Long-term outcome analysis of Y90 radioembolization in hepatocellular carcinoma.

Background: Yttrium-90 (Y90) radioembolization is a catheter-based therapy for hepatocellular carcinoma (HCC). Multiple trials have evaluated the efficacy of Y90 in HCC; however, few have assessed long-term hepatic function. This study aimed to evaluate a clinical real-world experience of Y90 effectiveness and long-term impact on hepatic function. Methods: A single-center retrospective chart review was performed for patients with Child-Pugh (CP) class A or B who received Y90 for primary HCC between 2008 and 2016. Model for end-stage liver disease (MELD) and CP scores were calculated on the day of treatment and 1, 3, 6, 12, and 24 months post-procedure. Results: Of the 134 patients included, the mean age was 60 years old and median overall survival (OS) from date of diagnosis was 28 months [95% confidence interval (CI): 22.21-38.05]. Patients with CP class A (85%) had a median progression-free survival (PFS) of 3 months (95% CI: 2.99-5.55) and median OS of 17 months (95% CI: 9.59-23.10) from date of Y90 treatment compared to a median PFS of 4 months (95% CI: 2.07-8.28) and OS of 8 months (95% CI: 4.60-15.64) for patients with CP class B. MELD scores were significantly higher post-treatment than pre-treatment, with significant recovery at 24 months. No significant differences were seen between cancer stage and OS, while PFS and cancer stage did show difference between cancer stage 1 and 3 with longer median PFS seen in stage 1. Conclusions: While our study supports the literature for OS in Y90-treated patients, we found a shorter PFS in this population. This may reflect the differences between the utilization of RECIST in clinical trials and clinical radiology practice in determining progression. Significant factors associated with OS were age, MELD, CP scores and portal vein thrombosis (PVT). For PFS, CP score and stage at diagnosis were significant. Increasing MELD scores over time likely reflected a combination of radioembolization-induced liver disease, liver decompensation or progression of HCC. The downtrend at 24 months is likely due to long term survivors with significant benefit from therapy with no long-term complications from Y90.

Refractory Immune Thrombocytopenic Purpura with Abdominal Splenosis: A Complex Case.

Immune thrombocytopenia (ITP) is an acquired thrombocytopenia resulting from immune-mediated platelet destruction via antiplatelet antibodies and T cells. Medical management of ITP includes corticosteroids and multiple other adjunct therapies, with splenectomy generally being reserved for severe, refractory cases. In this clinical case report, we describe the evaluation of a 35-year-old male with a history of prior traumatic splenic injury who presented to the emergency department endorsing easy bruising and a petechial rash, ultimately found to have severe thrombocytopenia. The patient was diagnosed with primary ITP that proved to be refractory to a number of first- and second-line medical therapies. His course was complicated by the presence of abdominal splenosis discovered at the time of planned splenectomy and intra-abdominal hemorrhage requiring splenic artery embolization thereafter. To our knowledge, this is one of few published cases of ITP complicated by abdominal splenosis, highlighting the need to consider splenosis and the presence of accessory splenic tissue in cases of refractory ITP.

Extreme hyperferritinemia without associated HLH in a patient with T-cell lymphoma.

Extreme hyperferritinemia has historically been associated with a short list of rare diagnoses, including hemophagocytic lymphohistiocytosis (HLH). However, hyperferritinemia is not specific for HLH in the adult population. Among other more common causes, T-cell lymphoma and other malignancies warrant evaluation prior to considering more rare diagnoses.

IgA Nephropathy Secondary to Ipilimumab Use.

Ipilimumab is a human monoclonal antibody targeting cytotoxic T-lymphocyte-associated protein 4 approved for the treatment of non-small-cell lung cancer (NSCLC) and other malignancies. Despite a high prevalence of other immune-related adverse events (irAEs), checkpoint inhibitor (CPI)-related nephrotoxicity has been reported less frequently. In this clinical case report, we describe the evaluation of a 70-year-old female with stage IV NSCLC who presented with nephrotic range proteinuria 4 weeks after receiving her first cycle of ipilimumab. She underwent a renal biopsy and was found to have IgA nephropathy that was presumed to be secondary to ipilimumab use, given recent initiation of therapy and clinical history. Unfortunately, despite prompt initiation of corticosteroids, her acute kidney injury progressed and she required hemodialysis, later transitioning to hospice. To our knowledge, this is one of few reported cases of IgA nephropathy secondary to CPI use. With increasing use of CPIs, this case further emphasizes the need for continued surveillance for irAEs, which can occur at any point in a patient's treatment course.

