Anamorelin for the Treatment of Cancer Anorexia-Cachexia Syndrome.

PURPOSE OF REVIEW: The following review will highlight the development of anamorelin to treat cancer anorexia-cachexia syndrome (CACS) including the potential benefits, limitations, and future directions. RECENT FINDINGS: Ghrelin, a 28-amino acid peptide hormone, is secreted by the stomach mucosa and regulates appetite, promotes lipogenesis, increases body weight, improves gastric motility, reduces catabolic wasting and inflammation. Several randomized, double-blind, placebo-controlled clinical trials evaluating anamorelin, a ghrelin agonist, for the treatment of CACS have reported improvement in appetite and body composition including both lean body and fat mass; however, most studies noted no improvement in physical function as assessed by measuring non-dominant hand-grip strength. Common adverse effects of anamorelin include the development of diabetes mellitus, hyperglycemia, and less frequently, hepatic abnormalities and cardiovascular events including conduction abnormalities, hypertension, and ischemic cardiomyopathy. Anamorelin has the potential to stimulate appetite, improve gastric movement, and may have anti-inflammatory effects on patients with CACS. In patients with cancer, studies involving anamorelin combined with other multimodal treatments including nutrition counseling (branched chain amino acids, omega 3 fatty acids, and other nutrients), exercise, treatment of hormonal abnormalities including hypogonadism and hypovitaminosis D, and anti-inflammatory agents are needed. Compliance with multimodality treatment has been a barrier and future studies may need to incorporate motivational counseling to promote adherence.

Factors associated with multimodal care practices for cancer cachexia among registered dietitians.

PURPOSE: This study aimed to determine factors associated with multimodal care practices for cancer cachexia among registered dietitians (RDs) working in cancer care. METHODS: A secondary analysis was performed using RDs' data. Data on knowledge, skills, and confidence in multimodal care were obtained. Nine items regarding multimodal care practices were evaluated. Subjects were divided into two groups based on their answers associated with the nine items. Comparisons were obtained using the Mann-Whitney U test or chi-squared test. Multiple regression analysis was performed to identify the critical factors involved in practicing multimodal care by determining the variables with significant differences between the two groups. RESULTS: Two hundred thirty-two RDs were included in this study. Significant differences were observed in their primary area of practice (p = 0.023), the number of clinical guidelines used (p < 0.001), the number of items used in cancer cachexia assessment (p = 0.002), the number of symptoms used in cancer cachexia assessment (p = 0.039), training for cancer cachexia (p < 0.001), knowledge of cancer cachexia (p < 0.001), and confidence in cancer cachexia management (p < 0.001). The number of symptoms used in cancer cachexia assessment (B = 0.42, p = 0.019), knowledge of cancer cachexia (B = 6.60, p < 0.001), and confidence in cancer cachexia management (B = 4.31, p = 0.010) were identified as critical factors according to the multiple regression analysis. CONCLUSION: The RDs' knowledge and confidence in cancer cachexia management were associated with their multimodal care practices.

Associations of nutrition impact symptoms with depression in patients with advanced cancer.

PURPOSE: Advanced cancer patients have nutrition impact symptoms (NISs), while many of them have depressive moods. This study aimed to determine the associations of NISs with depression. METHODS: This study was a secondary analysis. The dietary intake and 19 NISs in patients receiving palliative care were evaluated using 10-point scales, and the patients were categorized into two groups (non-depression and depression groups) using the cutoff based on the Patient Health Questionnaire-9 (PHQ-9). To determine associations between depression and the number of NISs with a score of ≥ 4, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the logistic regression model were calculated. RESULTS: A total of 225 participants were divided into the non-depression group (n = 148) and the depression group (n = 77). The prevalence of depression was 34.2%. Dietary intake was lower, and the number of NISs with a score of ≥ 4 was higher in the depression group (both p < 0.001). All NISs were more severe in the depression group. Significant differences were observed in 15 of the 19 NISs. In the logistic regression model, significantly higher adjusted ORs were observed in the groups with 4-6 NISs and 7 or more NISs with a score of ≥ 4 (10.76 [95% CI, 2.07-55.91], p = 0.016; 17.02 [95% CI, 3.08-94.22], p < 0.001) than in the group with no NISs with a score of ≥ 4. CONCLUSION: Having four or more NISs with a score ≥ 4 was associated with depression.

