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Cytomegalovirus enterocolitis in a patient with dihydropyrimidine dehydrogenase deficiency after capecitabine treatment: A case report.

ABSTRACT: INTRODUCTION:5-Fluorouracil (5-FU) is widely used for cancer treatment. The reduced activity of dihydropyrimidine dehydrogenase (DPD), the key enzyme in 5-FU inactivation, increases a patient's risk of developing severe 5-FU related toxicity. However, screening for DPD deficiency is rarely performed before 5-FU administration. PRESENTATION OF CASE:Our patient was a 69-year-old man with rectal cancer (T2N1bM0 stage IIIA) who underwent laparoscopic low anterior resection. He developed severe neutropenia and diarrhea 15 days after the administration of capecitabine for adjuvant chemotherapy, and was admitted to our hospital. Four days after admission, he was transferred to the intensive care unit for sepsis. DPD protein screening revealed DPD deficiency. On day 27, massive melena suddenly appeared. He died of continual bleeding 41 days after admission. Pathological autopsy revealed cytomegalovirus enterocolitis. DISCUSSION:The administration of 5-FU to patients with DPD deficiency is lethal. Genotypic and phenotypic assessments are reliable tests for DPD deficiency. A genetic study can effectively screen for DPD deficiency; however, its use has not been established in the national insurance system. Patients with DPD deficiency tend to develop severe neutropenia, so clinicians should pay attention to opportunistic infections such as cytomegalovirus enterocolitis. CONCLUSION:Screening for DPD deficiency is necessary prior to 5-FU administration.

SUBMITTER: Inoue F

PROVIDER: S-EPMC6403100 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Cytomegalovirus enterocolitis in a patient with dihydropyrimidine dehydrogenase deficiency after capecitabine treatment: A case report.

Inoue Fumiya F Yano Takuya T Nakahara Masahiro M Okuda Hiroshi H Amano Hironobu H Yonehara Shuji S Noriyuki Toshio T

International journal of surgery case reports 20190223

<h4>Introduction</h4>5-Fluorouracil (5-FU) is widely used for cancer treatment. The reduced activity of dihydropyrimidine dehydrogenase (DPD), the key enzyme in 5-FU inactivation, increases a patient's risk of developing severe 5-FU related toxicity. However, screening for DPD deficiency is rarely performed before 5-FU administration.<h4>Presentation of case</h4>Our patient was a 69-year-old man with rectal cancer (T2N1bM0 stage IIIA) who underwent laparoscopic low anterior resection. He develop ...[more]

PMID: 30831507

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Project description:BackgroundThe main cause for fluoropyrimidine-related toxicity is deficiency of the metabolizing enzyme dihydropyrimidine dehydrogenase (DPD). In 2020, the European Medicines Agency (EMA) recommended two methods for pre-treatment DPD deficiency testing in clinical practice: phenotyping using endogenous uracil concentration or genotyping for DPYD risk variant alleles. This study assessed the DPD testing implementation status in Europe before (2019) and after (2021) the release of the EMA recommendations.MethodsThe survey was conducted from 16 March 2022 to 31 July 2022. An electronic form with seven closed and three open questions was e-mailed to 251 professionals with DPD testing expertise of 34 European countries. A descriptive analysis was conducted.ResultsWe received 79 responses (31%) from 23 countries. Following publication of the EMA recommendations, 87% and 75% of the countries reported an increase in the amount of genotype and phenotype testing, respectively. Implementation of novel local guidelines was reported by 21 responders (27%). Countries reporting reimbursement of both tests increased in 2021, and only four (18%) countries reported no coverage for any testing type. In 2019, major implementation drivers were 'retrospective assessment of fluoropyrimidine-related toxicity' (39%), and in 2021, testing was driven by 'publication of guidelines' (40%). Although the major hurdles remained the same after EMA recommendations-'lack of reimbursement' (26%; 2019 versus 15%; 2021) and 'lack of recognizing the clinical relevance by medical oncologists' (25%; 2019 versus 8%; 2021)-the percentage of specialists citing these decreased. Following EMA recommendations, 25% of responders reported no hurdles at all in the adoption of the new testing practice in the clinics.ConclusionsThe EMA recommendations have supported the implementation of DPD deficiency testing in Europe. Key factors for successful implementation were test reimbursement and clear clinical guidelines. Further efforts to improve the oncologists' awareness of the clinical relevance of DPD testing in clinical practice are needed.

Dataset Information

Cytomegalovirus enterocolitis in a patient with dihydropyrimidine dehydrogenase deficiency after capecitabine treatment: A case report.

Publications

Cytomegalovirus enterocolitis in a patient with dihydropyrimidine dehydrogenase deficiency after capecitabine treatment: A case report.

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