Identifying the unmet physical and psychological intimacy and sexual needs of partners of patients with terminal cancer.

BACKGROUND: Palliative care aims to improve the quality of life of patients who are terminally ill, but support for the sexuality of these patients is often inadequate. AIM: To identify factors related to the unmet needs of bereaved partners whose significant others died of cancer during hospitalization. METHODS: Bereaved individuals in Japan aged >50 years who had lost their partners to cancer in a hospital in the last 5 years answered a questionnaire on the support desired for "time to nurture love with your partner." OUTCOMES: We used 3 sexual questions in the 34-item Supportive Care Needs Survey-Short Form (SCNS-SF34) and measured the unmet needs of partners of patients with terminal cancer. RESULTS: We obtained 290 responses (equal number of males and females). Respondents' age distribution was as follows: 50 to 59 years, 34.8%; 60 to 69 years, 44.5%; 70 to 79 years, 19.3%; ≥80 years, 1.4%. In total, 81% had children. Most partners died in the general ward (59.3%). Frequency of time to nurture love with one's partner before the illness was as follows: none at all, 44 (15.2%); very little, 84 (29.0%); once in a while, 76 (26.2%); occasionally, 45 (15.5%); and often, 41 (14.1%). Roughly 20% of participants reported experiencing unmet sexual needs across all 3 selected questions in the SCNS-SF34. Multivariate analysis showed that younger age (P = .00097) and a higher frequency of time to nurture love with one's partner before illness (P = .004) were positively associated with unmet needs for sexuality during hospitalization. CLINICAL IMPLICATIONS: The study may help health care workers identify patients who are seeking sexual support. STRENGTHS AND LIMITATIONS: This study identified the unmet needs and underlying factors regarding sexuality during hospitalization for partners of patients with terminal cancer. However, differences by cancer type could not be analyzed. Additionally, the modified version of the supportive care needs measure used in this study (SCNS-SF34) may have decreased validity owing to the alterations made for its use. CONCLUSION: Some hospitalized patients with terminal cancer could need support for time to nurture love with their partners. Health care providers can play a crucial role by anticipating the needs of patients, preparing them mentally, and offering counseling and information to help them maintain an intimate connection with their loved ones.

Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Than Transient Elastography.

BACKGROUND & AIMS: Noninvasive methods have been evaluated for the assessment of liver fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We compared the ability of transient elastography (TE) with the M-probe, and magnetic resonance elastography (MRE) to assess liver fibrosis. Findings from magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) measurements were compared with those from TE-based controlled attenuation parameter (CAP) measurements to assess steatosis. METHODS: We performed a cross-sectional study of 142 patients with NAFLD (identified by liver biopsy; mean body mass index, 28.1 kg/m(2)) in Japan from July 2013 through April 2015. Our study also included 10 comparable subjects without NAFLD (controls). All study subjects were evaluated by TE (including CAP measurements), MRI using the MRE and PDFF techniques. RESULTS: TE identified patients with fibrosis stage ≥2 with an area under the receiver operating characteristic (AUROC) curve value of 0.82 (95% confidence interval [CI]: 0.74-0.89), whereas MRE identified these patients with an AUROC curve value of 0.91 (95% CI: 0.86-0.96; P = .001). TE-based CAP measurements identified patients with hepatic steatosis grade ≥2 with an AUROC curve value of 0.73 (95% CI: 0.64-0.81) and PDFF methods identified them with an AUROC curve value of 0.90 (95% CI: 0.82-0.97; P < .001). Measurement of serum keratin 18 fragments or alanine aminotransferase did not add value to TE or MRI for identifying nonalcoholic steatohepatitis. CONCLUSIONS: MRE and PDFF methods have higher diagnostic performance in noninvasive detection of liver fibrosis and steatosis in patients with NAFLD than TE and CAP methods. MRI-based noninvasive assessment of liver fibrosis and steatosis is a potential alternative to liver biopsy in clinical practice. UMIN Clinical Trials Registry No. UMIN000012757.

Characteristics of non-obese non-alcoholic fatty liver disease: Effect of genetic and environmental factors.

