Impact of Perioperative Immunonutrition on Postoperative Outcomes for Patients Undergoing Head and Neck or Gastrointestinal Cancer Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To clarify whether perioperative immunonutrition is effective in adult patients with or without malnutrition undergoing elective surgery for head and neck (HAN) or gastrointestinal (GI) cancers. BACKGROUND: It is important to avoid postoperative complications in patients with cancer as they can compromise clinical outcomes. There is no consensus on the efficacy of perioperative immunonutrition in patients with or without malnutrition undergoing HAN or GI cancer surgery. MATERIALS AND METHODS: We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981 to 2022 using search terms related to immunonutrition and HAN or GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were total postoperative and infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. RESULTS: Of the 4825 patients from 48 included studies, 19 had upper GI cancer, 9 had lower, and 8 had mixed cancer, whereas 12 had HAN cancers. Immunonutrition reduced the total postoperative complications (relative risk ratio: 0.78; 95% CI, 0.66-0.93; certainty of evidence: high) and infectious complications (relative risk ratio: 0.71; 95% CI, 0.61-0.82; certainty of evidence: high) compared with standard nutritional therapy. CONCLUSIONS: Nutritional intervention with perioperative immunonutrition in patients with HAN and GI cancers significantly reduced total postoperative complications and infectious complications.

Feasibility of a fast-track randomized controlled trial of cell-free and concentrated ascites reinfusion therapy for patients with refractory malignant ascites.

BACKGROUND: Malignant ascites often causes discomfort in advanced cancer patients. Paracentesis is the most common treatment modality, but it requires frequently repeated treatment. Cell-free and concentrated ascites reinfusion therapy (CART) may prolong the paracentesis interval, but controlled trials are lacking. We assessed the feasibility of a randomized controlled trial of CART vs. paracentesis alone for patients with refractory malignant ascites. METHODS: This study was an open-label, fast-track, randomized controlled, feasibility trial. Patients admitted to four designated cancer hospitals who received no further anticancer treatments were eligible. Patients were randomly assigned 1:1 to a CART arm or control (simple paracentesis) arm. The feasibility endpoint was the percentage of patients who completed the study intervention. Secondary endpoints included paracentesis-free survival, patient's request on the questionnaire for paracentesis (PRO-paracentesis)-free survival (the period until the patients first reported that they would want paracentesis if indicated), and adverse events. RESULTS: We screened 953 patients for eligibility. Of 61 patients with refractory malignant ascites, 21 patients were determined as eligible. Finally, 20 patients consented and were allocated; 18 patients (90%, 95% CI: 68.3-98.8) completed the study intervention. All patients had an ECOG performance status of 3 or 4. The median drained ascites volume was 3,200 mL in the CART arm and 2,500 mL in the control arm. In the CART arm, the median reinfused albumin volume was 12.6 g. Median paracentesis-free survivals were 5 days (95% CI: 2-6) in the CART arm, and 6 days (3-9) in the control arm. Median PRO-paracentesis-free survivals were 4 days (2-5) and 5 days (1-9), respectively. A total of 73% of patients received paracentesis within 2 days from their first request for the next paracentesis. One patient in the CART arm developed Grade 1 fever. CONCLUSIONS: A fast-track randomized controlled trial of CART for patients with malignant ascites is feasible. The efficacy and safety of CART should be assessed in future trials. PRO-paracentesis-free survival may be a complementary outcome measure with paracentesis-free survival in future trials. TRIAL REGISTRATION: Registered at University Hospital Medical Information Network Clinical Trial Registry as UMIN000031029 . Registered on 28/01/2018.

Factors associated with good death of patients with advanced cancer: a prospective study in Japan.