Effectiveness of antipsychotics for managing agitated delirium in patients with advanced cancer: a secondary analysis of a multicenter prospective observational study in Japan (Phase-R).

PURPOSE: Delirium is a common and serious comorbidity in patients with advanced cancer, necessitating effective management. Nonetheless, effective drugs for managing agitated delirium in patients with advanced cancer remain unclear in real-world settings. Thus, the present study aimed to explore an effective pharmacotherapy for this condition. METHODS: We conducted a secondary analysis of a multicenter prospective observational study in Japan. The analysis included patients with advanced cancer who presented with agitated delirium and received pharmacotherapy. Agitation was defined as a score of the Richmond Agitation-Sedation Scale for palliative care (RASS-PAL) of ≥ 1. The outcome was defined as -2 ≤ RASS-PAL ≤ 0 at 72 h after the initiation of pharmacotherapy. Multiple propensity scores were quantified using a multinomial logistic regression model, and adjusted odds ratios (ORs) were calculated for haloperidol, chlorpromazine, olanzapine, quetiapine, and risperidone. RESULTS: The analysis included 271 patients with agitated delirium, and 87 (32%) showed -2 ≤ RASS-PAL ≤ 0 on day 3. The propensity score-adjusted OR of olanzapine was statistically significant (OR, 2.91; 95% confidence interval, 1.12 to 7.80; P = 0.030). CONCLUSIONS: The findings suggest that olanzapine may effectively improve delirium agitation in patients with advanced cancer.

Psychological symptom burden associated with malignant wounds: Secondary analysis of a prospective cohort study.

OBJECTIVES: Patients with malignant wounds suffer from physical and psychological symptom burden. Despite psychological support being required, the impact of malignant wounds on patients' psychological distress is poorly investigated. We evaluated psychological distress associated with malignant wounds for patients at their end of life. METHODS: This study used the secondary analysis of the results of a large prospective cohort study, which investigated the dying process among patients with advanced cancer in 23 palliative care units in Japan. The primary outcome of this study was the prevalence of moderate to severe psychological symptom burden, evaluated by the Integrated Palliative Care Outcome Scale (IPOS)-feeling at peace scores of 2-4. In addition, the factors affecting psychological symptoms were investigated. The quality of death was also evaluated upon death using the Good Death Scale score. RESULTS: Out of the total 1896 patients, 156 had malignant wounds (8.2%). Malignant wounds were more common in female and young people. The breast, head, and neck were the most prevalent primary sites. More patients with malignant wounds had IPOS-feeling at peace scores of 2-4 than patients without malignant wounds (41.0% vs. 31.3%, p = 0.024). Furthermore, psychological distress was associated with moderate to severe IPOS-pain and the frequency of dressing changes. The presence of malignant wounds did not affect the quality of death. SIGNIFICANCE OF RESULTS: This study showed increased psychological distress due to malignant wounds. Patients with malignant wounds require psychological support in addition to the treatment of physical symptoms for maintaining their quality of life.

Diagnostic and prognostic utility of phase angle in patients with cancer.

Patients with cancer experience dynamic and longitudinal changes in nutritional status and body composition along the disease trajectory. They often want to know about their outlook with regard to treatment outcomes and overall survival. One of the commonly used measures for body composition is bioelectrical impedance analysis (BIA). BIA is an easy-to-use, quick, inexpensive, noninvasive, and reproducible technique that is often incorporated in daily clinical practice. Phase angle (PA), which is derived from BIA, is an indicator of cell membrane health and integrity. Higher PA values reflect better cell function, higher muscle mass, and lower fat mass. PA is also thought to be a proxy of water distribution (ratio between extracellular water [ECW] and intracellular water [ICW]) and body cell mass. In this narrative review, we discuss studies examining the diagnostic and prognostic value of PA regarding nutritional status, body composition and physical function, complications of cancer treatments, overall survival, symptoms, and quality of life (QOL) in patients with cancer. The literature suggests that PA is moderately to strongly correlated with body composition and physical function but only weakly correlated with nutritional status, complications, survival, symptoms, and QOL. Furthermore, the PA cutoff values vary significantly according to study and patient population with the diversity of bioelectrical impedance technology and electrode composition and placement. Thus, PA has yet to be routinely incorporated into clinical practice for patients with cancer. Future research is needed to determine how to translate scientific understanding of PA to clinical practice.

