Three different polymorphisms of the DPYD gene associated with severe toxicity following administration of 5-FU: a case report

Abstract Background Dihydropyrimidine dehydrogenase deficiency secondary to polymorphisms in the DPYD gene can lead to significant toxicity associated with the administration of fluoropyrimidine chemotherapy. Case presentation We report a case of a 59-year-old Lebanese woman with metastatic pancreatic cancer who received FOLFIRINOX therapy and developed severe 5-fluorouracil toxicity after a single cycle. The entire DPYD gene was sequenced, and the patient was found to be heterozygous for three different polymorphisms that have reportedly been associated with dihydropyrimidine dehydrogenase deficiency. Conclusion Because data regarding the prevalence and clinical significance of several heterozygous polymorphisms in a single DPYD gene are very limited, we suggest that full gene sequencing should be carried out, at least in populations in which the allele frequencies are unknown

Prevalence of Insomnia among Pancreatic Cancer Patients following Pancreaticoduodenectomy

Introduction. Sleep disturbances are more common in cancer patients than in the general population; however, there is limited research pertaining to the occurrence of such disturbances that subsequently impact patients’ quality of life. The aim of our study is to describe the prevalence of insomnia among pancreatic cancer patients who have recently undergone recent pancreaticoduodenectomy. Methods. We performed a 6-year (2014-2020) retrospective cohort analysis of all adult patients aged 18 and above with pancreatic cancer who underwent pancreaticoduodenectomy at our institution. Insomnia was characterized using the Pittsburgh Sleep Quality Index (PSQI). Symptoms of insomnia and the impact caused by these symptoms on daily lives were assessed with the Insomnia Severity Index (ISI), and patients were divided into mild insomnia (ISI 8–14) or moderate to severe insomnia (ISI≥15). Results. Out of forty patients with pancreatic cancer that have undergone pancreaticoduodenectomy, 19 (47.2%) reported that their sleep disturbances had a significant effect on their quality of life. A total of 22 (55.0%) patients reported insomnia, with 63.2% reporting mild insomnia. Chemotherapy was found to significantly increase the risk of moderate to severe insomnia. The mean ISI score was 7.2±6.9, and the mean PSQI score was 7.0±5.1. ISI and PSQI showed a strong positive correlation (r=0.78, p<0.01). Conclusion. Sleep disturbances such as insomnia following pancreatic cancer surgery are highly prevalent. Treating physicians and surgeons should recognize and routinely screen for sleep disorders through the management of a multidisciplinary team in order to alleviate some of the burden on the patients’ mental well-being

Thymoquinone Radiosensitizes Human Colorectal Cancer Cells in 2D and 3D Culture Models

Resistance of cancer cells and normal tissue toxicity of ionizing radiation (IR) are known to limit the success of radiotherapy. There is growing interest in using IR with natural compounds to sensitize cancer cells and spare healthy tissues. Thymoquinone (TQ) was shown to radiosensitize several cancers, yet no studies have investigated its radiosensitizing effects on colorectal cancer (CRC). Here, we combined TQ with IR and determined its effects in two-dimensional (2D) and three-dimensional (3D) culture models derived from HCT116 and HT29 CRC cells, and in patient-derived organoids (PDOs). TQ sensitized CRC cells to IR and reduced cell viability and clonogenic survival and was non-toxic to non-tumorigenic intestinal cells. TQ sensitizing effects were associated with G2/M arrest and DNA damage as well as changes in key signaling molecules involved in this process. Combining a low dose of TQ (3 µM) with IR (2 Gy) inhibited sphere formation by 100% at generation 5 and this was associated with inhibition of stemness and DNA repair. These doses also led to ~1.4- to ~3.4-fold decrease in organoid forming ability of PDOs. Our findings show that combining TQ and IR could be a promising therapeutic strategy for eradicating CRC cells