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Rationale and Objectives Peer learning is a case-based group-learning model intended to improve performance. In this descriptive paper, we describe multi-institutional, multi-subspecialty, web-based radiology case conferences and summarize the participants’ experiences. Materials and Methods A semi-structured, 27-question survey was administered to radiologists participating in abdominal, cardiothoracic, and musculoskeletal case conferences. Survey questions included demographics, perceived educational value and challenges experienced. Survey question formats were continuous, binary, five-point Likert scale or text-based. The measures of central tendencies, proportions of responses and patterns were tabulated. Results From 57 responders, 12/57 (21.1%) were abdominal, 16/57 (28.1%) were cardiothoracic, and 29/57 (50.8%) were musculoskeletal conference participants; 50/56 (89.3%) represented academic practice. Median age was 45 years (range 35–74); 43/57 (75.4%) were male. Geographically, 16/52 (30.8%) of participants were from the East Coast, 16/52 (30.8%) Midwest, 18/52 (34.6%) West Coast, and 2/52 (3.8%) International. The median reported educational value was 5/5 (interquartile range 5–5). Benefits of the case conference included education (50/95, 52.6%) and networking (39/95, 41.1%). Participants reported presenting the following cases: “great call" 32/48 (66.7%), learning opportunity 32/48 (66.7%), new knowledge 41/49 (83.7%), “zebras” 46/49 (93.9%), and procedural-based 16/46 (34.8%). All 51/51 (100%) of responders reportedly gained new knowledge, 49/51 (96.1%) became more open to group discussion, 34/51 (66.7%) changed search patterns, and 50/51 (98%) would continue to participate. Reported challenges included time zone differences and support from departments for a protected time to participate. Conclusion Peer learning through multi-institutional case conferences provides educational and networking opportunities. Current challenges and desires include having department-supported protected time and ability to receive continuing medical education credit.

Highlights • Inflammatory pseudotumor are non-neoplastic tumors of the abdomen. • They may be large and invasive. • They may cause significant morbidity and mortality. • There is limited information in the literature about management., Introduction There is a wide differential diagnosis for intraabdominal tumors. Surgical resection and microscopic analysis of tissue structure can identify tumor origin in most cases. Most rapidly growing invasive tumors are neoplastic. Inflammatory pseudotumors are a subcategory of intraabdominal tumors that are non-neoplastic and can be rapidly growing. Urachal cysts originate from the dome of the bladder; however they are typically not invasive. There is limited literature on the appropriate management of these tumors. Presentation A 37-year-old female presenting with symptoms of abdominal pain was found to have a large intraabdominal mass invading multiple organs. Core biopsies demonstrated inflammation. The mass grew significantly over the course of a year and patient's abdominal pain worsened. The patient was taken to the operating room for resection. Final pathology revealed reactive fibrous tissue with acute and chronic inflammation invading bladder, urethra, abdominal wall, appendix, and ovary. Intraoperative frozen section demonstrated low grade spindle cells with concern for inflammatory pseudotumor but final pathology demonstrated inflammation. Discussion Although benign, these tumors cause significant morbidity due to their size and level of organ invasion. Management should involve surgical resection as well as potential post-operative chemotherapy or NSAIDs based off clinical picture. We demonstrate the importance of close follow up for residual disease or recurrence of patients with inflammatory pseudotumors of the abdomen. Conclusion This case highlights difficulties in diagnosis of a tumor that has potential to cause significant morbidity. There is need for further research to discover the best management after surgical resection of these tumors.

Highlights • Coat’s plus syndrome is a rare genetic condition. • Manifestations of this syndrome include ophthalmologic symptoms along with systemic manifestations such as gastrointestinal bleeding. • This case report demonstrates significant morbidity and ultimately mortality associated with this condition. • Further research is needed in this area to treat patients with GI bleeding in Coat’s plus syndrome., Introduction Coat’s plus syndrome is an extremely rare genetic syndrome that leads to a variety of symptoms. We are reporting a case of Coat's plus syndrome that had persistent GI bleeding and review of current literature. Presentation of case The patient is a female in her 40 s with a history of coat's disease and end stage renal failure on dialysis. The etiology of renal failure was not discovered, and the patient was being worked up for a kidney transplant. The patient required admission after deterioration of nutritional status with a BMI of 14.3. During admission the patient initially had intermittent GI bleeding requiring weekly blood transfusions. On work up of the GI bleed, no etiology was identified either. As a result persistent negative GI bleed work up, we pursued alternative diagnoses. The history of Coat’s disease prompted us to work up the patient for Coat's plus syndrome. A genetic test confirmed the presence of CTC-1 gene mutation, which results in Coat's plus syndrome. With no treatment available as of yet, the patient continued to deteriorate into multi-organ failure. Discussion We present an example of GI bleeding in Coat's plus syndrome, only identified thru genetic testing, that is very rare and complex in nature. Despite numerous workups, no specific etiology was identified for the GI bleeding. Conclusion Previous reports have not investigated cause of GI bleeding, since it is extremely rare in the literature. Further investigation is warranted to understand cause and effects of GI bleeding in this rare genetic disease.

