnecessary emergency endoscopy.

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage. Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis., Graphical Abstract

Objective: There are few existing data on the status of coronary artery disease (CAD) in patients with atherosclerosis of the cerebral artery detected by brain imaging studies. We aimed to analyze the predictors of asymptomatic angiographically significant CAD detected by simultaneous cerebral and coronary angiography. Methods: This retrospective cohort study screened data obtained between August 2009 and April 2019; 11,047 patients underwent cerebral angiography for atherosclerotic change (>50% stenosis or aneurysm) seen in brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) at a single center by endovascular neurosurgeon’s decision. Of these, 700 patients including 622 patients who underwent simultaneous coronary and cerebral angiography and 78 patients who underwent coronary angiography within a month were enrolled. We investigated the characteristics and predictors of angiographically significant CAD (>50% stenosis). Furthermore, we also analyzed the major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, myocardial infarction, and stroke for 5 years. Results: The frequency of significant CAD was 59% (413/700), the mean age was 68.9 ± 10.3 years, and 60.6% were male. During mean follow-up of 50 months, the MACCE rate of our whole cohort was significantly higher in the CAD group (21.5%) than in the non-CAD group (14.6%; hazard ratio 1.65, 95% CI 1.17–2.33, p value = 0.005). Considering that the embolic stroke is less associated with atherosclerotic change, our predictive model of significant CAD was made without embolic stroke (n = 599). In our multivariate model 2 including univariate p = 0.012), diabetes mellitus (OR 1.81, 95% CI 1.22–2.68, p = 0.003), previous stroke (OR 1.63, 95% CI 1.02–2.60, p = 0.039), low ankle-brachial index (ABI; p = 0.019), left ventricular ejection fraction (EF) p = 0.012), troponin I or T positive (OR 2.76, 95% CI 1.69–4.53, p < 0.001), and complex features on cerebral angiography (OR 2.73, 95% CI 1.78–4.19, p < 0.001). Conclusions: Accurate coronary evaluation by coronary angiography might be considered when patients with atherosclerotic cerebral artery detected on brain MRA or CTA planned cerebral angiography were male or have diabetes mellitus, previous stroke, low ABI (

As the Mental Health Welfare Act of 2017 is enacted, in order to grasp the concept of new mental health, the first priority is to understand the awareness of the community members who are the target of the service. The purpose of this study is to examine the changes in the perception of foreign mental illnesses through literature review, and developed a community mental health services project in comparison with Korea. There is a need for an active effort to look at patients discouraging prejudice on psychiatric patients. A place to learn social skills and live together, or a community health center should be used actively. We strongly urge that the construction of infrastructures such as human, material, social and economic support is needed and that a great deal of social attention and support is needed.

To investigate the association between headache outcomes and coil embolization and to identify potential factors associated with different headache outcomes in patients with unruptured intracranial aneurysms (UIAs) after treatment with coil embolization.A prospective study of patients with planned coil embolization for UIAs was conducted. The changes in headache patterns, headache-related disability, and depression were assessed before coil embolization and at 3 days and 2 and 6 weeks after coil embolization. All variables were analyzed to identify factors associated with different headache outcomes.Fifty-nine (72%) of 82 patients reported headaches before coil embolization. Of these, improvements in the severity of headaches were reported by 42 patients (71%). In addition to a significant reduction in headache severity, significant reductions in headache-related disability and depression scores also were observed. Demographic factors, aneurysmal characteristics, or procedural factors were not found to be significantly associated with improvement in the severity of headaches after coil embolization. In addition, the number of microemboli on diffusion-weighted imaging was not significantly associated with improvement of headaches after coil embolization. Twenty-three patients reported no headaches before coil embolization, and 3 (13%) patients reported new-onset headaches after coil embolization. All new-onset headaches were mild and dull in nature without combined symptoms in the temporal area.Our study suggested that regardless of headache characteristics, the aneurysm size (even those5 mm in diameter), technique used (stent-assisted or not stent-assisted), and coil embolization of UIAs resulted in headache improvement in most patients with pretreatment headaches.

Background Digital subtraction angiography is the gold standard to confirm complete removal of an arteriovenous malformation (AVM) nidus. However, the transfemoral approach requires specialized instrumentation and is cumbersome and difficult to perform with the patient in the prone or decubitus position. We report the use of intraoperative digital subtraction angiography (iDSA) with the transradial approach and examine its usefulness and safety. Materials and Methods We retrospectively reviewed clinical features, radiologic images, surgical findings, and iDSA findings of patients with AVM who underwent surgery for nidus removal. Transradial iDSA was performed within 30 minutes for patients who required angiographic confirmation after AVM resection. This procedure was simple with the radial arterial line for blood pressure monitoring used as digital subtraction angiography catheter access route. Results Transradial iDSA was performed in 23 patients. Twelve patients were not in the general supine position during neurosurgery; 7 patients were operated on in prone position, and 5 patients were operated on in the park bench position. Remnant nidus was identified by iDSA in 2 patients, and additional measures were required. Conclusions Intraoperative cerebral angiography during surgery for cerebral AVM could be performed safely via the transradial approach. This approach showed several merits in terms of easy access; no extra requirements, such as preoperative sheath implantation, anticoagulation during the surgery, or a radiolucent table; and usefulness in any surgical position. Further studies using this approach and comparison with the transfemoral approach are necessary.

Objective We evaluated the feasibility of angiographic computed tomography (ACT) for visualizing stent material in patients who underwent intracranial or extracranial stent placement to treat atherosclerotic lesions or stent assisted coil embolization. Materials and methods We performed intrarterial and intravenous ACT on biplane angiography system equipped with flat panel detectors (Axiom Arits dBA; Siemens Medical Solutions, Forchheim, Germany). Vistipaque 320 was injected for contrast medium, total 150 mL at flow rate of 5 mL/s through artery and 77 mL at flow rate of 3.5 mL/s through vein. Results ACT is a new imaging modality that provides a clear visualization of stent strut. Conclusion Therefore this new application has potential to become the noninvasive option for follow-up after endovascular surgery using stents.