Hyperdry Human Amniotic Membrane as a Protective Dressing for Open Wounds With Exposed Bowel in Mice.

INTRODUCTION: An enteroatmospheric fistula forms when the exposed bowel is perforated with chronic enteric fistula formation. Currently, there is no established preventative method for this condition. Hyperdry (HD) amniotic membrane (AM) can promote early granulation tissue formation on the exposed viscera and is suitable for dressing intractable wounds as it possesses anti-inflammatory, antibacterial, and immunomodulatory properties. This study investigated whether HD-AM promotes early formation of blood vessel-containing granulation tissue for enteroatmospheric fistula treatment. METHODS: An experimental animal model of an open wound with exposed bowel was developed. A 15 × 20 mm wound was prepared on the abdomen of Institute of Cancer Research mice, and the HD-AM was placed. The mice were assigned to one of the following groups: HD-AM group, in which the stromal layer of the HD-AM was placed in contact with the exposed bowel; HD-AM UD group, in which the epithelial layer of the HD-AM was placed in contact with the exposed bowel; and the HD-AM (-) or control group, in which the HD-AM was not used. RESULTS: On postoperative days 7 and 14, granulation tissue thickness significantly increased in the HD-AM and HD-AM UD groups compared with that in the HD-AM (-) group. Macrophages accumulated in the HD-AM epithelium only in the HD-AM group. During HD-AM contact, a subset of invading macrophages switched from M1 to M2 phenotype. CONCLUSIONS: HD-AM is a practical wound dressing with its scaffolding function, regulation of TGF ß-1 and C-X-C motif chemokine 5 (CXCL-5), and ability to induce M1-to-M2 macrophage conversion.

Perspectives of registered dietitians and factors associated with their personal accomplishment in the management of cancer cachexia.

PURPOSE: Registered dietitians (RDs) have the potential in cancer cachexia management. We investigated RDs' knowledge on cancer cachexia and assessed the effects of factors on RDs' perception of playing an important role in cancer cachexia management. METHODS: This is a secondary analysis of a survey examining the perspectives of health care professionals on cancer cachexia management. We sent the questionnaire to 451 RDs. RDs were divided into two groups: RDs with and without the perception. Comparisons were made using the Mann-Whitney U test or chi-square test. To examine the effects of factors on the perception, estimated crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the logistic regression model were calculated. RESULTS: A total of 237 RDs were analyzed. Significant differences were observed in the number of cancer patients/month, the primary area of practice, the number of clinical guidelines used, the number of items used, the number of symptoms used, and training for cancer cachexia management (p values all < 0.05). After adjustments, the factors of cancer care experience ≥ 20 years (OR 8.32, 95% CI 1.22-56.70; p = 0.030), the number of patients/month ≥ 50 (OR 27.35, 95% CI 3.99-187.24; p = 0.001), using the clinical guidelines (OR 2.69, 95% CI 1.29-5.61; p = 0.008), the number of items ≥ 5 (OR 3.52, 95% CI 1.47-8.40; p = 0.005), and receiving training (OR 3.91, 95% CI 1.77-8.67; p = 0.001) significantly associated with the perception. CONCLUSION: Specific knowledge and training as well as abundant experience were associated with the perception.

Multinational Association of Supportive Care in Cancer (MASCC) guidelines: cannabis for psychological symptoms including insomnia, anxiety, and depression.

PURPOSE: During the treatment of cancer, 18% of patients use cannabis for symptom management. Anxiety, depression, and sleep disturbances are common symptoms in cancer. A systematic review of the evidence for cannabis use for psychological symptoms in cancer patients was undertaken to develop a guideline. METHODS: A literature search of randomized trials and systematic reviews was undertaken up to November 12, 2021. Studies were independently assessed for evidence by two authors and then evaluated by all authors for approval. The literature search involved MEDLINE, CCTR, EMBASE, and PsychINFO databases. Inclusion criteria included randomized control trials and systematic reviews on cannabis versus placebo or active comparator in patients with cancer and psychological symptom management (anxiety, depression, and insomnia). RESULTS: The search yielded 829 articles; 145 from Medline, 419 from Embase, 62 from PsychINFO, and 203 from CCTR. Two systematic reviews and 15 randomized trials (4 on sleep, 5 on mood, 6 on both) met eligibility criteria. However, no studies specifically assessed the efficacy of cannabis on psychological symptoms as primary outcomes in cancer patients. The studies varied widely in terms of interventions, control, duration, and outcome measures. Six of 15 RCTs suggested benefits (five for sleep, one for mood). CONCLUSION: There is no high-quality evidence to recommend the use of cannabis as an intervention for psychological symptoms in patients with cancer until more high-quality research demonstrates benefit.

MASCC guideline: cannabis for cancer-related pain and risk of harms and adverse events.

BACKGROUND: Approximately 18% of patients with cancer use cannabis at one time as palliation or treatment for their cancer. We performed a systematic review of randomized cannabis cancer trials to establish a guideline for its use in pain and to summarize the risk of harm and adverse events when used for any indication in cancer patients. METHODS: A systematic review of randomized trials with or without meta-analysis was carried out from MEDLINE, CCTR, Embase, and PsychINFO. The search involved randomized trials of cannabis in cancer patients. The search ended on November 12, 2021. The Jadad grading system was used for grading quality. Inclusion criteria for articles were randomized trials or systematic reviews of randomized trials of cannabinoids versus either placebo or active comparator explicitly in adult patients with cancer. RESULTS: Thirty-four systematic reviews and randomized trials met the eligibility criteria for cancer pain. Seven were randomized trials involving patients with cancer pain. Two trials had positive primary endpoints, which could not be reproduced in similarly designed trials. High-quality systematic reviews with meta-analyses found little evidence that cannabinoids are an effective adjuvant or analgesic to cancer pain. Seven systematic reviews and randomized trials related to harms and adverse events were included. There was inconsistent evidence about the types and levels of harm patients may experience when using cannabinoids. CONCLUSION: The MASCC panel recommends against the use of cannabinoids as an adjuvant analgesic for cancer pain and suggests that the potential risk of harm and adverse events be carefully considered for all cancer patients, particularly with treatment with a checkpoint inhibitor.

Impact of taste/smell disturbances on dietary intakes and cachexia-related quality of life in patients with advanced cancer.

PURPOSE: Taste and smell are used to enjoy meals; however, impairments of these sensory perceptions seriously impact health and eating habits. This study is aimed at investigating the impact of taste and smell disturbances on dietary intakes and cachexia-related quality of life (QOL) in patients with advanced cancer. METHODS: Using a self-report questionnaire, we surveyed patients with advanced cancer undergoing treatment at 11 palliative care centers. Multivariate analyses were conducted to explore the impact of taste and smell disturbances on dietary intakes and cachexia-related QOL. Dietary intakes were assessed using the Ingesta-Verbal/Visual Analog Scale, while taste and smell disturbances were assessed using an 11-point Numeric Rating Scale (NRS). Cachexia-related QOL was assessed using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia Cachexia Subscale (FAACT ACS). RESULTS: Overall, 378 patients provided consent to participate. After excluding patients with missing data, data were analyzed for 343 patients. Among them, 35.6% (n = 122; 95% [confidence interval (CI)] 0.28-0.38) and 20.9% (n = 72; 95% CI 0.17-0.25) experienced disturbances in taste (NRS ≥ 1) and smell (NRS ≥ 1), respectively. Multivariate analyses revealed that, independent of performance status and cancer cachexia, taste and smell disturbances were significantly associated with worse dietary intakes and deteriorating FAACT ACS scores. CONCLUSION: More severe taste and smell disturbances were associated with poorer dietary intakes and cachexia-related QOL. Diagnosing and treating such disturbances may improve dietary intakes and cachexia-related QOL, regardless of performance status and cachexia.

Life-cycle analysis of environmental loads from household septic systems in Japan focusing on effluent water discharge.

Various types of small-scale wastewater treatment systems are widely used in rural areas, and life-cycle assessment (LCA) should be performed to evaluate their environmental performance. In this study, septic systems were first classified into five categories based on their wastewater treatment performance. Effluent samples from actual systems were collected, and their water qualities were determined. A model to evaluate the environmental load from the septic systems using LCA methods was then established. The water-quality values obtained were input to the model, and the life-cycle environmental costs of the classified septic systems were calculated. The mean environmental load of the effluent during the operation stage was 37.6%, confirming that evaluation of an effluent discharge inventory using LCA, inspection, and water-quality monitoring to improve operations is critical for reducing the environmental load. The operation stage accounts for over 99% of the involved eutrophication, biological toxicity, and toxic chemicals, which are strongly related to the quality of the effluent. Evaluation of the effluent discharge inventory using LCA is of great significance, even for small-scale wastewater treatment systems. The set of procedures developed in this study can be used to calculate comprehensive environmental impacts at wastewater treatment plants.

Psychological symptoms of illness and emotional distress in advanced cancer cachexia.

PURPOSE OF REVIEW: Cachexia induces both physical and psychological symptoms of illness in patients with advanced cancer and may generate emotional distress in patients and families. However, physical symptoms of cachexia received the most emphasis. The aims of this review are to elucidate a link between systemic inflammation underlying cachexia and psychological symptoms and emotional distress, and to advance care strategy for management of psychological symptoms and emotional distress in patients and families. RECENT FINDINGS: The main themes in the literature covered by this review are psychological symptoms in patients and emotional distress in patients and families. Studies of the underlying biology of cachexia identify the role of the central nervous system to amplify tumor-induced systemic inflammation. The brain mediates a cluster of symptoms, such as sleep disruption, anxiety, cognitive impairment, and reduction in motivated behavior (notably anorexia). These are distressing to patients as well as to families. SUMMARY: There is growing recognition that holistic multimodal interventions are needed to alleviate psychological symptoms and emotional distress and to improve quality of life in patients with cancer cachexia and families. This is an approach that addresses not only physical health but also psychological, emotional, and social well being issues.

Association between experiences of advanced cancer patients at the end of life and depression in their bereaved caregivers.

OBJECTIVE: Research on the association between circumstances of death in advanced cancer patients and depression in their bereaved caregivers is limited. METHODS: A longitudinal study was performed on patients admitted to 21 inpatient hospices/palliative care units (PCUs) in Japan. Patient symptoms were assessed at admission and in the last 3 days of life. Data on distressing events (unexpected death, bleeding) and received treatments (morphine prescriptions, continuous deep sedation, cardiopulmonary resuscitation) were also obtained. Bereaved caregiver depression was assessed 6 months or more after patient death via mail survey using the Patient Health Questionnaire-9 (PHQ-9). A multivariable logistic regression analysis was used to explore variables predicting bereaved caregiver depression. RESULTS: Of 1324 deceased patient-bereaved caregiver dyads, data were finally analyzed for 711 dyads. The proportion of probable depression (PHQ-9 scores ≥10) in bereaved caregivers was 13.6% (91/671; 95% confidence interval: 11.0-16.2). The multivariable logistic regression analysis showed that patient hyperactive delirium at PCU admission was significantly associated with the development of bereaved caregiver depression (odds ratio: 2.2, 95% CI: 1.2-3.8). Bereaved caregiver perceived low social support (OR: 4.7, 95% CI: 2.2-10.0) and low preparedness for death (OR: 4.5, 95% CI: 2.6-7.8) were also significantly associated with the development of depression. Other patient and bereaved caregiver variables had no association with depression. CONCLUSIONS: Hyperactive delirium in terminally ill cancer patients was associated with bereaved caregiver depression. The development of effective strategies to reduce delirium-related agitation and to provide educational interventions for caregivers may be needed.

Changes in quality of life and lower urinary tract symptoms over time in cancer patients after a total prostatectomy: systematic review and meta-analysis.

