scholarly journals Fluoropyrimidine-Induced Severe Toxicities Associated with Rare DPYD Polymorphisms: Case Series from Saudi Arabia and a Review of the Literature

2021 ◽  
Vol 11 (3) ◽  
pp. 467-471
Author(s):  
Nedal Bukhari ◽  
Abdulraheem Alshangiti ◽  
Emad Tashkandi ◽  
Mohammed Algarni ◽  
Humaid O. Al-Shamsi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Saudi Arabia ◽  
Standard Dose ◽  
Dihydropyrimidine Dehydrogenase ◽  
Case Series ◽  
Gene Sequencing ◽  
Review Of The Literature ◽  
Dpyd Gene ◽  
First Case ◽  
Arabian Population

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of 5-Fluorouracil (5-FU) and its prodrug capecitabine. We report cases from our institute with colorectal cancer who experienced severe toxicities to standard dose 5-FU based chemotherapy. DPYD gene sequencing revealed rare different polymorphisms that prompted dose adjustments of administered 5-FU and capecitabine. To our knowledge, this is the first case series looking at DPYD polymorphisms in the Saudi Arabian population.

scholarly journals A Genotyping/Phenotyping Approach with Careful Clinical Monitoring to Manage the Fluoropyrimidines-Based Therapy: Clinical Cases and Systematic Review of the Literature

2020 ◽  
Vol 10 (3) ◽  
pp. 113 ◽  
Author(s):  
Valeria Conti ◽  
Emanuela De Bellis ◽  
Valentina Manzo ◽  
Francesco Sabbatino ◽  
Francesco Iannello ◽  
...  
Keyword(s):  
Systematic Review ◽  
High Performance ◽  
Dosage Reduction ◽  
Dihydropyrimidine Dehydrogenase ◽  
Case Series ◽  
Clinical Monitoring ◽  
Tandem Mass ◽  
Severe Toxicity ◽  
Review Of The Literature ◽  
Dpyd Gene

Fluoropyrimidines (FP) are mainly metabolised by dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. FP pharmacogenetics, including four DPYD polymorphisms (DPYD-PGx), is recommended to tailor the FP-based chemotherapy. These polymorphisms increase the risk of severe toxicity; thus, the DPYD-PGx should be performed prior to starting FP. Other factors influence FP safety, therefore phenotyping methods, such as the measurement of 5-fluorouracil (5-FU) clearance and DPD activity, could complement the DPYD-PGx. We describe a case series of patients in whom we performed DPYD-PGx (by real-time PCR), 5-FU clearance and a dihydrouracil/uracil ratio (as the phenotyping analysis) and a continuous clinical monitoring. Patients who had already experienced severe toxicity were then identified as carriers of DPYD variants. The plasmatic dihydrouracil/uracil ratio (by high-performance liquid chromatography (HPLC)) ranged between 1.77 and 7.38. 5-FU clearance (by ultra-HPLC with tandem mass spectrometry) was measured in 3/11 patients. In one of them, it reduced after the 5-FU dosage was halved; in the other case, it remained high despite a drastic dosage reduction. Moreover, we performed a systematic review on genotyping/phenotyping combinations used as predictive factors of FP safety. Measuring the plasmatic 5-FU clearance and/or dihydrouracil/uracil (UH2/U) ratio could improve the predictive potential of DPYD-PGx. The upfront DPYD-PGx combined with clinical monitoring and feasible phenotyping method is essential to optimising FP-based chemotherapy.

