Gruenberg Jessica, Manivel J Carlos, Gupta Pankaj, Dykoski Richard, Mesa Hector
Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, 420 Delaware St. SE, Minneapolis, MN 55455, USA.
Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, 420 Delaware St. SE, Minneapolis, MN 55455, USA; Department of Pathology, Minneapolis VA Health Care System, One Veterans Drive, Minneapolis, MN 55417, USA.
J Infect Chemother. 2016 Feb;22(2):112-6. doi: 10.1016/j.jiac.2015.08.015. Epub 2015 Sep 28.
Bladder cancer (BC) accounts for ∼14,680 deaths annually in the U.S. The prognosis of advanced disease remains dismal with current therapies. A phase III intergroup trial for metastatic BC adding bevacizumab to first-line cisplatin-gemcitabine chemotherapy (GCB regimen) is currently ongoing. We report the clinical-pathologic findings of a patient who developed fatal acute cardiac microvascular toxicity while receiving this regimen.
A 66 year old man consulted for epigastric pain, nausea, intermittent diarrhea and lightheadedness two weeks after receiving the first cycle of GCB chemotherapy for metastatic BC. Physical evaluation, laboratory studies and electrocardiogram (EKG) were within normal limits except for marked thrombocytopenia that was attributed to his recent chemotherapy. The patient was admitted for observation, rehydrated and started on a proton pump inhibitor. The following day, however, he experienced sudden severe chest and right upper quadrant pain. EKG showed tachycardia, ST elevations in leads V2 and V3, laboratory analyses revealed marked elevation of cardiac troponin I, and an echocardiogram showed a markedly reduced ejection fraction of 10-20%, consistent with rapidly progressive cardiogenic shock. Emergent cardiac catheterization showed no significant coronary artery disease. Sepsis work-up was negative. He became progressively hypotensive, developed multi-organ failure, and died 48 h after admission. Postmortem examination showed diffuse microvasculopathy and changes due to global hypoperfusion of 12-48 h evolution.
We present the first case of acute, fatal cardiac failure due to microvasculopathy most consistent with bevacizumab-associated toxicity. The findings are discussed in light of the existing literature.
在美国，膀胱癌（BC）每年导致约14,680人死亡。当前疗法下，晚期疾病的预后仍然很差。一项针对转移性膀胱癌的III期组间试验正在进行，该试验在一线顺铂-吉西他滨化疗（GCB方案）中加入贝伐单抗。我们报告了一名患者在接受该方案治疗时发生致命性急性心脏微血管毒性的临床病理结果。
一名66岁男性在接受转移性膀胱癌的GCB化疗第一周期两周后，因上腹部疼痛、恶心、间歇性腹泻和头晕前来就诊。体格检查、实验室检查和心电图（EKG）均在正常范围内，除了因近期化疗导致的明显血小板减少。患者入院观察，补液并开始使用质子泵抑制剂。然而，第二天，他突然出现严重的胸部和右上腹疼痛。心电图显示心动过速，V2和V3导联ST段抬高，实验室分析显示心肌肌钙蛋白I明显升高，超声心动图显示射血分数明显降低至10%-20%，符合快速进展的心源性休克。紧急心脏导管检查显示无明显冠状动脉疾病。脓毒症检查结果为阴性。他的血压逐渐降低，出现多器官功能衰竭，入院48小时后死亡。尸检显示弥漫性微血管病变以及由于12 - 48小时进展的全身性灌注不足引起的变化。
我们报告了首例因微血管病变导致的急性致命性心力衰竭病例，最符合贝伐单抗相关毒性。结合现有文献对这些发现进行了讨论。
