Hemangioma

PRIMARY OBJECTIVES: I. To evaluate the relationship between 18F-FSPG PET/computed tomography (CT), pathology, and cancer metabolism in patients with suspected hepatocellular carcinoma (HCC) scheduled for liver resection surgery and orthotopic liver transplant (OLT). II. To compare 18F-FSPG PET/CT with standard-of-care (SOC) diagnostic MRI imaging in patients with suspected HCC scheduled for liver resection surgery or OLT. III. To compare the uptake of 18F-FSPG PET/CT with 11C-acetate PET/CT AND 18F-FDG PET/CT in suspected HCC and background liver in patients scheduled for liver resection surgery or OLT. IV. To evaluate uptake of 18F-FSPG PET/CT in benign liver lesions compared to background. V. To evaluate uptake of 18F-FSPG PET/CT in malignant non-HCC liver tumors. OUTLINE: Patients undergo 18F-FSPG PET and either carbon-11 (11C)-acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.

The aim of this study is to develop a comprehensive 10-minute protocol based on function and myocardial tissue characterization without the need for contrast injection, which can be standardized for 70% of cardiac patients. To test this 10-minute CMR protocol for its ability to significantly improve diagnostic decision-making and to reduce cost. To test its clinical feasibility, performance and cost-effectiveness in different populations including: Non-ischemic cardiomyopathies (-)OS-CMR and Ischemic Heart Disease and CAD (+)OS-CMR

Hemangiomas affect 5-10% of all children born in the United States and up to 20% of premature infants, with a higher incidence in girls. Most infantile hemangiomas (IHs) appear within a few weeks of birth, grow rapidly for months to years and eventually involute. "Benign neglect" (no treatment) is therefore recommended by most pediatricians. However, about 1/3 of cases (2-3% of all children born in the US) eventually require medical or surgical interventions for hemangiomas due to blocked vision, problems with breathing, feeding, pain, ulceration, infection, profuse bleeding or disfigurement. None of the interventions are benign. Occasionally, hemangiomas may be fatal. The broad objective of this study is to prevent injury and disfigurement of millions of children per year by developing a very safe, effective, and non-invasive treatment that inhibits the growth of cutaneous hemangiomas in newborns. Historically, pulsed dye laser has been known to bea very effective and safe treatment for hemangiomas; however, this treatment modality has not been studied for the treatment of very early hemangiomas. Recently, systemic beta-blockade with propanolol has also shown remarkable results in treating threatening hemangiomas. However, systemic propanolol is not benign and requires inpatient monitoring for cardiac side effects. Topical beta-blocker has been demonstrated in a case report to prevent the growth of infantile eyelid hemangioma. We propose a prospective, single blinded, randomized study of pulsed dye laser (PDL) and topical beta-blocker solution (timolol maleate ophthalmic gel forming solution) in the treatment of very early hemangiomas. Specifically the efficacy, side effects and outcome of PDL and timolol will be compared with no treatment, the present standard of care for early stage hemangiomas. The extent to which early laser treatment or topical timolol treatment prevents tumor growth and the need for future medical or surgical treatments will be determined. Infants will be recruited from the pediatric and neonatal practices at Massachusetts General Hospital, and randomized to receive either: (1) a series of weekly to semi-weekly laser treatments, (2) twice daily topical application of timolol ophthalmic gel-forming solution for six weeks, or (3) no treatment. Hemangiomas will be assessed clinically and with digital photography for serial repeated measures of hemangioma size at each study visit. A panel of blinded evaluators will also provide assessment from photographs. Response, side effects and need for additional treatments will be recorded for up to 2 years after PDL and topical timolol treatment. This clinical trial fills a large gap in evidence-based medical therapy for IHs. If indeed early laser treatment of hemangiomas with PDL or topical timolol, both relatively harmless treatments, can eliminate the potential for complications by treating hemangiomas prior to the growth phase, then this trial would present an attractive solution for the problem of when and how to treat.

The aim is to describ rare primary hepatic cancers clinical, histological and radiological features, to obtain a biological tumor and blood collection, and to evaluate the efficacy of treatments received in clinical practice in order to determine optimal therapeutic sequences.

The objective of this study is to evaluate the benefit of Karl Storz curved (11508AAK) and straight (11506AAK) fetoscopes for in-utero surgery. The investigators will assess the surgical outcomes, short and long-term morbidity, complications, and gestational age of participants who undergo intrauterine procedures with these devices. The scopes will be used to assist in intrauterine procedures across a variety of fetal conditions, such as TTTS (twin-twin transfusion syndrome), TAPS (twin anemia polycythemia sequence), sFGR (selective fetal growth restriction) or TRAP sequence (twin reversed arterial perfusion). Fetoscopic laser photocoagulation (FLP) can also be used during in-utero surgery to correct abnormal vessels in cases like chorioangioma or vasa previa. Other complex congenital anomalies may require fetal intervention or diagnostic fetoscopy using Storz scopes. Improvements in the technique, experience and equipment have been associated with better maternal, fetal, and neonatal outcomes in fetal surgery. Smaller fetoscopes are associated with lower rates of premature delivery following FLP. New fetoscopes (11508AAK and 11506AAK) have the potential to improve visualization and the photocoagulation angle. Compared to alternative scopes, these Storz scopes provide a wider angle of view and are longer, enabling better reach to distant areas at the edge of the placenta, especially in cases of higher BMI, higher gestational age, and significant polyhydramnios. This study is an un-blinded, non-randomized, single arm, feasibility study on a convenience cohort to demonstrate the role of a curved fetoscope device (11508AAK) or straight fetoscope device (11506AAK) among in-utero surgeries. Patients will be enrolled in a consecutive manner and all qualifying, patients who agreed to the use of the curved or straight fetoscopes will be enrolled in the study. Outcome data will be reported as a descriptive statistical analysis. The curved fetoscope (11508AAK) device will be used in monochorionic pregnancies with an anterior placenta requiring in-utero surgery, while the straight fetoscope (11506AAK) will be used in monochorionic pregnancies with a posterior placenta. This device is classified as a significant risk device because it is of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject.

