Citations

OBJECTIVE Tobacco smoking is among the factors known to significantly augment the risk of untreated intracranial aneurysm (IA) growth and rupture. Smoking appears to have a variable effect on different endovascular treatment modalities. The impact of smoking on the safety, efficacy, and outcomes of Woven EndoBridge (WEB) device use for wide-neck IAs has not been evaluated. This study aimed to investigate the outcomes of WEB devices by smoking status. METHODS A retrospective multicenter analysis was conducted on the data of patients from 36 sites worldwide treated with the WEB device for intracranial saccular aneurysms. Patients were stratified based on smoking status (current, former, and never smokers). The Student t-test and chi-square test were performed for continuous and categorical variables, respectively. Multivariable logistic regression was used to adjust for confounders. RESULTS Of 1376 patients with available smoking status, 504 were current smokers, 358 were former smokers, and 514 were never smokers. Upon adjusting for significant confounders, no association was found between smoking and recurrence outcomes (OR 1.39, 95% CI 0.69–2.80; p = 0.36), thromboembolic and hemorrhagic complications, and mortality among IAs treated with the WEB device. There was no statistically significant difference in outcomes between former and never smokers (OR 1.23, 95% CI 0.70–2.18; p = 0.46). The location of aneurysms differed between smoking groups, with former smokers having more anterior circulation aneurysms compared with current and never smokers (99.0% vs 96.9% vs 95.3%; p = 0.01). In terms of clinical symptoms, headache and dizziness were more common in the never smokers compared with current and former smokers (13.9% vs 8.9% vs 7.7%, p = 0.01). CONCLUSIONS This large-scale study suggests no significant correlation between smoking and the recurrence of IAs treated with the WEB device. Biological studies are warranted to better understand the biological impact of smoking on the growth and rupture of treated IAs.

OBJECTIVE The Woven EndoBridge (WEB) device is an intrasaccular flow disruptor designed for wide-necked bifurcation aneurysms. These aneurysms may require the use of a concomitant stent. The objective of this study was to determine the clinical and radiological outcomes of patients undergoing stent-assisted WEB treatment. In addition, the authors also sought to determine the predictors of a concomitant stent in aneurysms treated with the WEB device. METHODS The data for this study were taken from the WorldWideWEB Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups based on treatment: stent-assisted WEB and WEB device alone. The authors compared clinical and radiological outcomes of both groups. Univariable and multivariable binary logistic regression analyses were performed to determine factors that predispose to stent use. RESULTS The study included 691 intracranial aneurysms (31 with stents and 660 without stents) treated with the WEB device. The adequate occlusion status did not differ between the two groups at the latest follow-up (83.3% vs 85.6%, p = 0.915). Patients who underwent stenting had more thromboembolic (32.3% vs 6.5%, p < 0.001) and procedural (16.1% vs 3.0%, p < 0.001) complications. Aneurysms treated with a concomitant stent had wider necks, greater heights, and lower dome-to-neck ratios. Increasing neck size was the only significant predictor for stent use. CONCLUSIONS This study demonstrates that there is no difference in the degree of aneurysm occlusion between the two groups; however, complications were more frequent in the stent group. In addition, a wider aneurysm neck predisposes to stent assistance in WEB-treated aneurysms.

Background The Woven EndoBridge (WEB) device is a novel intrasaccular flow disruptor tailored for bifurcation aneurysms. We aim to describe the degree of aneurysm occlusion at the latest follow-up, and the rate of complications of aneurysms treated with the WEB device stratified according to rupture status. Methods Our data were taken from the WorldWideWeb Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups: ruptured and unruptured. We compared clinical and radiologic outcomes of both groups. Propensity score matching (PSM) was done to match according to age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up. Results The study included 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device. The PSM analysis had 55 pairs. In both the unmatched (85.8% vs 84.3%, p=0.692) and matched (94.4% vs 83.3%, p=0.066) cohorts there was no significant difference in the adequate occlusion rate at the last follow-up. Likewise, there were no significant differences in both ischemic and hemorrhagic complications between the two groups. There was no documented aneurysm rebleeding after WEB device implantation. Conclusion There was no significant difference in both the radiologic outcomes and complications between unruptured and ruptured aneurysms. Our findings support the feasibility of treatment of ruptured aneurysms with the WEB device.

Abstract Rationale: Appendiceal mucocele is a rare entity of mucinous cystic dilatation of the appendix. It has no typical clinical presentation and is considered a potentially premalignant condition. Patient concerns: We present a case of accidental intraoperative finding of an appendiceal mucocele in a 54-year old woman that clinically presented with an exacerbated chronic tubo-ovarian abscess. Diagnoses: Trans-vaginal ultrasonography showed an encapsulated, oval, unilocular mass above the uterus with a heteroechogenic structure, homogeneous fluid content, and smooth regular walls without inner proliferation. The histopathologic diagnosis was consistent with an appendiceal cystadenoma. Interventions: The patient underwent a simple appendectomy. Outcomes: There were no clinical, biochemical or imaging signs of the disease recurrence at 6 months follow up. Lessons: To our knowledge, this is the only well-documented case of appendiceal mucocele mimicking exacerbated chronic tubo-ovarian abscess reported in the literature. Awareness of a rare entity such as an appendiceal mucocele, which is frequently misdiagnosed as a potential cause of acute abdomen, is necessary for the appropriate management strategy in order to prevent complications.

