Parenting experiences of cancer patients with minor children and their conversations about the possibility of death: a cross-sectional web-based survey for an online cancer community.

PURPOSE: Many cancer patients with minor children experience difficulty talking about their illness with their children. This study aimed to investigate the parenting experiences of cancer patients with minor children and their conversations about the possibility of death. METHODS: A cross-sectional web-based survey was conducted between April and May 2019. Cancer patients with at least one child aged < 18 years were recruited from an online peer support group called "Cancer Parents." The participants were asked to complete a questionnaire about their experiences of talking about their illnesses with their children. The participants were classified into those who disclosed their cancer to their children ("disclosing group"), and those who did not disclose ("non-disclosing group"). The association between whether they talked with their children about their cancer, and whether it included conversations about the possibility of death, was examined. RESULTS: A total of 370 parents participated (with 80.8% female parents, with a median age of 43.0 years). The disclosing group (n = 274, 74.1%) wanted to know what their child felt, more than the non-disclosing group did (p < 0.001). Members of the non-disclosing group had a greater tendency than those in the disclosing group to report that they did not want their children to see their suffering (p = 0.002) and did not know how to explain their disease status (p < 0.002). Some members of both the disclosing (42.1%) and non-disclosing (6.5%) groups told their children about the possibility of death. CONCLUSION: This study showed that 74.1% of the patients with minor children disclosed their cancer to their children. The parents' feelings when thinking about interacting with their children differed significantly between the disclosing and non-disclosing groups. It is important for healthcare professionals treating patients with cancer to provide appropriate multidisciplinary support for discussing their diagnosis and prognosis with their children.

Palliative care physicians' recognition of patients after immune checkpoint inhibitors and immune-related adverse events.

PURPOSE: This study investigated the experience of palliative care physicians (PCPs) and their knowledge and recognition of immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs) in clinical practice as well as the need to provide palliative care services for patients after ICI treatments. METHODS: A cross-sectional survey with self-administered questionnaires was conducted between February and April 2020. A total of 759 questionnaires were sent to PCPs in Japan. The changes in the PCPs' knowledge and recognition of ICIs and irAEs due to the increased experiences of treating patients after ICI treatments were analyzed. RESULTS: Four hundred ninety-two responses (64.8%) were analyzed. Only 15.0% of respondents had no experience of patients after ICI treatments, while 53.9% had experience of more than six patients. On the other hand, 40% of respondents had no experience of patients with suspected irAEs, while only 13.4% had experience of more than six patients. Respondents with more experience of patients after ICI treatments or those with suspected irAEs had extensive knowledge of ICIs and irAEs, were more confident in treating these patients, and tended to consider irAEs as therapeutic indications. The majority of respondents required guidelines and efficient consultation systems with oncologists. CONCLUSION: This study demonstrated that PCPs with experience had extensive knowledge and confidence of ICIs and irAEs and tended to recognize irAEs as therapeutic indications. The establishment of a more intimate relationship between PCPs and oncologists is important for providing better treatment for these patients.

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.

Availability of and factors related to interventional procedures for refractory pain in patients with cancer: a nationwide survey.