PURPOSE: It is important for palliative care providers to identify what factors are associated with a "good death" for patients with advanced cancer. We aimed to identify factors associated with a "good death" evaluated by the Good Death Scale (GDS) score among inpatients with advanced cancer in palliative care units (PCUs) in Japan. METHODS: The study is a sub-analysis of a multicenter prospective cohort study conducted in Japan. All variables were recorded on a structured data collecting sheet designed for the study. We classified each patient into better GDS group or worse GDS group, and examined factors associated with better GDS using multivariate analysis. RESULTS: Between January and December 2017, 1896 patients were enrolled across 22 PCUs in Japan. Among them, a total of 1157 patients were evaluated. Five variables were significantly associated with a better GDS score in multivariate analysis: preferred place of death at PCU (odds ratio [OR] 2.85; 95% confidence interval [CI] 1.72-4.71; p < 0.01), longer survival time (OR 1.02; 95% CI 1.00-1.03; p < 0.01), not sudden death (OR 1.96; 95% CI 1.27-3.04; p < 0.01), better spiritual well-being in the last 3 days in life (OR 0.53; 95% CI 0.42-0.68; p < 0.01), and better communication between patient and family (OR 0.81; 95% CI 0.66-0.98; p = 0.03). CONCLUSIONS: We identified factors associated with a "good death" using GDS among advanced cancer patients in Japanese PCUs. Recognition of factors associated with GDS could help to improve the quality of end-of-life care.

Pre-emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer.

BACKGROUND: Intensive cytotoxic chemotherapy for people with cancer can cause severe and prolonged cytopenia, especially neutropenia, a critical condition that is potentially life-threatening. When manifested by fever and neutropenia, it is called febrile neutropenia (FN). Invasive fungal disease (IFD) is one of the serious aetiologies of chemotherapy-induced FN. In pre-emptive therapy, physicians only initiate antifungal therapy when an invasive fungal infection is detected by a diagnostic test. Compared to empirical antifungal therapy, pre-emptive therapy may reduce the use of antifungal agents and associated adverse effects, but may increase mortality. The benefits and harms associated with the two treatment strategies have yet to be determined.  OBJECTIVES: To assess the relative efficacy, safety, and impact on antifungal agent use of pre-emptive versus empirical antifungal therapy in people with cancer who have febrile neutropenia. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, and ClinicalTrials.gov to October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared pre-emptive antifungal therapy with empirical antifungal therapy for people with cancer. DATA COLLECTION AND ANALYSIS: We identified 2257 records from the databases and handsearching. After removing duplicates, screening titles and abstracts, and reviewing full-text reports, we included seven studies in the review. We evaluated the effects on all-cause mortality, mortality ascribed to fungal infection, proportion of antifungal agent use (other than prophylactic use), duration of antifungal use (days), invasive fungal infection detection, and adverse effects for the comparison of pre-emptive versus empirical antifungal therapy. We presented the overall certainty of the evidence for each outcome according to the GRADE approach. MAIN RESULTS: This review includes 1480 participants from seven randomised controlled trials. Included studies only enroled participants at high risk of FN (e.g. people with haematological malignancy); none of them included participants at low risk (e.g. people with solid tumours).  Low-certainty evidence suggests there may be little to no difference between pre-emptive and empirical antifungal treatment for all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72 to 1.30; absolute effect, reduced by 3/1000); and for mortality ascribed to fungal infection (RR 0.92, 95% CI 0.45 to 1.89; absolute effect, reduced by 2/1000). Pre-emptive therapy may decrease the proportion of antifungal agent used more than empirical therapy (other than prophylactic use; RR 0.71, 95% CI 0.47 to 1.05; absolute effect, reduced by 125/1000; very low-certainty evidence). Pre-emptive therapy may reduce the duration of antifungal use more than empirical treatment (mean difference (MD) -3.52 days, 95% CI -6.99 to -0.06, very low-certainty evidence). Pre-emptive therapy may increase invasive fungal infection detection compared to empirical treatment (RR 1.70, 95% CI 0.71 to 4.05; absolute effect, increased by 43/1000; very low-certainty evidence). Although we were unable to pool adverse events in a meta-analysis, there seemed to be no apparent difference in the frequency or severity of adverse events between groups. Due to the nature of the intervention, none of the seven RCTs could blind participants and personnel related to performance bias. We identified considerable clinical and statistical heterogeneity, which reduced the certainty of the evidence for each outcome. However, the two mortality outcomes had less statistical heterogeneity than other outcomes. AUTHORS' CONCLUSIONS: For people with cancer who are at high-risk of febrile neutropenia, pre-emptive antifungal therapy may reduce the duration and rate of use of antifungal agents compared to empirical therapy, without increasing over-all and IFD-related mortality; but the evidence regarding invasive fungal infection detection and adverse events was inconsistent and uncertain.

Development of a national health policy logic model to accelerate the integration of oncology and palliative care: a nationwide Delphi survey in Japan.