OBJECTIVE Early progressive infarction (EPI) is frequently observed and related to poor functional outcome in patients with middle cerebral artery (MCA) infarction caused by MCA occlusion. We evaluated the perfusion parameters of magnetic resonance imaging (MRI) as a predictor of EPI. METHODS We retrospectively analyzed patients with acute MCA territory infarction caused by MCA occlusion. EPI was defined as a National Institutes of Health Stroke Scale increment ≥2 points during 24 hours despite receiving standard treatment. Regional parameter ratios, such as cerebral blood flow and volume (rCBV) ratio (ipsilateral value/contralateral value) on perfusion MRI were analyzed to investigate the association with EPI. RESULTS Sixty-four patients were enrolled in total. EPI was present in 18 (28%) subjects and all EPI occurred within 3 days after hospitalization. Diabetes mellitus, rCBV ratio and regional time to peak (rTTP) ratio showed statically significant differences in both groups. Multi-variate analysis indicated that history of diabetes mellitus [odds ratio (OR), 6.13; 95% confidence interval (CI), 1.55-24.24] and a low rCBV ratio (rCBV

We report transradial access (TRA) for emergency carotid artery stenting (CAS) as a useful alternative when the femoral artery cannot be accessed. A 63-year-old man arrived at our emergency room 30 minutes after left hemiplegia and loss of consciousness. Brain computed tomography (CT) anigograpy showed occlusion of the right interntal carotid artery (ICA) and CT perfusion revealed delayed time-to-peak in the territory of the middle cerebral artery. For, endovascular treatment, trans-femoral access (TFA) was attempted but failed due to occlusion of the abdominal aorta. So, we changed access route via radial artery and confirmed proximal ICA dissection. CAS was attempted via TRA and it was successfully performed. Final angiography showed recanalization of ICA and patient was clinically improved.

Purpose Considerable molecular heterogeneity exists among human epidermal growth factor receptor 2 (HER2) –positive breast cancer regarding gene expression and mutation profiling. Evidence from preclinical, clinical neoadjuvant, and metastatic clinical trials suggested that PIK3CA mutational status and PAM50 intrinsic subtype of a tumor were markers of response to anti-HER2 therapies. We evaluated the predictive value of these two biomarkers in the adjuvant setting using archived tumor blocks from National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31. Patients and Methods Expression data for 49 genes using the nCounter platform were used to generate PAM50 intrinsic subtypes for 1,578 archived tumor blocks from patients in the B-31 trial. Six PIK3CA hotspot mutations were examined by mass spectrometry of the primer extension products in a randomly selected subset (n = 671). We examined the heterogeneity of trastuzumab treatment effect across different subsets defined by each marker using Cox regression and disease-free survival as the end point. Results Seven hundred forty-one (47.0%) of 1,578 tumors were classified as HER2-enriched (HER2E) subtype, and 166 (24.7%) of 671 tumors had PIK3CA mutations. Hazard ratios (HRs) for trastuzumab in HER2E and other subtypes were 0.44 (95% CI, 0.34 to 0.58; P < .001) and 0.47 (95% CI, 0.35 to 0.62; P < .001), respectively (interaction P = .67). HRs for trastuzumab in PIK3CA wild-type and mutated tumors were 0.51 (95% CI, 0.37 to 0.71; P < .001) and 0.44 (95% CI, 0.24 to 0.82; P = .009), respectively (interaction P = .64). Conclusion Unlike results seen in the metastatic and neoadjuvant clinical trials, PIK3CA and PAM50 intrinsic subtypes were not predictive biomarkers for adjuvant trastuzumab in NSABP B-31. These data suggest that results from the metastatic and neoadjuvant setting may not be always applicable to the adjuvant setting.

Patients with middle cerebral artery (MCA) infarction accompanied by MCA occlusion with or without internal carotid artery (ICA) occlusion have a poor prognosis, as a result of brain cell damage caused by both the infarction and by space-occupying and life-threatening edema formation. Multiple treatments can reduce the likelihood of edema formation, but tend to show limited efficacy. Decompressive hemicraniectomy with duroplasty has been promising for improving functional outcomes and reducing mortality, particularly improved functional outcomes can be achieved with early decompressive surgery. Therefore, identifying patients at risk for developing fatal edema is important and should be performed as early as possible. Sixty-four patients diagnosed with major MCA infarction with MCA occlusion within 8 hours of symptom onset were retrospectively reviewed. Early clinical, laboratory, and computed tomography angiography (CTA) parameters were analyzed for malignant brain edema (MBE). Twenty of the 64 patients (31%) had MBE, and the clinical outcome was poor (3month modified Rankin Scale >2) in 95% of them. The National Institutes of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early Computed Tomography Score, Clot Burden Score, and Collateral Score (CS) showed statically significant differences in both groups. Multivariable analyses adjusted for age and sex identified the independent predictors of MBE: NIHSS score >18 (odds ratio [OR]: 4.4, 95% confidence interval [CI]: 1.2-16.0, p=0.023) and CS on CTA

Cerebral venous sinus thrombosisis an uncommon entity and its clinical presentations are highly variable. We present the case of superior sagittal sinus thrombosis. Although it was medical refractory, successfully treated with mechanical thrombectomy using the Solitaire FR device. A 27-year-old man who presented with venous infarction accompanied by petechial hemorrhage secondary to the superior sagittal sinus (SSS) thrombosis. Due to rapid deterioration despite of anticoagulation therapy, the patient was taken for endovascular treatment. We deployed the Solitaire FR device (4×20 mm) in the anterior portion of the thrombosed SSS, and it was left for ten minutes before the retraction. Thus, we removed a small amount of thrombus. But the sinus remained occluded. We therefore performed the thrombectomy using the same methods using the Solitaire FR (6×20 mm). Thus, we were successful in removing larger clots. Our case highlights not only that the mechanical thrombectomy using the Solitaire FR is effective in achieving revascularization both rapidly and efficiently available, but also that it might be another option in patients with cerebral venous sinus thrombosis who concurrently had rapid clinical deterioration with devastating consequences.

Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.

Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecological system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

Purpose: Considerable molecular heterogeneity exists among HER2-positive breast cancer regarding gene expression and mutation profiling. Evidence from preclinical, clinical neoadjuvant, and metastatic clinical trials suggested PIK3CA mutational status and PAM50 intrinsic subtype of a tumor were markers of response to anti-HER2 therapies. We evaluated the predictive value of these two biomarkers in the adjuvant setting using archived tumor blocks from NSABP trial B-31. Methods: Expression data for 49 genes using the nCounter platform was used to generate PAM50 intrinsic subtypes for 1,578 archived tumor blocks from B-31. Five PIK3CA hotspot mutations were examined by mass spectrometry of the primer extension products in a randomly selected subset (N=671). We examined the heterogeneity of trastuzumab treatment effect across different subsets defined by each marker using Cox regression and disease free survival as the endpoint. Results: 741/1578 (47.0%) tumors were classified as HER2E subtype; and 166/671 (24.7%) had PIK3CA mutations. Hazard ratios (HR) for trastuzumab in HER2E and other subtypes were 0.44 (95%CI: 0.34-0.58, p Conclusion: Unlike results seen in the metastatic and neoadjuvant clinical trials, PIK3CA and PAM50 intrinsic subtypes were not biomarkers for differential response to trastuzumab in NSABP B-31. These data suggest that results from the metastatic and neoadjuvant setting may not be always applicable to the adjuvant setting. Support: National Cancer Institute, Department of Health and Human Services, Public Health Service, Grants U10-CA-12027, U10-CA-69651, U10-CA-37377, and U10-CA-69974, and by a grant from the Pennsylvania State Department of Health. The latter Department specifically disclaims responsibility for any analysis, interpretations or conclusions. Citation Format: Soonmyung Paik, Katherine L Pogue-Geile, Nan Song, Patrick G Gavin, Seong-Rim Kim. Intrinsic subtypes, PIK3CA mutation, and the degree of benefit from adjuvant trastuzumab in NSABP trial B-31 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S3-05.

