Comparison of the prevalence and associated factors of hyperactive delirium in advanced cancer patients between inpatient palliative care and palliative home care.

BACKGROUND: Hyperactive delirium is known to increase family distress and the burden on health care providers. We compared the prevalence and associated factors of agitated delirium in advanced cancer patients between inpatient palliative care and palliative home care on admission and at 3 days before death. METHODS: This was a post hoc exploratory analysis of two multicenter, prospective cohort studies of advanced cancer patients, which were performed at 23 palliative care units (PCUs) between Jan and Dec 2017, and on 45 palliative home care services between July and Dec 2017. RESULTS: In total, 2998 patients were enrolled and 2829 were analyzed in this study: 1883 patients in PCUs and 947 patients in palliative home care. The prevalence of agitated delirium between PCUs and palliative home care was 5.2% (95% CI: 4.2% - 6.3%) vs. 1.4% (0.7% - 2.3%) on admission (p < 0.001) and 7.6% (6.4% - 8.9%) vs. 5.4% (4.0% - 7.0%) 3 days before death (p < 0.001). However, multivariate logistic regression analysis revealed that the place of care was not significantly associated with the prevalence of agitated delirium at 3 days before death after adjusting for prognostic factors, physical risk factors, and symptoms. CONCLUSIONS: There was no significant difference in the prevalence of agitated delirium at 3 days before death between inpatient palliative care and palliative home care after adjusting for the patient background, prognostic factors, symptoms, and treatment.

Patient perceptions of curability and physician-reported disclosures of incurability in Japanese patients with unresectable/recurrent cancer: a cross-sectional survey.

BACKGROUND: Although reports have described the perceptions of curability among patients with unresectable/recurrent cancer and the quality of death and dying, the association between patients' perceptions and physicians' disclosures of incurability remained unexplored. This survey aimed to evaluate the association between patients' perceptions of curability and physicians' disclosures of incurability. METHODS: In this cross-sectional, multicenter, observational study in Japan, we asked outpatients with unresectable/recurrent solid cancers about their perceptions of incurability. The patient inclusion criteria were unresectable/recurrent solid cancer, failure of first-line chemotherapy and an age ≥ 20 years. Additionally, we surveyed their primary responsible physicians regarding disclosures to patients regarding incurability. RESULTS: Although we estimated the necessary sample size as 250, we discontinued recruitment because the responsible researcher transferred to another hospital. Among the 135 included and surveyed patients, 39% responded that their cancer was incurable, 33% responded that their cancer was curable and 23% responded 'I don't know' or 'I don't wish to answer'. No significant association was observed between patients' perceptions of curability and physician-reported disclosures of incurability. CONCLUSION: In this Japanese population, 39% of patients with unresectable/recurrent solid cancers perceived that their cancers were incurable. However, such perceptions did not appear to be significantly affected by physician-reported disclosures. We recommend additional research to determine the best disclosure method to ensure that patients truly understand their disease status.

Nationwide Japanese Survey About Deathbed Visions: "My Deceased Mother Took Me to Heaven".

OBJECTIVES: Primary aim was to clarify the prevalence and factors associated with the occurrence of deathbed visions, explore associations among deathbed visions, a good death, and family depression. Additional aim was to explore the emotional reaction, perception, and preferred clinical practice regarding deathbed visions from the view of bereaved family members. METHODS: A nationwide questionnaire survey was conducted involving 3964 family members of cancer patients who died at hospitals, palliative care units, and home. RESULTS: A total of 2827 responses (71%) were obtained, and finally 2221 responses were analyzed. Deathbed visions were reported in 21% (95% CIs, 19-23; n = 463). Deathbed visions were significantly more likely to be observed in older patients, female patients, female family members, family members other than spouses, more religious families, and families who believed that the soul survives the body after death. Good death scores for the patients were not significantly different between the families who reported that the patients had experienced deathbed visions and those who did not, whereas depression was more frequently observed in the former than latter, with marginal significance (20 vs. 16%, respectively, adjusted P = 0.068). Although 35% of the respondents agreed that deathbed visions were hallucinations, 38% agreed that such visions were a natural and transpersonal phenomenon in the dying process; 81% regarded it as necessary or very necessary for clinicians to share the phenomenon neutrally, not automatically labeling them as medically abnormal. CONCLUSIONS: Deathbed vision is not an uncommon phenomenon. Clinicians should not automatically regard such visions as an abnormal phenomenon to be medically treated and rather provide an individualized approach.

Validation of the Simplified Palliative Prognostic Index Using a Single Item From the Communication Capacity Scale.

