Successful management of hyperammonemia with hemodialysis on day 2 during 5-fluorouracil treatment in a patient with gastric cancer: a case report with 5-fluorouracil metabolite analyses

Ozaki, Y., Imamaki, H., Ikeda, A. et al. Correction to: Successful management of hyperammonemia with hemodialysis on day 2 during 5‑fluorouracil treatment in a patient with gastric cancer: a case report with 5‑fluorouracil metabolite analyses. Cancer Chemotherapy and Pharmacology (2020) 86:693-699.Purpose: Hyperammonemia is an important adverse event associated with 5-fluorouracil (5FU) from 5FU metabolite accumulation. We present a case of an advanced gastric cancer patient with chronic renal failure, who was treated with 5FU/leucovorin (LV) infusion chemotherapy (2-h infusion of LV and 5FU bolus followed by 46-h 5FU continuous infusion on day 1; repeated every 2 weeks) and developed hyperammonemia, with the aim of exploring an appropriate hemodialysis (HD) schedule to resolve its symptoms. Methods: The blood concentrations of 5FU and its metabolites, α-fluoro-β-alanine (FBAL), and monofluoroacetate (FA) of a patient who had hyperammonemia from seven courses of palliative 5FU/LV therapy for gastric cancer were measured by liquid chromatography–mass spectrometry. Results: On the third day of the first cycle, the patient presented with symptomatic hyperammonemia relieved by emergency HD. Thereafter, the 5FU dose was reduced; however, in cycles 2–4, the patient developed symptomatic hyperammonemia and underwent HD on day 3 for hyperammonemia management. In cycles 5–7, the timing of scheduled HD administration was changed from day 3 to day 2, preventing symptomatic hyperammonemia. The maximum ammonia and 5FU metabolite levels were significantly lower in cycles 5–7 than in cycles 2–4 (NH3 75 ± 38 vs 303 ± 119 μg/dL, FBAL 13.7 ± 2.5 vs 19.7 ± 2.0 μg/mL, FA 204.0 ± 91.6 vs 395.9 ± 12.6 ng/mL, mean ± standard deviation, all p < 0.05). After seven cycles, partial response was confirmed. Conclusion: HD on day 2 instead of 3 may prevent hyperammonemia in 5FU/LV therapy

Cancer diagnosis and prognosis after initiation of hemodialysis: Multicenter Japan Cancer and DialYsis (J-CANDY) study

血液透析導入後のがんの診断と予後 --多施設共同J-CANDY研究-- . 京都大学プレリリース. 2024-12-27[Background] Cancer is a leading cause of death among patients on hemodialysis; however, the data on its diagnosis, treatment and prognosis are limited. Here we analyzed the surgical practice patterns and outcomes of patients on hemodialysis with cancer and compared them with those of general cancer patients from the National Cancer Center database. [Methods] This nationwide registry enrolled hemodialysis patients who were subsequently diagnosed with primary cancers of the kidney, colorectum, stomach, lung, liver, bladder, pancreas and breast in 20 hospitals in Japan between 2010 and 2012. The primary endpoint was the overall 3-year survival rate. We also examined the association of factors with mortality using Cox regression analysis. [Results] Of the 502 patients, 370 (74%) underwent surgery. More than half of the patients (57%) were asymptomatic at diagnosis and diagnosed with cancer through screening. Among the patients who underwent surgery, most (99%) had resectable cancers; while among those who did not undergo surgery, more than half (52%) had metastatic cancers. The 3-year overall survival in the surgery and non-surgery groups was 83% and 32%, respectively. Non-cancer-related deaths were dominant (80%) in the surgery group, whereas cancer-related deaths were dominant in the non-surgery group (70%). Pancreatic cancer and anemia were associated with a poor prognosis in the surgery group. Surgery and 3-year overall survival rates were comparable between the patients on hemodialysis and the general cancer patients. [Conclusion] Prognosis in hemodialysis cancer patients might be equivalent to that of general cancer patients

Comprehensive genomic profiling for patients with chemotherapy‐naïve advanced cancer

Comprehensive genomic profiling (CGP) testing by next-generation sequencing has been introduced into clinical practice as part of precision cancer medicine to select effective targeted therapies. However, whether CGP testing at the time of first-line chemotherapy could be clinically useful is not clear. We conducted this single-center, prospective, observational study to investigate the feasibility of CGP testing for chemotherapy-naïve patients with stage III/IV gastrointestinal cancer, rare cancer, and cancer of unknown primary, using the FoundationOne® companion diagnostic (F1CDx) assay. The primary outcome was the detection rate of at least one actionable/druggable cancer genomic alteration. Actionable/druggable cancer genomic alterations were determined by the F1CDx report. An institutional molecular tumor board determined the molecular-based recommended therapies. A total of 197 patients were enrolled from October 2018 to June 2019. CGP success rate was 76.6% (151 of 197 patients), and median turnaround time was 19 days (range: 10-329 days). Actionable and druggable cancer genomic alterations were reported in 145 (73.6%) and 124 (62.9%) patients, respectively. The highest detection rate of druggable genomic alterations in gastrointestinal cancers was 80% in colorectal cancer (48 of 60 patients). Molecular-based recommended therapies were determined in 46 patients (23.4%). CGP testing would be a useful tool for the identification of a potentially effective first-line chemotherapy

Clinical characteristics and treatment strategies for A20 haploinsufficiency in Japan: a national epidemiological survey

BackgroundThe severity of A20 haploinsufficiency (HA20) varies, with no established clinical guidelines for treatment. This study aimed to elucidate the clinical characteristics of, and the efficacy of treatments attempted in, patients with HA20 in Japan.MethodsClinical information on HA20 patients from medical records was retrospectively collected through the attending physicians.ResultsSeventy-two HA20 patients were identified in Japan. And, 54 patients from 37 unrelated families were analyzed in detail. HA20 patients exhibited common features, including recurrent fever, gastrointestinal and musculoskeletal symptoms, and autoimmune disease; various organ disorders (e.g. neurological, liver, and pulmonary diseases) were less common complications. Molecular target drugs (MTDs) were administered in 44.4% of patients, among which anti-tumor necrosis factor (TNF)-α agents showed efficacy in 59.5% of patients. Eleven patients did not experience control of inflammation with initial MTDs, most commonly because of relapse due to secondary failure of MTDs. Anti-drug antibodies were related to the secondary failure of adalimumab in one patient and infusion reactions to infliximab in two patients. In such refractory cases, other treatments (e.g. switching the first MTD to an alternative agent or adding a Janus kinase inhibitor or immunomodulators, or allogeneic hematopoietic cell transplantation [HCT]) were attempted.ConclusionsOur survey revealed that anti-TNF-α agents showed high efficacy. However, secondary failure of MTDs was a significant refractory-related factor in HA20 patients in Japan. Although anti-interferon therapies, thalidomide, and HCT might be potential treatment options, the results of this study suggest that further research is necessary to establish suitable treatments for HA20, especially for those with refractory disease

慢性維持透析中に発症したがん患者における抗がん薬治療の国内実態調査

京都大学0048新制・課程博士博士(医学)甲第21256号医博第4374号新制||医||1029(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 中山 健夫, 教授 小川 修, 教授 川村 孝学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA