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Summary: Background & Aims: The prevalence of artificially administered nutrition and hydration (AANH) in different age groups among patients with advanced cancer remains unknown. The present study investigated the current utilization of AANH according to age groups in palliative care units. Methods: This was a secondary analysis of a prospective cohort study. We obtained information on primary nutritional administration routes during the first week of admission and data on the averaged calorie sufficiency rate or total calorie intake on the 7th day of admission. Patients were divided into five age groups (18–39, 40–59, 60–74, 75–89, and 90- years). Among patients receiving AANH, the proportions of higher-calorie AANH were compared between the five age groups. Results: A total of 1453 patients were included. The proportion of patients categorized as receiving nutrition and hydration via the parenteral route was the highest in the 18–39 and 40–59 groups (52.4 and 41.1%, respectively). Among patients receiving AANH (n = 534), the proportions of patients categorized into the

Parenteral morphine is widely used for dyspnea of imminently dying cancer patients (terminal dyspnea). However, the efficacy of other opioids such as oxycodone remains largely unknown.To explore the efficacy of parenteral oxycodone vs. morphine by continuous infusion over 24 hours in cancer patients with terminal dyspnea.This was a pre-planned subgroup analysis of a multicenter prospective observational study. Inclusion criteria were advanced cancer patients admitted to palliative care units, Eastern Cooperative Oncology Group performance status = 3-4, and a dyspnea intensity ≥2 on the Integrated Palliative care Outcome Scale (IPOS) for which oxycodone or morphine was initiated by continuous infusion. We measured dyspnea IPOS scores over 24 hours.We analyzed 164 patients who received oxycodone (n = 26) and morphine (n = 138) for dyspnea (median survival = 5 days). The mean age was 70 years, 58 patients (35%) had lung cancer, and 97 (59%) had lung metastases. Complete case analysis revealed that mean dyspnea IPOS scores decreased from 3.0 (standard deviation = 0.7) to 1.5 (0.7) in the oxycodone group (difference in means = 1.5; P 0.001), and from 2.9 (0.7) to 1.6 (1.0) in the morphine group (difference in means = 1.3; P 0.001). No significant between-group differences existed in the IPOS scores at 24 hours (P = 0.753). Adverse events were seen in no and 5 patients in the oxycodone and morphine groups, respectively.Parenteral oxycodone may be equally effective and safe as morphine in the treatment of terminal dyspnea in cancer patients. Future randomized controlled trials should confirm the efficacy and safety of opioids other than morphine for terminal dyspnea.

Background: When the suffering of a terminally ill patient is intolerable and refractory, sedatives are sometimes used for symptom relief. Objective: To describe the main principles of revised Japanese clinical guidelines about palliative sedation therapy. Design: Consensus methods using the Delphi technique were used. Results: The main principles of the guidelines that were newly defined or developed are as follows: (1) palliative sedation was defined as "administration of sedatives for the purpose of alleviating refractory suffering" (excluding the aim of reducing patient consciousness); (2) palliative sedation was classified according to the method of administration of sedatives: respite sedation versus continuous sedation (including (continuous) proportional sedation and continuous deep sedation); (3) a description of state-of-the-art recommended treatments for difficult symptoms such as delirium, dyspnea, and pain before the symptom was determined as refractory was included; (4) the principle of proportionality was newly defined from an ethical point of view; and (5) families' consent was regarded as being desirable (mandatory in the previous version). Conclusions: We described the main principles of revised Japanese clinical guidelines about palliative sedation therapy. Further consensus building is necessary.

Context Dyspnea is one of the most distressing symptoms for terminally ill cancer patients and a predictor of poor prognosis. Identification of simple clinical signs, such as heart rate, indicating clinical course of each patient is of value. Objectives To explore the potential association between heart rate and reversibility of the symptom, treatment response to palliative intervention, and survival in terminally ill cancer patients with dyspnea at rest. Methods This is a secondary analysis of a multicenter prospective cohort study of patients with advanced cancer to validate multiple prognostic tools. In the patients with dyspnea at rest at the baseline, we examined a potential association between heart rate and the reversibility of dyspnea and refractoriness to palliative treatment using logistic regression analysis. Survivals were compared using the Cox proportional hazards model among four groups with different levels of the heart rate (≤74, 75–84, 85–97, and ≥98). Results A total of 2298 patients were enrolled, and 418 patients (18%) had dyspnea at rest. Reversibility of dyspnea was significantly higher in the patients with lower heart rate (P for trend = 0.008), and the refractoriness to palliative treatment tended to be higher in the patients with higher heart rate (P for trend = 0.101). The median survival for each heart rate quartile groups was significantly higher in the lower heart rate group (24 vs. 21 vs. 14 vs. 9 days; heart rate ≤74, 75–84, 85–97, and ≥98, respectively; log-rank P Conclusion Heart rate may help clinicians to make the prediction of the patient's clinical course more accurate.

Context: Some patients require continuous deep sedation (CDS) for refractory symptoms despite intensive palliative care. The principle of proportionality is proposed on the basis of clinical decisions, but no validated tools to assist such decision making are available. Aim: To develop a scoring system to determine whether CDS is proportionally appropriate. Subjects and Methods: A secondary analysis of a nationwide questionnaire survey of Japanese palliative care specialists was performed. Physicians were asked to rate the degree that they believed CDS to be appropriate in a total of 27 scenarios based on a combination of 3 factors with 3 levels: (1) the estimated survival (days, weeks, and months), (2) the patient's wish (clear and consistent, somewhat unclear and/or inconsistent, and unclear or inconsistent), and (3) confidence in refractoriness of the symptom (definite, probable, and unsure). Based on logistic regression analyses, a scoring system with two formulas (the proportionality score to determine that continuous deep sedation is appropriate [ProScoreCDS-appropriate] and proportionality score to determine that continuous deep sedation is inappropriate [ProScoreCDS-inappropriate]) to predict specialists' decision that CDS is appropriate or inappropriate was developed. The accuracy of the formulas was investigated. Results: Among 695 palliative care specialists, 469 returned the questionnaire (response rate, 69%) and 440 were analyzed. Logistic regression analyses identified that all three factors were significantly associated with physicians' decisions about the appropriateness of performing CDS. Using weighted value, the total score ranged from 3 to 67 for ProScoreCDS-appropriate, and 3 to 27 for ProScoreCDS-inappropriate. The area under the curve (AUC) values of ProScoreCDS-appropriate and ProScoreCDS-inappropriate were 0.88 (95% confidence interval [CI], 0.87-0.89) and 0.81 (95% CI, 0.81-0.82), respectively. Using cutoff points of 41 and 14, sensitivity and specificity were 68.6% and 88.9% for ProScoreCDS-appropriate and 67.7% and 76.0% for ProScoreCDS-inappropriate, respectively. Conclusion: A scoring system to determine whether CDS is proportionally appropriate can be constructed, and a further study to develop a clinical tool is promising.