Cost implications of reactive versus prospective testing for dihydropyrimidine dehydrogenase (DPD) deficiency in patients with colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3627-3627
Author(s):  
Gul Ahmed ◽  
Jo O' Keeffe ◽  
Denise O Mullane ◽  
Alison Bransfield ◽  
Andrew Kenny ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Standard Dose ◽  
Dihydropyrimidine Dehydrogenase ◽  
Severe Toxicity ◽  
First Line ◽  
Time Period ◽  
Cost Implications ◽  
The Cost ◽  
First Time

3627 Background: DPD is an enzyme encoded by the DPYD gene involved in the metabolism of the chemotherapy drug 5-fluorouracil (5FU) and the oral 5FU prodrug capecitabine. Patients (pts) with DPYD mutations are at risk of severe toxicities from standard dose 5FU, although they may safely receive lower dose therapy with careful monitoring and dose escalation. Methods: In this retrospective study we identified all pts starting 5FU-based chemotherapy for colorectal cancer (CRC) at our institution between Jan 1 2010 and Dec 31 2012. During this time DPD testing was usually performed in a reactive manner, typically for pts experiencing severe toxicities. We reviewed the charts of pts who tested positive for DPYD mutations and assessed the financial implications of their hospitalizations with toxicity. These costs were compared to the costs which would have incurred if all pts starting such therapy had been proactively tested. Results: A total of 134 pts started first-line 5FU-based chemotherapy for CRC over the study period, 66 in the adjuvant setting and 68 for metastatic disease. 31 pts had DPYD mutation testing performed. 6 tests (19% of those tested, 4.5% of the total population) revealed heterozygote DPYD mutations. 5 pts had already experienced severe treatment-related toxicity resulting in cessation of therapy, while one was tested prospectively and received chemotherapy with dose reduction ab initio. The total cost related to hospitalization with toxicity for these 5 pts was €155,083. At €177 per test, the cost to prospectively test all pts starting first-line 5FU-based therapy over the time period would have been €23,718 representing a saving of €131,365 through avoiding these admissions alone. 4 pts who tested positive for DPYD mutations were receiving adjuvant therapy and none restarted therapy following severe toxicity early in their therapy. 2 pts subsequently relapsed with metastatic disease. Conclusions: Prospective testing for DPYD mutations in pts with CRC starting 5FU-based therapy for the first time represents a considerable cost-saving opportunity, in addition to potentially avoiding prolonged hospitalization and morbidity for a sizeable minority of pts.

scholarly journals Tegafur–uracil is a safe alternative for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle

2012 ◽  
Vol 4 (4) ◽  
pp. 167-172 ◽  
Author(s):  
Daniel I.G. Cubero ◽  
Felipe Melo Cruz ◽  
Patrícia Santi ◽  
Ismael Dale C.G. Silva ◽  
Auro del Giglio
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Dehydrogenase Deficiency ◽  
Dihydropyrimidine Dehydrogenase ◽  
Gene Sequencing ◽  
Severe Toxicity ◽  
Safe Alternative ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Proof Of Principle

Objective: The objective of this study was to evaluate the safety of using tegafur–uracil (UFT) in colorectal cancer patients with partial dihydropyrimidine dehydrogenase (DPD) deficiency. Patients and Methods: The study included five colorectal cancer patients who presented with acute toxicity (grades 3 and 4) after being given the first cycle of chemotherapy using 5-fluorouracil. The DPD deficiency was confirmed by gene sequencing. After a full recovery from all side effects, we changed the regimen to UFT (300 mg/m2/day) associated with leucovorin (90 mg/day) for 21 days, with an empirical dose reduction of at least 10% in the first cycle. Results: We prospectively analysed 22 UFT cycles in 5 patients. We did not observe any episodes of grade 3 or 4 toxicity. The predominant toxicities were of grades 1 and 2 (nausea, vomiting and diarrhoea). Conclusion: Here, we demonstrate a complete absence of severe toxicity in all patients and cycles analysed. We believe that UFT is a safe alternative for the treatment of patients with partial DPD deficiency.

scholarly journals Pediatric invasive disease due to Haemophilus influenzae serogroup A in Riyadh, Saudi Arabia: case series

2016 ◽  
Vol 10 (05) ◽  
pp. 528-532 ◽  
Author(s):  
Zailaie Roaa ◽  
Alawfi Abdulsalam ◽  
Ghazi Shahid ◽  
Baba Kamaldeen ◽  
Al Fawaz Tariq
Keyword(s):  
Saudi Arabia ◽  
Blood Culture ◽  
Haemophilus Influenzae ◽  
Vaccine Development ◽  
Good Condition ◽  
Case Series ◽  
Invasive Disease ◽  
Medical Illness ◽  
Serotype A ◽  
First Case