PURPOSE: This study aimed to clarify associations between and changes over time in lower urinary tract symptoms (LUTS) and quality of life (QOL) in cancer patients after a total prostatectomy. METHODS: The subjects were cancer patients who had undergone total prostatectomy and had participated in non-randomized controlled trials, cohort studies, or case-control studies with outcomes of changes over time in LUTS or QOL. Fourteen studies were included for systematic review and meta-analysis. RESULTS: Compared to preoperatively, the International Prostate Symptom Score (IPSS)-a LUTS indicator-yielded the following, 3 months after operation (MD [95% confidence interval, CI] = -0.27 [-2.22 to 1.68], p = .7855), 6 months after operation (MD [95% CI] = -2.12 [-3.04 to -1.20], p < .0001), and 12 months after operation (MD [95% CI] = -2.27 [-2.63 to -1.92], p < .0001), demonstrating significant decrease and, therefore, improvement of symptoms after 6 months. International Prostate Symptom Score-Quality of Life (IPSS-QOL), a QOL indicator, was significantly reduced at 12 months after surgery, indicating improved QOL (MD [95% CI] = -0.49 [-0.87 to -0.11], p = .0107), but there was heterogeneity between different studies (I2 = 89.19%). A cumulative meta-analysis showed a tendency for greater improvements in IPSS-QOL at 12 months after surgery, the older the mean age and the higher the mean pre-surgery IPSS. Factors of age, prostate volume, and pre-surgery IPSS were related to postoperative LUTS; exacerbation of both urinary incontinence and urinary tract obstruction was related to QOL. CONCLUSION: While LUTS improves over time after total prostatectomy, it takes 6 to 12 months after surgery. As there is an association between LUTS and QOL, support to promote self-management of LUTS is important.

Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/guidance on the use of clinically assisted nutrition in patients with advanced cancer.

PURPOSE: The pro vision of clinically assisted nutrition (CAN) in patients with advanced cancer is controversial, and there is a paucity of specific guidance, and so a diversity in clinical practice. Consequently, the Palliative Care Study Group of the Multinational Association of Supportive Care in Cancer (MASCC) formed a Subgroup to develop evidence-based guidance on the use CAN in patients with advanced cancer. METHODS: This guidance was developed in accordance with the MASCC Guidelines Policy. A search strategy for Medline was developed, and the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were explored for relevant reviews/trials respectively. The outcomes of the review were categorised by the level of evidence, and a "category of guideline" based on the level of evidence (i.e. "recommendation", "suggestion", or "no guideline possible"). RESULTS: The Subgroup produced 11 suggestions, and 1 recommendation (due to the paucity of evidence). These outcomes relate to assessment of patients, indications for CAN, contraindications for CAN, procedures for initiating CAN, and re-assessment of patients. CONCLUSIONS: This guidance provides a framework for the use of CAN in advanced cancer, although every patient needs individualised management.

Effect of paracentesis on the survival of patients with terminal cancer and ascites: a propensity score-weighted analysis of the East Asian Collaborative Cross-cultural Study to Elucidate the Dying Process.

PURPOSE: Paracentesis is among the most widely utilized treatments for malignant ascites (MA). However, paracentesis in patients with MA has the potential to be associated with life-shortening effects. Thus, this study aimed to investigate whether paracentesis affected the duration of survival in such patients. METHODS: We performed a post hoc analysis of a prospective multicenter observational study investigating the dying process and end-of-life care in patients with terminal cancer, admitted to 23 palliative care units in Japan. Survival duration was compared between patients who did (paracentesis group) and did not undergo paracentesis (non-paracentesis group). We used inverse probability of treatment weighting (IPTW) to control for baseline covariates between groups. RESULTS: Among the 1896 initially enrolled patients, 568 with ascites were included in the study cohort. Eighty-five (15.0%) patients underwent paracentesis. The primary tumor site was the pancreas (51.9%, n = 295), followed by the gastrointestinal tract (22.7%, n = 129). Non-adjusted median durations of survival were 22 days (95% confidence interval [CI]: 16-25) and 12 days (95% CI: 11-13) in the paracentesis and non-paracentesis groups, respectively (hazard ratio [HR]: 0.69, 95% CI: 0.54-0.88; p = 0.003). The IPTW-adjusted median survival durations were 22 (95% CI: 16-25) and 16 days (95% CI: 12-22) in the paracentesis and non-paracentesis groups, respectively (HR: 0.89, 95% CI: 0.64-1.24; p = 0.492). No serious adverse events occurred in the paracentesis group. CONCLUSIONS: Paracentesis does not negatively affect the survival of patients with cancer and MA and can be a standard treatment in palliative care settings.

Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer.

BACKGROUND: Gastrointestinal symptoms are common in patients with cancer, whether related to treatment or a direct effect of the disease itself. Patients may choose to access cannabinoids outside of their formal medical prescriptions to palliate such symptoms. However, clinical guidelines are lacking in relation to the use of such medicines for gastrointestinal symptoms in patients with cancer. METHODS: A systematic review of the evidence for the use of cannabinoids for symptom control in patients with cancer was undertaken. Search strategies were developed for Medline, Embase, PsychINFO, and the Cochrane Central Register of Controlled Trials, including all publications from 1975 up to 12 November 2021. Studies were included if they were randomized controlled trials of cannabinoids compared with placebo or active comparator in adult patients with cancer, regardless of type, stage, or treatment status. Articles for inclusion were agreed by all authors, and data extracted and summarized by two authors. Each study was scored according to the Jadad scale. This review was specifically for the purpose of developing guidelines for the use of cannabis for gastrointestinal symptoms, including chemotherapy-induced nausea and vomiting (CINV), chronic nausea, anorexia-cachexia syndrome, and taste disturbance. RESULTS: Thirty-six randomized controlled trials were identified that met the inclusion criteria for this review of gastrointestinal symptoms: 31 relating to CINV, one to radiotherapy-induced nausea and vomiting, and the remaining four to anorexia-cachexia and altered chemosensory disturbance. The populations for the randomized controlled trials were heterogeneous, and many studies were of poor quality, lacking clarity regarding method of randomization, blinding, and allocation concealment. For CINV, eleven RCTs showed improvement with cannabis compared to placebo, but out of 21 trials where cannabis was compared to other antiemetics for CINV, only 11 favoured cannabis. CONCLUSION: Tetrahydrocannabinol (THC) and nabilone were more effective in preventing CINV when compared to placebo but are not more effective than other antiemetics. For refractory CINV, one study of THC:CBD demonstrated reduced nausea as an add-on treatment to guideline-consistent antiemetic therapy without olanzapine. The MASCC Guideline Committee found insufficient evidence to recommend cannabinoids for the management of CINV, nausea from advanced cancer, cancer-associated anorexia-cachexia, and taste disturbance. High-quality studies are needed to inform practice.

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.

Effects of parenteral nutrition and hydration on survival in advanced cancer patients with malignant bowel obstruction: secondary analysis of a multicenter prospective cohort study.

PURPOSE: The benefits of parenteral nutrition and hydration (PNH) in patients with advanced cancer remain unknown. Therefore, we conducted a prospective multicenter cohort study to assess the effects of PNH on survival in patients with malignant bowel obstruction (MBO). METHODS: The present study was a secondary analysis. Data on primary nutritional administration routes during the first week of admission to palliative care units, i.e., parenteral nutrition and parenteral hydration, were obtained. Data on the averaged calorie sufficiency rate/total calorie intake (75% ≤ or 750 kcal/day ≤ , 50-75% or 500-750 kcal/day, 25-50% or 250-500 kcal/day, and < 25% or < 250 kcal/day) were also obtained. Participants with MBO were included and divided into two groups: PNH-high (25% ≤ or 250 kcal/day ≤) and PNH-low (< 25% or < 250 kcal/day). We performed time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses. RESULTS: Patients were divided into the PNH-high (n = 68) and PNH-low (n = 76) groups. A significant difference was observed in survival rates between the two groups (log-rank P < 0.001). Median survival times were 35.5 (95% CI 27-44) and 17.5 (95% CI 13-21) days, respectively. In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the PNH-high group (HR 0.55 (95% CI 0.36-0.83), P = 0.005) than in the PNH-low group. CONCLUSION: The present results indicated the beneficial effects of PNH for prolonging survival in advanced cancer patients with MBO in palliative care units.