The benefits of artificial nutrition and hydration in patients with advanced cancer remain unknown. Therefore, we conducted a prospective study to evaluate effects of enteral nutrition (EN) and parenteral nutrition and hydration (PNH) on survival in palliative care units.This study involved a secondary analysis of a multicenter cohort study. Data of primary nutritional administration routes during the first week after admission (oral intake, enteral tube feeding, parenteral nutrition, parenteral hydration, poor oral intake) were obtained. Data of averaged calorie sufficiency rate/total calorie intake [high (75% ≤ or 750 kcal/day ≤), moderate (50-75% or 500-750 kcal/day), low (25-50% or 250-500 kcal/day), very low (25% or250 kcal/day)] were also obtained. After investigating the implementation of artificial nutrition and hydration, participants were divided into three groups according to the nutritional administration route and calorie sufficiency rate/total calorie intake: EN, PNH, and control. We conducted time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses.Patients were divided into the EN group (n = 730), PNH group (n = 190), and control group (n = 533). Differences in survival rates among the three groups were significant (Log-rank P 0.001). Median survival times were 43.0 (95% CI 40-46), 33.0 (95% CI 29-37), and 15.0 (95% CI 14-16) days, respectively (P 0.001). In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the EN group and PNH groups (HR 0.43 [95% CI 0.37-0.49], P 0.001; and HR 0.52 [95% CI 0.44-0.62], P 0.001, respectively) than in the control group.This study indicated the clinical benefits of EN and PNH for patients with advanced cancer. Nevertheless, managing symptoms to improve oral intake is essential before initiation of PNH, because EN was superior to PNH.

Context Although there has long been debate about physicians' intentions and what physicians consider to be proportionally appropriate when performing palliative sedation, few large studies have been performed. Objectives To identify physicians' intentions when starting continuous deep sedation and to clarify what factors determine whether physicians regard sedation as proportionally appropriate in relation to expected survival, the patients' wishes, and refractoriness. Methods A nationwide questionnaire survey of Japanese palliative care specialists was performed from August to December 2016. We defined continuous deep sedation as the continuous use of sedatives to relieve intolerable and refractory symptoms with the loss of consciousness until death. Results Of the 695 palliative care specialists enrolled, 440 were analyzed (response rate, 69%). A total of 95% and 87% of the physicians reported that they explicitly intended to perform symptom palliation and decrease consciousness levels, respectively. Moreover, 38% answered that they explicitly intended to maintain unconsciousness until death, and 11% reported that they intended to shorten survival to some extent. The respondents considered that continuous deep sedation is more appropriate when the predicted survival is shorter, the patients' wishes are consistent and clear, and confidence in the refractoriness of symptoms is higher. Conclusions Japanese palliative care specialists explicitly intend to control symptoms and reduce the level of consciousness when performing continuous deep sedation, but there are differences in their intentions with regard to maintaining unconsciousness until death. Predicted survival, patients' wishes, and confidence in refractoriness are associated with physicians' judgment that sedation is proportionally appropriate.

BACKGROUND Survival prediction systems such as the Palliative Prognostic Index (PPI), which includes the Palliative Performance Scale (PPS), are used to estimate survival for terminally ill patients. Oncologists are, however, less familiar with the PPS in comparison with the Eastern Cooperative Oncology Group (ECOG) performance status (PS). This study was designed to validate a simple survival prediction system for oncologists, the Performance Status–Based Palliative Prognostic Index (PS-PPI), which is a modified form of the PPI based on the ECOG PS. METHODS This multicenter, prospective cohort study enrolled all consecutive patients who were referred to 58 palliative care services in Japan. The primary responsible physicians rated the variables required to calculate the PS-PPI and the PPI. Patient survival in these risk groups was compared, and the sensitivity and specificity of the PS-PPI and the PPI were evaluated. Patients were subclassified as patients receiving care from in-hospital palliative care teams, palliative care units, or home-based palliative care services. Subsets of patients receiving chemotherapy were also analyzed. RESULTS This study included 2346 patients. Survival predictions based on the PPI and the PS-PPI differed significantly among the 3 risk groups (P 0.78 for predicting survival at all times, from 3 weeks to 180 days. CONCLUSIONS In predicting the prognosis of patients with advanced cancer, the PS-PPI was as accurate as the PPI. The PS-PPI was useful for short- and long-term survival prediction and for the prediction of survival for patients undergoing chemotherapy. Cancer 2017;123:1442–1452. © 2016 American Cancer Society.

Background: Advance care planning is a crucial end-of-life care practice. However, an advance care planning educational programme for practitioners in an acute care setting has not yet been established. Consequently, we examined the effects of an advance care planning educational programme in an acute hospital in the hope of achieving increased awareness of end-of-life care. Design: A mixed-methods, pre- and post-design was employed to evaluate the change in attitudes of practitioners post-programme. The intervention programme was conducted thrice over 3 months in 90-min sessions. Setting/participants: This study included 85 participants in the baseline assessment working at B acute hospital in Osaka. Results: Participants’ scores on the ‘Positive attitude for end-of-life care’ subscale on the short version of the Frommelt Attitude Toward Care of Dying scale significantly increased after the 6-month intervention. A ‘Positive attitude for end-of-life-care’ implies that participants would not be afraid to practice end-of-life care. Further, participants’ scores on the ‘Death relief’ subscale of the Death Attitude Inventory also significantly increased. The term ‘Death relief’ means that death helps in ending suffering. It means participants are not afraid of death. Qualitative results implied that participants believed advance care planning implementation and communicating with patients and patients’ families were critical. Conclusions: Six months post-intervention, participants displayed sustained positive attitudes towards end-of-life care. These results suggest that the present programme was effective at improving practitioners’ attitudes towards patients’ end-of-life care.