We describe the first two cases of invasive disease caused by Haemophilus influenzae serotype A in Saudi Arabia. This is the first known reported invasive Haemophilus influenzae serotype A from Saudi Arabia. Case presentation: A ten-month-old and three-month-old male not known to have any past history of any medical illness and who had received H. influenzae type b (Hib) vaccine presented to our hospital mainly with fever of few days’ duration. A provisional diagnosis of meningitis with sepsis was made and laboratory tests were requested. The chest radiograph was normal. The laboratory results revealed leukocytosis, but leukopenia was noticed in the younger infant. Blood culture and cerebrospinal fluid specimens yielded a pure culture of Haemophilus influenzae and serotyping showed the isolates to be serogroup A. Both patients were started on vancomycin and third-generation cephalosporin. On receiving the blood culture result, vancomycin was stopped. Fever subsided after 48 hours, while in the second case, it continued for 12 days from the admission date. The repeat blood cultures were negative. Antibiotic therapy was given for 10 days for the first case with an unremarkable hospital course, while the second case was complicated by seizure and received a longer duration of antibiotics. Both infants were discharged home in good condition. Conclusions: Invasive non-typeable H. influenzae strains are emerging and there is a need for surveillance of this disease. This has implications in future vaccine development.

Hantavirus infection—Hemorrhagic fever with renal syndrome: the first case series reported in Romania and review of the literature

2011 ◽  
Vol 44 (4) ◽  
pp. 1185-1191 ◽  
Author(s):  
Irinel-Doina Maftei ◽  
Liviu Segall ◽  
Raluca Panculescu-Gatej ◽  
Cornelia Ceianu ◽  
Adrian Covic
Keyword(s):  
Case Series ◽  
Hemorrhagic Fever ◽  
Hantavirus Infection ◽  
Review Of The Literature ◽  
First Case

scholarly journals Takotsubo cardiomyopathy: Report of the first case series in Serbia and review of the literature

2010 ◽  
Vol 63 (1-2) ◽  
pp. 75-81 ◽  
Author(s):  
Biljana Putnikovic ◽  
Vojkan Cvorovic ◽  
Milos Panic ◽  
Predrag Milicevic ◽  
Gordana Vojinovic-Maglic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Acute Heart Failure ◽  
Takotsubo Cardiomyopathy ◽  
Coronary Artery Spasm ◽  
Case Series ◽  
Left Ventricular ◽  
Coronary Microvascular Dysfunction ◽  
Review Of The Literature ◽  
First Case

Introduction. Takotsubo cardiomyopathy is a relatively novel cardiac syndrome that is characterized by transient left ventricular asynergy involving apical and mid-ventricular segments. Epidemiology and pathophisiology. It occurs predominantly in elderly women in the absence of obstructive coronary artery disease and is usually associated with severe emotional or physical stress. This syndrome is manifested with chest pain, electrocardiographic changes that mimic acute myocardial infarction, and minimal myocardial enzy?matic release. Several different mechanisms have been proposed: coronary artery spasm, dynamic left ventricular outflow/intracavitary obstruction, coronary microvascular dysfunction and direct catecholamine-mediated cardiomyocite injury. Therapy and prognosis. Complete recovery usually occurs after dramatic presentation, frequently complicated with acute heart failure. Therapy is empiric and directed towards supportive measures against cardiogenic shock, acute heart failure, dysrhythmias. In-hospital mortality rate is less than 1%, but long-term prognosis is still unknown. In addition to the review of the literature on takotsubo cardiomyopathy, we present the first series of patients with this syndrome detected in Clinical Hospital Center Zemun.

scholarly journals Identifying a Novel DPYD Polymorphism Associated with Severe Toxicity to 5-FU Chemotherapy in a Saudi Patient

