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Item Adult Diffuse Hepatic Hemangiomatosis: A Rare Cause of Dilated Cardiomyopathy and Sudden Cardiac Arrest(Springer, Part of Springer Science+Business Media, 2014-01) Supakul, Rodjawan; Vakili, Saeed T.; Liangpunsakul, Suthat; Department of Medicine, IU School of MedicineItem Association of Demographic Factors and Infantile Hemangioma Characteristics With Risk of PHACE Syndrome(American Medical Association, 2021) Cotton, Colleen H.; Ahluwalia, Jusleen; Balkin, Daniel M.; Frieden, Ilona J.; Haggstrom, Anita N.; Castelo-Soccio, Leslie A.; Liy-Wong, Carmen; Pope, Elena; Steiner, Jack E.; Siegel, Dawn H.; Fernandez-Faith, Esteban; Morel, Kimberly D.; Lauren, Christine T.; Garzon, Maria C.; Mancini, Anthony J.; Chamlin, Sarah L.; Tollefson, Megha M.; Liang, Marilyn G.; Delano, Sophia; Glick, Sharon A.; Hogeling, Marcia; Barrio, Victoria R.; PHACE Retrospective Study Group; Dermatology, School of MedicineImportance: A 2010 prospective study of 108 infants estimated the incidence of PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome to be 31% in children with facial infantile hemangiomas (IHs) of at least 22 cm2. There is little evidence regarding the associations among IH characteristics, demographic characteristics, and risk of PHACE syndrome. Objectives: To evaluate demographic characteristics and comorbidities in a large cohort of patients at risk for PHACE syndrome and assess the clinical features of large head and neck IH that may be associated with a greater risk of a diagnosis of PHACE syndrome. Design, setting, and participants: This multicenter, retrospective cohort study assessed all patients with a facial, head, and/or neck IH who were evaluated for PHACE syndrome from August 1, 2009, to December 31, 2014, at 13 pediatric dermatology referral centers across North America. Data analysis was performed from June 15, 2017, to February 29, 2020. Main outcomes and measures: The main outcome was presence or absence of PHACE syndrome. Data included age at diagnosis, sex, patterns of IH presentation (including size, segment location, and depth), diagnostic procedures and results, and type and number of associated anomalies. Results: A total of 238 patients (mean [SD] age, 2.96 [4.71] months; 184 [77.3%] female) were included in the analysis; 106 (44.5%) met the criteria for definite (n = 98) or possible (n = 8) PHACE syndrome. A stepwise linear regression model found that a surface area of 25 cm2 or greater (odds ratio [OR] 2.99; 95% CI, 1.49-6.02) and involvement of 3 or more locations (OR, 17.96; 95% CI, 6.10-52.85) to be statistically significant risk factors for PHACE syndrome. Involvement of the parotid gland (OR, 0.39; 95% CI, 0.18-0.85) and segment S2 (OR, 0.38; 95% CI, 0.16-0.91) was associated with a lower risk. Race and ethnicity may also be associated with PHACE syndrome risk, although more studies are needed. Conclusions and relevance: This cohort study further described factors associated with both a higher and lower risk of PHACE syndrome. The presence of multiple anatomical sites and large surface area were associated with greater risk, whereas S2 or parotid IHs were associated with lower, but still potential, risk. These findings can help in counseling families and decision-making regarding evaluation of infants with large head and neck IHs.Item CT and MRI imaging and interpretation of hepatic arterioportal shunts(AME Publishing Company, 2019-05-21) Wang, Qiushi; Koniaris, Leonidas G.; Milgrom, Daniel P.; Patel, Aash; Hu, Maoqing; Cui, Enming; Deng, Yu; Akisik, Fatih; Radiology and Imaging Sciences, School of MedicineHepatic arterioportal shunts (HAPS) occur due to organic or functional fistulization of blood flow between arterial hepatic vasculature and venous portal systems. It is a type of hemodynamic abnormality of the liver being observed increasingly with the use of temporal imaging modalities. HAPS occur due to other underlying hepatic abnormalities including the presence of an underlying tumor or malignancy. When a HAPS is present, the appearance of these abnormalities on imaging studies suggests an underlying abnormality, must be considered atypical even if asymptomatic, and warrants careful evaluation. Over time, and as a function of degree of fistulae, symptoms and potential life-threatening complications may arise from the HAPS. These systemic complications may include the development of portal hypertension, splenomegaly, as well as accelerated metastasis in patients with malignant tumors. This manuscript reviews common underlying conditions associated with HAPS and their radiologic interpretation.Item Incidental adrenal hemangioma clinically suspicious for malignancy: diagnostic considerations and review of the literature(e-Century Publishing, 2022-11-15) Toklu, Ani; Mesa, Hector; Collins, Katrina; Pathology and Laboratory Medicine, School of MedicineAdrenal hemangiomas are rare lesions often found incidentally during unrelated diagnostic work-up. We report a case of a 67-year-old man with history of hypertension, hyperlipidemia, anemia, arthralgia, joint swelling and unexplained weight loss, which prompted imaging studies. Computed tomography scan revealed a 5.4 cm adrenal mass. The patient had no clinical manifestations of adrenal medullary or cortical hyperfunction. Urine and plasma metanephrines and aldosterone/renin ratio were within normal range. The patient was taking prednisone for hand