CONTEXT: Although the Palliative Prognostic Index (PPI) is a reliable and validated tool to predict the survival of terminally ill cancer patients, all clinicians cannot always precisely diagnose delirium. OBJECTIVES: The primary aim of this study was to examine the predictive value of a simplified PPI. In the simplified PPI, a single item from the Communication Capacity Scale was substituted for the delirium item of the original. METHODS: This multicenter prospective cohort study was conducted in Japan from September 2012 through April 2014 and involved 16 palliative care units, 19 hospital-based palliative care teams, and 23 home-based palliative care services. Palliative care physicians recorded clinical variables at the first assessment and followed up patients six months later. RESULTS: A total of 2425 subjects were recruited; 2343 had analyzable data. The C-statistics of the original and simplified PPIs were 0.801 and 0.800 for three week and 0.800 and 0.781 for six-week survival predictions, respectively. The sensitivity and specificity for survival predictions using the simplified PPI were 72.9% and 67.6% (for three week) and 80.3% and 61.8% (for six week), respectively. CONCLUSION: The simplified PPI showed essentially the same predictive value as the original PPI and is an alternative when clinicians have difficulties in diagnosing delirium.

The Accuracy of Physicians' Clinical Predictions of Survival in Patients With Advanced Cancer.

CONTEXT: Accurate prognoses are needed for patients with advanced cancer. OBJECTIVES: To evaluate the accuracy of physicians' clinical predictions of survival (CPS) and assess the relationship between CPS and actual survival (AS) in patients with advanced cancer in palliative care units, hospital palliative care teams, and home palliative care services, as well as those receiving chemotherapy. METHODS: This was a multicenter prospective cohort study conducted in 58 palliative care service centers in Japan. The palliative care physicians evaluated patients on the first day of admission and followed up all patients to their death or six months after enrollment. We evaluated the accuracy of CPS and assessed the relationship between CPS and AS in the four groups. RESULTS: We obtained a total of 2036 patients: 470, 764, 404, and 398 in hospital palliative care teams, palliative care units, home palliative care services, and chemotherapy, respectively. The proportion of accurate CPS (0.67-1.33 times AS) was 35% (95% CI 33-37%) in the total sample and ranged from 32% to 39% in each setting. While the proportion of patients living longer than CPS (pessimistic CPS) was 20% (95% CI 18-22%) in the total sample, ranging from 15% to 23% in each setting, the proportion of patients living shorter than CPS (optimistic CPS) was 45% (95% CI 43-47%) in the total sample, ranging from 43% to 49% in each setting. CONCLUSION: Physicians tend to overestimate when predicting survival in all palliative care patients, including those receiving chemotherapy.

[A case of left breast cancer resulting in complete response by primary systemic therapy].

The patient was a 39-year-old woman, who noted a mass in her left breast. She was diagnosed with the left breast cancer (T4N2M0, stage IIIB) in our hospital. As primary systemic therapy, she received 4 cycles of FEC 100 every 21 days, and then 4 cycles of paclitaxel (180 mg/m(2)) every 21 days. Clinical CR was maintained, and a total mastectomy with axillary lymph node dissection was performed. The resected specimen showed no visible cancer cells in both the primary site and axillary lymph nodes. The effect of the chemotherapy was grade 3, pathological CR, and all lymph node metastases disappeared.

A novel germline mutation of the LKB1 gene in a patient with Peutz-Jeghers syndrome with early-onset gastric cancer.

The gene responsible for Peutz-Jeghers syndrome (PJS), LKB1 (also called STK11) was mapped to chromosome 19p13.3 and was found to encode a putative serine/threonine protein kinase, LKB1. As only a limited number (approximately 100) of germline mutations of the gene have been reported, and because the protein function is still unclear, information about LKB1 mutations and their expression should be accumulated to understand the phenotype-genotype correlation of this disease. Here we report a patient with sporadic PJS with early-onset gastric cancer. We found a novel germline frameshift mutation (757-758insT) in the LKB1 gene and a marked reduction in LKB1 protein expression in the carcinoma cells, suggesting that the loss of LKB1 function may have led to the carcinogenesis of the gastric cancer.

Identification and evaluation of 55 genetic variations in the BRCA1 and the BRCA2 genes of patients from 50 Japanese breast cancer families.

We sequenced approximately 23 kb genomic regions containing all the coding exons and their franking introns of two breast cancer susceptibility genes, BRCA1 and BRCA2, of 55 individuals from 50 unrelated Japanese breast cancer families. We identified 55 single-nucleotide polymorphisms (SNPs) (21 in BRCA1 and 34 in BRCA2) containing nine pathogenic protein-truncating mutations (four in BRCA1 and five in BRCA2 from ten patients). Among the remaining 46 SNPs, allele frequencies of 40 were examined in both the breast cancer patients and 28 healthy volunteers with no breast cancer family history by PCR-RFLP or by direct DNA sequencing. Twenty-eight SNPs were common and were also found in the healthy volunteers and/or a SNP database. The remaining 18 were rare (allele frequency <0.05) and were not found in the healthy volunteers and/or the database. The pathogenic significance of these coding SNPs (cSNPs) remains to be clarified. The SNP information from this study will be useful in the future genetic testing of both BRCA1 and BRCA2 genes in the Japanese population.