National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31 suggested the efficacy of adjuvant trastuzumab, even in HER2-negative breast cancer. This finding prompted us to develop a predictive model for degree of benefit from trastuzumab using archived tumor blocks from B-31.Case subjects with tumor blocks were randomly divided into discovery (n = 588) and confirmation cohorts (n = 991). A predictive model was built from the discovery cohort through gene expression profiling of 462 genes with nCounter assay. A predefined cut point for the predictive model was tested in the confirmation cohort. Gene-by-treatment interaction was tested with Cox models, and correlations between variables were assessed with Spearman correlation. Principal component analysis was performed on the final set of selected genes. All statistical tests were two-sided.Eight predictive genes associated with HER2 (ERBB2, c17orf37, GRB7) or ER (ESR1, NAT1, GATA3, CA12, IGF1R) were selected for model building. Three-dimensional subset treatment effect pattern plot using two principal components of these genes was used to identify a subset with no benefit from trastuzumab, characterized by intermediate-level ERBB2 and high-level ESR1 mRNA expression. In the confirmation set, the predefined cut points for this model classified patients into three subsets with differential benefit from trastuzumab with hazard ratios of 1.58 (95% confidence interval [CI] = 0.67 to 3.69; P = .29; n = 100), 0.60 (95% CI = 0.41 to 0.89; P = .01; n = 449), and 0.28 (95% CI = 0.20 to 0.41; P.001; n = 442; P(interaction) between the model and trastuzumab.001).We developed a gene expression-based predictive model for degree of benefit from trastuzumab and demonstrated that HER2-negative tumors belong to the moderate benefit group, thus providing justification for testing trastuzumab in HER2-negative patients (NSABP B-47).

The predictors of graft infection after cranioplasty (GIC) following decompressive craniectomy are not well established. Knowledge of the risk factors for GIC will allow development of preventive measures designed to reduce infection rates. Therefore, the objective of this study was to identify risk factors for the development of GIC.A total of 85 patients underwent reconstructive cranioplasty after decompressive craniectomy between January 2009 and July 2011 and had a follow-up period of1 year; charts were reviewed retrospectively. Although autograft was used whenever possible, artificial bone was used for cranioplasty. GIC was defined as infection requiring removal of the bone graft.GIC occurred in six patients (7.05 %). GIC was not related to the indications for craniectomy, the interval of cranioplasty, graft material, or the size of the bone defect (p = 0.433, p = 0.206, p = 0.665, and p = 0.999, respectively). The GIC rate was significantly related to previous temporalis muscle resection, preoperative subgaleal fluid collection, operative times120 min, and postoperative wound disruptions (p = 0.001, p 0.001, p = 0.035, and p = 0.016, respectively). Multiple logistic regression showed that the presence of a subgaleal fluid collection before cranioplasty significantly increased the risk of GIC (OR: 38.53; 95 % CI: 2.77-535.6; p = 0.006).The results of this study suggest that long operative times (120 min), craniectomy with temporalis muscle resection, the presence of preoperative subgaleal fluid collection, and postoperative wound disruption may be risk factors for graft infection after cranioplasty. Surgical techniques should be developed to reduce operative time and to avoid temporalis muscle resection when possible. In addition, meticulous dural closure aimed at reducing the formation of subgaleal fluid collection is important for the prevention of graft infections after cranioplasty.

Background Intrinsic thrombosis and stenosis are complications associated with the use of neck-remodeling devices in the treatment of intracranial aneurysms. Objective To examine the technical and anatomic factors that predict short- and long-term stent patency. Methods We undertook a retrospective review of 161 patients who underwent coil embolization of 168 ruptured and unruptured aneurysms assisted by the use of a neck-remodeling device. One hundred twenty-seven patients had catheter-based angiographic follow-up to evaluate 133 stent-coil constructs (mean, 15.4 months; median, 12.7 months). The technique of microcatheter jailing was used in a majority of patients; nonstandard stent configurations were also used. Results Clinical follow-up for all patients who had catheter-based angiograms demonstrated that among 133 stent constructs, a total of 9 (6.8%) had an in-stent event: 6 acute or subacute thrombosis (4.5%) and 3 delayed stenosis or occlusion (2.3%). Seven of these constructs were associated with a symptomatic event (5.3%). A significantly higher rate of in-stent events was seen with the use of constructs to treat anterior communicating artery aneurysms. When all patients are considered, including those who did not receive catheter-based follow-up imaging, 2 of 168 procedures (1.2%) resulted in the death of a patient, and procedural morbidity was 14.9%. Conclusion From these results and those in the published literature, in-stent complication rates are low in carefully selected patients. The use of dual antiplatelet therapy, sensitivity assays, and glycoprotein IIb/IIIa inhibitors may decrease the rate of acute and chronic in-stent complications.

Spontaneous vertebrobasilar dissecting aneurysm (VBD) is a very challenging disease with an unpredictable clinical course and controversies on treatment strategy. The present study reports radiological and clinical outcomes of stent-alone treatment (SAT) for VBD. Twenty-four VBDs treated with SAT are included in the present study. Clinical and angiographic data were reviewed retrospectively. A total of 24 lesions in 22 patients with a mean follow-up period of 16.21 months were included. Of the 24 individual lesions, 23 were intracranial vertebral artery lesions and 1 lesion was located in the basilar artery. There were six cases of ruptured dissections with the other cases having various symptoms. The immediate post-SAT angiographic outcomes included 5 lesions with good remodeling over 90% recovery and 19 poorly remodeled lesions. The latest angiographic outcomes included 17 cases of good remodeling (remodeling rate over 90%), 6 cases of poor remodeling (remodeling rate below 70%), and 1 case with morphological aggravation. The overlapping stent technique was used in seven cases and it was significantly associated with good angiographic results. None of the rupture cases underwent re-rupture post SAT. There was one case of a symptomatic complication of a femoral arteriovenous fistula. The SAT could be a feasible alternative for the treatment of VBD. The overlapping technique was significantly associated with good angiographic outcome. We expect that technological development of the intracranial stent will allow better procedural outcomes of SAT.

Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed in many cancer and is emerging as a potential therapeutic target. Yet data on the expression of eIF4E in endometrial cancer are lacking.Immunohistochemistry was used to evaluate the expression of eIF4E in 62 endometrial cancer surgical specimens. We subsequently evaluated whether inhibition of eIF4E by siRNA would have an impact on cell growth in endometrial cancer cell lines, using the MTT cell proliferation assay.According to a chosen cutoff value, 36 (58.1%) of 62 patient specimens scored as eIF4E positive. The positivity of eIF4E was significantly more frequent in tumors extending outside the uterus (stage III/IV vs. stage I/II, P = 0.027). Lastly, downregulation of eIF4E by siRNA reduced the growth of HEC-1A cells significantly but had a somewhat weaker effect in Ishikawa cells (P 0.001).Expressions of eIF4E correlated with prognosis of endometrial adenocarcinomas. Our results suggest that eIF4E might be a promising therapeutic target in endometrial cancer.

A 68-year-old woman with progressive paraparesis and altered sensation lasting approximately five days was admitted to our clinic. Magnetic resonance imaging (MRI) revealed an advanced stage T7-8 epidural mass ventral to the spinal cord, which was believed to be a metastatic tumor considering the patient's age. A highly enhanced epidural mass and pedicle appeared during the MR scan. However, the pathologic findings were compatible with the diagnosis of a primary meningeal melanocytic tumor. Primary epidural melanomas are extremely rare lesions. This case was finally diagnosed as a primary thoracic spinal epidural melanoma.

The authors report a case of in-stent restenosis (ISR) of the middle cerebral artery (MCA) following bare-metal stent (BMS) deployment and subsequent treatment using a drug-eluting stent (DES). This 65-year-old woman presented with frequent transient ischemic attacks. Initial studies revealed occlusion of the left internal carotid artery and severe stenosis of the right MCA with decreased cerebral perfusion in the bilateral MCA territories. Stent-assisted angioplasty of the right MCA was performed using a BMS, and satisfactory results were obtained with no complications. Six months after the procedure the patient presented with recurrent symptoms, and workups revealed ISR with decreased cerebral perfusion. A DES was successfully placed without complications. Follow-up studies at 3 and 8 months after retreatment showed sustained luminal integrity and cerebral perfusion. A combination of CT angiography and perfusion CT exhibited the anatomical results and hemodynamic status of the stenotic lesion, and these findings coincided with the patient's clinical symptoms and the results of conventional cerebral angiography. In-stent restenosis of the MCA after placement of a BMS can be treated using a DES. A combination of CT angiography and perfusion CT can be an alternative to conventional angiography. Low-profile devices with an amelioration of trackability are essential for the further incorporation of the DES into the field of endovascular neurosurgery. More clinical experiences and long-term follow-ups are mandatory to evaluate the safety, efficacy, and durability of the DES.

Background: The NSABP FB-7 trial, reported at SABCS 2015 (Jacobs et al., abstract # PD5-04), enrolled HER2-positive breast cancer patients (pts) with locally advanced disease who were randomly assigned to trastuzumab (T) or neratinib (N) or the combination (T+N) with weekly paclitaxel (P) followed by standard AC. Dual anti-HER2 therapy yielded greater pathological complete response (pCR) rates than single targeted therapies in the overall cohort. The purpose of this study was to evaluate the technical qualities of a new custom, targeted AmpliSeq panel and to use it to assess mutations in FB-7 pretreatment biopsies and surgical samples. Methods: To identify mutations that could act as resistance markers to anti-HER2 therapy, we designed a custom panel, termed the NSABP Anti-HER2 Resistance AmpliSeq (NAR) panel, interrogating 117 genes involved in HER2 signaling pathways and/or previously implicated as resistance markers to trastuzumab. The NAR panel, including 3,847 amplicons in 2 pools, was used to sequence HDx™ reference standards with the Ion Torrent sequencing platform. First, the panel and our mutation-calling pipeline were tested for reproducibility and accuracy using the reference samples. Subsequently, DNA from pretreatment biopsies and matched surgical samples (when available) from FB-7 pts were assayed for mutations using the NAR panel. Results: Across the NAR panel, the average target coverage was 94.25%. For the ERBB2 gene, the coverage was 96.0%. HDx™ reference standards, with known allele frequencies as evaluated by ddPCR, were used to assess the accuracy of the NAR panel, using a custom pipeline to filter SNVs. HDx™ reference standards were sequenced with the NAR panel, and the resulting allele frequencies compared with the known allele frequencies. Based on examination of the following mutations, BRAF-V600E, KRAS-G13D, KRAS-G12D, NRAS-Q61K, PIK3CA-H1047R, MET-Del-FS, PDGFRA-G426D, EGF-G719S, we observed a Pearson correlation coefficient of 0.9822. Next, we used our NAR Ampliseq panel to sequence a subset of colon samples collected as part of the NSABP Genome Assessment Guided Medicine (N-GAMe) cohort. Comparison of our NAR AmpliSeq results and those from a CLIA certified Illumina sequencing platform over all ERBB2 polymorphism and mutation sites demonstrated a correlation coefficient of 0.978. We also assessed the association of copy number determined with the Ion Torrent sequencing software with pCR. We confirmed that the pCR rates were higher in patient samples with greater amplification of ERBB2 (P < 0.05). Mutant allele frequencies were compared in the before-treatment biopsies to surgical samples. The mutant allele frequencies of PIK3CA-E545K, MAP2K4-S184L, MTOR-R491Q, and MAP2K4-D150N were increased after treatment, suggesting that these mutations may have provided a selective advantage during treatment, implicating a potential resistance marker. We predicted that N or T+N-treated patients with an ERBB2-V777L mutation would achieve pCR, but such a patient did not achieve pCR. Other mutations in this patient may have been responsible for the failure to achieve pCR. One patient with an ERBB2-S310F mutation and treated with N, did achieve pCR, as predicted. Conclusion: Preliminary analysis of FB-7 suggests that sequence analysis with Ion torrent sequencing using the NAR panel may be clinically useful. Support: Puma Biotechnology and PA state grant, PA DOH disclaims responsibility for analysis, interpretations, or conclusions Citation Format: Huichen Feng, Ying Wang, Peter Lucas, Seong-Rim Kim, Corey Lipchik, Patrick Gavin, Samuel Jacobs, Ashok Srinivasan, Katherine L. Pogue-Geile. Assessment of mutations with a custom NSABP anti-HER2 resistance AmpliSeq (NAR) panel in NSABP clinical trial FB-7 [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A22.