BACKGROUND: Despite recommendations to deliver palliative care to cancer patients and their caregivers, their distress has not been alleviated satisfactorily. National health policies play a pivotal role in achieving a comprehensive range of quality palliative care delivery for the public. However, there is no standardised logic model to appraise the efficacy of these policies. This study aimed to develop a logic model of a national health policy to deliver cancer palliative care and to reach consensus towards specific policy proposals. METHODS: A draft version of the logic model and specific policy proposals were formulated by the research team and the internal expert panel, and the independent external expert panel evaluated the policy proposals based on the Delphi survey to reach consensus. RESULTS: The logic model was divided into three major conceptual categories: 'care-delivery at cancer hospitals', 'community care coordination', and 'social awareness of palliative care'. There were 18 and 45 major and minor policy proposals, which were categorised into four groups: requirement of government-designated cancer hospitals; financial support; Basic Plan to Promote Cancer Control Programs; and others. These policy proposals were independently evaluated by 64 external experts and the first to third Delphi round response rates were 96.9-98.4%. Finally, 47 policy proposals reached consensus. The priority of each proposal was evaluated within the four policy groups. CONCLUSIONS: A national health policy logic model was developed to accelerate the provision of cancer palliative care. Further research is warranted to verify the study design to investigate the efficacy of the logic model.

Development of a list of competencies and entrustable professional activities for resident physicians during death pronouncement: a modified Delphi study.

BACKGROUND: The appropriate delivery of death pronouncements potentially affects bereaved families' wellbeing positively. Although younger physicians need to learn the competencies and entrustable professional activities (EPAs) to conduct death pronouncement independently, both of which have not been clarified. Therefore, this study aimed to develop a list of competencies and EPAs necessary for death pronouncement practice, which resident physicians need to acquire by the end of their residency training (postgraduate year 2). METHODS: An anonymous modified Delphi study was conducted with a panel of 31 experts. The experts were invited online from general wards in hospitals with resident physicians across Japan to participate in the study using the purposive and snowball sampling method. A non-anonymous web conference was held with three additional external evaluators to finalize the item list. The consensus criterion was defined as a mean response of at least 4 points on a 5-point Likert scale for each competency and EPA item and a rating of 4 or 5 points by at least 80% of the participants. RESULTS: Consensus was achieved, with consistently high levels of agreement across panel members, on 11 competencies and 9 EPA items. Additionally, a correspondence matrix table between competencies and EPAs was developed. CONCLUSIONS: This study clarified the standardized educational outcomes as competencies in death pronouncement practice and the unit of professional practice of physicians who can perform this independently (EPAs), serving as a blueprint to aid the development of an educational model and evaluation method for clinical educational institutions and developers of medical school curriculums.

A model six-month workshop for developing systematic review protocols at teaching hospitals: action research and scholarly productivity.

BACKGROUND: Research engagement contributes to the improvement of patient care. A systematic review is a suitable first scholarly activity because it entails summarization of publicly available data and usually requires neither rigorous ethical review nor research funding. METHODS: This study aimed to develop a model workshop for healthcare staff to acquire skills in creating systematic review protocols based on their own clinical questions at teaching hospitals. We used an action research method to create a model workshop at four hospitals in Japan from April 2015 to March 2017. To improve the program, we solicited reflections using participant questionnaires for each lecture and examined the quality of homework submitted by participants after each lecture. We administered a revised final version of the workshop at five hospitals from April 2016 to March 2017. We evaluated the participants' scholarly productivity related to these workshops. The observation period was a minimum of 2 years following the workshops. RESULTS: Most participants had never developed a formal clinical research protocol and voluntarily participated in the workshop. The action research was developed and implemented at nine teaching hospitals in Japan, including one university hospital. The study developed a model nine-step workshop curriculum: 1) Research question development, 2) Search strategy development, 3) Search strategy brush-up, 4) Exclusion and inclusion criteria development, 5) Risk of bias assessment planning, 6) Meta-analysis planning, 7) Subgroup and sensitivity analysis planning, 8) Planning the presentation of results, and 9) Presentation protocols. A total of 233 participants, including medical doctors and other health professionals, produced 414 research questions. Seventy-nine participants (34%) completed the workshop, and 47 review teams accomplished systematic review protocols. The participants published 13 peer-reviewed articles as a result of the workshop. CONCLUSIONS: We developed a structured scholarly productive model workshop for healthcare staff working at hospitals. We found healthcare staff with clinical subspecialties were able to develop an unexpectedly high number of research questions through this workshop. Medical teachers at hospitals with prior systematic review experience could teach how to develop systematic review protocols using this model. Further research is needed to increase the academic productivity of such workshops. TRIAL REGISTRATION: UMIN (https://www.umin.ac.jp/ctr/), UMIN000017107 (4/15/2015), UMIN000025580 (1/10/2017).