OBJECTIVE Carotid body tumors (CBTs), extraadrenal paragangliomas, are extremely rare neoplasms in children that often require multimodal surgical treatment, including preoperative anesthesia workup, embolization, and resection. With only a few cases reported in the pediatric literature, treatment paradigms and surgical morbidity are loosely defined, especially when carotid artery infiltration is noted. Here, the authors report two cases of pediatric CBT and provide the results of a systematic review of the literature. METHODS The study was divided into two sections. First, the authors conducted a retrospective review of our series of pediatric CBT patients and screened for patients with evidence of a CBT over the last 10 years (2007–2017) at a single tertiary referral pediatric hospital. Second, they conducted a systematic review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of all reported cases of pediatric CBTs to determine the characteristics (tumor size, vascularity, symptomatology), treatment paradigms, and complications. RESULTS In the systematic review (n = 21 patients [includes 19 cases found in the literature and 2 from the authors’ series]), the mean age at diagnosis was 11.8 years. The most common presenting symptoms were palpable neck mass (62%), cranial nerve palsies (33%), cough or dysphagia (14%), and neck pain (19%). Metastasis occurred only in 5% of patients, and 19% of cases were recurrent lesions. Only 10% of patients presented with elevated catecholamines and associated sympathetic involvement. Preoperative embolization was utilized in 24% of patients (external carotid artery in 4 and external carotid artery and vertebral artery in 1). Cranial nerve palsies (cranial nerve VII [n = 1], IX [n = 1], X [n = 4], XI [n = 1], and XII [n = 3]) were the most common cause of surgical morbidity (33% of cases). The patients in the authors’ illustrative cases underwent preoperative embolization and balloon test occlusion followed by resection, and both patients suffered from transient Horner’s syndrome after embolization. CONCLUSIONS Surgical management of CBTs requires an extensive preoperative workup, anesthesia, and multimodal surgical management. Due to a potentially high rate of surgical morbidity and vascularity, balloon test occlusion with embolization may be necessary in select patients prior to resection. Careful thorough preoperative counseling is vital to preparing families for the intensive management of these children. ABBREVIATIONS BTO = balloon test occlusion; CBT = carotid body tumor; CN = cranial nerve; ECA = external carotid artery; ICA = internal carotid artery; MIBG = iodine-123-meta-iodobenzylguanidine; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Toca 511, a clinical-stage tumor-selective retroviral replicating vector (RRV) encoding an optimized yeast cytosine deaminase (CD) prodrug activator gene, in combination with Toca FC (extended-release 5-fluorocytosine (5-FC)), produces 5-fluorouracil (5-FU) within infected cancer cells, which in preclinical models has also been shown to kill immunosuppressive myeloid cells in the tumor microenvironment, leading to anti-cancer immune activation and long-term survival. This combination treatment is under evaluation in a registrational Phase 3 trial in patients with recurrent high-grade glioma. Here, we investigated the feasibility of applying Toca 511 & Toca FC to medulloblastoma, the most common malignant tumor of the pediatric nervous system. Established (HDMB03, DAOY) and primary (PDX10) human medulloblastoma cells were transduced with RRVs encoding either Emerald green fluorescent protein reporter (RRV-EMD) or the CD enzyme (RRV-CD, i.e. Toca 511). RRV replication in vitro, examined by flow cytometry for EMD fluorescence, showed spread to >90% of cells in culture by day 10 post-inoculation. In contrast to non-transduced or RRV-EMD-transduced controls, RRV-CD-transduced medulloblastoma cells exhibited significant dose-dependent reduction of viability upon exposure to 5-FC, as measured by MTS assay. In vivo, stereotactic intracerebellar implantation of HDMB03 cells into nude mice without treatment resulted in cell dose-dependent median survival time and eventual 100% lethality at all cell doses tested, with median survival of 28 days after implantation of 1x10^5 tumor cells. In this orthotopic medulloblastoma model, mice with RRV-CD-transduced intracerebellar HDMB03 tumors exhibited long-term survival upon 5-FC treatment, as compared to mice treated with PBS or implanted with non-transduced cells (p=0.00007). No deaths occurred in these mice with RRV-CD-transduced HDMB03 tumors while on sequential cycles of 5-FC prodrug, until prodrug treatment was stopped, after which 25% long-term survival was observed (median survival 110 days). The results of this proof-of-concept study support further preclinical investigation of RRV-CD-mediated prodrug activator gene therapy for this pediatric malignancy.

