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Dyspnea is one of the most common and distressing symptoms in patients with cancer and noncancer advanced diseases. The Japanese Society for Palliative Medicine revised previous guidelines for the management of respiratory symptoms in patients with cancer and newly developed clinical guidelines for managing dyspnea in patients with advanced disease, based on the result of systematic reviews for each clinical question and consensus among experts. We describe the recommendations of the guidelines as well as provide insights into the reasoning behind the recommendations and their development process. There has been a paucity of evidence regarding the interventions for dyspnea in patients with advanced disease. Thus, more clinical research that includes not only randomized controlled trials but also real-world observational studies is warranted. [ABSTRACT FROM AUTHOR]

Background: Appropriate use of anti-infective drugs is essential in clinical practice. No evidence-based guidelines or protocols have been published on the appropriate use of anti-infective drugs in patients receiving palliative care as yet. Methods: The medical records, which included the demographic data of patients, anti-infective drug use, bacteriologic findings, symptoms, and hematologic findings were reviewed retrospectively to determine the potential factors that contribute to symptom improvement of patients in terminal phase. Results: Seventy-one patients (64%) who received anti-infective drugs and had a total of 326 episodes of infection were assessed. Symptom improvement was seen in 33.1%. A total of 22.6% of episodes were started on anti-infective drugs during the last week of life and the symptom improvement in these episodes was 9.2%. Symptom improvement was hardly observed when the anti-infective drug was administered during the last week of life. The association between the decrease in the C-reactive protein (CRP) levels, the decrease of the leukocyte count, reduction of fever, and symptom improvement was determined. The decrease of CRP levels was 42.4%; leukocyte, 56.7%; and reduction of fever was 28.4%. The symptom improvement of individual treatment history was also investigated. The symptom improvement of the group who took positive treatment such as chemotherapy, radiotherapy, surgery, and catheter placement was significantly lower than that of no-treatment group. Conclusions: Active cancer treatment probably induces the symptoms related to infection and the use of anti-infective drugs. Unnecessary and excessive treatment should be avoided, and the symptoms should be managed with consideration of the patient's state of mind in order to improve the quality of life of terminally ill patients. [ABSTRACT FROM AUTHOR]

Gefitinib-sensitive nonsmall cell lung cancers (NSCLC) are characterized by somatic mutations in the kinase domain of epidermal growth factor receptor (EGFR). The mutant EGFR forms are reported to mediate characteristic signal transduction pathways that are different from those mediated by the wild-type EGFR and are involved in transformation in vivo. We have examined signal transduction pathways initiated from a frequently identified gefitinib-sensitizing mutant EGFR lacking residues 746–750 by employing a mouse fibroblast cell line that is free of endogenous EGFR and transiently transfected COS-7 cells. Upon EGF stimulation, the deletion-mutant EGFR mediated prolonged downstream signals. The analysis of the phosphotyrosine patterns of the receptor revealed that the deletion-mutant EGFR lacked phosphorylation at tyrosine residue 1045, which is the major binding site of Cbl. The EGF-induced endocytosis of the deletion-mutant EGFR was impaired. The ubiquitination and downregulation of the deletion-mutant EGFR were also reduced. On the other hand, another mutant, EGFR, possessing a L858R substitution, exhibited phosphorylation at 1045 and its downstream signalings were not prolonged. These data suggest that the signal transduction pathways initiated from these mutant forms are different, and that impaired endocytosis might be responsible for the prolonged signals mediated by the deletion-mutant EGFR. [ABSTRACT FROM AUTHOR]

Background: Milnacipran is one of the classes of drugs that are serotonin and norepinephrine reuptake inhibitors (SNRIs). It is a promising drug for the treatment of neuropathic pain in patients with advanced cancer. However, we found that neuromuscular and somatosensory disorders occurred when milnacipran was used as an adjuvant analgesic. Case report: A 66-year-old woman with a history of neuropathic pain was given 15 mg of milnacipran after dinner. The next morning she developed stiffness of the fingers, numbness in the mandible, and the soles of her feet felt swollen. Milnacipran was discontinued and her symptoms disappeared immediately. We managed this case, which was becoming severe, by discontinuing milnacipran on early detection of symptoms. Discussion: This is the first report that demonstrates an adverse reaction of milnacipran when used as an analgesic adjuvant, and not as an antidepressant drug, for neuropathic pain in patients with advanced cancer. The analgesic effect of SNRIs will likely be used in the management of neuropathic pain in the future; however, clinicians should be aware of the early adverse reactions to these agents. [ABSTRACT FROM AUTHOR]