Adding a Wider Range and "Hope for the Best, and Prepare for the Worst" Statement: Preferences of Patients with Cancer for Prognostic Communication.

INTRODUCTION: Although various phrases to communicate prognoses based on a certain concept have been proposed, no study has systematically investigated preferences of patients with cancer for actual phrases. We investigated whether phrases with a wider range and additional "hope for the best, and prepare for the worst" (hope/prepare) statement would be more preferable and explored variables associated with patients' preferences. MATERIALS AND METHODS: In a cross-sectional survey, 412 outpatients with cancer self-assessed their preferences for 13 phrases conveying prognostic information (e.g., phrases with or without median, typical range, and/or best/worst cases, and those with or without a hope/prepare statement) on a 6-point scale (1 = not at all preferable; 6 = very preferable). We evaluated demographic data and the Coping Inventory for Stressful Situations and conducted multivariate regression analysis. RESULTS: Regarding phrases with various ranges, the one including the median, typical range, and best/worst cases was more preferable (mean ± SD, 3.8 ± 1.3; 95% confidence interval [CI], 3.6-3.9) than the one with the median and typical range (3.4 ± 1.2; 3.3-3.6) or the one with only the median (3.2 ± 1.3; 3.1-3.3). Concerning the hope/prepare statement, the phrase including the median, typical range, uncertainty, and hope/prepare statement was more preferable (3.8 ± 1.4; 3.7-3.9) than the one without the statement (3.5 ± 1.2; 3.4-3.6). In multivariate analyses, task-oriented coping was significantly correlated with preferences for phrases with explicit information. CONCLUSION: Overall, phrases with a wider range and the hope/prepare statement were preferable to those without them. When patients with cancer ask about prognoses, especially those with task-oriented coping, clinicians may provide explicit information with a wider range and the hope/prepare statement. IMPLICATIONS FOR PRACTICE: Discussing prognoses with patients with advanced cancer is among the most important conversations for clinicians. In this cross-sectional survey to systematically investigate preferences of 412 patients with cancer for phrases conveying prognostic information, phrases with the median, typical range, and best/worst cases and those with the "hope for the best and prepare for the worst" (hope/prepare) statement were the most preferred. When patients with cancer ask about prognoses, clinicians may provide explicit information with a wider range and include the hope/prepare statement.

Severe esophagitis associated with cytomegalovirus during concurrent chemoradiotherapy for esophageal cancer.

Although radiation esophagitis is one of the most common adverse events that occurs during chemoradiotherapy (CRT) in patients with esophageal cancer, CRT-associated cytomegalovirus (CMV) esophagitis is rare. CMV esophagitis typically occurs in patients with an immunosuppressed status. Here we report a case of CMV esophagitis during CRT initially treated as radiation esophagitis. A 64-year-old man with mid-thoracic esophageal cancer was admitted to our hospital with clinical stage cT4bN1M1 (supraclavicular lymph node metastasis) Stage IV according to the UICC ver. 7 guidelines, and he was administered definitive concurrent CRT. From the 39th day of CRT onwards, he presented with a sustained fever and severe odynophagia that was resistant to antibiotic therapy. An esophagoscopy revealed severe esophagitis with a circumferential ulcer throughout the entire esophagus, and CMV esophagitis was clinically suspected because of positive result of CMV antigenemia. Subsequently, antiviral therapy for CMV provided dramatic relief of his symptoms. Later, CMV DNA was confirmed with a polymerase chain reaction in the biopsy specimen.The symptoms of CMV esophagitis resemble those of radiation esophagitis and can make the diagnosis difficult. Thus, CMV esophagitis associated CRT may be overlooked or masked by radiation esophagitis and can cause a delay in healing. Therefore, CMV esophagitis may be considered when severe intractable esophagitis is observed during CRT.

Association between UGT1A1*28*28 genotype and lung cancer in the Japanese population.