BACKGROUND: Cancer pain may be refractory to standard pharmacological treatment. Interventional procedures are important for quality of analgesia. The aim of the present study was to clarify the availability of four interventional procedures (celiac plexus neurolysis/splanchnic nerve neurolysis, phenol saddle block, epidural analgesia, and intrathecal analgesia), the number of procedures performed by specialists, and their associated factors. In addition, we aimed to establish how familiar home hospice physicians and oncologists are with the different interventional procedures available to manage cancer pain. METHODS: A cross-sectional survey using a self-administered questionnaire was conducted. Subjects were certified pain specialists, interventional radiologists, home hospice physicians, and clinical oncologists. RESULTS: The numbers of valid responses/mails were 545/1,112 for pain specialists, 554/1,087 for interventional radiology specialists, 144/308 for home hospice physicians, and 412/800 for oncologists. Among pain specialists, depending on intervention, 40.9-75.2% indicated that they perform each procedure by themselves, and 47.5-79.8% had not performed any of the procedures in the past 3 years. Pain specialists had performed the four procedures 4,591 times in the past 3 years. Among interventional radiology specialists, 18.1% indicated that they conduct celiac plexus neurolysis/splanchnic nerve neurolysis by themselves. Interventional radiology specialists had performed celiac plexus neurolysis/splanchnic nerve neurolysis 202 times in the past 3 years. Multivariate analysis revealed that the number of patients seen for cancer pain and the perceived difficulty in gaining experience correlated with the implementation of procedures among pain specialists. Among home hospice physicians and oncologists, depending on intervention, 3.5-27.1% responded that they were unfamiliar with each procedure. CONCLUSIONS: Although pain specialists responded that the implementation of each intervention was possible, the actual number of the interventions used was limited. As interventional procedures are well known, it is important to take measures to ensure that pain specialists and interventional radiology physicians are sufficiently utilized to manage refractory cancer pain.

Effects of once-yearly zoledronic acid on bone density and incident vertebral fractures in nonmetastatic castration-sensitive prostate cancer patients with osteoporosis.

BACKGROUND: Androgen deprivation therapy (ADT) is the effective treating prostate cancer but is often accompanied by cancer treatment-induced bone loss (CTIBL), which impairs the patient's quality of life. In patients with nonmetastatic castration-sensitive prostate cancer (M0CSPC) who already have osteoporosis before starting ADT, appropriate bone-modifying agent intervention must be performed in parallel, as the patient has a high risk of future fracture. However, little is known about therapeutic interventions aimed at preventing the progression of CTIBL and new fractures. The present study explored the effect of once-yearly zoledronic acid 5 mg (ZOL 5 mg) on bone mineral density (BMD) and new vertebral fractures (VFs) in M0CSPC patients with coexisting osteoporosis before starting ADT. METHODS: We conducted a retrospective, multi-institutional, cohort study involving 42 M0CSPC patients with osteoporosis who had undergone ADT with/without a single intravenous infusion of ZOL 5 mg at the start of ADT (ZOL 5 mg group, n = 26; control group, n = 16). The association of the ZOL 5 mg with changes in the BMD from baseline to 12 months and the incidence of VFs were evaluated. RESULTS: Prevalent VFs were found in 47.6% of all patients at baseline. ZOL 5 mg significantly increased the lumbar spine BMD (LS-BMD) (mean rate of change: + 4.02%, p < 0.0001) and significantly decreased the TRACP-5b (mean rate of change: - 52.1%, p < 0.0001) at 12 months after starting ADT. Incident VFs were identified in 19.0% of all patients at 12 months after starting ADT. After adjusting for the age, BMI, and changes in the LS-BMD, ZOL 5 mg was not significantly associated with incident VFs (odds ratio 0.66, 95% confidence interval 0.04-11.3, p = 0.7774). CONCLUSION: ZOL 5 mg significantly increased the LS-BMD 12 months after starting ADT, and our short-term results showed that ZOL 5 mg was not significantly correlated with the suppression of incident vertebral fractures.

The association between health-related quality of life and achievement of personalized symptom goal.