The authors report on a case of intravascular ultrasonography (IVUS)-guided stent angioplasty for iatrogenic extracranial vertebral artery (VA) dissection in a 49-year-old man after coil embolization for an unruptured aneurysm of the right posterior inferior cerebellar artery. Insignificant dissections occurred during the procedure. Postoperatively, the patient experienced gradually worsening posterior neck pain and headache, and follow-up angiography 8 months after the coil embolization revealed expansion of the dissection. The patient underwent stent angioplasty with IVUS guidance and his symptoms improved. To the authors' knowledge, this is the first report of IVUS-guided stent angioplasty of an extracranial VA dissection. It was safe and feasible to treat extracranial VA dissections with stent placement under IVUS guidance. Intravascular environments are in real time with IVUS, and this technique is useful in the confirmation of a true lumen and evaluation of appropriate stent apposition. More clinical experience with this technique is necessary and mandatory, and devices with smaller diameters with improved trackability are essential for further introduction of IVUS into the field of endovascular neurosurgery.

The purpose of this study was to identify the risk factors related to the hemorrhagic progression (HP) of brain contusion in patients after traumatic brain injury (TBI). Recently, many studies have reported abnormal lipid levels associated with hemorrhagic stroke. Unlike hemorrhage stroke, however, the lipid profiles in patients with TBI have not been examined. Therefore, we evaluated the risk factors of HP in patients with TBI and focused on lipid profiles. Fifty-six patients with TBI with mild to moderate injuries (Glasgow Coma Scale ≥9) who initially did not need surgical intervention were enrolled in this study. Patients underwent repeated computed tomography (CT) scans at 4 h and 24 h after injury. Magnetic resonance imaging (MRI) was performed 7 days after the initial injury. In each noncontrast CT scan, the hemorrhage volume was quantified using the ABC/2 technique. Clinical features, previous medical history, initial CT, and microbleeding on follow-up MRI were analyzed retrospectively. There were 31 (55%) patients in whom significant HP developed (volume30%). Current smoking (p=0.034), higher initial systolic blood pressure (p=0.035), and lower triglyceride levels (p=0.039) were significantly associated with HP. Current smoking and a triglyceride (TG) level150 mg/dL were the only statistically significant predictors of HP in the multivariate analysis (p=0.019, p=0.021, respectively). HP with TBI is common in patients who currently smoke and have lower TG levels (150 mg/dL). These patients should be monitored closely, and surgery may be considered before deterioration occurs.

Objective Intraarterial thrombolysis (IA-Tx) with stent retriever is accepted as an additional treatment for selected patients and the clinical benefit is well reported. Each intravenous tissue plasminogen activator administration (IV-tPA) and perfusion diffusion mismatching (P/D-mismatching) is well known the beneficial effects for recanalization and clinical outcomes. In this report, authors analyzed the clinical outcomes of additional IA-Tx with retrieval stent device, according to the combined IV-tPA and P/D-mismatching or not. Methods Eighty-one treated IA-Tx with the Solitaire stent retriever device, diagnosed as anterior circulation larger vessel occlusion were included in this study. Computed tomography-angiography (CTA) was done as an initial diagnostic image and acute stroke magnetic resonance image (MRI) followed after the IV-tPA. Forty-two patients were in the tPA group and 39 patients were in the non-tPA group. Recanalization rate, clinically significant hemorrhagic (sICH) and clinical outcomes were recorded according to the IV-tPA and P/D-mismatching. Results Recanalization rate was 81.0% in IV-tPA group, and it was 69.2% in non-tPA group (p = 0.017). While sICH were 19.9% and 25.6%, respectively (p = 0.328). Neurologic outcomes did not influence by IV-tPA administration or not. But according to the P/D-mismatching, the recanalization rate and sICH were 91.9% and 16.7% in the mismatched group and 46.7% and 46.7% in the matched group (p = 0.008 and p = 0.019, respectively). Conclusion For patients treated with IA-Tx with retrieval stent, IV-tPA infusion does not influence on the sICH, recanalization rate and neurologic outcomes. But P/D-mismatching was correlated well with sICH, recanalization rate and clinical outcomes.

To record diaphragm excursion via M-mode ultrasonography in stroke patients with dysphagia and determine whether they present reduced diaphragm excursion during voluntary cough compared with stroke patients without dysphagia and healthy subjects.Prospective cross-sectional study.University rehabilitation hospital.Acute stroke patients with dysphagia (n=23), acute stroke patients without dysphagia (n=24), and healthy control participants (n=27) (N=74).Not applicable.Diaphragm motions during quiet breathing, deep breathing, and voluntary coughing were recorded via ultrasonography using M-mode tracing (mm). Maximum inspiratory and expiratory pressures (cmH2O) and peak cough flow (L/min) during voluntary coughing were measured.The mean diaphragm movement (mm) of the hemiplegic side for all groups during quiet breathing, deep breathing, and voluntary coughing was 14.8±4.3, 17.6±4.8, and 20.9±3.7 (P.001); 23.8±7.1, 32.7±10.6, and 44.7±10.3 (P.001); and 16.8±4.8, 28.5±4.9, and 36.0±8.2 (P.001), respectively. The differences were statistically significant. Differences were observed in the maximum inspiratory (P.001) and expiratory (P.001) pressures and peak cough flow (P=.027) among the 3 groups. Forward selection stepwise regression analysis, which was performed to determine variables that help predict diaphragm excursion during voluntary coughing, showed that the presence of dysphagia explained up to 60% (P.001) of the hemiplegic diaphragm movement during voluntary coughing in patients with stroke.M-mode ultrasonography showed that stroke patients with dysphagia have decreased diaphragm excursion and compromised respiratory function during voluntary coughing.

National Surgical Adjuvant Breast and Bowel Project protocol C-08 tested the worth of adding 1 year of bevacizumab to oxaliplatin-based standard adjuvant chemotherapy regimen in the treatment of stage II/III colon cancer. Although the overall result was negative, the possibility that a molecularly defined subset could benefit from bevacizumab cannot be ruled out. We performed post hoc Cox regression analyses to test for marker-by-treatment interactions for standard pathological features and survival analyses using the Kaplan-Meier method. All statistical tests were two-sided and considered statistically significant at the .05 level. Patients diagnosed with mismatch repair defective (dMMR) tumors derived statistically significant survival benefit from the addition of bevacizumab (hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.29 to 0.94; P = .02) in contrast with no benefit in patients diagnosed with mismatch repair proficient tumors (HR = 1.03; 95% CI = 0.84 to 1.27; p = .78; P(interaction)= .04). Although a post hoc finding, this data suggests that a molecularly defined subset of colon cancer patients may derive clinical benefit from antiangiogenesis agents and underscores the need for independent validation in other clinical trials.