ObjectivesVoluntarily stopping eating and drinking (VSED) could be regarded as a patients’ own non-treatment decision that hastens death, which involves patients voluntarily forgoing food and liquid until death. The aims of this study were to investigate the experience of home hospice physicians and palliative care specialists who care for patients during VSED in Japan, and their opinions on continuous deep sedation (CDS) as a means to relieve patient symptoms during VSED.Methods219 home hospice physicians and 695 palliative care specialists across Japan were surveyed by mail questionnaire in 2016.ResultsA total of 571 (62%) responses were analysed. A total of 185 (32%) had experience of patients who selected VSED. In response to questions about CDS to provide relief to patients during VSED, the number of physicians who replied that CDS was acceptable was 88 (15%).ConclusionsIn Japan, 32% of physicians surveyed replied that they had experience of caring for patients during VSED in a clinical setting and 15% considered CDS acceptable.

Plasma C-reactive protein (CRP) levels are elevated in patients with advanced cancer.To investigate CRP as a prognostic marker in palliative settings.This multicenter prospective cohort study comprised 2426 patients. Laboratory data were obtained at baseline, and all patients were followed until death or six months after their enrollment. A total of 1511 patients were eligible for the analyses. They were divided into four groups: low-CRP (CRP1 mg/dL), moderate-CRP (1 ≤ CRP5 mg/dL), high-CRP (5 ≤ CRP 10 mg/dL), and very high-CRP (10 mg/dL ≤ CRP) groups. Survival was investigated by the Kaplan-Meier method with the log-rank test. The 30-, 60-, and 90-day mortality rates were tested by Chi-squared tests. Univariate- and multivariate-adjusted hazard ratios (HRs) and 95% CIs in each group were calculated using Cox proportional hazard models.Survival rate decreased and mortality rate increased with increasing CRP level. The differences in survival and 30-, 60-, and 90-day mortality rates among the groups were statistically significant (P 0.001). Baseline CRP level was significantly associated with a higher risk of mortality after adjustment for age, gender, primary tumor site, metastasis, chemotherapy, Eastern Cooperative Oncology Group Performance Status, and setting of care (moderate-CRP: HR 1.47 [95% CI 1.24-1.73], high-CRP: HR 2.09 [95% CI 1.74-2.50], and very high-CRP: HR 2.55 [95% CI 2.13-3.05] vs. low-CRP).Clear dose-effect relationships between elevated CRP levels and prognoses indicate that CRP could be useful in predicting prognoses in patients with advanced cancer.

Summary Background Continuous deep sedation (CDS) before death is a form of palliative sedation therapy that has become a focus of strong debate, especially with respect to whether it shortens survival. We aimed to examine whether CDS shortens patient survival using the propensity score-weighting method, and to explore the effect of artificial hydration during CDS on survival. Methods This study was a secondary analysis of a large multicentre prospective cohort study that recruited and followed up patients between Sept 3, 2012, and April 30, 2014, from 58 palliative care institutions across Japan, including hospital palliative care settings, inpatient palliative care units, and home-based palliative care services. Adult patients (aged ≥20 years) with advanced cancer who received care through the participating palliative care services were eligible for this secondary analysis. Patients with missing data for outcome variables or who lived for more than 180 days were excluded. We compared survival after enrolment between patients who did and did not receive CDS. We used a propensity score-weighting method to control for patient characteristics, disease status, and symptom burden at enrolment. Findings Of 2426 enrolled patients with advanced cancer, we excluded 289 (12%) for living longer than 180 days and 310 (13%) with missing data, leaving an analysis population of 1827 patients. 269 (15%) of 1827 patients received CDS. Unweighted median survival was 27 days (95% CI 22–30) in the CDS group and 26 days (24–27) in the no CDS group (median difference −1 day [95% CI −5 to 4]; HR 0·92 [95% CI 0·81–1·05]; log-rank p=0·20). After propensity-score weighting, these values were 22 days (95% CI 21–24) and 26 days (24–27), respectively (median difference −1 day [95% CI −6 to 4]; HR 1·01 [95% CI 0·87–1·17]; log-rank p=0·91). Age (p interaction =0·67), sex (p interaction =0·26), performance status (p interaction =0·90), and volume of artificial hydration (p interaction =0·14) did not have an effect modification on the association between sedation and survival, although care setting did have a significant effect modification (p interaction =0·021). Interpretation CDS does not seem to be associated with a measurable shortening of life in patients with advanced cancer cared for by specialised palliative care services, and could be considered a viable option for palliative care in this setting. Funding Japanese National Cancer Center Research and Development Fund.

Introduction There have been no reports about predicting survival of patients with advanced cancer constructed entirely with objective variables. We aimed to develop a prognostic model based on laboratory findings and vital signs using a fractional polynomial (FP) model. Methods A multicentre prospective cohort study was conducted at 58 specialist palliative care services in Japan from September 2012 to April 2014. Eligible patients were older than 20 years and had advanced cancer. We developed models for predicting 7-day, 14-day, 30-day, 56-day and 90-day survival by using the FP modelling method. Results Data from 1039 patients were analysed to develop each prognostic model (Objective Prognostic Index for advanced cancer [OPI-AC]). All models included the heart rate, urea and albumin, while some models included the respiratory rate, creatinine, C-reactive protein, lymphocyte count, neutrophil count, total bilirubin, lactate dehydrogenase and platelet/lymphocyte ratio. The area under the curve was 0.77, 0.81, 0.90, 0.90 and 0.92 for the 7-day, 14-day, 30-day, 56-day and 90-day model, respectively. The accuracy of the OPI-AC predicting 30-day, 56-day and 90-day survival was significantly higher than that of the Palliative Prognostic Score or the Prognosis in Palliative Care Study model, which are based on a combination of symptoms and physician estimation. Conclusion We developed highly accurate prognostic indexes for predicting the survival of patients with advanced cancer from objective variables alone, which may be useful for end-of-life management. The FP modelling method could be promising for developing other prognostic models in future research.