BACKGROUND: Lung cancer is the leading cause of cancer death and is closely linked to tobacco smoking. Genetic polymorphisms in genes that encode enzymes involved in metabolizing tobacco carcinogens could affect an individual's risk for lung cancer. While polymorphism of UDP-glucuronosyltransferase1A1 (UGT1A1) is involved in detoxification of benzo(a)pyrene-7,8-dihydrodiol(-), a major tobacco carcinogen, the association between UGT1A1 genotype and lung cancer has not been examined. METHODS: We retrieved the clinical data of 5,285 patients who underwent systemic chemotherapy at Kyoto University Hospital. A total of 765 patients (194 lung cancer patients and 671 patients with other malignancies) with UGT1A1 genotyping data were included in this analysis. We used logistic regression with recessive, dominant, and additive models to identify differences in genotype frequencies between lung cancer and other malignancies. RESULTS: In the recessive model, UGT1A1*28*28 genotype was significantly associated with lung cancer compared to other malignancies (odds ratio 5.3, P = 0.0083). Among lung cancer patients with a smoking history, squamous cell carcinoma was significantly predominant in patients with UGT1A1*28*28 compared to those with other UGT1A1 genotypes (P = 0.024). CONCLUSION: This is the first study to demonstrate a significant association between the homozygous UGT1A1*28 genotype and lung cancer.

Successful Management of Malignant Pericarditis Using Nivolumab for Metastatic Esophageal Squamous Cell Carcinoma.

Esophageal cancer is a malignant disease with a poor prognosis and is one of the most common causes of cardiac metastasis. Malignant pericarditis may cause the repetitive accumulation of pericardial effusion, which can occasionally pose a clinical challenge. We herein report a case of malignant pericarditis in a patient with metastatic esophageal squamous cell carcinoma with cardiac tamponade, which was successfully managed with single pericardial drainage and systemic nivolumab monotherapy. This is the first case report to suggest that systemic therapy with nivolumab is a promising option for the management of malignant pericarditis.

Impacts of fluid retention on prognostic abilities of cachexia diagnostic criteria in cancer patients with refractory cachexia.

BACKGROUND & AIMS: The international cancer cachexia criteria with a cutoff of 5% weight loss (WL) was proposed in Western patients. The Asian Working Group for Cachexia (AWGC) developed new criteria in Asian patients. The AWGC criteria are not cancer-specific and employ a cutoff of 2% WL. However, it is unclear whether both criteria are useful in patients with very advanced cancer because WL can be underestimated owing to fluid retention. Therefore, this study aimed to investigate the impacts of fluid retention on the prognostic abilities of both criteria in cancer patients with weeks of survival. METHODS: This study involved a secondary analysis of a prospective cohort study. The inclusion criteria constrained the study to adult patients with advanced cancer. Patients were divided into Non-cachexia and Cachexia groups using the international criteria and AWGC criteria. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: A total of 402 patients were included in the analysis. Using the international criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.55 and 0.18, respectively. Using the AWGC criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.38 and 0.12, respectively. Without considering the impacts of fluid retention, no significant differences were observed between the Non-cachexia and Cachexia groups for both criteria. After adjusting for the status of fluid retention, significantly higher risks of mortality were not observed in the Cox proportional hazard model for the Cachexia group compared with the Non-cachexia group, for both criteria. However, significant associations were observed between fluid retention and overall survival. CONCLUSIONS: The international criteria and AWGC criteria lost their prognostic abilities in cancer patients with weeks of survival. Since measurements of %WL were significantly confounded by fluid retention, fluid retention-adjusted criteria for cachexia need to be developed for cancer patients with refractory cachexia.

Barriers and Facilitators to the Implementation of an Electronic Patient-Reported Outcome System at Cancer Hospitals in Japan.

Background and objective Implementing electronic patient-reported outcomes (ePROs) in oncology practice has shown substantial clinical benefits. However, it can be challenging in routine practice, warranting strategies to adapt to different clinical contexts. In light of this, this study aimed to describe the implementation process of the ePRO system and elucidate the provider-level implementation barriers and facilitators to a novel ePRO system at cancer hospitals in Japan. Methods We implemented an ePRO system linked to electronic medical records at three cancer hospitals. Fifteen patients with solid cancers at the outpatient oncology unit were asked to regularly complete the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) questionnaire and European Organization for Research and Treatment Core Quality of Life questionnaire (EORTC QLQ C30) by using the smartphone app between October 2021 and June 2022. Thirteen healthcare professionals were interviewed to identify implementation barriers and facilitators to the ePRO system by using the Consolidated Framework for Implementation Research framework. Results The healthcare professionals identified a lack of clinical resources and a culture and system that emphasizes treatment over care as the main barriers; however, the accumulation of successful cases, the leadership of managers, and the growing needs of patients can serve as facilitators to the implementation. Conclusions Our experience implementing an ePRO system in a few Japanese oncology practices revealed comprehensive barriers and facilitators. Further efforts are warranted to develop more successful implementation strategies.