Purpose The purpose of this study was to assess the safety and early outcomes of the Pipeline device for large/giant or fusiform aneurysms. Materials and Methods The Pipeline was implanted in a total of 45 patients (mean age, 58 years; M:F=10:35) with 47 large/giant or fusiform aneurysms. We retrospectively evaluated the characteristics of the treated aneurysms, the periprocedural events, morbidity and mortality, and the early outcomes after Pipeline implantation. Results The aneurysms were located in the internal carotid artery (ICA) cavernous segment (n=25), ICA intradural segment (n=11), vertebrobasilar trunk (n=8), and middle cerebral artery (n=3). Procedure-related events occurred in 18 cases, consisting of incomplete expansion (n=8), shortening-migration (n=5), transient occlusion of a jailed branch (n=3), and in-stent thrombosis (n=2). Treatment-related morbidity occurred in two patients, but without mortality. Both patients had modified Rankin scale (mRS) scores of 2, but had an improved mRS score of 0 at 1-month follow-up. Of the 19 patients presenting with mass effect, 16 improved but three showed no changes in their presenting symptoms. All patients had excellent outcomes (mRS, 0 or 1) during the follow-up period (median, 6 months; range, 2-30 months). Vascular imaging follow-up (n=31, 65.9%; median, 3 months, range, 1-25 months) showed complete or near occlusion of the aneurysm in 24 patients (77.4%) and decreased sac size in seven patients (22.6%). Conclusion In this initial multicenter study in Korea, the Pipeline seemed to be safe and effective for large/giant or fusiform aneurysms. However, a learning period may be required to alleviate device-related events.

Therapeutic decision for adjuvant systemic therapy for breast cancer involves assessment of baseline risk and estimated benefit from systemic therapy. Molecular profiling studies have clearly demonstrated heterogeneity of chemotherapy response across different molecular subtypes of breast cancer. Meta-analyses of publicly available data from gene expression profiling studies have demonstrated that breast cancer can be divided into 4 basic categories based on expression levels of estrogen receptor (ER), HER2, and proliferation-associated genes; ER-, HER2+, ER+/HER2-/low proliferation, and ER+/HER2-/high proliferation. Notably ER- or HER2+ tumors are associated with high levels expression of proliferation genes, although there is a wide spectrum of expression levels of proliferation genes among ER+/HER2- tumors. Estrogen receptor-positive/HER2-/low-proliferation tumors are associated with a favorable prognosis. Synthetic lethal screening approach has demonstrated that most of the chemotherapeutic agents do not have specific molecular targets. Therefore, it could be hypothesized that chemosensitivity would be largely dictated by proliferation activity of tumor cells. Therefore, tumors with ER-, HER2+, or ER+/HER2-/high proliferation gene expression profile can be categorized as chemosensitive tumors, whereas ER+/HER-/low proliferation tumors categorized as chemoresistant. Therefore, clinical utility of gene expression profiling is mainly in aiding the chemotherapy decision for ER+ patients. Although evidence from prospective randomized clinical trials are lacking, because of the excellent baseline prognosis of patients with ER+/HER2-/low proliferation tumors when treated with endocrine therapy and because of scientific evidence of chemoresistance of these tumors, a comfort zone has been reached among oncologists to allow clinical use of gene expression tests to identify patients who do not require chemotherapy among node-negative ER+ patients. However, these tools are still probabilistic at best in their performances, and one cannot exactly predict which patient will have recurrence after assigned therapies until the time of recurrence. Therefore, strategies have to be established to identify patients who will fail standard chemoendocrine therapies among high-risk patients (ER+/HER2-/high proliferation, HER2+, or ER-) before recurrence events. Neoadjvant therapy can provide such venue because regardless of regimens used the prognosis of those achieving complete pathological response is excellent. Postneoadjuvant setting can be then used for patients with gross residual disease to test novel therapeutic agents.

Objective : Some neurosurgeons intentionally ligate the branches of the superficial temporal artery (STA) that are not used in standard STA-tomiddle cerebral artery (MCA) anastomosis for the purpose of improving the flow rate in the bypass graft. We investigated changes in bypass flow during temporary occlusion of such unused branches of the STA. Methods : Bypass blood flow was measured by a quantitative microvascular ultrasonic flow probe before and after temporary occlusion of branches of the STA that were not used for anastomosis. We performed measurements on twelve subjects and statistically assessed changes in flow. We also examined all the patients with digital subtraction angiography in order to observe any post-operative changes in STA diameter. Results : Initial STA flow ranged from 15 mL/min to 85 mL/min, and the flow did not change significantly during occlusion as compared with preocclusion flow. The occlusion time was extended by 30 minutes in all cases, but this did not contribute to any significant flow change. Conclusion : The amount of bypass flow in the STA seems to be influenced not by donor vessel status but by recipient vessel demand. Ligation of the unused STA branch after completion of anastomosis does not contribute to improvement in bypass flow immediately after surgery, and furthermore, carries some risk of skin necrosis. It is better to leave the unused branch of the STA intact for use in secondary operation and to

Objective: Endometrial adenocarcinoma has been proposed, due to frequent activation of the PI3K/AKT pathway, as a candidate neoplasm for treatment with mTOR inhibitors. However, data on the expression of mTOR in endometrial cancer are lacking. Study design: We used immunohistochemistry to evaluate the expression of pmTOR in 62 endometrial cancer surgical specimens. Results: The pmTOR protein was diffusely expressed in the cytoplasm of neoplastic epithelial cells, showing variable intensity. According to the chosen cutoff value, 34 (54.8%) out of 62 patients were scored as pmTOR-positive. pmTOR expression was significantly decreased in carcinomas with deep infiltration into the myometrium (P = .009), though it was not correlated with disease stage or lymph node metastasis. Univariate analysis showed that increased expression of pmTOR was significantly associated with better disease-free survival (P = .021). Conclusions: We show for the first time an association between pmTOR and better survival in patients with endometrial cancer. Future studies to stratify endometrial tumors by pmTOR status are needed.