The breast is a rare site for metastases, and their molecular characteristics have not been studied yet. Intrinsic molecular genetics, cancer characteristics, and breast tissue immune responses in diverse metastases to the breast have not been previously studied. We identified 64 patients with cancers metastatic to the breast: 51 carcinomas and 13 melanomas. Programmed death ligand 1 (PD-L1), steroid receptors, and HER2/neu expressions were evaluated using immunohistochemistry. Gene sequencing, copy number alterations, microsatellite instability, and tumor mutational burden were performed using next-generation sequencing platforms. The 3 most common primary sites for metastatic carcinomas were lung (37%), ovary (29%), and fallopian tubes/peritoneum (14%). TP53 mutations were commonly (50%) observed among the carcinoma cases, while other mutations were characteristic for the primary cancers (VHL in renal, BRCA1 in the fallopian tube, and BRAF in melanomas). High tumor mutational burden was detected in 5/14 carcinomas and 3/7 melanomas. Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells’ expression of PD-L1 was seen in 17 carcinomas and 6 melanomas. Estrogen receptor status was positive in 13/49 carcinomas including 12 adenocarcinomas originating from the ovary and fallopian tube or peritoneum and 1 duodenal neuroendocrine carcinoma. No carcinoma was HER2/neu positive. Intrinsic genetic characteristics of the metastases to the breast followed the pattern commonly seen in primary tumors. Biomarkers of potential benefit to immune checkpoint inhibition therapy were limited to PD-L1-positive non–small cell lung cancer. No common characteristics of the heterogeneous group of tumor metastases to this organ were identified.

Abstract Introduction: Breast metastases from non-mammary carcinomas are very rare and the molecular characteristics of these metastases have not been studied. Due to the uniqueness of this type of metastases, we evaluated whether there was any molecular or immunologic similarities among the patients with metastases to the breast. Patients and Methods: Fifty-one patients with metastatic carcinomas to the breast (49 female and 2 male) were identified in the files of Caris Life Sciences (Phoenix, AZ). Average age at presentation was 57 years (range, 20-90 years). Immunohistochemistry for PD-L1 was performed using SP142 (Ventana) or 22c3 (DAKO) antibodies; 592 genes sequencing (n=47), DNA microsatellite instability (MSI) (n=6) and total mutational burden (TMB) (n=14) were obtained from a next generation sequencing platform (Illumina). Results: Three most common primary sites were lung (19, 37%), ovary (15, 29%) and fallopian tubes/peritoneum (7, 14%). Ten metastases (20%) demonstrated neuroendocrine differentiation. When 1% cutoff was applied, tumor cells PD-L1 expression was detected in 10 cases (20%), and immune cells expression of PD-L1 in 19 patients (37%). Three cases (6%) had PD-L1 staining in both cancer and infiltrating immune cells. 50% of the cases exhibited mutations in TP53 gene, while other mutated genes followed the pathways typically seen in their primary sites (e.g. VHL in renal carcinomas, BRCA1 in fallopian tube carcinoma). Total mutational burden was high (≥10 mutations/Mb) in five out of 14 successfully analyzed cases (36%) and no case (0%) exhibited high microsatellite instability. Interestingly, estrogen receptor status was positive in 13/49 patients (26.5%) including 12 adenocarcinomas originating from ovary, Fallopian tube or peritoneum and one duodenal neuroendocrine. No tumor was HER2 positive. Conclusions: Metastases to the breast proved to be heterogeneous but there were molecular, endocrine and immunologic findings that yielded information that could be used to make therapeutic decisions which including the use of new immunotherapeutic strategies. Citation Format: Gatalica Z, Senarathne W, Vranic S, Pockaj BA. Profiling of metastatic carcinomas to the breast for the biomarkers of immuno-oncology therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-27.

Abstract Introduction: Malignant phyllodes tumors are rare breast malignancies (0.1% of all breast tumors) with limited effective treatment options for recurrent and metastatic disease. Recent trials indicated a potential for anti-angiogenic therapy in soft tissue sarcomas, which led us to investigate these pathways. Materials and Methods: Thirty-five malignant phyllodes tumors (including two cases with matched primary and metastatic tumors) were profiled using gene sequencing (Next-generation and Sanger), gene copy number analysis (in-situ hybridization), whole genome RNA expression, and protein expression (immunohistochemical assay). Results: RNA microarray assay showed consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin2, VCAM1, PDGFRA, PTTG1, and CYP3A5 in all cases analyzed (n=5). No mutations in KDR (VEGFR2) were detected (0/26). EGFR protein overexpression was observed in 25/26 (96%) of cases with amplification of the EGFR gene in 8 cases (33%). EGFR gene mutations were identified in 2 cases (8%) including one case with presumed pathogenic V774M mutation and one case with EGFRvIII mutation. The most common mutations included those of TP53 (50%) and PIK3CA (15%) while other mutations (BRCA1, BRCA2, RET, CDH1, MLH1, ATM) were rare affecting single phyllodes cases. Two cases with matched primary and metastatic cancers harbored the same mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Conclusions: Comprehensive multiplatform profiling approach to phyllodes tumors identifies various molecular alterations of which some are potentially actionable. Our data suggests that anti-angiogenic therapy may also be effective in patients with malignant phyllodes tumor. Evaluation of EGFR pathway discovered consistent protein over-expression but rare activating mutations, which necessitates refinement in patient selection targeting these pathways. Citation Format: Gatalica Z, Vranic S, Ghazalpour A, Xiu J, Ocal I, McGill J, Bender R, Discianno E, Sanati S, Reddy S, Pockaj B. Comprehensive multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-19.