2019 ◽  
Vol 2019 ◽  
pp. 1-3
Author(s):  
Nedal Bukhari ◽  
Faisal Azam ◽  
Mohammed Alfawaz ◽  
Mohammed Zahrani
Keyword(s):  
Dose Reduction ◽  
Adjuvant Treatment ◽  
Standard Dose ◽  
Dihydropyrimidine Dehydrogenase ◽  
Rectal Adenocarcinoma ◽  
Severe Toxicity ◽  
First Case

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of 5-Fluorouracil (5-FU) and its prodrug capecitabine. We report a 65-year-old female with rectal adenocarcinoma who experienced severe toxicities secondary to standard dose 5-FU based chemotherapy. She was found to be heterozygous for rs371313778, c.2434G>A. This finding prompted restarting 5-FU at 50% dose reduction with further titration in subsequent cycles. We herein report the first case of rs371313778, c.2434G>A (p.Val812lle) DPYD polymorphism leading to severe 5-FU toxicities. The patient eventually completed a 6-month course of adjuvant treatment with modification of 5-FU dose.

Neurosyphilis is more common in malignant syphilis: A case series and review of the literature

2019 ◽  
Vol 30 (8) ◽  
pp. 779-785
Author(s):  
Lin Zhu ◽  
Mei Shi ◽  
Rui-Rui Peng ◽  
Xin Gu ◽  
Zhifang Guan ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Chart Review ◽  
Case Series ◽  
Secondary Syphilis ◽  
Common Type ◽  
Review Of The Literature ◽  
First Case ◽  
Direct Association ◽  
The Common ◽  
The Relationship

Malignant syphilis is a rare skin manifestation of secondary syphilis, which has been reported primarily in the HIV-infected population. This study aimed to investigate the relationship between HIV infection, malignant syphilis, and neurosyphilis through a systematic chart review of 26 malignant syphilis patients seen at our hospital. We also performed a literature review of 83 reported malignant syphilis cases since 1987, when the first case of malignant syphilis co-infected with HIV was reported. We found there was no direct association between HIV infection and malignant syphilis or neurosyphilis. In contrast, we found that much higher proportion (30%) of malignant syphilis patients develop concurrent neurosyphilis compared to those with the common type of secondary syphilis (13.1%). Physicians should be aware of the fact that neurosyphilis is more common among patients with malignant syphilis and the importance of investigating for neurosyphilis in such patients.

scholarly journals Hemophagocytic Lymphohistiocytosis: Single-Center Series of 12 Cases from Saudi Arabia

2016 ◽  
Vol 10 ◽  
pp. CMPed.S35853 ◽  
Author(s):  
Ghaleb Elyamany ◽  
Azzah Alzahrani ◽  
Huda Elfaraidi ◽  
Omar Alsuhaibani ◽  
Nada Othman ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Mutational Analysis ◽  
Age Of Onset ◽  
Positive Family History ◽  
Case Series ◽  
Cell Transplant ◽  
First Case ◽  
Response To Chemotherapy ◽  
Female Predominance

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease that commonly appears in infancy, although it has been reported in adults. Chemoimmunotherapy-based treatments have improved the survival of patients with HLH; however, overall survival is still poor. We retrospectively analyzed the data of 12 HLH patients who were admitted between 2005 and 2014. All patients were Saudi Arabia in origin with a female predominance (75%) and a median age of onset of 9.5 months. The consanguinity rates were significantly high (75%) with a positive family history in 41% of cases. Of the 12 patients, nine were defined as primary HLH patients and three were confirmed to be secondary HLH patients. All patients fulfilled the 2004 diagnostic criteria for HLH and received HLH-2004 treatment. Six of these patients showed a good response to chemotherapy, while the remainder of the patients showed partial or no response to chemotherapy. Five patients in this cohort received stem cell transplant, and these patients are currently in remission. The mortality rate of this cohort is currently 50%. Genetic mutational analysis showed a positive STX11 mutation in five patients and a PRF1 ( perforin) mutation in two patients. To the best of our knowledge, this is the first case series of HLH from Saudi Arabia.

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