Summary Adult T-cell leukaemia-lymphoma (ATL) is a malignancy of peripheral T lymphocytes caused by human T-lymphotropic virus type I (HTLV-1), and its prognosis is poor. There are an estimated 5 ...million to 20 million HTLV-1 infected individuals worldwide; their lifetime risk of developing ATL is 3–5%, and high HTLV-1 proviral loads have been shown to be an independent risk factor. Recent advances in the treatment of ATL are the introduction of treatment targeted against CC chemokine receptor 4 (CCR4), which is abundantly expressed on most ATL cells, and allogeneic haemopoietic stem-cell transplantation for aggressive ATL. Promising outcomes are also reported with early intervention for indolent ATL with interferon α and zidovudine. Clinical trials should incorporate a validated prognostic index to assess the results, because of the difficulties associated with undertaking large-scale trials and significant diversity of clinical features with ATL, even in the same clinical subtypes (acute, lymphoma, chronic, and smoldering).
Abstract
Background
A questionnaire survey was conducted to assess the implementation status of geriatric assessment in cancer treatment and the potential for collaboration between medical care and ...the long-term care insurance system.
Methods
Questionnaires were sent to 795 facilities in Japan. The questions were instructed to be answered via an online survey (SurveyMonkey®), which began in September 2020 and closed on 31 October 2020. The questionnaire consisted of 8 questions on the status of geriatric assessment implementation and 15 questions on the long-term care insurance system.
Results
In total, 631 departments in 340 (42.8%) of 795 hospitals and clinics provided responses. Approximately 81.5% of the departments did not perform geriatric assessment. The common reasons were lack of knowledge about geriatric assessment (54.0%) and lack of personnel (35.5%). Even if geriatric assessment was conducted, 63.6% of departments did not utilize geriatric assessment results in clinical practice. Approximately 61.7% of respondents were familiar with the long-term care insurance system and 62.9% with the certification process. Moreover, 28% of respondents used certification examination results in treatment planning.
Conclusions
Geriatric assessment is less recognized than the long-term care insurance system, and its results are rarely used in clinical practice. However, 28% of certification examination results are utilized in treatment decision-making. Notably, this survey first showed the incorporation of the long-term care insurance system into the medical care of vulnerable elderly patients with cancer.
Geriatric assessment is less recognized than the long-term care insurance system, and its results are rarely used in oncological clinical practice.
Li‐Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, and the majority of patients with LFS have been identified with germline variants in the p53 tumor suppressor (TP53) gene. ...In the past three decades, considerable case reports of TP53 germline variants have been published in Japan. To the best of our knowledge, there have been no large‐scale studies of Japanese patients with LFS. In this study, we aimed to identify Japanese patients with TP53 germline variants and to reveal the characteristics of LFS in Japan. We collected reported cases by reviewing the medical literature and cases diagnosed at the institutions of the authors. We identified 68 individuals from 48 families with TP53 germline pathogenic or likely pathogenic variants. Of the 48 families, 35 (72.9%) had missense variants, most of which were located within the DNA‐binding loop. A total of 128 tumors were identified in the 68 affected individuals. The 128 tumor sites were as follows: breast, 25; bones, 16; brain, 12; hematological, 11; soft tissues, 10; stomach, 10; lung, 10; colorectum, 10; adrenal gland, 9; liver, 4; and others, 11. Unique phenotype patterns of LFS were shown in Japan in comparison with those in a large national LFS cohort study in France. Above all, a higher frequency of patients with stomach cancer was observed in Japanese TP53 germline variant carriers. These results may provide useful information for the clinical management of LFS in Japan.
Comparing this study in Japan with a large national Li‐Fraumeni syndrome cohort study in France, the unique phenotype patterns of Li‐Fraumeni syndrome was shown in Japan. Especially, the higher frequency of patients with stomach cancer in Japanese TP53 germline variants carriers was shown.
Lynch syndrome is a cancer-predisposing syndrome inherited in an autosomal-dominant manner, wherein colon cancer and endometrial cancer develop frequently in the family, it results from a ...loss-of-function mutation in one of four different genes (
MLH1
,
MSH2
,
MSH6
, and
PMS2
) encoding mismatch repair proteins. Being located immediately upstream of the
MSH2
gene,
EPCAM
abnormalities can affect
MSH2
and cause Lynch syndrome. Mismatch repair proteins are involved in repairing of incorrect pairing (point mutations and deletion/insertion of simple repetitive sequences, so-called microsatellites) that can arise during DNA replication. MSH2 forms heterodimers with MSH6 or MSH3 (MutSα, MutSβ, respectively) and is involved in mismatch-pair recognition and initiation of repair. MLH1 forms a complex with PMS2, and functions as an endonuclease. If the mismatch repair system is thoroughly working, genome integrity is maintained completely. Lynch syndrome is a state of mismatch repair deficiency due to a monoallelic abnormality of any mismatch repair genes. The phenotype indicating the mismatch repair deficiency can be frequently shown as a microsatellite instability in tumors. Children with germline biallelic mismatch repair gene abnormalities were reported to develop conditions such as gastrointestinal polyposis, colorectal cancer, brain cancer, leukemia, etc., and so on, demonstrating the need to respond with new concepts in genetic counseling. In promoting cancer genome medicine in a new era, such as by utilizing immune checkpoints, it is important to understand the genetic and genomic molecular background, including the status of mismatch repair deficiency.
