RESUMEN
Thymoma is a rare type of malignancy but is considered one of the most common neoplasms that occur in the anterior mediastinum. A large proportion of thymomas are associated with paraneoplastic syndromes, such as myasthenia gravis. Whenever feasible, the standard of care for the treatment of thymoma should focus on the control of paraneoplastic syndromes, surgical resection, and adjuvant therapy if appropriate. A 36-year-old female patient with a significant past medical history of obesity and iron deficiency anemia who underwenten bloc resection of thymoma three months prior now presented to the benign hematology clinic to establish care for the management of anemia. Upon review of systems, the patient incidentally reported fatigue, weakness with repetitive motion, occasional blurred vision, headaches, and exertional dyspnea. Physical examination was positive for horizontal nystagmus. Given the patient's history and clinical findings, suspicion of myasthenia gravis was high. Further work-up demonstrated anti-acetylcholine receptor titers of 5.70 nmol/L (normal < 0.21 nmol/L), supporting a diagnosis of myasthenia gravis in this patient. She was subsequently started on pyridostigmine. Often, patients with thymoma experience paraneoplastic syndrome-related symptoms prior to thymectomy, and in many cases thymectomy is curative. However, in the case presented, we examine a patient that was asymptomatic prior to surgery and subsequently reported the onset of symptoms following what we suspect was an exacerbation due to general anesthesia and pain control medications. We argue that all patients with thymoma should undergo systematic evaluation and treatment of paraneoplastic syndromes, regardless of clinical symptoms and prior to surgery, in order to improve patient quality of life and hospital outcomes.
RESUMEN
BACKGROUND: Immune-related adverse events (irAEs) are secondary reactions related to treatment with immune checkpoint inhibitors (ICIs). There have been six cases published reporting on an association between patients undergoing treatment with ICIs and the occurrence of acquired thrombotic thrombocytopenic purpura (TTP). CASE REPORT: We report a 61-year-old male receiving treatment with chemoimmunotherapy followed by pembrolizumab maintenance therapy for advanced non-small-cell lung cancer, presenting with bleeding symptoms, anemia, and thrombocytopenia. The patient received pembrolizumab seven times in total, in three-week cycles. Laboratory testing demonstrated hemolytic anemia, which, in combination with other findings, suggested thrombotic microangiopathy (TMA). PLASMIC scoring and specialized testing with ADAMTS13 activity and inhibitor confirmed a diagnosis of TTP. The patient was started on therapy with plasmapheresis and glucocorticoids, resulting in clinical improvement. The patient chose to leave the hospital under the care of home hospice and died approximately one month after being discharged. CONCLUSIONS: Of the six cases of ICI-induced TTP, only one other was treated with pembrolizumab to our knowledge to date. Our patient experienced an adverse reaction marked by thrombocytopenia and hematuria after drug exposure. With symptom improvement after ICI discontinuation and recurrence on readministration, a presumptive diagnosis of ICI-associated TTP was made. This case report and literature review emphasize the need for close observation of patients undergoing ICI therapy for potential rare irAEs. The further investigation aimed at the study of risk factors, disease severity, and treatment response to this form of secondary TTP is needed to guide treatment decisions.
RESUMEN
BACKGROUND: Aberrant expression of small noncoding endogenous RNA molecules known as microRNAs (miRNAs) is documented to occur in multiple cancer types including esophageal adencarcinoma (EAC) and its only known precursor, Barrett's esophagus (BE). Recent studies have linked dysregulation of specific miRNAs to histological grade, neoplastic progression and metastatic potential. MATERIALS AND METHODS: Herein, we present a summary of previously reported dysregulated miRNAs in BE and EAC tissues as well as EAC cell lines and evaluate a cranberry proanthocyanidin rich extract's (C-PAC) ability to modulate miRNA expression patterns of three human EAC cell lines (JHEso-Ad-1, OE33 and OE19). RESULTS: A review of 13 published studies revealed dysregulation of 87 miRNAs in BE and EAC tissues, whereas 52 miRNAs have been reported to be altered in BE or EAC cell lines, with 48% overlap with miRNA changes reported in tissues. We report for the first time C-PAC-induced modulation of five miRNAs in three EAC cell lines resulting in 26 validated gene targets and identification of key signaling pathways including p53, angiogenesis, T-cell activation and apoptosis. Additionally, mutiple cancer related networks were ideintified as modulated by C-PAC utilizing Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein Analysis Through Evolutionary Relationships (PANTHER), and MetaCore analysis tools. CONCLUSIONS: Study results support the cancer inhibitory potential of C-PAC is in part attributable to C-PAC's ability to modify miRNA profiles within EAC cells. A number of C-PAC-modulated miRNAs have been been identified as dysregulated in BE and EAC. Further insights into miRNA dysregulation and modulation by select cancer preventive agents will support improved targeted interventions in high-risk cohorts.
