Management of hepatic artery aneurysm: A case series.

Hepatic artery aneurysms are rare, but their diagnosis is important because of high mortality and complications. Common risk factors for developing these aneurysms include hypertension, vascular disease, pancreatitis, diabetes, tobacco use, autoimmune diseases, and previous transplantation. Frequent imaging for trauma and tumor surveillance has increased the incidence of naive hepatic aneurysms. These aneurysms can be difficult to manage, and it can be challenging to decide the correct treatment modality for the patient. Hereby, we present four cases of hepatic artery aneurysm and discuss various treatment options. Patient 1 suffered from a proper and right hepatic artery aneurysm discovered incidentally; repaired with an endovascular intervention later complicated by an endoleak which was further managed by another stenting. Patient 2 had a common hepatic artery aneurysm followed with serial imaging without any intervention. Patient 3 had a hepatic artery aneurysm and liver mass diagnosed concurrently. The patient underwent an open surgical repair of his aneurysm with graft and liver resection which was complicated later with rupture of aneurysm followed by surgical bypass repair. Patient 4 suffered from a large hepatic artery aneurysm causing bile duct compression. Her aneurysm was repaired open with splenic artery grafting. Patients were managed from careful observation to surgery with different outcomes.

Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer.

Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as melanoma, smoking-induced lung cancers and bladder cancer-with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary1-7. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers8-11. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins-SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.

Tumor- and Neoantigen-Reactive T-cell Receptors Can Be Identified Based on Their Frequency in Fresh Tumor.

Adoptive transfer of T cells with engineered T-cell receptor (TCR) genes that target tumor-specific antigens can mediate cancer regression. Accumulating evidence suggests that the clinical success of many immunotherapies is mediated by T cells targeting mutated neoantigens unique to the patient. We hypothesized that the most frequent TCR clonotypes infiltrating the tumor were reactive against tumor antigens. To test this hypothesis, we developed a multistep strategy that involved TCRB deep sequencing of the CD8(+)PD-1(+) T-cell subset, matching of TCRA-TCRB pairs by pairSEQ and single-cell RT-PCR, followed by testing of the TCRs for tumor-antigen specificity. Analysis of 12 fresh metastatic melanomas revealed that in 11 samples, up to 5 tumor-reactive TCRs were present in the 5 most frequently occurring clonotypes, which included reactivity against neoantigens. These data show the feasibility of developing a rapid, personalized TCR-gene therapy approach that targets the unique set of antigens presented by the autologous tumor without the need to identify their immunologic reactivity. Cancer Immunol Res; 4(9); 734-43. ©2016 AACR.

Pheochromocytoma Screening Initiation and Frequency in von Hippel-Lindau Syndrome.

CONTEXT: Patients with von Hippel-Lindau (VHL) syndrome have a 25-30% chance of developing pheochromocytoma. Although practice guidelines recommend biochemical and radiological screening every 1-2 years for pheochromocytoma in patients with VHL, there are limited data on the optimal age and frequency for screening. OBJECTIVE: Our objective was to determine the earliest age of onset and frequency of contralateral and recurrent pheochromocytomas in patients with VHL syndrome. METHODS: This is a retrospective analysis of a prospective cohort of patients with VHL enrolled in a natural history study. RESULTS: A total of 273 patients diagnosed with VHL were enrolled in a natural history clinical study. Thirty-one percent (84) were diagnosed with pheochromocytoma. The mean age of diagnosis was 28.8 ± 13.9 years. The earliest age at diagnosis was 5.5 years. Median follow-up for the cohort was 116.6 months (range, 0.1-613.2). Ninety-nine percent (83) of patients underwent adrenalectomy. Fifty-eight and 32% of patients had metanephrines and/or catecholamines elevated more than two times and more than four times the upper limit of normal, respectively. Twenty-five percent (21) of pheochromocytomas were diagnosed in pediatric patients younger than 19 years of age, and 86% and 57% of pediatric patients had an elevation more than two times and more than four times upper limit of normal, respectively. Eight patients had a total of nine recurrences. The median age at recurrence was 33.5 years (range, 8.8-51.9). Recurrences occurred as short as 0.5 years and as long as 39.7 years after the initial operation. CONCLUSIONS: Our findings among VHL pediatric patients supports the need for biochemical screening starting at age 5 with annual lifelong screening.

Nonoperative management of pediatric aortic injury with seat belt syndrome.

"Seat belt syndrome" was first described by Garret and Braunstein in 1962. The syndrome involves skin and abdominal wall ecchymosis (seat belt sign) intra-abdominal solid organ and visceral injuries, as well as Chance fractures (compression and/or wedging deformity of the anterior portion of the vertebral body with disruption or fracture of the posterior elements, generally at L1-L3). We present a case of a 12-year-old male involved in a high-speed motor vehicle collision wearing only a lap belt resulting in seat belt syndrome, with disruption of the abdominal wall, mesenteric avulsion with multiple intestinal perforations, abdominal aortic dissection, and an L2 Chance fracture with cord transection. Intraoperative decision making is outlined with this scenario of complex injuries, and the literature of seat belt syndrome associated with blunt aortic injuries and its management is reviewed.

Update on the surgical management of Paget's disease.

Mammary Paget's disease is a rare form of breast neoplasm that often presents with a pruritic eczema-like rash involving the nipple-areolar complex, and is refractory to common remedies. It is often associated with underlying breast cancer, and is sometimes difficult to diagnose. In this review, we present an update of the approach to Paget's disease and its surgical treatment.