Background and Objectives: Falls are common among older females. This study investigated the relationships among falls and dietary patterns, nutritional inadequacy and prefrailty in ...community-dwelling older Japanese females. Methods and Study Design: This cross-sectional study involved 271 females aged 65 and over. Prefrailty was defined as exhibiting one or two of the five Japanese version of the Cardiovascular Health Study criteria. Frailty was excluded (n=4). Energy, nutrient and food intakes were estimated using a validated FFQ. Dietary patterns were determined from intakes of 20 food groups assessed with FFQ, by cluster analysis. Nutritional inadequacy for the selected 23 nutrients in each dietary pattern was examined based on DRIs. Binomial logistic regression was applied to examine the relationships among falls and dietary patterns, prefrailty, and inadequate nutrients. Results: Data from 267 participants were included. The incidence of falls was 27.3%, and 37.4% of participants were classified as prefrailty. Three dietary patterns identified were namely; 'rice and fish and shellfish' (n=100); 'vegetables and dairy products' (n=113); and 'bread and beverages' (n=54). A binomial logistic regression analysis revealed that dietary patterns of 'rice and fish and shellfish' (OR, 0.41; 95% CI, 0.16-0.95), and 'vegetables and dairy products' (OR, 0.30; 95% CI, 0.12-0.78) were negatively correlated with falls, and falls was positively associated with prefrailty. Conclusions: Dietary patterns characterized by 'rice and fish and shellfish', and 'vegetables and dairy products' were associated with a reduced incidence of falls in communitydwelling older Japanese females. Larger prospective studies are needed to validate these results.
Background
Many cancer patients suffer from the common side effect of chemotherapy-induced nausea and vomiting (CINV). Guidelines recommend a combination of two prophylactic antiemetics for ...moderately emetogenic chemotherapy (MEC) and three for highly emetogenic chemotherapy (HEC) and certain MEC regimens.
Methods
This multicenter, prospective, observational study analyzed data for 1,910 patients in Japan scheduled for MEC or HEC. Use of antiemetic prophylaxis in relation to type of chemotherapy, incidences of and risk factors for nausea, vomiting, and acute versus delayed CINV, and estimated incidence of CINV by staff were analyzed using Fisher’s exact test and multivariate logistic regression. The patients recorded the incidence of CINV and severity of nausea by visual analogue scales daily for 7 days after receiving chemotherapy.
Results
A total of 240 (20.1 %) HEC and 476 MEC patients (66.6 %) received 2 antiemetics, compared with 883 (73.9 %) and 200 (28.0 %), respectively, who received 3 antiemetics. Approximately 74 % of HEC and 95 % of MEC patients received antiemetic therapy in compliance with guidelines. Acute nausea and vomiting were well controlled, but high incidences of delayed nausea occurred in both HEC and MEC patients. Delayed vomiting (
p
< 0.0001) was significantly less frequent in patients receiving three compared with 2 antiemetics. Female sex was a major risk factor for CINV. Medical staff tended to overestimate the incidence of CINV. Among HEC regimens, the incidence of CINV and the degree of nausea on day 1 of anthracycline–cyclophosphamide combination therapy were higher than with a cisplatin-based regimen.
Conclusions
Adherence to antiemetic guidelines effectively controls vomiting but is less effective against delayed nausea in HEC and MEC patients. Identification of individual risk factors, such as female sex, will assist in the development of personalized treatments for CINV. More intensive antiemetic therapy or a different modality of prophylaxis should be considered for the control of acute CINV in an anthracycline–cyclophosphamide regimen.
We conducted a multicenter prospective study on whether a comprehensive geriatric assessment (CGA) can predict the adverse events (AEs) of chemotherapy in elderly patients with diffuse large B-cell ...lymphoma (DLBCL). Patients aged ≥ 65 years with newly diagnosed DLBCL underwent a pretreatment baseline CGA consisting of six assessment tools: activities of daily living (ADL), instrumental ADL (IADL), mood, nutritional status, comorbidities, and cognitive function. An attending physician chose each patient's treatment but was blind to CGA results. Patients were grouped as "dependent" or "independent" according to the CGA. The primary endpoint was to evaluate the association between chemotherapy-induced grade 3-4 toxicity and CGA. Of 86 patients, 78 completed the designated CGA. The median age was 79 years (65-89). Seventy-two patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP-like) regimen, and six were treated with low-toxicity regimens. Forty-one patients were classified as dependent and 37 as independent. In multivariate analysis, an impairment of IADL was independently associated with grade 3-4 leukopenia (odds ratio OR 0.63; 95% confidence interval CI 0.43-0.92, p = 0.017) and anemia (OR 0.67; 95% CI 0.50-0.90, p = 0.008). The presence of a comorbidity was also associated with grade 3-4 non-hematological toxicity (OR 2.17; 95% CI 1.37-3.43, p = 0.001). The 4-year survival rate tended to be longer in the independent (72.7%) compared to dependent (56.9%) group. Overall, a CGA may be a useful tool for predicting serious AEs associated with chemotherapy in elderly patients with DLBCL.
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