and ankle swelling, precluding assessment for Cushing syndrome. Given the size of the lesion, the possibility of malignancy was considered, and the patient elected for surgical management. The left adrenalectomy specimen weighed 54 g and revealed a 4.9 cm tan-brown mass with congested cut surface and a thin rim of residual adrenal gland parenchyma. Histologic examination showed thick and thin-walled vessels intermingled with adrenocortical elements at the periphery characteristic of a hemangioma. Surgical resection is the mainstay treatment for large, isolated adrenal masses to exclude malignancy and prevent retroperitoneal hemorrhage. Herein, we report a case of adrenal hemangioma, review a variety of other diagnostic considerations occurring in the adrenal gland, and highlight useful distinguishing features to assist in accurate diagnosis.Item Mapping of Segmental and Partial Segmental Infantile Hemangiomas of the Face and Scalp(American Medical Association, 2021) Endicott, Alyson A.; Chamlin, Sarah L.; Drolet, Beth A.; Mancini, Anthony J.; Siegel, Dawn H.; Vitcov, Sterling; Mathes, Erin F.; Frieden, Ilona J.; Haggstrom, Anita N.; Dermatology, School of MedicineImportance: Recognizing segmental infantile hemangioma (IH) patterns is important for risk stratification and provides clues to pathogenesis. Previously, segmental hemangiomas were mapped to 4 facial regions, 3 corresponding to known facial metameres. Objectives: To refine existing maps of facial segmental IHs, examine so-called indeterminate hemangiomas as they relate to known segmental patterns, and define a novel pattern of segmental scalp hemangiomas. Design, setting, and participants: This retrospective cohort study was conducted at 4 pediatric dermatology centers (University of California, San Francisco; Indiana University; Medical College of Wisconsin; and Northwestern University/Ann & Robert H. Lurie Children's Hospital of Chicago) using photographic archives of patients younger than 12 years with segmental and indeterminate hemangiomas on the face and scalp. Clinical images were used to map hemangioma distribution onto standardized facial templates. Heat map densiometry identified recurrent patterns that were compared with previously published patterns of facial segmental hemangiomas. Patterns of indeterminate hemangiomas were compared with those of segmental hemangiomas. Data collection took place in 2017, and analysis took place from 2017 to 2019. Main outcomes and measures: Distribution and patterning of segmental and indeterminate IHs of the face and scalp. Results: A total of 549 IHs were mapped. The borders of the frontotemporal (S1) and frontonasal (S4) segments agreed with previous segmental maps; however, the maxillary (S2) and mandibular (S3) segment borders differed with respect to the preauricular skin. In contrast with previous reports, preauricular skin segregated with the mandibular (S3) rather than the maxillary (S2) segment. Indeterminate hemangiomas occurred within and respected the same borders as segmental hemangiomas. Hemangiomas on the lateral scalp commonly occurred in a C shape extending from the posterior auricular region. Conclusions and relevance: This cohort study provides an updated map of facial segmental IHs with redefined maxillary (S2) and mandibular (S3) segment borders. It provides evidence that indeterminate hemangiomas are partial segmental hemangiomas respecting anatomic boundaries of their larger segmental counterparts. A newly recognized C-shaped pattern of segmental scalp hemangioma is reported.Item Tissue nanotransfection causes tumor regression by its effect on nanovesicle cargo that alters microenvironmental macrophage state(Elsevier, 2023) Gordillo, Gayle M.; Guda, Poornachander Reddy; Singh, Kanhaiya; Biswas, Ayan; Abouhashem, Ahmed S.; Rustagi, Yashika; Sen, Abhishek; Kumar, Manishekhar; Das, Amitava; Ghatak, Subhadip; Khanna, Savita; Sen, Chandan K.; Roy, Sashwati; Surgery, School of MedicineExtracellular vesicles (EVs) are nanovesicles released by all eukaryotic cells. This work reports the first nanoscale fluorescent visualization of tumor-originating vesicles bearing an angiogenic microRNA (miR)-126 cargo. In a validated experimental model of lethal murine vascular neoplasm, tumor-originating EV delivered its miR-126 cargo to tumor-associated macrophages (TAMs). Such delivery resulted in an angiogenic (LYVE+) change of state in TAM that supported tumor formation. Study of the trafficking of tumor-originating fluorescently tagged EV revealed colocalization with TAM demonstrating uptake by these cells. Ex vivo treatment of macrophages with tumor-derived EVs led to gain of tumorigenicity in these isolated cells. Single-cell RNA sequencing of macrophages revealed that EV-borne miR-126 characterized the angiogenic change of state. Unique gene expression signatures of specific macrophage clusters responsive to miR-126-enriched tumor-derived EVs were revealed. Topical tissue nanotransfection (TNT) delivery of an oligonucleotide comprising an anti-miR against miR-126 resulted in significant knockdown of miR-126 in the tumor tissue. miR-126 knockdown resulted in complete involution of the tumor and improved survival rate of tumor-affected mice. This work identifies a novel tumorigenic mechanism that relies on tumorigenic state change of TAM caused by tumor-originating EV-borne angiomiR. This disease process can be effectively targeted by topical TNT of superficial tumors.