PURPOSE: The aim of study was to explore the potential association between patient's self-reported physical symptom management goals as personalized symptom goal (PSGs) and health-related quality of life (HRQOL) in cancer patients. The secondary outcome was to investigate the relationship between number of physical symptoms not achieving the PSGs and HRQOL in cancer patients. METHODS: This single-center prospective observational study comprised 140 consecutive outpatients. We evaluated the PSGs and HRQOL using the Functional Assessment of Cancer Therapy-General (FACT-G). Patients were administered a self-report questionnaire, including reports on their physical symptom intensity and PSGs using Edmonton Symptom Assessment System-revised (ESAS-r) scores. We investigated the correlation between PSGs achievement (ESAS-r score ≤ PSG score) and FACT-G total scores, and relationship between and number of physical symptoms not achieving the PSGs (ESAS-r score > PSG score) and FACT-G total scores. RESULTS: The patients who did not achieve PSGs of pain, tiredness, lack of appetite, and shortness of breath had a lower FACT-G total score (p < 0.05). Multivariate linear regression showed that higher number of physical symptoms not achieving the PSGs correlated with lower FACT-G scores (decreasing by 1.826 points for each such symptom, p < 0.01). Predictors of increased number of physical symptoms not achieving the PSGs were younger age and a higher symptom intensity of anxiety. CONCLUSION: PSGs achievement was associated with HRQOL in cancer patients. Additionally, the number of unachieved PSGs were independent determinant of poor HRQOL, particularly in younger cancer patients and those with higher symptom intensity of anxiety.

Correction to: Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.

In the Original publication of the article, the legend appearing inside the flow chart has been incorrectly published.

Low Phase Angle Is Correlated With Worse General Condition in Patients with Advanced Cancer.

OBJECTIVES: Phase angle (PA) is a poor prognostic factor in patients with advanced cancer. This study aimed to identify possible correlations between PA and symptoms, quality of life, fluid retention, and laboratory data in cancer patients in palliative care settings. METHODS: Individuals who visited the outpatient clinic or were admitted to the palliative care unit were eligible. Patients with a performance status of 4 and/or those unable to complete questionnaires were excluded. PA was evaluated using a bioanalyzer device. The correlation coefficient between PA and the variables of interest was analyzed. RESULTS: A total of 102 patients were analyzed. PA was weakly correlated with age (ρ = -0.22), performance status (ρ = -0.30), functional well-being (ρ = 0.20), anorexia/cachexia subscale (ρ = 0.22), and Functional Assessment of Anorexia/Cachexia Therapy trial outcome index (ρ = 0.26). PA was also correlated with fluid retention (ρ = -0.34) and albumin (ρ = 0.32), C-reactive protein (ρ = -0.31), and hemoglobin (ρ = 0.41) levels. Sub-analysis stratified according to sex revealed that males demonstrated the same results; however, female sex demonstrated a correlation between PA and social well-being (ρ = -0.43). CONCLUSIONS: PA was correlated with physical condition, but not with psychological well-being.

Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.

There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9 mmHg vs. + 2.7 mmHg; p = 0.0002, diastolic BP; - 3.9 mmHg vs. + 0.6 mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.

Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients.

Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with Abca1 knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (P < 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats (P < 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats (P < 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls (P < 0.05). The level of hepatic liver X receptor (LXR)ß mRNA was correlated with ABCA1 mRNA levels in PBC patients. The expression of hepatic ABCA1 transporter was upregulated in both the cholestatic rat model and PBC patients. Upregulated hepatic ABCA1 may lead to efflux of cholesterol into plasma, thus explaining the mechanism of cholestasis leading to hypercholesterolemia.

Differences in the diurnal variation of salivary stress biomarkers during the coronavirus (COVID-19) pandemic between telecommuters and office workers.