The effects of the load mass and load position on body sway in supporting a load on the back.

We examined the effects of a load's mass and position on body sway during standing with a load on the back. Three healthy male subjects participated in this experiment. The subjects supported loads of 23kg, 33kg, and 43kg on their backs using a carrier frame. They were asked to stand for 75s on a force platform with their eyes open while being as quiet as possible. Time series data of center-of-pressure (COP) were collected at a sampling rate of 50Hz during the last 60s of the 75s standing period. The COP was measured under three conditions in terms of the load position on the frame: lower (close to the hip), middle, and upper (close to the shoulder). All subjects showed that the lower the position of the load, the more anteriorly the mean COP coordinate was located in the anteroposterior (AP) direction, and the smaller the total distance of the COP trajectories became. Regarding carrying the heavier loads, each subject showed a specific tendency in the mean AP coordinate. The three subjects had different physical characteristics in terms of body height and experience at carrying heavy loads. These results suggest that the examintion of the COP in a static posture can help our understanding of individual information on the posture supporting loads and the general positioning of the body.

Evaluation of the diagnostic accuracy of the stop codon (SC) assay for identifying protein-truncating mutations in the BRCA1and BRCA2genes in familial breast cancer.

Screening for protein-truncating mutations of the BRCA1 and BRCA2 genes is useful in genetic testing for familial breast cancer because, first, the methods are usually simple and not expensive, and second, the detected mutations indicate pathogenic mutations in general. We evaluated the diagnostic accuracy of the stop codon (SC) assay for detecting protein-truncating mutations in the BRCA1 and BRCA2 genes by comparing the results with DNA sequencing in samples from 29 patients with breast cancer from 24 Japanese families with a history of breast cancer. Protein-truncating mutations were detected in 5 of the 24 families (20.8%; two in the BRCA1 gene and three in the BRCA2 gene). Among the 176 DNA fragments examined using the SC assay, the existence of three protein-truncating mutations (one in the BRCA1 gene and two in the BRCA2gene) was predicted correctly by the assay. Only one reverse transcriptase-polymerase chain reaction fragment was positive for the SC assay but was negative using DNA sequencing. Our study showed clearly that the SC assay is sensitive (3 of 3, 100%) and specific (172 of 173, 99%) for detecting pathogenic protein-truncating mutations in the BRCA1 and BRCA2 genes, and that it could be useful for screening larger populations.

Thymidine phosphorylase expression in gastric carcinoma as a marker for metastasis.

BACKGROUND: Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECCF) and has a function of angiogenesis in vitro and in several types of human carcinoma tissues. We have reported that expression of dThdPase was an independent prognostic factor in 116 gastric carcinomas by immunohistochemical analysis. MATERIALS AND METHODS: In the present study, we updated the analysis of recurrence in 116 patients with gastric carcinomas to find how dThdPase plays an important role in progression of gastric carcinoma. RESULTS: Expression of dThdPase was significantly involved in the progression and metastasis of gastric carcinoma. Further, the proportion of recurrence of the patients with dThdPase-positive gastric carcinoma (23 out of 50, 46.0%) was significantly higher than that with -negative gastric carcinoma (5 out of 66, 7.6%) (p < 0.05). Interestingly, the proportion of hematogenous metastasis (liver, lung) of the patients with dThdPase-positive gastric carcinoma (8 out of 8, 100%) was significantly higher than that with -negative gastric carcinoma (0 out of 8, 0%)) (p < 0.05). The proportion of peritoneal metastasis of the patients with dThdPase-positive gastric carcinoma (10/13, 76.9%) was also significantly higher than that with -negative gastric carcinoma (3 out of 13, 23.1%)) (p < 0.05). CONCLUSION: These findings suggested that dThdPase promotes hematogenous and peritoneal metastases in gastric carcinoma. Inhibition of dThdPase may suppress hematogenous and peritoneal metastases in gastric carcinoma and improve prognosis of patients with gastric carcinoma.

Kinetic study of seita-fitting.

We have already presented two studies of the traditional carrier frame, the seita. In our first study, we reported on seita users supporting loads not on the lumbar vertebrae but on the sacrum. In the second study, we showed that carrying a load on the sacrum was efficient in terms of metabolic rate, muscle activity, cadence and subjective responses. The purpose of this study was to verify the effect of carrying a load on the sacrum in terms of gait pattern. We compared the kinetic parameters produced while carrying a load on the sacrum (LOS) with those produced while carrying a load on the lumbar vertebrae (LOLV). Maximum propulsive force and medial impulse were significantly larger in LOS than in LOLV. These results suggested that a normal gait pattern was maintained more in LOS conditions than in LOLV conditions. This indicated that seita-fitting was efficient for carrying and transporting loads.