Survival prediction systems such as the Palliative Prognostic Index (PPI), which includes the Palliative Performance Scale (PPS), are used to estimate survival for terminally ill patients. Oncologists are, however, less familiar with the PPS in comparison with the Eastern Cooperative Oncology Group (ECOG) performance status (PS). This study was designed to validate a simple survival prediction system for oncologists, the Performance Status-Based Palliative Prognostic Index (PS-PPI), which is a modified form of the PPI based on the ECOG PS.This multicenter, prospective cohort study enrolled all consecutive patients who were referred to 58 palliative care services in Japan. The primary responsible physicians rated the variables required to calculate the PS-PPI and the PPI. Patient survival in these risk groups was compared, and the sensitivity and specificity of the PS-PPI and the PPI were evaluated. Patients were subclassified as patients receiving care from in-hospital palliative care teams, palliative care units, or home-based palliative care services. Subsets of patients receiving chemotherapy were also analyzed.This study included 2346 patients. Survival predictions based on the PPI and the PS-PPI differed significantly among the 3 risk groups (P .001). The PS-PPI was more sensitive, whereas the PPI was more specific. All areas under the receiver operating characteristic curves of both indices were0.78 for predicting survival at all times, from 3 weeks to 180 days.In predicting the prognosis of patients with advanced cancer, the PS-PPI was as accurate as the PPI. The PS-PPI was useful for short- and long-term survival prediction and for the prediction of survival for patients undergoing chemotherapy. Cancer 2017;123:1442-1452. © 2016 American Cancer Society.

終末期がん患者の神経障害性疼痛に対するガバペンチンの鎮痛効果, 適切な投与方法, 安全性を明らかにするため, 200X年11月から200X＋2年10月に淀川キリスト教病院ホスピスでがんに伴う神経障害性疼痛に対しガバペンチンを投与した患者の観察研究を行った. numerical rating scale (NRS)で疼痛評価し, 投与前, 1週間後, 維持投与時のNRSをWilcoxonの符号付順位和検定で比較検討した. 調査を開始した44名中19名が投与終了まで調査可能で, 投与期間平均52.0日, 死亡まで平均67.2日であった. 1週間後の投与量は平均358 (200～1,200) mg/日, 維持投与開始は平均11.6日, 維持投与量は平均463 (200～2,400) mg/日で男性620 mg/日, 女性289 mg/日であった. NRSの平均値は投与前5.7, 1週間後 2.1 (p＜0.001), 維持投与時1.9 (p＜0.001)で, 有意に低下した. 57.9％で副作用を認め, 眠気52.6％, せん妄5.3％, 振戦5.3％であった. ガバペンチンを少量から副作用に注意して調整することで, がんに伴う神経障害性疼痛に対し鎮痛効果が得られ, 終末期でも長期間安全に投与可能である. Palliat Care Res 2011; 6(1): 101-108

Objective: The aim of this study was to evaluate the efficacy and safety of octreotide for malignant bowel obstruction in a multicenter study. Methods: Terminally ill patients diagnosed with inoperable malignant bowel obstruction were treated with octreotide 300 mg/day. The primary endpoint was the overall improvement rate of subjective abdominal symptoms. The degrees of nausea, vomiting, abdominal pain, distension, anorexia, fatigue, thirst and overall quality of life were evaluated by the self-rating scores selected from the MD Anderson Symptoms Inventory and Kurihara’s Face Scale. Results: Forty-nine patients were enrolled in the study, and 46 patients received study treatment, including 17 gastric, 13 colorectal, 7 ovarian and other cancers. The median survival time was 25 days. The number of vomiting episodes significantly correlated with the MD Anderson Symptoms Inventory nausea and vomiting scores (P , 0.001) before octreotide treatment. Of 43 patients evaluable for efficacy, the scores of all the MD Anderson Symptoms Inventory items except abdominal pain and the number of vomiting episodes improved during the first 4 days of octreotide treatment (P , 0.0062). The MD Anderson Symptoms Inventory scores were decreased in 59‐72% of patients, and overall quality-of-life scores improved in 56% of patients. No serious adverse events were observed. Conclusions: The high improvement rate in abdominal symptoms suggested the efficacy of octreotide in terminally ill patients with malignant bowel obstruction.

Although delirium is a common complication in terminally ill cancer patients and can cause considerable distress for family members, little is known about effective care strategies for terminal delirium. The primary aims of this study were 1) to clarify the distress levels of bereaved families and their perceived necessity of care; and 2) to explore the association between these levels and family-reported professional care practice, family-reported patient behavior, and their interpretation of the causes of delirium. A multicenter questionnaire survey was conducted on 560 bereaved family members of cancer patients who developed delirium during their final two weeks in eight certified palliative care units across Japan. We obtained 402 effective responses (response rate, 72%) and, as 160 families denied delirium episodes, 242 responses were analyzed. The bereaved family members reported that they were very distressed (32%) and distressed (22%) about the experience of terminal delirium. On the other hand, 5.8% reported that considerable or much improvement was necessary, and 31% reported some improvement was necessary in the professional care they had received. More than half of the respondents had ambivalent wishes, guilt and self-blame, and worries about staying with the patient. One-fourth to one-third reported that they felt a burden concerning proxy judgments, burden to others, acceptance, and helplessness. High-level emotional distress and family-perceived necessity of improvement were associated with a younger family age; male gender; their experience of agitation and incoherent speech; their interpretation of the causes of delirium as pain/physical discomfort, medication effects, or mental weakness/death anxiety; and their perception that medical staff were not present with the family, not respecting the patient's subjective world, not explaining the expected course with daily changes, and not relieving family care burden. In terminal delirium, a considerable number of families experienced high levels of emotional distress and felt some need for improvement of the specialized palliative care service. Control of agitation symptoms with careful consideration of ambivalent family wishes, providing information about the pathology of delirium, being present with the family, respecting the patient's subjective world, explaining the expected course with daily changes, and relieving family care burden can be useful care strategies.

Purpose The aim of this study was to investigate the feasibility and accuracy of the Palliative Prognostic Score (PaP score), Delirium-Palliative Prognostic Score (D-PaP score), Palliative Prognostic Index (PPI) and modified Prognosis in Palliative Care Study predictor model (PiPS model). Patients and methods This multicentre prospective cohort study involved 58 palliative care services, including 19 hospital palliative care teams, 16 palliative care units and 23 home palliative care services, in Japan from September 2012 to April 2014. Analyses were performed involving four patient groups: those treated by palliative care teams, those in palliative care units, those at home and those receiving chemotherapy. Results We recruited 2426 participants, and 2361 patients were finally analysed. Risk groups based on these instruments successfully identified patients with different survival profiles in all groups. The feasibility of PPI and modified PiPS-A was more than 90% in all groups, followed by PaP and D-PaP scores; modified PiPS-B had the lowest feasibility. The accuracy of prognostic scores was ⩾69% in all groups and the difference was within 13%, while c-statistics were significantly lower with the PPI than PaP and D-PaP scores. Conclusion The PaP score, D-PaP score, PPI and modified PiPS model provided distinct survival groups for patients in the three palliative care settings and those receiving chemotherapy. The PPI seems to be suitable for routine clinical use for situations where rough estimates of prognosis are sufficient and/or patients do not want invasive procedure. If clinicians can address more items, the modified PiPS-A would be a non-invasive alternative. In cases where blood samples are available or those requiring more accurate prediction, the PaP and D-PaP scores and modified PiPS-B would be more appropriate.

Background. Predicting the short-term survival in cancer patients is an important issue for patients, family, and oncologists. Although the prognostic accuracy of the surprise question has value in 1-year mortality for cancer patients, the prognostic value for short-term survival has not been formally assessed. The primary aim of the present study was to assess the prognostic value of the surprise question for 7-day and 30-day survival in patients with advanced cancer. Patients and Methods. The present multicenter prospective cohort study was conducted in Japan from September 2012 through April 2014, involving 16 palliative care units, 19 hospital-based palliative care teams, and 23 home-based palliative care services. Results. We recruited 2,425 patients and included 2,361 for analysis: 912 from hospital-based palliative care teams, 895 from hospital palliative care units, and 554 from home-based palliative care services. The sensitivity, specificity, positive predictive value, and negative predictive value of the 7-day survival surprise question were 84.7% (95% confidence interval [CI], 80.7%–88.0%), 68.0% (95% CI, 67.3%–68.5%), 30.3% (95% CI, 28.9%–31.5%), and 96.4% (95% CI, 95.5%–97.2%), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the 30-day surprise question were 95.6% (95% CI, 94.4%–96.6%), 37.0% (95% CI, 35.9%–37.9%), 57.6% (95% CI, 56.8%–58.2%), and 90.4% (95% CI, 87.7%–92.6%), respectively. Conclusion. Surprise questions are useful for screening patients for short survival. However, the high false-positive rates do not allow clinicians to provide definitive prognosis prediction. Implications for Practice: The findings of this study indicate that clinicians can screen patients for 7- or 30-day survival using surprise questions with 90% or more sensitivity. Clinicians cannot provide accurate prognosis estimation, and all patients will not always die within the defined periods. The screened patients can be regarded as the subjects to be prepared for approaching death, and proactive discussion would be useful for such patients.

Although palliative sedation therapy is often required in terminally ill cancer patients, its efficacy and safety are not sufficiently understood. The primary aims of this multicenter observational study were to 1) explore the efficacy and safety of palliative sedation therapy, and 2) identify the factors contributing to inadequate symptom relief and complications, using a prospective study design, clearly defined measurement methods, and a consecutive sample from 21 specialized palliative care units in Japan. A sample of 102 consecutive adult cancer patients who received continuous deep sedation were enrolled. Physicians prospectively evaluated the intensity of patient symptoms, communication capacity, respiratory rate, and complications related to sedation. Symptoms were measured on the Agitation Distress Scale, the Memorial Delirium Assessment Scale, and the ad hoc symptom severity scale (0 = no symptoms, 1 = mild and tolerable symptoms, 2 = intolerable symptoms for less than 15 minutes in the previous one hour, and 3 = intolerable symptoms continuing for more than 15 minutes in the previous one hour). Inadequate symptom relief was defined as presence of hyperactive delirium (item 9 of the Memorial Delirium Assessment Scaleor=2) or grade 2 or 3 symptom intensity 4 hours after sedation. The degree of communication capacity was measured on the Communication Capacity Scale. Palliative sedation therapy succeeded in symptom alleviation in 83% of the cases. Median time elapsed before patients initially had one continuous hour of deep sedation was 60 minutes, but 49% of the patients awakened once after falling into a deeply sedated state. The percentage of patients who were capable of explicit communication decreased from 40% before sedation to 7.1% 4 hours after sedation, and the mean Communication Capacity Score significantly decreased to the level of 15 points (P0.001). The respiratory rates did not significantly decrease after sedation (18 +/- 9.0 to 16 +/- 9.4/min, P = 0.62), but respiratory and/or circulatory suppression (respiratory rateor= 8/min, systolic blood pressureor= 60mHg, or 50% or more reduction) occurred in 20%, with fatal outcomes in 3.9%. There were no statistically significant differences in patient age, sex, performance status, target symptoms, or classes and initial dose of sedative medications between the patients with adequate and inadequate symptom relief. Respiratory and/or circulatory suppression was significantly more likely to occur in patients receiving sedation for delirium and those with higher levels on the Agitation Distress Scale. Higher dose of midazolam was significantly correlated with younger age, absence of icterus, pre-exposure to midazolam, and length of sedation. Palliative sedation therapy is effective and safe in the majority of terminally ill cancer patients with refractory symptoms. However, a small number of patients experience fatal complications related to sedation. Comparison studies of different sedation regimens are needed to determine the most effective and safe sedation protocol.

Purpose To clarify the bereaved family's perceptions about the appropriateness of timing when physicians first referred patients to palliative care units, and to identify the factors contributing to family-perceived late referrals. Subjects and Methods A multicenter questionnaire survey was conducted on 630 bereaved family members of cancer patents who were admitted to palliative care units in Japan. A total of 318 responses were analyzed (effective response rate, 62%). Results Half of the bereaved family members regarded the timing of referrals to palliative care units as late or very late, while less than 5% of families reported early referrals (very late [19%, n = 59], late [30%, n = 96], appropriate [48%, n = 151], early [1.6%, n = 5], and very early [2.2%, n = 7]). Multiple regression analyses revealed that the independent determinants of family-perceived late referrals were: family belief before admission that palliative care shortens the patient's life, insufficient in-advance discussion about preferred end-of-life care between patients/families and physicians, families' insufficient preparation for changes of patient conditions, and hospital admission before referrals. Conclusion In Japan, the timing of referrals to palliative care units was late or very late from the families' perspectives. The independent determinants of family-perceived late referrals were: family misconception about palliative care, inadequate communication with physicians, and families' insufficient preparation for deterioration of patients' conditions. Systematic strategies to overcome these barriers would contribute to providing appropriate palliative care at all stages of cancer.

Background: To explore the association between hydration volume and symptoms during the last 3 weeks of life in terminally ill cancer patients. Patients and methods: This was a multicenter, prospective, observational study of 226 consecutive terminally ill patients with abdominal malignancies. Primary responsible physicians and nurses evaluated the severity of membranous dehydration (dehydration score calculated from three physical findings), peripheral edema (edema score calculated from seven physical findings), ascites and pleural effusion (rated as physically undetectable to symptomatic), bronchial secretion, hyperactive delirium (Memorial Delirium Assessment Scale), communication capacity (Communication Capacity Scale), agitation (Agitation Distress Scale), myoclonus and bedsores. Results: Patients were classified into two groups: the hydration group (n = 59) who received 1 l or more of artificial hydration per day, 1 and 3 weeks before death, and the non-hydration group (n = 167). The percentage of patients with deterioration in dehydration score in the final 3 weeks was significantly higher in the non-hydration group than the hydration group (35% versus 14%; P = 0.002), while the percentages of patients whose symptom scores for edema, ascites and pleural effusion increased were significantly higher in the hydration group than the non-hydration group (44% versus 29%, P = 0.039; 29% versus 8.4%, P

Symptomatic sedation is often required in terminally ill cancer patients and could cause significant distress to their families. The aim of this study was to gather vivid family descriptions about their experiences in palliative sedation therapy.This report is an additional analysis of a multicenter questionnaire survey. We performed content analysis on 48 statements described by 185 bereaved family members of patients who received palliative sedation therapy.Family members reported guilt, helplessness, and physical and emotional exhaustion when patients received palliative sedation therapy. They were concerned about whether sedated patients experienced distress, wished to know that the maximum efforts had been made, wished to prepare for patient death, wished to tell important things to patients before sedation, wished to understand patients' suffering, and wanted medical professionals to treat patients with dignity.To alleviate family distress, clinicians should understand families' emotional distress, ensure that unconscious patients feel no distress, reassure family members that the symptoms are truly refractory despite maximum efforts for symptom relief, give information and coordinate the situation to enable families to prepare for patient death and to tell important things to patients before sedation, help families to share patients' suffering, and treat patients the same as when they remained conscious.

Although bronchial secretion is frequently observed in terminally ill cancer patients and can cause significant distress for both patients and family members, the pathophysiology is unclear. The primary aim of this study was to investigate the incidence and underlying etiologies of bronchial secretion. A multicenter, prospective, observational study was conducted on consecutive terminally ill patients with lung or abdominal malignancies. Primary physicians and nurses prospectively evaluated patients' symptoms. Of 310 patients enrolled, bronchial secretions were observed in 41% in the final 3 weeks, and oral/bronchial suctioning, with considerable distress, was required in 9%; bronchial secretions were severe in 4.5% of all patients. Multiple logistic regression analyses revealed that the determinants of the development of bronchial secretion were primary lung cancer, pneumonia, and dysphagia. There were no statistically significant effects of severity of peripheral edema and pleural effusion on development of bronchial secretions and requirement for oral/bronchial suctioning. Etiology-based classification of bronchial secretion is useful to identify the most suitable palliative treatments and to clarify treatment efficacy in each specific pathophysiology.

We made detailed research for relationships among physical condition, self-efficacy and psychological adjustment of patients with advanced cancer in Japan. The sample consisted of 85 (42 males and 43 females) advanced cancer patients. Interviews were conducted with some measurement scales including the Self-efficacy scale for Advanced Cancer (SEAC), and the Hospital Anxiety and Depression Scale (HADS). Karnofsky Performance Status (KPS) and medication status were also recorded from the evaluation by physicians. We used structural equation modeling (SEM) for statistical analysis. The analysis revealed that the model, including three self-efficacy subscales, depression, anxiety, KPS, meal-, liquid-intake, prognosis and three latent variables: 'Self-efficacy', 'Emotional Distress', and 'Physical Condition,' fit the data (chi-square(24)=28.67, p=0.23; GFI=0.93; CFI=0.98; RMSEA=0.05). In this model, self-efficacy accounted for 71% of the variance in emotional distress and physical condition accounted for 8% of the variance in self-efficacy. Overall, our findings suggest clearly that close relationships existed among physical condition, self-efficacy and emotional distress. That is, patients in good physical condition had a high self-efficacy, and patients with high self-efficacy were less emotionally distressed. These results imply that psychological intervention which emphasizes self-efficacy would be effective for advanced cancer patients.

Context Although the psychometric properties of the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL) have been examined previously, that study had several limitations, for example, small sample size. Objectives To examine the validity and reliability, including test-retest reliability, of the Japanese version of EORTC QLQ-C15-PAL for cancer patients with metastasis or recurrence. Methods A cross-sectional anonymous questionnaire was administered to cancer patients who were being treated on an oncology inpatient ward, in an oncology outpatient clinic, and in seven inpatient palliative units in Japan, from August 2007 to March 2008. Results Data from a total of 312 cancer patients were analyzed. The proportion of missing values was less than 4% for all items. The factor structure was reproduced identically with the original EORTC QLQ-C15-PAL, English version. The correlation of subscales showed a reasonable matrix. Cronbach's alpha coefficients were 0.76 to 0.86, and intraclass correlation coefficients, which indicate test-retest reliability, ranged from 0.52 to 0.77. All subscales, especially physical functioning, fatigue, and pain, were significantly correlated with self-reported Eastern Cooperative Oncology Group performance status. Conclusion The Japanese version of EORTC QLQ-C15-PAL has sufficient validity, acceptable reliability, and feasibility for patients with advanced cancer.

The primary aim of this study was to clarify the effect of sublingual scopolamine on the intensity of nausea. This was an open uncontrolled study, and the study participants were cancer patients consecutively admitted to a palliative care unit in Japan. When the patients had nausea, they were administered a solution of scopolamine at 0.15 mg sublingually. The intensities of nausea were assessed using the 6-point Numerical Rating Scale (NRS 0 = no nausea to 5 = worst nausea) before and 15, 30, and 60 min after administration. Primary endpoints were (1) changes in the NRS of nausea and (2) percentage of patients who achieved a decrease in NRS of 1 or more points 15 min after treatment. Twenty-six patients were recruited for this study. The median NRS significantly decreased from 3.0 (range, 1–5) to 1.5 (0–5) after 15 min, and 84 % (n = 21) of the patients achieved a decrease in NRS of 1 or more points after 15 min. In addition, the median NRS significantly decreased from 3.0 (before) to 0 (30 min) and 0 (60 min). The percentage of patients who achieved a decrease in NRS over 1 point was 96 % (n = 25) in 30 min and 100 % (n = 26) in 60 min. Fifteen percent (n = 4) showed drowsiness. No other adverse effects were reported. Sublingually administered scopolamine may be effective for managing nausea in terminally ill cancer patients. Randomized controlled trials are promising.

末期がん患者においては,インフォームドコンセントと自己決定権の普及により,延命処置が再検討されるようになってきた.またその一方で,残された命を苦しみなく自分らしい生活を送るための緩和医療が発展してきている.これまで延命処置や症状緩和は主治医の個人的な経験に基づいて行われることが多かったが,今後,科学的な研究の必要性が高まってくるであろう.そして,生命予後の推測や医学的処置の転帰について検討することは,患者の病態に合った正確な診断と対応に貢献することになるであろう.

More than 85% of cancer-related pain is pharmacologically controllable, but some patients require interventional treatments. Although audit assessment of these interventions is of importance to clarify the types of patients likely to receive benefits, there have been no multicenter studies in Japan. The primary aims of this study were (1) to clarify the frequency of neural blockade in certified palliative care units and palliative care teams, (2) determine the efficacy of interventions, and (3) explore the predictors of successful or unsuccessful intervention. All patients who received neural blockade were consecutively recruited from seven certified palliative care units and five hospital palliative care teams in Japan. Primary responsible physicians reported pain intensity on the Support Team Assessment Schedule, performance status, communication levels on the Communication Capacity Scale, presence or absence of delirium, opioid consumption, and adverse effects before and one week after the procedure on the basis of retrospective chart review. A total of 162 interventions in 136 patients were obtained, comprising 3.8% of all patients receiving specialized palliative care services during the study period. Common procedures were epidural nerve block with local anesthetic and/or opioids (n = 84), neurolytic sympathetic plexus block (n = 24), and intrathecal nerve block with phenol (n = 21). There were significant differences in the frequency of neural blockade between palliative care units and palliative care teams (3.1% vs. 4.6%, respectively, P = 0.018), and between institutions whose leading physicians are anesthesiologists or have other specialties (4.8% vs. 1.5%, respectively, P0.001). Pain intensity measured on the Support Team Assessment Schedule (2.9 +/- 0.8 to 1.7 +/- 0.9, P0.001), performance status (2.7 +/- 1.0 to 2.4 +/- 1.0, P0.001), and opioid consumption (248 +/- 348 to 186 +/- 288 mg morphine equivalent/day, P0.001) were significantly improved after interventions. There was a tendency toward improvement in the communication level measured on the Communication Capacity Scale. There was no significant improvement in the prevalence of delirium, but six patients (32%) recovered from delirium after interventions. Adverse effects occurred in 9.2%, but all were predictable or transient. No fatal complications were reported. Pain intensity was significantly more improved in patients who survived 28 days or longer than others (P = 0.002). There were no significant correlations of changes in pain intensity with the performance status or previous opioid consumption. In conclusion, neural blockade was performed in 3.8% of cancer patients who received specialized palliative care services in Japan. Neural blockade could contribute to the improvement of pain intensity, performance service status, and opioid consumption without unpredictable serious side effects.

Objective: This research explores the potential benefit of a spiritual pain assessment sheet to clinical practice. With spiritual pain defined as “pain caused by extinction of the being and meaning of the self,” the spiritual pain assessment sheet was developed by Hisayuki Murata from his conceptual framework reflecting the three dimensions of a human being as a being founded on temporality, a being in relationship, and a being with autonomy. The assessment sheet was developed from reviews of the literature and examinations from a philosophical perspective on the structure of spiritual pain.Methods: Patients admitted to palliative care units in Japan were interviewed using the assessment sheet. The responses were analyzed qualitatively. The usefulness of the assessment sheet and the burden placed on the patients by its use were also investigated.Results: The spiritual pain elucidated by the assessment sheet was the same as that revealed in the earlier research of Morita. The patients reported that they did not find the use of the assessment sheet a burden, and more than half reported that it was useful. The burden of the assessment sheet on the subjects was thus determined to be low. Positive feedback on the assessment sheet was also received from the nurses who conducted the patient interviews, who said the assessment sheet made it easier to talk with the patients about their spiritual pain.Significance of research: The research results indicate that the spiritual pain assessment sheet provided an appropriate assessment of spiritual pain among terminal cancer patients, showing that such a sheet could be used as an assessment tool in the future.

Pain management for painful bony metastases is the most important problem for symptom relief of terminally-ill cancer patients. Pathological fractures often decrease the activity of daily life (ADL) of patients, and cause deterioration of the quality of life (QOL) and prognosis. Basically pharmacological therapies of the World Health Organization (WHO) method are essential for symptom relief from cancer pain. This article provides the latest pain managements (palliative irradiation, bisphosphonate, orthopedic surgery, percutaneous vertebroplasty and radiopharmaceutical therapy) of bony metastases, and mentions the indications and the problems of these interventions. In consideration to prognosis, the QOL and patient's needs, medical staffs have to perform multidisciplinary approach for providing suitable palliative care.

To explore the association between hydration volume and laboratory findings, and between calculated fluid balance and changes in clinical signs of dehydration and fluid retention in terminally ill cancer patients, a secondary analysis of a large multicenter, prospective, observational study was performed. The study enrolled 125 abdominal cancer patients who received laboratory examinations in the last week before death. Patients were classified into two groups: the hydration group (n = 44), who received 1L or more of artificial hydration per day both 1 and 3 weeks before death, and the nonhydration group (n = 81). The mean albumin level 1 week before death was significantly lower in the hydration group than in the nonhydration group, and the interaction between hydration group and decrease in the albumin level was statistically significant after adjusting multiple covariates (from 2.8 +/- 0.68 mg/dL 3 weeks before death to 2.4 +/- 0.56 mg/dL 24 hours before death in the hydration group vs. a decrease of 2.8 +/- 0.53 to 2.6+ /- 0.45 mg/dL in the nonhydration group, P = 0.015). There was no significant difference between the groups in the mean blood urea nitrogen/creatinine, sodium, or potassium levels 1 week before death. Among 53 patients who had oral fluid intake of less than 500 mL/day throughout the last 3 weeks and completed a fluid balance study, the median of calculated fluid balance was -400 mL/day 3 weeks before death, -521 mL/day 1 week before death, and -421 mL/day 24 hours before death. Calculated fluid balances did not significantly differ between the patients with deterioration of dehydration signs, edema, ascites, and pleural effusion during the final 3 weeks and those without. These data suggest that active artificial hydration might result in hypoalbuminemia, with no clear beneficial effects on normalizing blood urea nitrogen/creatinine, sodium, or potassium levels. Fluid balance did not significantly correlate with changes in dehydration-and fluid retention-signs. Calculated fluid balance is not an appropriate alternative to direct monitoring of patient symptoms. More studies are needed to determine the clinical efficacy of artificial hydration for terminally ill cancer patients.

