The assessment of suffering in cancer patients affected by dementia can be challenging. We report a patient with advanced skin cancer and dementia who was admitted to our hospital without appropriate diagnosis as having cerebral infarction at previous hospitals. Case:An 85-year-old woman presented with existing cognitive dysfunction from 2009 and progression of a left facial skin tumor existing from 2013. She was admitted to hospital A for facial skin tumor with dysphagia, and diagnosed as having advanced skin cancer with dementia in June 2014. After palliative therapy for the skin tumor, she was transferred to hospital B. The physicians at both hospitals explained the presenting symptoms as complications of her advanced skin cancer and dementia. She was admitted to our hospital at 36 days after symptom onset, and we diagnosed subacute cerebral infarction based on head CT and MRI examinations. In this case, the patient’s advanced cancer and dementia might have interfered with the recognition of her symptoms of cerebral infarction. A detailed interview on admission might have contributed to our decision for further examination. Although the diagnosis of cerebral infarction could not palliate her physical symptoms, it might assist the family to recognize her suffering or to provide care perceiving her poor prognosis. Additionally, the diagnosis might have an effect for emotional satisfaction of the family.

BACKGROUND/AIMS: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD). METHODS: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing. RESULTS: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined. CONCLUSIONS: Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.
6-Mercaptopurine ; Asian Continental Ancestry Group* ; Azathioprine ; Clinical Coding ; Hair ; Humans ; Inflammatory Bowel Diseases* ; Leukopenia

Corticosteroids are used in the treatment of many diseases; however, they also induce various side effects. Dexamethasone is one of the most potent corticosteroids, and it has been reported to induce the side effect of impaired salivary gland function. This study aimed to evaluate the effects of dexamethasone on mouse submandibular gland function to gain insight into the mechanism of dexamethasone-induced salivary hypofunction. The muscarinic agonist carbachol (CCh) induced salivary secretion and was not affected by short-term dexamethasone treatment but was decreased following long-term dexamethasone administration. The expression levels of the membrane proteins Na-K-2Cl cotransporter, transmembrane member 16A, and aquaporin 5 were comparable between the control and long-term dexamethasone treatment groups. The CCh-induced increase in calcium concentration was significantly lower in the presence of extracellular Ca in the long-term dexamethasone treatment group compared to that in the control group. Furthermore, CCh-induced salivation in the absence of extracellular Ca and Ca ionophore A23187-induced salivation was comparable between the control and long-term dexamethasone treatment groups. Moreover, salivation induced by the Ca-ATPase inhibitor thapsigargin was diminished in the long-term dexamethasone treatment group. In summary, these results demonstrate that short-term dexamethasone treatment did not impair salivary gland function, whereas long-term dexamethasone treatment diminished store-operated Ca entry, resulting in hyposalivation in mouse submandibular glands.
Acinar Cells ; drug effects ; metabolism ; Animals ; Calcium ; metabolism ; Calcium Signaling ; drug effects ; Carbachol ; pharmacology ; Dexamethasone ; therapeutic use ; Mice ; Muscarinic Agonists ; pharmacology ; Saliva ; metabolism ; Salivation ; drug effects ; Submandibular Gland ; drug effects ; metabolism