Even though p16(INK4a) (p16) immunocytochemistry has proven a useful accessory tool verifying the identification of atypical squamous cells of undetermined significance (ASC-US) categorized smears, the procedure still has limitations. To date few studies examining the usefulness of p16 immunocytochemistry in atypical squamous cells which cannot exclude HSIL (ASC-H), compared with ASC-US in liquid-based cervical smears. Therefore, we examined the correlation of p16 immunocytochemical staining with follow-up biopsy results on ASC-H categorized smears and compared the data with those classified as ASC-US on 105 liquid-based cytology samples. We found no statistical significance in the p16 expression of ASC-US smears and the presence of squamous intraepithelial lesions (SIL) in follow-up biopsies (p = 0.546). However, p16 expression did significantly correlate with the presence of SIL (p = 0.002) in ASC-H smears. There was a statistically significant relationship between p16 expression and presence of high grade squamous intraepithelial lesions (HSIL) or more on the follow-up biopsies in both ASC-US (p = 0.012) and ASC-H (p < 0.001) categorized smears. In ASC-US categorized smears, there was no statistical significance between p16 expression and the HR-HPV viral load (p = 0.091). But there was a statistical significance between p16 expression and the HR-HPV viral load (p < 0.001) in ASC-H categorized smears. Our results indicate that p16 immunostaining is a much better useful marker for HR-HPV infection and detection of SIL in ASC-H categorized smears compared to those defined as ASC-US.

✓ The authors report two cases of stent fracture and restenosis after placement of a drug-eluting device in the vertebral artery (VA) origin, and describe management of restenosis with the stent-in-stent technique. Two women, one 62 and the other 67 years of age, underwent stent placement in the VA origin to treat symptomatic and angiographically significant stenosis in this vessel. Sirolimus-eluting coronary stents (Cypher) were used in both cases. Four months after placement of the devices, the symptoms recurred. Follow-up angiography performed 5 months after insertion of the devices revealed a transverse stent fracture with separation of the fragments and severe in-stent restenosis in both cases. The restenoses were treated with reinsertion of coronary stents (Cypher and Jostent FlexMaster) by using the stent-in-stent technique. After stent reinsertion, the patients exhibited relief of symptoms. This paper is the first report of fracture in a drug-eluting stent and restenosis after stent placement in the VA origin. Restenosis caused by such a fracture can be managed successfully by performing the stent-in-stent maneuver. The physical properties of metallic devices, stent strut geometry, and anatomical peculiarities of the subclavian artery may be associated with stent fractures. Earlier follow-up angiography studies (within 6 months) are warranted.

Background: The FCGR3A-158V and FCGR2A-131H alleles are referred to as favorable alleles with regards to trastuzumab response because the FCGR3A-V/V and FCGR2A-H/H genotypes have been associated with higher trastuzumab induced antibody-dependent cell-mediated cytotoxicity (ADCC) response in vitro. The objective of this study was to assess the interaction between these genotypes and the degree of benefit from trastuzumab in a phase III trial which demonstrated the benefit of adding trastuzumab to the standard adjuvant chemotherapy in the treatment of HER2-positive breast cancer (NSABP B-31). Methods: Genotypes for FCGR3A-158V/F and FCGR2A-131H/R alleles were determined in a representative cohort of NSABP clinical trial B-31 which included all available pre-treatment blood samples (N = 1251). Genotypes were determined by Typeplex chemistry and mass spectrometry on the Seqeunom platform. A custom nested PCR design was required to enable specific amplification of the FCGR3A gene due to the extensive homology between the FCGR3A and FCGR3B genes. Cox regression analyses were used to test for genotype-treatment interactions. Endpoint was disease free survival (DFS). Results: The genotyped cohort resembled the entire B-31 cohort based on clinical variables and the degree of benefit from trastuzumab. Results are summarized in the table. While there were trends for interaction between polymorphisms and trastuzumab for both genes, only FCGR3A-158 polymorphism reached statistical significance for interaction (p = 0.005). Conclusion: In NSABP B-31 there was a trend for benefit in the favorable genotypes of the FCGR2A-131 SNP, but only the favorable FCGR3A-158 genotypes showed a significant association with trastuzumab benefit with genotype-treatment interaction. However, polymorphism alone could not identify a subgroup with no benefit from trastuzumab, since even the patients with less favorable genotypes received significant benefit. Support: NCI U10-CA-12027, -69651, -37377, -69974. PA DOH disclaims responsibility for analysis, interpretations, or conclusions. Citation Format: Patrick G. Gavin, Nan Song, Nicole L. Johnson, Corey Lipchik, Seong-Rim Kim, Melanie Finnigan, Hanna Bandos, Jong-Hyeon Jeong, Joseph P. Costantino, Priya Rastogi, Edward H. Romond, Louis Fehrenbacher, Eleftherios P. Mamounas, Sandra M. Swain, D. Lawrence Wickerham, Charles E. Geyer, Jr., Norman Wolmark, Soonmyung Paik, Katherine L. Pogue-Geile. Association of the FCGR2A and FCGR3A genotypes with trastuzumab benefit in NSABP B-31. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT129. doi:10.1158/1538-7445.AM2015-CT129

Background: Tumor infiltrating lymphocytes (TILs) have demonstrated to be predictive of trastuzumab as well as chemotherapy benefit in adjuvant FinHER and neoadjuvant GeparQuattro phase III trials of trastuzumab in HER2-positive breast cancer patients (pts). Since TILs assessment is subject to inter-observer variations, we attempted to develop a surrogate gene expression signature of TILs and evaluate it as a potential predictive marker for the degree of benefit from trastuzumab plus standard adjuvant chemotherapy in NSABP B-31. Methods: Two hundred cases selected from the discovery cohort of B-31 with Affymetrix gene expression data were assessed for the percentage of TILs using International TILs Working Group guidelines. Gene set enrichment analysis (GSEA) was done to identify functionally enriched biologic pathways. Genes strongly associated with high TILs were identified (N = 119). Hierarchical clustering analysis of TILs signature was performed in Affymetrix gene expression data set from 731 cases randomly selected from B-31. Proportional hazard models were used to test the heterogeneity of degree of benefit from trastuzumab subgroups identified by TILs signature with disease-free survival as the end point. Results: Among 200 cases, 34 were classified as morphologic high (>50%) TILs. GSEA revealed that tumors with high TILs expressed up-regulation of genes in several immune activation pathways involving T and B cells. Tumors with low TILs had up-regulation of muscular, fibrous tissue, extracellular matrix, and estrogen receptor (ER) gene sets. ER status by immunohistochemistry (IHC) was also inversely associated with TILs (p = 0.002). Hierarchical clustering of genes most strongly associated with TILs identified a small subset (N = 86, 12%) out of 731 pts with high expression of TILs-associated genes and more benefit from trastuzumab (HR = 0.06, CI 0.01-0.47, p = 0.007) versus samples with low or intermediate TILs (HR = 0.57, CI 0.43-0.76, p Conclusions: High TILs are associated with high immune, low stromal, and low ER gene expression levels. Identification of a subgroup with increased benefit from trastuzumab in breast cancer confirms previous studies on TILs as another complementary predictive marker for trastuzumab benefit in HER2-positive breast cancer. Furthermore, our study provides a comprehensive gene expression analysis and its relationship to TILs in breast cancer. While the clinical utility of TILs or its gene expression signature is limited because even low TILs are associated with significant benefit from trastuzumab, they may prove to be useful as biomarkers for immunotherapy. Support NCI U10-CA-12027, -69651, -37377, -69974; PA U24-CA-114732; PA DOH disclaims responsibility for analysis, interpretations, or conclusions. Citation Format: Seong-Rim Kim, Patrick G. Gavin, Katherine L. Pogue-Geile, Nan Song, Melanie Finnigan, Hanna Bandos, Jong-Hyeon Jeong, Priya Rastogi, Edward H. Romond, Louis Fehrenbacher, Eleftherios P. Mamounas, Sandra M. Swain, D. Lawrence Wickerham, Charles E. Geyer, Joseph P. Costantino, Norman Wolmark. A surrogate gene expression signature of tumor infiltrating lymphocytes (TILs) predicts degree of benefit from trastuzumab added to standard adjuvant chemotherapy in NSABP (NRG) trial B-31 for HER2+ breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2837. doi:10.1158/1538-7445.AM2015-2837

Clinicopathological features of four cases of oncocytic adrenocortical carcinomas were studied. All tumors were large, circumscribed tumors with average size and weight of 11.5 cm and 586 g, respectively. The cut surfaces were yellow or brown and tan with areas of hemorrhage, necrosis, fibrosis, myxoid and cystic change. The tumor cells were exclusively oncocytic with a diffuse or compact and solid arrangement. Nuclear atypia was identified but mitosis was rare. Capsular invasion was identified in all tumors and vascular invasion was identified in one tumor. All tumors were immunoreactive for vimentin and inhibins. Immunoreactivity for pancytokeratin, synaptophysin and S-100 protein was variable and focal. All tumors had low proliferative indices, of less than 1%, and were negative for p53 protein. Ultrastructurally, the cytoplasm of tumor cells showed numerous mitochondria in a compact arrangement. Oncocytic adrenocortical carcinomas showed a similar sex ratio, slightly older mean age, similar left predilection, slightly smaller size and lighter weight compared with the conventional carcinomas. We suggest that most oncocytic adrenocortical carcinomas might be low-grade malignancies with less aggressive histological features compared with conventional carcinomas. However, they should be excised completely because of the likelihood of recurrence and metastasis during the follow-up period.

Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-01.

Fibrous polyp of the gallbladder is a rare variant of benign gallbladder polyp. Differentiation between a benign polyp and polypoid carcinoma of the gallbladder is often difficult when the polyp is more than 1 cm in diameter. We report a rare case of a large fibrous polyp of the gallbladder mimicking a carcinoma. A 44-year-old Korean woman who presented with abdominal pain was diagnosed with a large gallbladder polyp, measuring 1.26 cm in diameter, by abdominal ultrasonography. The lesion was echogenic with a nodular surface on ultrasonography, and showed contrast enhancement on computed tomography. Neither evidence of infiltration into the gallbladder wall nor lymph node enlargement was shown. The resected gallbladder showed a 1.2 × 0.8-cm-sized polyp with a nodular surface. Histologically, it showed a leaf-like configuration and loose or cellular connective stroma containing scattered duct-like structures, varying-sized vessels, and patchy infiltration of chronic inflammatory cells. Stromal cells were immunoreactive for vimentin and smooth-muscle actin and negative for S-100 protein and desmin. Large fibrous polyps of the gallbladder should be considered in the differential diagnosis of benign and malignant polypoid lesions of the gallbladder.

55 Background: The purpose of this study was to identify biomarkers that define a subset of patients who received benefit from bevacizumab (bev) in NSABP trial C-08, even though bev did not improve outcomes over standard adjuvant chemotherapy (CT) in the treatment of stage II and III colon cancer. Methods: A randomly selected cohort of C-08 cases (N=500) were profiled for whole genome expression (N=445) and for mutations (N=463) in KRAS, NRAS, PIK3CA, and MET. BRAF mutations and mismatch repair (MMR) status were profiled on the available cases (N=1,764 and 1,993, respectively). Cox proportional hazard models were used to assess prognosis and prediction for the value of bev using overall survival (0S) and time to recurrence (TTR) as end points. Results: The effect of bev was different for MMR deficient (MMR-d) and proficient tumors for OS (interaction p=.035) but not TTR (interaction p=.08). Patients with MMR-d (N=252) tumors showed a significant benefit from the addition of bev to CT for OS (hazard ratio =0.52 (95% CI: 0.29-0.94, p=0.028). KRAS, NRAS, PIK3CA, and MET were not significant for interaction with bev in the discovery cohort. BRAF mutations were associated with MMR status (p

1 Background: RS predicts outcome in node- and node+, ER+ pts treated with adjuvant endocrine therapy as well as benefit from adjuvant chemotherapy, with high RS receiving most of the benefit. We studied the prognostic impact of RS in node+, ER+ pts treated with adjuvant chemotherapy plus endocrine therapy as part of the NSABP B-28 trial. Methods: B-28 compared doxorubicin/cyclophosphamide (ACX4) with ACX4 followed by paclitaxel X4. Pts >50 yrs and those

Objective : Although a transradial angiography is accepted as the gold standard for cardiovascular procedures, cerebral angiography has been performed via transfemoral approach in most institutions. The purpose of this study is to present our experience concerning the feasibility, efficacy, and safety of a transradial approach to cerebral angiography as an alternative to a transfemoral approach. Methods : Between February 2007 and October 2009, a total of 1,240 cerebral angiographies were performed via a transradial approach in a single center. The right radial approach was used as an initial access route. The procedure continued only after the ulnar artery was proven to provide satisfactory collateral perfusion according to two tests (a modified Allen’s test and forearm angiography). Results : The procedural success rate was 94.8% with a mean duration of 28 minutes. All supra-aortic vessels were successfully catheterized with a success rate of 100%. The success rates of selective catheterization to the right vertebral artery, right internal carotid artery, left internal carotid artery, and left vertebral artery were 96.1%, 98.6%, 82.6% and 52.2%, respectively. The procedure was performed more than twice in 73 patients (5.9%), including up to 4 times in 2 patients. The radial artery occlusion was found in 4 patients (5.4%) on follow-up cerebral angiography, but no ischemic symptoms were observed in any of the cases. Conclusion : This study suggests that cerebral angiography using a transradial approach can be performed with minimal risk of morbidity. In particular, this procedure might be useful for follow-up angiographies and place less stress on patients. 10.3340/jkns.2010.47.5.332