Symptomatic sedation is often required in terminally ill cancer patients, and could cause significant distress to their family. The aims of this study were to clarify the family experience during palliative sedation therapy, including their satisfaction and distress levels, and the determinants of family dissatisfaction and high-level distress. A multicenter questionnaire survey assessed 280 bereaved families of cancer patients who received sedation in 7 palliative care units in Japan. A total of 185 responses were analyzed (response rate, 73%). The families reported that 69% of the patients were considerably or very distressed before sedation. Fifty-five percent of the patients expressed an explicit wish for sedation, and 89% of families were clearly informed. Overall, 78% of the families were satisfied with the treatment, whereas 25% expressed a high level of emotional distress. The independent determinants of low levels of family satisfaction were: poor symptom palliation after sedation, insufficient information-giving, concerns that sedation might shorten the patient's life, and feelings that there might be other ways to achieve symptom relief. The independent determinants of high levels of family distress were: poor symptom palliation after sedation, feeling the burden of responsibility for the decision, feeling unprepared for changes in the patient's condition, feeling that the physicians and nurses were not sufficiently compassionate, and shorter interval to patient death. Palliative sedation therapy was principally performed to relieve severe suffering based on family and patient consent. Although the majority of families were comfortable with this practice, clinicians should minimize family distress by regular monitoring of patient distress and timely modification of sedation protocols, providing sufficient information, sharing the responsibility of the decision, facilitating grief, and providing emotional support.

Background Communication about the ending of anticancer treatment and transition to palliative care is a difficult task for oncologists. The primary aims of this study were to clarify family-reported degree of emotional distress and the necessity for improvement in communication methods when communicating about the ending of anticancer treatment, and to identify factors contributing to the levels of emotional distress and the necessity for improvement. Methods A multi-center questionnaire survey was conducted on 630 bereaved family members of cancer patents who received specialized palliative care in Japan. A total of 318 responses were analyzed (effective response rate, 62%). Results Thirty-nine percent of the bereaved family members reported that they were ‘very distressed’ in receiving information about the ending of anticancer treatment, and 19% reported ‘considerable’ or ‘much’ improvement was necessary in the communication methods. High-level emotional distress was significantly associated with younger patient age, female family gender, the experience of the physician stating she/he could do nothing for the patient, the physician's unwillingness to explore their feelings, and prognostic disclosure of definite survival periods without probabilities or ranges. High levels of perceived necessity for improvement in the communication methods were significantly associated with the experience of the physician stating she/he could do nothing for the patient, physicians not explaining treatment goals in specific terms, physicians not pacing the explanation with the state of family preparation, physicians not being knowledgeable about the most advanced treatments, and the atmosphere not being relaxing enough to ask questions. Conclusions In receiving the information about ending anticancer treatment, a considerable number of families experienced high levels of emotional distress and felt a need for improvement of the communication methods. The strategies to alleviate family distress could include: (i) assuring that physicians will do their best to achieve specific goals, without saying that they can do nothing for the patient; (ii) providing information, including estimated prognosis, in careful consideration of families' preparation and the uncertainty for each patient; (iii) exploring families' emotions and providing emotional support; (iv) acquiring knowledge about advanced treatments; and (v) making the atmosphere relaxing enough to allow families to ask questions.

Context The many benefits of hospital palliative care teams (PCTs) are well known. However, their specific activities have not been fully clarified, and no standardized methods for reporting PCT activities are available. Objectives The aim of this study was to investigate, through the use of a standard format, the activities performed by hospital PCTs in Japan. Methods This was a prospective observational study. A total of 21 hospital PCTs were included in this study, and each recruited approximately 50 consecutively referred patients. Participating PCTs filled in a standard form for reporting activities. Results We obtained data from 1055 patients who were referred to PCTs. Of the 1055 patients, 1005 patients (95%) had cancer. The median number of reasons for referral and problems identified by PCTs was two (0–22) and four (0–18), respectively. The two major reasons for referral were pain (63%) and anxiety/depression/grief/emotional burden (22%). The major recommendations were pharmacological treatment (74%), care for the patient's physical symptoms (49%), and support for patient's decision making (38%). The major activities performed by the PCTs were comprehensive assessment (90%), care for the patient's physical symptoms (77%), and pharmacological treatment (74%). Conclusion The components of hospital PCT activities were successfully measured using the Standard Format for Reporting Hospital PCT Activity. The results of this study and the format for reporting hospital PCT activity could be effective in improving hospital PCT practice and for the education of new hospital PCT members.

We conducted a prospective study of symptom prevalence in 206 terminally ill cancer patients and a retrospective study of the incidence and treatment of malignant intestinal obstruction in 110 patients (30 with gastric cancer, 30 with colon cancer, 30 with rectal cancer, and 20 with ovarian cancer). In the prospective study, pain was the most frequent symptom in patients surviving more than 1 month. The frequencies of general malaise, anorexia, constipation, and insomnia increased during the patient’s final month. The frequency of confusion increased during the final 2 weeks. The frequencies of agitation and death rattle increased during the final days. The incidence of intestinal obstruction was 16%. In the retrospective study, we defined malignant intestinal obstruction as a final obstruction continuing for more than 1 week and for which surgery was not indicated. Malignant intestinal obstruction developed in 63% of patients with gastric cancer, 45% with ovarian cancer, and 40% with colorectal cancer. Symptoms of malignant intestinal obstruction in many patients were successfully controlled with opioids (morphine, buprenorphine, fentanyl), anticholinergic agents (scopolamine butylbromide, scopolamine hydrobromide), a major tranquilizer (haloperidol), and a somatostatin analogue (octreotide). Nausea and vomiting due to malignant intestinal obstruction were effectively treated in 75% of patients by continuous subcutaneous infusion of octreotide, with a median dose of 300 μ g/day. However, a nasogastric tube was necessary in 33% of patients with ovarian cancer, 21% with gastric cancer, and 8% with colorectal cancer.