OBJECTIVES: It is necessary to objectively assess the stress state of workers, from the standpoint of holistic palliative care, in order to determine how the rapid change in work styles in the "live with coronavirus era"-in which people will coexist and live with the coronavirus (COVID-19)-will affect their physical and mental health. The aim of this study is to assess the impact of rapid changes in work patterns during the COVID-19 pandemic on the neuroendocrine stress response of workers. DESIGN AND METHODS: A total of sixteen subjects, 9 telecommuters (2 males, 7 females; age, 37.1±2.6 years) and 7 office workers (3 males, 4 females; age, 37.3±3.0 years) who provided their informed consent were enrolled in this prospective observational study. Saliva was collected four times a day (after waking, noon, evening, and before bedtime) and three times a week (Monday, Wednesday, and Friday) during May and June 2020. The saliva samples were stored at -20°C until measurement. Saliva components were analyzed by ELISA for cortisol, melatonin, s-IgA, and oxytocin. RESULTS: The diurnal variation of salivary components between telecommuting and office work groups was investigated. Cortisol showed diurnal variation with higher secretion during waking hours and lower secretion toward nighttime in both groups, and no modulation was observed. In the office work group Melatonin showed diurnal variation, with increased secretion at night. In contrast, the telecommuting group showed modulation, with higher secretion at waking and lower secretion at night. s-IgA showed diurnal variation with a high level at waking and a low level thereafter in both groups, and no modulation was observed. The telecommuting group showed higher oxytocin levels in comparison to the office work group. CONCLUSIONS: These results suggest that the absence of commuting in the telecommuting group reduces anxiety due to infection, and that the diurnal variation of melatonin may be due to the alteration of circadian rhythm caused by being at home all day.

A Japanese Nationwide Survey of Nutritional Counseling for Cancer Patients and Risk Factors of Burnout among Registered Dietitians.

Purpose: Registered dietitians have played a key role in the nutritional management of cancer patients; however, no study has investigated the prevalence of burnout and associated factors among this population. The aim of this study was to investigate the following: (1) experiences, approaches, and perspectives during nutritional counseling, (2) the prevalence of burnout, and (3) burnout-associated factors among registered dietitians. Methods: A nationwide survey with self-administered questionnaires was conducted for 1070 registered dietitians belonging to all 390 designated cancer hospitals in Japan. Nutrition counseling, the prevalence of burnout, and burnout-associated factors were analyzed. Results: A total of 631 responses were analyzed. Half of the respondents recommended a consultation about treatment of symptoms or listened to their patients' distress and anxiety of death. Respondents with a severe level of burnout for emotional exhaustion, depersonalization, and personal accomplishment (PA) were 21.1%, 2.8%, and 71.9%, respectively. Burnout was associated with fewer years of clinical experience, more overtime hours, higher score of Patient Health Questionnaire-9, higher score of K-6, not so positive attitude about caring for dying patients, the approach of listening to the patients and family distress and anxiety about death, the uneasiness interacting with patients and families without an effective proposal, the difficulty of allocating staff without increasing medical costs, and the absence of feeling of a good contribution to patients and families. Conclusions: The prevalence of burnout on PA was quite high. Registered dietitians who engaged in nutritional counseling for cancer patients and families might benefit from education to help protect against burnout.

A Comparison of the Predictive Role of the Geriatric Nutritional Risk Index and Immunonutritional Parameters for Postoperative Complications in Elderly Patients with Renal Cell Carcinoma.

BACKGROUND: The geriatric nutritional risk index (GNRI) is reportedly a useful factor for predicting postoperative complications in elderly patients with several cancers. The aim of this study was to investigate the relationship between postoperative complications and the GNRI in elderly patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: The clinical data of 62 patients who were ≥65 years old and underwent open surgery for RCC were analyzed retrospectively. The American Society of Anesthesiologists physical status, Charlson comorbidity index, surgical procedure, body mass index, GNRI, platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), psoas muscle index (PMI), visceral fat area, and subcutaneous fat area were examined. The association of the GNRI and immunonutritional parameters with postoperative complications was analyzed by the univariate and multivariate analyses. RESULTS: Grade ≥ II postoperative complications evaluated by the Clavien-Dindo classification were seen in 11 out of 62 cases. In the Spearman's correlation test, the GNRI showed a significant negative correlation with the PLR and NLR and a significant positive correlation with the PMI. The group with postoperative complications showed a significantly lower GNRI, higher PLR, and higher NLR than those without complications. In the multivariate analysis, a GNRI ≤92 was independently associated with postoperative complications. CONCLUSION: The GNRI might play an important role in evaluation of the risk of postoperative complications in open surgery for elderly RCC patients.