AIM: There are a considerable number of patients with non-obese non-alcoholic fatty liver disease (NAFLD). However, the clinical characteristics of non-obese NAFLD is not fully understood. We investigated genetic and other clinical parameters in non-obese and obese NAFLD. METHODS: The single nucleotide polymorphism rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was genotyped by the Invader assay in 540 NAFLD patients (134 non-obese and 406 obese) and 1012 control subjects (782 non-obese and 230 obese). All NAFLD patients underwent liver biopsy. Odds ratios were calculated by multiple logistic regression analysis using age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) and rs738409 genotype as explanatory variables. RESULTS: Non-obese NAFLD subjects had a higher rs738409 GG genotype than obese NAFLD. Multiple logistic regression analysis indicated that the odds ratios of T2DM and rs738409 GG genotype for NAFLD were higher in non-obese than in obese groups. In non-obese NAFLD, rs738409 GG genotype was associated with lobular inflammation, hepatocyte ballooning and NAFLD activity score. In obese NAFLD, BMI and T2DM but not rs738409 GG genotype were associated with severity of histology. CONCLUSION: We demonstrated that the risk factors for the development and progression of NAFLD were different between non-obese and obese patients and that PNPLA3 rs738409 was strongly associated with the development and progression of non-obese NAFLD.

Non-alcoholic fatty liver disease comorbid with major depressive disorder: The pathological features and poor therapeutic efficacy.

BACKGROUND AND AIM: Major depressive disorder (MDD) is an important public health problem, and it is often comorbid with many chronic diseases. The purpose of this study was to identify the clinical features of non-alcoholic fatty liver disease (NAFLD) patients comorbid with MDD and to investigate the influence of MDD on the effect of treatment in patients with NAFLD. METHODS: A total of 258 patients with biopsy-proven NAFLD were included. MDD was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. The patients were followed up for 48 weeks under standard care for NAFLD, which consisted mainly of lifestyle modification. RESULTS: There were 32 patients comorbid with MDD. They were characterized by more severe histological steatosis and higher NAFLD activity score, and also significantly higher levels of serum aminotransferase, γ-glutamyl transpeptidase and ferritin, than age-and-sex-matched NAFLD patients without MDD. Moreover, NAFLD patients with MDD showed poor response to the standard care for NAFLD, in body weight loss and in other parameters. Particularly, NAFLD patients with unstable MDD (not in full/partial remission) showed severe resistance to the treatment. CONCLUSION: This is the first study to demonstrate the clinical features and response to therapy of NAFLD patients comorbid with MDD. The comorbid state of MDD was associated with more severe histological liver steatosis and worse treatment outcomes in patients with NAFLD. Further investigations are required to develop new lifestyle modification programs that enable NAFLD patients with MDD to achieve the treatment goal.

Psychological Barriers to the Use of Opioid Analgesics for Treating Pain in Patients With Advanced Recurrent Cancer: A Multicenter Cohort Study.

Background: We aimed to gain insight into psychological barriers toward initiation of strong opioid analgesic use in patients with advanced recurrent cancer. Methods: This study included 46 patients who were prescribed with opioid analgesics for advanced recurrent cancer. The primary outcome was psychological barriers assessed using the Japanese version of the Barriers Questionnaire-II (JBQ-II). The secondary outcomes were psychological changes and pain relief one week after the induction of strong opioid analgesics. Results: The mean age of participants was 63.6 years. Furthermore, 26.1% had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥3. The mean JBQ-II total score was 1.97 (95% confidence interval: 1.75-2.19). At the initiation of opioid therapy, there was no difference in the total scores between the baseline and one week later. Nevertheless, there was a significant difference in the subscale "disease progression" score (mean 2.97 vs. 2.59, difference in means 0.38, standard error 0.16, p = 0.026). Personalized Pain Goal (PPG) was achieved in about half of the participants, and a trend toward a higher score in the subscale "harmful effects" (concern about adverse events) was observed in those who did not achieve PPG. Conclusion: This study showed that patients with advanced recurrent cancer have psychological barriers to opioid induction. The relationship between the presence of psychological barriers before and after induction of opioid analgesics and the speed of pain improvement was determined. The results may provide fundamental information for prospective intervention studies to develop individualized education programs for patients with psychological barriers to opioids.Clinical Trial Registration Number UMIN000042443.

Evaluation of the Liver Fibrosis Index calculated by using real-time tissue elastography for the non-invasive assessment of liver fibrosis in chronic liver diseases.