Dietary intervention for adult survivors of cancers other than breast cancer: A systematic review.

INTRODUCTION: Healthy eating and weight control are recommended for cancer survivors; however, dietary interventions are not routinely offered to them. This study aimed to assess the effects of dietary interventions on survival, nutritional status, morbidity, dietary changes, health-related quality of life (QOL), and clinical measures in cancer survivors. METHODS: Searches were conducted from October 1, 2018 to November 21, 2011 in the Medline, EMBASE, CENTRAL, Emcare, and DARE electronic databases. We included randomized controlled trials (RCTs) that involved individuals diagnosed with cancer, excluding conference abstracts, case studies, other reviews, and meta-analyses, and screened the articles. RESULTS: Eight studies were included in this meta-analysis. We observed significant improvements in QOL and clinical data in 3 of 6 studies and in one study, respectively, significant weight loss on anthropometry in 2 of 5 studies, and dietary improvement in 4 of 5 studies of adult cancer survivors. However, we did not observe any benefits of dietary intervention for cancer survivors with undernutrition. DISCUSSION: Dietary interventions for adult cancer survivors might contribute to improving their nutritional status; however, further clarification requires a study that standardizes the intervention method. Furthermore, RCTs are required to determine the effects on cancer survivors with undernutrition.

Fluid retention and weight loss in refractory cancer cachexia.

OBJECTIVES: It is unknown to what extent the fluid retention (FR) status disrupts the detection of weight loss rate (WLR) in adult patients with advanced cancer. This study aimed to determine the association of FR status with WLR. METHODS: This study was a secondary analysis of a prospective cohort study. FR was evaluated as follows: oedema (0, no; 1, yes), pleural effusion (0, no; 1, yes but asymptomatic; 2, symptomatic) and ascites (0, no; 1, yes but asymptomatic; 2, symptomatic). Patients were divided into three groups according to their FR scores: no-FR (0), moderate-FR (1-2) and high-FR (3-5). Multiple regression analysis was performed. RESULTS: Four hundred and twenty patients were categorised: no-FR group (n=164), moderate-FR group (n=158) and high-FR group (n=98). The prevalence of oedema, pleural effusion and ascites was 63.9%, 27.8% and 36.7% in the moderate-FR group, and 93.9%, 61.3% and 82.6% in high-FR group. The means of WLR were 9.2, 8.4 and 3.8 in the groups. The high-FR group and the FR score of 5 were correlated with WLR (estimate -4.71, 95% CI -7.84 to -1.58; estimate -10.29, 95% CI -17.84 to -2.74). CONCLUSIONS: The coexistence of FR was significantly correlated with WLR.

Determinants of Attitude Toward End-of-Life Care Among Junior Physicians: Findings from a Nationwide Survey in Japan.

Background: Physicians' attitudes can be critical in quality end-of-life care. However, the determinants of the attitudes and whether the attitudes can be modified remain unclear. Objectives: To investigate factors correlated with physicians' positive attitudes toward end-of-life care and whether these attitudes are modifiable through acquired factors (e.g., education or mentorship). Design: A nationwide survey was conducted in 300 institutions and selected randomly from 1037 clinical training hospitals in Japan. Participants: From each selected institution, two resident physicians of postgraduate year (PGY) 1 or 2 and two clinical fellows from PGY 3-5 were requested to answer the survey. Measurements: The primary outcome was the Frommelt Attitudes Toward the Care of the Dying (FATCOD) scale score. Factors (e.g., the respondents' age, sex, number of years of clinical experience, training environment, religion, and beliefs around death) were examined for correlation with FATCOD score. Results: In all, 198 physicians and 134 clinical fellows responded to the survey (response rate: 33.0% and 22.3%, respectively). Factors with the strongest correlation with FATCOD scores were mostly unmodifiable factors (e.g., being female and one's beliefs around death). Modifiable factors were also identified-number of patient deaths experienced, level of interest in palliative care, availability of support from senior mentors, and frequency of consultation with nonphysician medical staff. Conclusion: Physicians' attitudes toward end-of-life care correlate more strongly with nonmodifiable factors, but attitudes can be meaningfully improved via mentoring by senior physicians. Future studies are warranted to determine the effective interventions to foster positive attitudes among physicians involved in end-of-life care.