How Successful Is Parenteral Oxycodone for Relieving Terminal Cancer Dyspnea Compared With Morphine? A Multicenter Prospective Observational Study.

CONTEXT: 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. OBJECTIVES: To explore the efficacy of parenteral oxycodone vs. morphine by continuous infusion over 24 hours in cancer patients with terminal dyspnea. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Comprehensive assessment of the impact of horticultural activities on salivary stress biomarkers, psychological status, and the autonomic nervous system response visualized using a wearable biosensor.

OBJECTIVES: This study aims to comprehensively investigate the changes of salivary stress biomarkers, psychological status, and autonomic nervous system (ANS) response due to horticultural activities (HAs). DESIGN AND METHODS: A prospective observational study was conducted in twenty Japanese healthy adults (mean age, 58.4 years). Flower appreciation, flower arrangement, and farm work experience were performed as three HAs with different working concepts. Five salivary stress biomarkers (cortisol, α-amylase, S-IgA, chromogranin A, and oxytocin) were measured to quantify the stress levels before and after each HA. The Profile of Mood Status 2nd edition (POMS2) was used as a subjective psychological evaluation. Wearable biosensors were used to visualize the continuous ANS response throughout the process. RESULTS: In the POMS2 investigation, the negative factors, which included Anger-Hostility, Confusion-Bewilderment, Depression-Dejection, Tension-Anxiety, and Total Mood Disturbance, were significantly decreased (p=0.0135, p=0.0004, p=0.0024, p=0.0015, p=0.0063, respectively). In the measurement of salivary stress biomarkers, flower appreciation decreased cortisol (p=0.0134), and farm work experience not only decreased cortisol but also increased oxytocin (p=0.0041, p=0.0128 respectively). In the visualization results of the ANS response, a graph demonstrated that the difference in activity between the sympathetic nerve and the parasympathetic nerve was narrowed by a series of HAs. CONCLUSIONS: In healthy adults, HAs had a stress-reducing effect, which was evidenced by neuroendocrinological and psychological evaluations, a study of POMS2, salivary stress biomarkers, and visualization of the ANS response.

Association Between Loneliness and the Frequency of Using Online Peer Support Groups Among Cancer Patients With Minor Children: A Cross-Sectional Web-Based Study.

CONTEXT: Cancer patients with minor children are increasing; however, they do not receive sufficient support. OBJECTIVE: This study aimed to investigate the association between loneliness and the frequency of using online peer support groups among cancer patients with minor children. METHODS: A cross-sectional web-based survey was conducted from April to May 2019. Cancer patients with minor children were recruited from an online peer support group called "Cancer Parents." Individuals diagnosed with cancer and whose youngest children were younger than 18 years were enrolled. Materials included: the UCLA Loneliness Scale version 3 (UCLA-LS), K6 scale, abbreviated Lubben Social Network Scale, and the sociodemographic/clinical characteristics questionnaire. Multivariate logistics regression analysis was performed to determine the factors associated with the high loneliness group (defined as those above the median score on the UCLA-LS). RESULTS: A total of 334 patients participated (79.9% female; mean age 43.1 years, standard deviation 5.8). The most common primary cancer type was breast (34.1%). The median score of the UCLA-LS was 45 (interquartile range 37-53). The multivariate logistics regression analysis revealed that the high loneliness group was significantly associated with the frequent use of online peer support group less than once a week (odds ratio [OR] = 0.47; 95% CI = 0.26-0.85; P = 0.012), with a smaller social network (OR = 0.78; 95% CI = 0.73-0.83; P < 0.001), and higher psychological distress (OR = 1.16; 95% CI = 1.09-1.23; P < 0.001). CONCLUSIONS: Frequent use of online peer support groups was associated with less loneliness among cancer patients with minor children.

Alternative transporter pathways in patients with untreated early-stage and late-stage primary biliary cirrhosis.