AIM: A rapid and non-invasive method of detecting fibrosis in patients with chronic liver diseases is of major clinical interest. The purpose of this study was to comparatively investigate the effectiveness of the Liver Fibrosis Index (LF Index) calculated using real-time tissue elastography (RTE) in patients with non-alcoholic fatty liver disease (NAFLD) and patients with chronic hepatitis C (CHC). METHODS: Twenty-seven patients with biopsy-proven NAFLD and 93 patients with biopsy-proven CHC were included. They underwent transient elastography (TE), serum liver fibrosis marker testing and RTE to calculate the LF Index. RESULTS: The LF Index showed a stepwise increase with increasing histological severity of fibrosis in CHC patients (P = 0.0102), whereas no significant correlation of the LF Index with the histological severity of liver fibrosis in NAFLD patients (P = 0.852). There was a significant correlation between the LF Index and liver stiffness measured by TE in CHC patients (r = 0.319, P = 0.0009). On the other hand, no such correlation was observed in NAFLD patients. While in CHC patients, the LF Index was correlated with the FIB-4 index, no such correlation was observed in NAFLD patients. CONCLUSION: The LF Index calculated by RTE is effective for assessment of liver fibrosis in patients with CHC. On the other hand, it is not useful in patients with NAFLD. This is the first study to compare the clinical usefulness of RTE as non-invasive assessment of liver fibrosis between CHC and NAFLD. Further investigations are required to refine statistical assessment of RTE.

Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia and type 2 diabetes mellitus. However, other risk factors for the development of NAFLD are unclear. With the association between periodontal disease and the development of systemic diseases receiving increasing attention recently, we conducted this study to investigate the relationship between NAFLD and infection with Porphyromonas gingivalis (P. gingivalis), a major causative agent of periodontitis. METHODS: The detection frequencies of periodontal bacteria in oral samples collected from 150 biopsy-proven NAFLD patients (102 with non-alcoholic steatohepatitis (NASH) and 48 with non-alcoholic fatty liver (NAFL) patients) and 60 non-NAFLD control subjects were determined. Detection of P. gingivalis and other periodontopathic bacteria were detected by PCR assay. In addition, effect of P. gingivalis-infection on mouse NAFLD model was investigated. To clarify the exact contribution of P. gingivalis-induced periodontitis, non-surgical periodontal treatments were also undertaken for 3 months in 10 NAFLD patients with periodontitis. RESULTS: The detection frequency of P. gingivalis in NAFLD patients was significantly higher than that in the non-NAFLD control subjects (46.7% vs. 21.7%, odds ratio: 3.16). In addition, the detection frequency of P. gingivalis in NASH patients was markedly higher than that in the non-NAFLD subjects (52.0%, odds ratio: 3.91). Most of the P. gingivalis fimbria detected in the NAFLD patients was of invasive genotypes, especially type II (50.0%). Infection of type II P. gingivalis on NAFLD model of mice accelerated the NAFLD progression. The non-surgical periodontal treatments on NAFLD patients carried out for 3 months ameliorated the liver function parameters, such as the serum levels of AST and ALT. CONCLUSIONS: Infection with high-virulence P. gingivalis might be an additional risk factor for the development/progression of NAFLD/NASH.

Revision of Pharmacological Treatment Recommendations for Cancer Pain: Clinical Guidelines from the Japanese Society of Palliative Medicine.

Background: Pain is one of the most common symptoms in cancer patients. The Japanese Society for Palliative Medicine (JSPM) first published its clinical guidelines for the management of cancer pain in 2010. Since then, more research on cancer pain management has been reported, and new drugs have become available in Japan. Thus, the JSPM has now revised the clinical guidelines using a validated methodology. Methods: This guideline was developed through a systematic review, discussion, and the Delphi method, following a formal guideline development process. Results: Thirty-five recommendations were created: 19 for the pharmacological management of cancer pain, 6 for the management of opioid-induced adverse effects, and 10 for pharmacological treatment procedures. Due to the lack of evidence that directly addressed our clinical questions, most of the recommendations had to be based on consensus among committee members and other guidelines. Discussion: It is critical to continue to build high-quality evidence in cancer pain management, and revise these guidelines accordingly.

Development and Validation of the Death Pronouncement Burden Scale for Oncology Practice.

