A novel outpatient regimen in management of fluoropyrimidine-induced cardiotoxicity.

INTRODUCTION: Fluoropyrimidines (FP) are cornerstone drugs in the treatment of gastrointestinal (GI) malignancies. Cardiotoxicity secondary to an FP chemotherapy is a serious complication. There are no standardized guidelines on the treatment of FP induced cardiotoxicity which may result in interruption and even discontinuation of life saving treatment. We present our experience in FP rechallenge using a novel outpatient regimen based on our "up-front" triple agent antianginal protocol. METHODS: We report the retrospective study of the patients with suspected FP induced cardiotoxicity. Patients meeting the criteria were selected by C3OD (curated cancer clinical outcomes database) at Kansas University Medical Center (KUMC). We identified all patients with gastrointestinal malignancies who had suspected FP induced cardiotoxicity from January 2015 to March 2022. We then included the patients who were rechallenged with planned fluoropyrimidine regimen utilizing the three drug KU-protocol. We utilized a novel regimen by repurposing the already FDA-approved anti-anginal drugs in a manner that minimizes the risk of hypotension and bradycardia. RESULTS: In this retrospective study, 10 patients with suspected fluoropyrimidine induced cardiotoxicity were included from January-2015 to March-2022 at KUMC. Out of 10 patients who were rechallenged utilizing KU-protocol, eight patients (80%) were able to complete the previously planned fluoropyrimidine regimen. None of the patients required ER visits or hospital admission due to cardiac symptoms during the rechallenge utilizing the KU-protocol. CONCLUSIONS: Utilizing our novel outpatient regimen, we have successfully and safely allowed re-challenge of FP chemotherapy with good tolerability and completion of the intended course of chemotherapy without recurrent morbidity.

Vanishing Bile Duct Syndrome in the Presence of Hodgkin Lymphoma.

Vanishing bile duct syndrome (VBDS) is an acquired condition characterized by the destruction and loss of intrahepatic bile ducts resulting in cholestasis. VBDS has been described in various conditions including neoplastic and immunologic disorders, infections, hepatic ischemia, and drug toxicity. The diagnosis is confirmed by liver biopsy revealing the loss of interlobular bile ducts in greater than 50% of portal tracts. Prognosis is variable and often unpredictable but appears to be influenced by the etiology of bile duct destruction and overall patient health. VBDS has been described as a rare paraneoplastic process in patients with Hodgkin lymphoma. This case describes a 26-year-old female who presented with a neck mass, jaundice, and pruritus. Initial workup revealed direct hyperbilirubinemia, transaminitis, elevated alkaline phosphatase, and elevated international normalized ratio. She went on to receive a diagnosis of stage II classical Hodgkin lymphoma, nodular sclerosing subtype, and biopsy-proven VBDS. Over the course of chemotherapy, complete metabolic resolution of Hodgkin lymphoma and complete normalization of bilirubin were achieved. She was given gemcitabine and cyclophosphamide as a liver sparing regimen initially with some improvement in liver function tests and a reduction in lymph node volumes. She received six cycles of adriamycin/bleomycin/vinblastine/dacarbazine (ABVD) with complete remission attained after four cycles by positron emission tomography/computed tomography criteria. This report illustrates asafe chemotherapy regimen in the presence of marked liver dysfunction. Workup for VBDS including liver biopsy should be pursued in Hodgkin lymphoma patients with evidence of cholestasis in the absence of extrahepatic bile duct damage or other known etiology of liver injury.

Nivolumab Use for First-Line Management of Hepatocellular Carcinoma: Results of a Real-World Cohort of Patients.

BACKGROUND: Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis. First-line multikinase inhibitors like sorafenib and lenvatinib are poorly tolerated and have low response rates. Several clinical trials have shown tolerability and efficacy of immunotherapy in this setting. The objective of this retrospective study was to determine the outcomes of front-line nivolumab in a frail real-world population. OBSERVATIONS: In this retrospective study conducted between January 2016 and December 2019, 14 men (median age, 63.5 years; range, 58-72 years) with HCC received nivolumab as front-line systemic therapy. Only 2 patients had a response to immunotherapy (14.3%), of which 1 patient had a complete response (7.1%). The median progression-free survival was 4 months and median overall survival was 8 months. Incidence of grade 3 or higher toxicity was 35%. CONCLUSIONS: In our small, real-world cohort of patients receiving immunotherapy as front-line systemic treatment for HCC, outcomes were poor with front-line immunotherapy.

Anti-n-Methyl-d-Aspartate-Receptor (NMDAR) Encephalitis in Association with Ovarian Teratoma.

Anti-N-methyl-D-aspartate-Receptor (NMDAR) encephalitis is an autoimmune disorder with a multifaceted presentation that involves memory deficits, psychiatric symptoms, and autonomic instability. This case report describes the classic presentation of Anti-NMDAR encephalitis and highlights its association with ovarian teratomas. We present a 26 -year-old female who came in with new onset seizures and altered mentation who subsequently developed automatism. Electroencephalograms (EEG) showed left frontal spikes and right temporal delta activity. Magnetic resonance imaging (MRI) revealed right temporal hyper-intensity. The diagnosis was established with positive anti-NMDAR antibodies in the cerebrospinal fluid (CSF). The patient was initially treated with steroids and valproic acid, however, her condition progressively worsened. A five-day course of intravenous immunoglobulins (IVIG) was started followed by rituximab. The clinical course was complicated with the patient developing neutropenic fever and cerebrospinal fluid cultures (CSF) growing methicillin-sensitive Staphylococcus aureus (MSSA). She underwent pelvic imaging which showed a right ovarian teratoma. Evidence suggests that removal of ovarian tumor leads to better clinical and mortality outcomes in patients with Anti-NMDAR encephalitis. It is important for the internist to consider paraneoplastic syndromes in patients with Anti-NMDAR encephalitis.

Life-Threatening Thrombocytopenia Secondary to Trimethoprim/Sulfamethoxazole.

Thrombocytopenia is an uncommon side effect of trimethoprim/sulfamethoxazole (TMP/SMX) when given in the usual recommended adult dosage. We report a case of severe and possibly life-threatening thrombocytopenia associated with TMP/SMX therapy. A 92-year-old female presented after a mechanical fall and subsequent intractable bleeding from a laceration on her left leg. She had a history of cellulitis of the lower extremities treated with a 10-day course of TMP/SMX. Her last dose was two days before the visit. The physical examination was significant for a small laceration on her left shin, with persistent oozing of blood. Her blood work was notable for white blood cells (WBC) 9.4×10^9/L (9.4×10^3/mm^3), hemoglobin 125g/L (12.5 g/dL) and platelets 5×10^9/L (5×10^3/mm^3). A repeat platelet count was 4×10^9/L. Prothrombin time was 11 seconds and the international normalized ratio (INR) was one. The TMP/SMX was discontinued and one unit of platelets was transfused. Her platelet count subsequently increased to 108×10^9/L. Severe thrombocytopenia with a platelet count of ≤10×10^9/Lmay rarely result in the catastrophic spontaneous bleeding. Thus, low platelet counts associated with TMP/SMX carry potential life-threatening complications. The clinicians should be aware of this adverse effect of TMP/SMX, which appears to be dose/duration independent. We suggest careful monitoring of complete blood cell count, especially platelet count, before and during TMP/SMX therapy.