TARGET-VM is a modular open-label, signal seeking, phase II trial of targeted therapies for patients with vascular malformations. Patients with vascular malformations which are refractory to standard therapies, or in whom standard therapy is not appropriate, are potentially eligible for the clinical trial. Vascular malformations will be classified as slow-flow or fast-flow lesions using established clinical criteria. Genetic testing to identify causative variants in genes affecting the phosphoinositide 3-kinase (PI3K) signalling pathway for slow-flow vascular malformations or the Mitogen-Activated Protein Kinase (MAPK) signalling pathway for fast-flow vascular malformations must be performed using research protocols or commercial testing assays that are external to this clinical trial. The study consists of individual modules, each evaluating the clinical efficacy of 48 weeks of targeted therapy. The treatment modules are: 1. Module 1 - Treatment for slow-flow vascular malformations Eligible patients with slow-flow vascular malformations with an identified causative variant in the PI3K signalling pathway will receive alpelisib, an oral alpha-specific PI3-kinase inhibitor for a total duration of 48 weeks as monotherapy (treatment period), followed by 24 weeks of follow-up (follow-up period). 2. Module 2 - Treatment for fast-flow vascular malformations Eligible patients with fast-flow vascular malformations with an identified causative variant in the MAPK signalling pathway will receive mirdametinib, an investigational oral MEK inhibitor for a total duration of 48 weeks as monotherapy (treatment period), followed by 24 weeks of follow-up (follow-up period). TARGET-VM will be conducted only in Victoria, Australia.

Infantile hemangioma (IH) is the most common benign tumor in infants, with an estimated prevalence of 4%-5%. Although most IH resolves over time without serious sequelae, a significant proportion can lead to serious complications such as ulcers. Propranolol is considered to be an effective treatment modality for ulceration IH, and there are retrospective studies suggesting that starting treatment at a low dose is safe and effective. However, due to the lack of prospective study, the effectiveness of different doses of propranolol for initiating treatment of ulceration IH is unknown. Therefore, a prospective study of ulceration IHs in Chinese children was conducted to clarify its efficacy.

\[Study Population and Sample Size\] This is an exploratory, prospective, multicenter study. A predefined sample size is not required. With an estimated enrollment of approximately 100 cases per institution over one year and participation of four institutions, approximately 400 cases are expected. \[Eligibility Criteria\] Eligible participants are adults aged 19 years or older with a focal hepatic lesion ≥1 cm that has been definitively diagnosed or is expected to be diagnosed within one month after FLI examination, and who provide informed consent. Patients unable to hold their breath for at least 5 seconds, those with inadequate B-mode image quality, lesions \<1 cm on ultrasound, or without definitive diagnosis within one month are excluded. \[Reference Standard\] The reference standard for lesion diagnosis was defined as follows: hepatic hemangiomas were confirmed by histopathology or by typical imaging features with size stability for at least two years; hepatocellular carcinoma was confirmed by histopathology or by the presence of an LR-5 lesion in patients with liver cirrhosis; all other hepatic lesions (including metastasis, cholangiocarcinoma, adenoma, focal nodular hyperplasia, and angiomyolipoma) required histopathological confirmation. \[Study Design and Statistical Analysis\] After informed consent, FLI is performed on the target lesion. FLI maps are anonymized and independently reviewed by four readers, each classifying findings as positive or negative. The primary endpoint is comparison of FLI-positive proportions between hemangioma and non-hemangioma groups using chi-square or Fisher's exact tests. Interreader agreement will be evaluated using Fleiss' kappa. The secondary endpoint of this study is to explore how the diagnostic performance of FLI for hepatic hemangioma varies according to lesion echogenicity and lesion depth. Continuous variables will be analyzed using Student's t-test or Mann-Whitney U test, as appropriate. A p-value \< 0.05 will be considered statistically significant.

While vascular anomalies are rare diseases, they can be life-threatening and devastating to affected children and their families. Advances in diagnosis, monitoring and therapies will be significantly improved if non-invasive biomarkers that are sensitive and specific can be identified. Obtaining a tissue biopsy to help in diagnosis can actually worsen the disease and so identification of specific blood biomarkers is highly desirable. Studies will measure angiogenic factors in serum and plasma samples at baseline and on therapy. Tissue removed during surgical resection or blood removed prior to sclerotherapy will be used to obtain cells and tissue for the assessment of where biomarkers are coming from and to identify disease-causing pathways for new therapeutic targeting.

Rare Diseases (RD) pose a health challenge due to their complexity and low prevalence, generating a burden in terms of morbidity and mortality and costs. The fragmentation of data on these diseases makes it difficult to understand them comprehensively. Therefore, the creation of a macro institutional registry that brings together information on RD would facilitate research in this field. The registries are organized systems of systematic data collection of a large number of patients quickly and efficiently on a particular disease at a given time. The main difficulty of the registries is the guarantee of the quality of their data. The main objectives of the registry are: Understand risk factors and prognosis. Evaluate the diagnostic and therapeutic comparison with current standards. Advance knowledge of the disease to optimize the assessment, treatment and monitoring of patients. Analyze the effectiveness of new therapies. Studying differences between populations. Quickly estimate the morbidity, mortality and resource utilization associated with a disease entity. Examine the course of a disease Formulate novel hypotheses for further prospective studies.