Background: Informing families of a patient's death is one of the most challenging responsibilities of clinicians who provide care for terminally ill patients. Although death pronouncement can be a highly stressful event for clinicians, no previous study has reported qualitative characteristics of the burden experienced by clinicians related to death pronouncements. Moreover, no scale has been developed to assess this burden. Objective: This study sought to develop a scale to evaluate clinicians' burden related to death pronouncement (Death Pronouncement Burden Scale for oncology practice [DPBS-oncol]) and examine its reliability and validity in Japan. Methods: We presented the DPBS-oncol to clinicians involved in oncology practice and examined its reliability and discriminant validity. To investigate the test-retest reliability of the scale, the DPBS-oncol was presented a second time to a subsample of the clinicians. Results: Factor analysis required a grouping of the 15 DPBS-oncol items into one factor. Cronbach's α coefficient of the total score of DPBS-oncol was 0.94, and the intraclass correlation coefficient of the total score of DPBS-oncol was 0.89. Regarding discriminant validity, DPBS-oncol total score was moderately correlated with other available scales for assessing clinicians' attitudes to end-of-life care. Conclusion: This study was the first to develop a scale to evaluate clinicians' burden related to death pronouncement. The DPBS-oncol, which includes 15 items, was validated and shown to have sufficient reliability.

Psychological barriers to the use of opioid analgesics for treating pain in patients with advanced recurrent cancer (BAROC): protocol for a multicentre cohort study.

INTRODUCTION: Opioid analgesics are essential for treating cancer pain. However, patients are sometimes reluctant to use them because of concerns about addiction and dependence. Rapid pain relief following opioid administration may help overcome the psychological barriers to opioid analgesic use. This study aims to determine the relationship between psychological resistance to strong opioid analgesic use and pain amelioration speed in patients with advanced recurrent cancer. METHODS AND ANALYSIS: This ongoing, multicentre, observational study enrols patients aged 20 years or older with distant metastasis or advanced recurrent cancer receiving strong opioid analgesics for cancer pain for the first time. All participants, both inpatient and outpatient, were recruited from five Japanese hospitals. We are investigating the relationship between psychological barriers at the start of treatment and pain relief during the first week of treatment in these patients. The primary outcome is the Japanese version of the Barriers Questionnaire-II score at baseline. The secondary outcomes are the relationships between psychological barriers to strong opioid analgesic use and changes in pain over time. The participants are asked to fill out an electronic patient-reported outcome daily during the first week of treatment. The sample size was determined based on the number of patients in the year prior to study commencement who used strong opioid analgesics, met the eligibility criteria and could be expected to consent to participate in the study. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committee (approval ID B200600091) of Yokohama City University on 24 August 2020. The protocol has been reviewed by the institutional review boards at the four participating study sites. The results will be published in a peer-reviewed journal and will be presented at a relevant meeting. TRIAL REGISTRATION NUMBER: UMIN000042443.

Effective treatment for duodenal variceal bleeding using endoscopic ligation.

Duodenal variceal rupture is rare, and there is little agreement on the best therapeutic option. A 72-year old man treated for liver cirrhosis with HCV visited the emergency room complaining of dizziness and tarry stool. Fiberscope images showed varices (F2CbRC+) with white plaques at the horizontal region of the duodenum. The patient was treated using endoscopic variceal ligation (EVL), and no more bleeding has been detected.

Tapentadol Safety and Patient Characteristics Associated with Treatment Discontinuation in Cancer Therapy: A Retrospective Multicentre Study in Japan.

INTRODUCTION: Tapentadol has analgesic effects comparable to those of conventional opioids and is associated with fewer side effects, including gastrointestinal symptoms, drowsiness, and dizziness, than other opioids. However, the safety of tapentadol in the Japanese population remains unclear; the present multicentre study aimed to examine the safety of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events. METHODS: The safety of tapentadol was assessed retrospectively in patients with any type of cancer treated between August 18, 2014 and October 31, 2019 across nine institutions in Japan. Patients were examined at baseline and at the time of opioid discontinuation. Multivariate analysis was performed to identify factors associated with tapentadol discontinuation owing to adverse events. RESULTS: A total of 906 patients were included in this study, and 685 (75.6%) cases were followed up until tapentadol cessation for any reason. Among patients who discontinued treatment, 119 (17.4%) did so because of adverse events. Among adverse events associated with difficulty in taking medication, nausea was the most common cause of treatment discontinuation (4.7%), followed by drowsiness (1.8%). Multivariate analysis showed that those who were prescribed tapentadol by a palliative care physician (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.36-4.99, p = 0.004), patients switching to tapentadol due to side effects from previous opioids (OR 2.19, 95% CI 1.05-4.56, p = 0.037), and patients who did not use naldemedine (OR 5.06, 95% CI 2.47-10.37, p < 0.0001) had an increased risk of treatment discontinuation owing to adverse events. CONCLUSIONS: This study presents the safety profile of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events in the Japanese population. Prospective controlled trials are required to evaluate the safety of tapentadol and validate the present findings. TRIAL REGISTRATION NUMBER: UMIN 000044282 (University Hospital Medical Information Network).