Drug-induced immune-mediated thrombocytopenia secondary to durvalumab use.

Immunotherapy is an expanding area of cancer treatment with significant promise. Despite their efficacy, checkpoint inhibitors are associated with a number of immune-related adverse events; here, we described thrombocytopenia secondary todurvalumab.

Myeloid Cell Infiltration Correlates With Prognosis in Cholangiocarcinoma and Varies Based on Tumor Location.

Cholangiocarcinoma (CC) is an uncommon malignancy with increasing incidence and dismal prognosis. We conducted a comprehensive analysis of the CC tumor immune microenvironment (TIME) based on tumor location to identify therapeutic targets. We hypothesized that the TIME of CC would vary by primary tumor location and that high tumor infiltration by CD8+ T cells and low infiltration by M2 macrophages would be associated with improved survival. A retrospective analysis was conducted of 99 CC tumor samples surgically resected between 2000 and 2014. Tissue microarrays were constructed from each tumor and stained by immunohistochemistry for 24 markers of immune cells, immune activation or inhibition, programmed cell death-ligand 1, and mesothelin. Most tumors were amply infiltrated with by CD4+, CD8+, and FoxP3+ T cells, as well as by myeloid cells. Mesothelin expression ≥1+ by immunohistochemistry was found in 68% of tumors. We identified higher densities of M1 macrophages in primary distal extrahepatic CC, as well as metastatic lesions. Mesothelin expression was also significantly higher in distal extrahepatic CC. There was no association with survival of infiltration by CD4+, CD8+, or FoxP3+ T cells, mesothelin expression, or programmed cell death-ligand 1 percentage expression, however, high CD14+ myeloid cells and high CD163+ M2 macrophages were associated with worse survival. In conclusion, the CC TIME is a heterogenous milieu highly infiltrated by innate and adaptive immune cells, which differs based on primary tumor location and between primary tumors and metastatic lesions. The correlation of intratumoral M2 macrophages and myeloid cells with a worse prognosis may suggest promising immunotherapeutic targets in CC.

Extracorporeal Membrane Oxygenation in Severe Acute Eosinophilic Pneumonia.

Acute Eosinophilic Pneumonia (AEP) is a potentially fatal cause of hypoxemic respiratory failure characterized by fever, diffuse bilateral pulmonary infiltrates, and pulmonary eosinophilia. Shown to be associated with a number of environmental exposures and lifestyle choices, AEP has a good prognosis when diagnosed early and treated with corticosteroids. In this clinical case report, we detail the presentation, evaluation, diagnosis, and management of a 40-year old male who presented to the emergency department with dyspnea, chills, and diaphoresis. He had a history of pulmonary embolism 8 years prior but was otherwise healthy, though he had re-started smoking cigarettes a week prior to presentation. Initial chest CT scan revealed widespread mixed groundglass and solid airspace opacities; over the next 12 hours, he rapidly decompensated and after not responding to other invasive mechanical ventilation, was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO). Bronchoalveolar lavage later revealed pulmonary eosinophilia, and after an infectious workup was negative, a diagnosis of AEP was reached and the patient was started on corticosteroids. To our knowledge, this is one of few published cases of AEP requiring V-V ECMO for clinical stabilization, highlighting the utility of this treatment modality in severe disease.

A Chromosomal Deletion and New Frameshift Mutation Cause ARSACS in an African-American.

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a rare, progressive, neurodegenerative disease characterized by ataxia, spasticity and polyneuropathy. First described in the French-Canadian population of Quebec in 1978, ARSACS has since been identified in multiple patients worldwide. In this clinical case report, we describe the evaluation of an 11-years-old African-American male who presented to neuromuscular clinic for assessment of a gait abnormality. He had a history of gross motor delay since early childhood, frequent falls and a below average IQ. Chromosomal microarray revealed a 1.422 megabase loss in the 13q12.12 region, which includes the SACS gene. Next Generation Sequencing then showed a novel, predicted to be pathogenic missense mutation (c.11824dup) of this gene. His clinical presentation and neurological imaging further confirmed the diagnosis of ARSACS. To our knowledge, this is the first reported case of this disease in the African-American population of the United States. This case report further highlights the growing trend of identifying genetic diseases previously restricted to single, ethnically isolated regions in many different ethnic groups worldwide.