Nutritional counseling for patients with incurable cancer: Systematic review and meta-analysis.

BACKGROUND & AIMS: This systematic review aims to determine whether nutritional counseling by registered dietitians and/or nutritional specialists is recommended for adult patients with incurable advanced or recurrent cancer who are refractory to or intolerant of anticancer therapy. METHODS: This systematic review analyzed randomized controlled trials (RCTs) of nutritional counseling in cancer patients older than 18 years, primarily those with stage 4 cancer. Nutrition counseling was performed by registered dietitians and/or nutritional specialists using any method, including group sessions, telephone consultations, written materials, and web-based approaches. We searched the Medline (PubMed), Medline (OVID), EMBASE (OVID), CENTRAL, Emcare, and Web of Science Core Collection databases for articles published from 1981 to 2020. Two independent authors assessed the risk of bias used the Cochrane Risk of Bias 2 tool. Meta-analysis was performed for results and outcomes that allowed quantitative integration. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (ID: CRD42021288476) and registered in 2021. RESULTS: The search yielded 2376 studies, of which 7 assessed 924 patients with cancer aged 24-95 years. Our primary outcome of quality of life (QoL) was reported in 6 studies, 2 of which showed improvement with nutritional counseling. Our other primary outcome of physical symptoms was reported in two studies, one of which showed improvement with nutritional counseling. Quantitative integration of both QoL and physical symptoms was difficult. A meta-analysis of energy and protein intake and body weight was performed for secondary outcomes. Results showed that nutrition counseling increased energy and protein intake, but total certainty of evidence (CE) was low. Bodyweight was not improved by nutrition counseling. CONCLUSIONS: Nutrition counseling is shown to improve energy and protein intake in patients with incurable cancer. Although neither nutrient intake can be strongly recommended because of low CE, nutrition counseling is a noninvasive treatment strategy that should be introduced early for nutrition intervention for patients with cancer. This review did not find sufficient evidence for the effect of nutrition counseling on QoL, a patient-reported outcome. Overall, low-quality and limited evidence was identified regarding the impact of nutrition counseling for patients with cancer, and further research is needed.

Case report on the legal assurance of Advance Care Planning in collective culture.

This case report shows that there is a lack of a legal framework in Japan to protect patients' right during the end-of-life period, which hinders the implementation of ACP in medical practice. This report suggests that legal support can contribute to the advancement of ACP while addressing cultural differences.

Difficulties Facing Junior Physicians and Solutions Toward Delivering End-of-Life Care for Patients with Cancer: A Nationwide Survey in Japan.

Background: Junior physicians' perceived difficulty in end-of-life care of patients with cancer has not been structurally investigated; therefore, current challenges and solutions in this area remain unknown. Objectives: To identify some difficulties junior physicians face in delivering end-of-life care for patients with cancer and to clarify the support required to reduce these difficulties. Design: A nationwide survey was conducted in over 300 institutions selected randomly from 1037 clinical training hospitals in Japan. Participants: From each of these institutions, two resident physicians of postgraduate year (PGY) 1 or 2, two clinical fellows of PGY 3-5, and an attending physician were requested to respond to the survey. Measurements: The survey investigated issues regarding end-of-life care using the palliative care difficulties scale with two additional domains ("discussion about end-of-life care" and "death pronouncement"). Items related to potential solutions for alleviating the difficulties as well were investigated. Results: A total of 198 resident physicians, 134 clinical fellows, and 96 attending physicians responded to the survey (response rate: 33.0%, 22.3%, and 32.0%). The results revealed that junior physicians face difficulties within specific domains of end-of-life care. The most challenging domain comprised communication and end-of-life discussion with patients and family members, symptom alleviation, and death pronouncement. The most favored supportive measure for alleviating these difficulties was mentorship, rather than educational opportunities or resources regarding end-of-life care. Conclusion: The findings of this study reveal the need for further effort to enrich the mentorship and support systems for junior physicians delivering end-of-life care.