Pseudomyxoma peritonei:Sudden Cardiac Death Complicating Post operative Intraperitoneal Treatment with 5-Fluorouracil

El-Attar, Ayman F.; Skeel, Roland T.; Howard, John M.

doi:10.1159/000018682

Cited by 3 publications

(3 citation statements)

References 19 publications

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“…However, nephrotoxicity, and cardiotoxicity had been reported in non‐PMP animal studies, as well as case report on sudden cardiac death after i.p. administration of 5‐FU . Besides, though i.p.…”

Section: Discussionmentioning

confidence: 99%

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Establishment of patient‐derived xenograft model of peritoneal mucinous carcinomatosis with signet ring cells and in vivo study on the efficacy and toxicity of intraperitoneal injection of 5‐fluorouracil

et al. 2019

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Background: Pseudomyxoma peritonei (PMP) is an indolent malignancy and insensitive to systemic chemotherapy. The authors established patient-derived xenograft (PDX) model of PMP, and evaluated the efficacy and toxicity of intraperitoneal (i.p.) administration of 5-fluorouracil (5-FU) in this model. Methods: Human PMP sample was collected to establish subcutaneous (s.c.) and i.p. model. In vivo study of i.p. injection of 5-FU was performed in i.p. model, with experimental peritoneal cancer index (ePCI) score and pathological examinations for evaluating the efficacy and toxicity. Results: Both s.c. and i.p. models were constructed. The average passage interval of s.c. model was 44.2 ± 5.2 days, and the i.p. model was characterized by disseminated solid tumor nodules in abdominal-pelvic cavity. Both models were diagnosed as peritoneal mucinous carcinomatosis with signet ring cells (PMCA-S). Immunohistochemical characteristics was similar to human. GNAS mutation was detected in both model and patient. In the in vivo study, average ePCI of treatment group was lower than control and vehicle group (P = .004). Histopathology revealed obvious tumor necrosis in treatment group, and decreased Ki67 positive rate (P = .010). In toxicity study, 5-FU significantly influenced body weight (P = .010) and 1 animal from treatment group died on day 14. Congestive splenomegaly was observed (88.9%). Hepatotoxicity presented as acidophilic body (55.6%), cholestasis (100%), bile canaliculus hyperplasia and obstruction (22.2%), and lymphocyte accumulation (77.8%). Conclusions: PDX model of PMCA-S was established successfully, and i.p. 5-FU could inhibit tumor proliferation and progression, with decreased Ki67 positive rate and ePCI score. Hepatotoxicity was the main side effect. K E Y W O R D S 5-FU, intraperitoneal injection, organ toxicity, PDX model, pseudomyxoma peritonei | 1105 LIN et aL.

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Section: Discussionmentioning

confidence: 99%

“…administration of 5-FU. 28 Besides, though i.p. injection of 5-FU had been applied in clinical treatment of PMP, [29][30][31] the efficacy is unclear because of the influence of large volumes of mucus.…”

mentioning

confidence: 99%

Establishment of patient‐derived xenograft model of peritoneal mucinous carcinomatosis with signet ring cells and in vivo study on the efficacy and toxicity of intraperitoneal injection of 5‐fluorouracil

et al. 2019

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“…Although many of the clinical reports in the literature have focused on continuous infusion 5-FU therapy as a risk factor, patients also have experienced cardiotoxicity from bolus 5-FU infusions as well as intraperitoneal 5-FU infusions (El-Attar, Skeel, & Howard, 1999;Lomeo, Avolio, Iacobellis, & Manzione, 1990).…”

Section: Fluoropyrimidine Cardiotoxicitymentioning

confidence: 99%

Cardiotoxicity and Capecitabine: A Case Report

Singer¹

2003

Clinical Journal of Oncology Nursing

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Oral fluoropyrimidines increasingly are being developed and studied as a novel treatment for breast, colorectal, and other cancers. Fluoropyrimidines are designed to generate 5-fluorouracil (5-FU) preferentially within tumors. Cardiotoxicity is a rare complication associated with 5-FU and oral fluoropyrimidine treatments. Chest pain is the most common presenting symptom, and, in many cases, the cardiotoxicity is partly or completely reversible. This article reviews fluoropyrimidine-induced cardiotoxicity and presents a case report of a woman who experienced this complication during capecitabine treatment.

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Cardiac lesions induced by 5-fluorouracil in the rabbit

Tsibiribi¹,

Bui‐Xuan²,

Bui‐Xuan

et al. 2006

Hum Exp Toxicol

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Cardiotoxicity is a rare, but well-recognized complication of treatments with the anti-cancer drug 5-fluorouracil (5FU). The underlying mechanism, however, is not fully elucidated. A spasm of the coronary arteries is often considered to be the leading cause of myocardial ischemia and decreased contractility associated with 5FU. As spasm cannot account for all reported adverse cardiac effects, the present study was undertaken to search for alternative mechanisms. Groups of six rabbits were given either a single intravenous dose of 50 mg/kg 5FU or four intravenous doses of 15 mg/kg 5FU at 7-day intervals. A third group served as control. The heart was removed shortly after death or scheduled sacrifice of the animals, to perform macroscopic and microscopic examinations of the heart and to evidence apoptosis by the TUNEL method. Following a single dose of 50 mg/kg 5FU, all animals rapidly developed a massive hemorrhagic myocardial infarct with spasms of the proximal coronary arteries. Repeated infusions of 15 mg/kg 5FU induced left ventricular hypertrophy, foci of myocardial necrosis, thickening of intra-myocardial arterioles, and disseminated apoptosis in myocardial cells of the epicardium, as well as endothelial cells of the distal coronary arteries. These results indicate that a spasm of the coronary arteries is not the only mechanism of 5FU cardiotoxicity, and that apoptosis of myocardial and endothelial cells can result in inflammatory lesions mimicking toxic myocarditis.

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Pseudomyxoma peritonei:Sudden Cardiac Death Complicating Post operative Intraperitoneal Treatment with 5-Fluorouracil

Cited by 3 publications

References 19 publications

Establishment of patient‐derived xenograft model of peritoneal mucinous carcinomatosis with signet ring cells and in vivo study on the efficacy and toxicity of intraperitoneal injection of 5‐fluorouracil

Establishment of patient‐derived xenograft model of peritoneal mucinous carcinomatosis with signet ring cells and in vivo study on the efficacy and toxicity of intraperitoneal injection of 5‐fluorouracil

Cardiotoxicity and Capecitabine: A Case Report

Cardiac lesions induced by 5-fluorouracil in the rabbit

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