Serum ferritin is a clinical biomarker in Japanese patients with nonalcoholic steatohepatitis (NASH) independent of HFE gene mutation.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Iron is regarded as a putative element that interacts with oxygen radicals, and high rates of hyperferritinemia and increased hepatic iron stores have been demonstrated in NASH. We investigated serum ferritin concentrations, HFE gene mutations, and insulin resistance in Japanese NASH patients and the diagnostic utility of serum ferritin concentrations as a means of distinguishing NASH. Serum ferritin concentrations were measured in 86 patients with histopathologically verified NAFLD (24 with steatosis and 62 with NASH) and 20 control subjects, they were tested for HFE gene mutations and their insulin resistance was measured. The serum ferritin concentration was significantly higher in the NASH patients than in the patients with simple steatosis (P = 0.006). There was no significant difference between the groups in HFE gene mutation (C282Y, H63D, and S65C), and the serum ferritin level was related with insulin resistance. The area under the ROC curve was 0.732 for distinguishing NASH from simple steatosis (P = 0.005; 95% CI, 0.596-0.856). In conclusion high serum ferritin concentrations are a distinguishing feature of Japanese NASH patients independent of HFE gene mutations.

Risky endoscopic ultrasonography-guided fine-needle aspiration for asymptomatic retroperitoneal tumors.

Paraganglioma, a sporadically occurring rare tumor should be included in the differential diagnosis of retroperitoneal tumors, such as malignant lymphomas, gastrointestinal stromal tumors, sarcoma and carcinoma of unknown primary site. A 58-year-old Japanese woman presented with a large retroperitoneal tumor detected by ultrasonography (US). She had no medical history of hypertension. Computed tomography showed a mass, 7 cm in diameter, located between the pancreas and the inferior vena cava. It was unclear whether the mass originated from the duodenum or the mesentery. Endoscopic ultrasonography (EUS) demonstrated a large solid paraduodenal mass. Doppler US revealed sparse vascularity in the tumor. With the differential diagnosis of retroperitoneal tumor, we carried out EUS-FNA. At the time of the third needle puncture, transient severe hypertension was noted, with a blood pressure measurement of 269/130 mmHg. Data obtained from urine and blood examinations after EUS-fine-needle aspiration indicated a diagnosis of paraganglioma.

"Guidebook on Doctors' Behaviors for Death Diagnosis Created by Community Healthcare Providers" Changed Residents' Mind for Death Diagnosis.

BACKGROUND: Education regarding death diagnosis is not often included in the medical education. OBJECTIVE: To investigate the change minds at the time of death diagnosis among residents after lectures based on our guidebook. DESIGN: Uncontrolled, open-label, multi-center trial. SUBJECTS: A total of 131 doctors undergoing their initial training were enrolled this study. MEASUREMENTS: Questionnaires were administered to volunteers before and after the lecture by the clinical training instructor presented information regarding doctors' behaviors at the death diagnosis based on our guidebook at each hospital. RESULTS: The subjects had an average age of 27.1 years and comprised 76 men (58.0%) and 54 women (41.2%). A total of 83 subjects (63.4%) had learned how to diagnose death as medical students, and 52 subjects (39.7%) had experienced death diagnosis scenes as medical students. Among those who had difficulties related to death diagnoses, the highest number (88.4%) indicated that "I do not know what to say to the family after a death diagnosis". Self-evaluation significantly increased after the lecture for many items concerning explanations to and considerations of the family: the effect size for "Give words of comfort and encouragement to family" increased significantly after the lecture to 0.9. CONCLUSIONS: Few of the residents felt that they had received education regarding death diagnoses; they reported difficulties with diagnosing death and responding to patients' families. After the lecture using our guidebook, residents' mind changed significantly for death diagnosis, suggesting that the guidebook at the time of death diagnosis may be useful.