Toca 511, a clinical-stage tumor-selective retroviral replicating vector (RRV), encodes optimized yeast cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU) within infected cancer cells. In preclinical models of intracerebral glioblastoma, 5-FU generated locally by Toca 511 (RRV-CD) prodrug activator gene therapy has also been shown to kill immunosuppressive myeloid cells in the tumor microenvironment, leading to anti-cancer immune activation and long-term survival. Early-phase clinical trials of Toca 511 in recurrent high-grade glioma showed highly promising evidence of therapeutic benefit, leading to a Phase III trial completed in late 2019 (n=400 patients, randomized 1:1 vs. standard chemotherapy), which appeared to show negative results overall. However, additional analysis showed possible efficacy in prespecified subgroups, and further clinical investigation is being pursued. In preclinical studies, we have also evaluated RRV for use in medulloblastoma, the most common malignant tumor of the pediatric nervous system. Both established and primary human medulloblastoma cell lines supported efficient RRV replication in vitro, with spread to >90% of cells by day 10 post-inoculation, and RRV-CD-transduced medulloblastoma cells showed significant dose-dependent reduction of viability upon exposure to 5-FC, compared to controls. In an intracerebellar HDMB03 medulloblastoma model, RRV-CD-treated mice exhibited long-term survival while on sequential cycles of 5-FC prodrug, until prodrug treatment was stopped, after which 25% long-term survival was observed (median survival 110 days) as compared to controls (median survival 28 days, 100% lethality) (p=0.00007). These results support further evaluation of RRV-mediated prodrug activator gene therapy for pediatric brain tumors.

Toca 511, a clinical-stage retroviral replicating vector (RRV) encoding an optimized yeast cytosine deaminase (CD) prodrug activator gene, in combination with Toca FC (extended-release 5-fluorocytosine (5-FC)), is designed to produce 5-FU which kills cancer cells and immune-suppressive myeloid cells in the tumor microenvironment, leading to anti-cancer immune activation and long-term survival. This combination treatment is currently under evaluation in an international Phase 2/3 trial in patients with recurrent high-grade glioma. In the present study, we investigated the feasibility of further applying Toca 511 & Toca FC in medulloblastoma, the most common malignant tumor of the pediatric nervous system. Aggressive chemotherapy regimens increase survival in children with this disease; however, systemic toxicity limits efficacy. Here we have initiated the first preclinical studies to evaluate RRV-mediated prodrug activator gene therapy in medulloblastoma. Human medulloblastoma cell lines (HDMB03, DAOY) or patient-derived primary medulloblastoma cells were transduced with RRVs encoding either Emerald green fluorescent reporter (RRV-EMD) or the CD enzyme (RRV-CD). RRV replication in vitro, examined by flow cytometry for EMD fluorescence, showed spread to >90% of cells in culture by day 10 post-inoculation. In contrast to non-transduced or RRV-EMD-transduced controls, RRV-CD-transduced medulloblastoma cells exhibited significant dose-dependent reduction of viability upon exposure to 5-FC, as measured by MTS assay. In vivo, stereotactic intracerebellar implantation of non-transduced HDMB03 cells into nude mice resulted in cell dose-dependent median survival time and eventual 100% lethality at all cell doses tested. In this orthotopic medulloblastoma model, mice with RRV-CD-transduced intracerebellar HDMB03 tumors demonstrated increased survival upon 5-FC treatment, as compared to mice treated with PBS or implanted with non-transduced cells. These results support further investigation of RRV-CD-mediated prodrug activator gene therapy for this pediatric malignancy.