BACKGROUND/AIMS: The hepatic expression of bile acid transporters is altered in experimental cholestasis and it is unclear whether regulation exists in human cholestatic diseases. We investigated the expression of genes involved in bile acid detoxification, basolateral export and nuclear factor regulation in untreated primary biliary cirrhosis (PBC). METHODS: Liver tissues were obtained from patients with early-stage and late-stage PBC. The hepatic expression levels of messenger RNAs were determined by the real-time reverse transcription polymerase chain reaction. RESULTS: The hepatic expression of multidrug-resistance protein 4 messenger RNA was significantly upregulated in early-stage and late-stage PBC patients compared with controls. The hepatic expression of multidrug-resistance protein 2 and multidrug-resistance protein 3 messenger RNAs was significantly elevated only in early-stage PBC patients. The hepatic expression levels of farnesoid X receptor, fetoprotein transcription factor and constitutive androstane receptor mRNAs were correlated with those of multidrug-resistance protein 2, multidrug-resistance protein 3 and multidrug-resistance protein 4 respectively. CONCLUSIONS: The hepatic expression of multidrug-resistance protein 4 was enhanced in patients with untreated PBC at all stages. However, the hepatic expression of multidrug-resistance protein 2 and multidrug-resistance protein 3 was enhanced only in early-stage patients. The lack of upregulation of these proteins might contribute to the progression of PBC.

Altered expression of alkaline phosphatase (ALP) in the liver of primary biliary cirrhosis (PBC) patients.

Serum alkaline phosphatase (ALP) is a representative marker of cholestasis, in diseases such as primary biliary cirrhosis (PBC). However, the hepatic localization of ALP in patients with cholestatic liver diseases has not been fully clarified. Accordingly, we studied the expression of ALP in the liver of PBC, chronic hepatitis C and controls. By immunohistochemistry, in the liver tissue of controls and chronic hepatitis C patients, ALP was found to be localized in the canalicular membrane of hepatocytes and the apical area of the cytoplasm of bile duct epithelial cells. In PBC, ALP was localized in both the canalicular and baso-lateral membranes of hepatocytes and in the whole cytoplasm of the remaining bile duct epithelial cells. The expression of ALP in liver tissues evaluated by Western blotting was increased to 3.6-fold in PBC compared with that in the controls and chronic hepatitis C patients, while the expression of mRNA of ALP evaluated by RT-PCR was increased to 7.0-fold in PBC compared with that in the controls and chronic hepatitis C patients. The present study is the first study to reveal altered localization and increased expression of ALP which may result in the elevation of serum ALP in PBC.

Postoperative recurrence in hepatocellular carcinoma: Comparison between percutaneous ethanol injection and radiofrequency ablation.

AIM: Recently percutaneous ethanol injection (PEI) turned into percutaneous radiofrequency ablation (PRFA), and it has become widely used for the treatment of hepatocellular carcinoma (HCC). The present study was to compare the incidence in postoperative HCC recurrence between these two therapeutic approaches. METHODS: One hundred and sixty-eight first-time HCC in patient cases were chosen for PEI (n=94) and PRFA (n=74). The localized recurrence rate based on the operator's experience in percutaneous treatment for HCC (on <5 years versus >/=5 years experience) was examined. RESULTS: The PRFA group demonstrated a significantly lower localized recurrence rate within 2 years than the PEI group (8% and 22%, respectively, P<0.01). The local recurrence rate of HCC within 2 years after PEI was significantly lower in those for whom the operator's experience was more than 5 years compared to those for whom it was less than 5 years (12% versus 24%, respectively, P<0.05). In contrast, after PRFA there was no significant difference between these two groups of <5 years and of >/=5 years experience (8% versus 8%, respectively, P=0.98). CONCLUSION: The present study demonstrated that PRFA resulted in a lower rate of local recurrence in comparison to conventional PEI, regardless of the operator's experience.