Association between angiotensin II type 1 receptor polymorphisms and the occurrence of nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver injury in many countries. Genetic factors are important for the development of NAFLD, as well as environmental factors. Recently an angiotensin II type 1 receptor (AGTR1) has been recognized as important in the aetiology of fibrosis in the liver. OBJECTIVE: In this study we investigated the association between angiotensin II type 1 receptor gene polymorphism (ATGR1) and NAFLD. METHODS: One hundred and sixty-seven NAFLD patients [106 with nonalcoholic steatohepatitis (NASH) and 61 with simple steatosis] with a positive diagnosis by liver biopsy and 435 healthy control subjects were recruited in this study. RESULTS: We investigated 12 single nucleotide polymorphisms (SNPs) of the ATGR1 gene, among which rs3772622 showed the lowest P-value of allele frequency model (P=0.0000012) with an odds ratio (95% confidence interval) of 1.95 (1.49-2.55). Five SNPs (rs3772622, rs3772633, rs2276736, rs3772630 and rs3772627) were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs3772622 and another four SNPs (rs3772633, rs2276736, rs3772630 and rs3772627) were in the same block. We investigated the association between rs3772622 genotypes and the fibrosis index. The results of the analysis revealed an additive increase of the fibrosis index in the patients with the A allele of rs3772622. CONCLUSIONS: This is the first report to demonstrate the genetic variations in ATGR1 that may influence the risk of NAFLD and liver fibrosis in NAFLD.

Outcomes and factors influencing survival in cirrhotic cases with spontaneous rupture of hepatocellular carcinoma: a multicenter study.

BACKGROUND: Spontaneous rupture is rare complication of hepatocellular carcinoma (HCC) with high mortality rate in cirrhotic cases. The aim of this study was to determine the factors influencing prognosis in cases of spontaneously ruptured HCC and to investigate the outcomes of the treatments employed, especially transcatheter arterial embolization (TAE). METHODS: A retrospective multicenter study was conducted in 48 cirrhotic patients with spontaneous rupture of HCC. Conservative treatment was employed in 32 patients (ConT group) and TAE was performed in 16 patients (TAE group). RESULTS: The median survival time (MST) in the ConT group was only 13.1 days and the survival rate was extremely poor: 59.4% at 7 days, 37.5% at 14 days, and 6.3% at 30 days. On the other hand, the MST in the TAE group was 244.8 days and the survival rate was 87.5% at 1 month, 56.3% at 3 months, 23.4% at 12 months, and 15.6% at 24 months. According to the results of univariate analyses, factors associated with poor hepatic function and poor suitability for TAE was important determinants of short-term death (less than 3 weeks) among the patients (p < 0.05). On the other hand, among the patients in whom initial TAE was successfully performed (n = 15), a multivariate analysis showed that a maximum tumor size not exceeding 7 cm was the only independent factor determining long-term survival (p = 0.0130). CONCLUSION: Despite the inherent limitations of this retrospective study, TAE appears to be a useful treatment strategy for cirrhotic patients with spontaneous HCC rupture, as it yielded a longer survival period compared with conservative treatment in patients with ruptured HCC. Among the patients with ruptured HCC in whom initial TAE was successfully performed, the maximum tumor size was an important factor influencing survival.

Influence of inducible nitric oxide synthase polymorphisms in Japanese patients with non-alcoholic fatty liver disease.

AIM: Genetic factors as well as environmental factors play an important role in the development of non-alcoholic fatty liver disease (NAFLD). Recently, inducible nitric oxide synthase (iNOS) was significantly higher in the severest form of non-alcoholic steatohepatitis (NASH), and nitric oxide (NO) has been determined to play an important role in the process of fibrosis in NASH. In this study, we investigated iNOS gene polymorphisms for associations with NAFLD. METHODS: A total of 115 NAFLD patients, consisting of 65 patients with NASH and 50 patients with simple steatosis, in whom a positive diagnosis had been made by liver biopsy, and 435 healthy control subjects, were recruited into this study. RESULTS: We investigated 10 single nucleotide polymorphisms (SNP) of the iNOS gene, one of which, rs1060822, had the lowest P-value in the allele frequency model (P = 0.00078) with an odds ratio (95% confidence interval) of 0.49 (0.32-0.75). Four SNP, rs2297510, rs2297511, rs2797512 and rs1060822, were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs1060822 and three other SNP, rs2297510, rs2297511 and rs2797512, were in the same block. We also investigated associations between rs1060822 genotypes and the fibrosis index, and the results of the analysis revealed an additive increase in the fibrosis index and intrahepatic iNOS mRNA expression in the patients with the T allele of rs1060822. CONCLUSION: This is the first study to identify genetic variations in iNOS that may influence the risk of NAFLD and liver fibrosis in NAFLD.

Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) is one of the most commonly occurring malignances worldwide. Curative therapies such as resection, percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) have been applied to patients with early-stage HCC. Patients with more advanced cancers require local or systemic therapies. We present the results of our retrospective review conducted to evaluate whether transarterial chemoembolization (TACE) alone and combined TACE with percutaneous ablation for HCC exhibited superior efficacy to palliative treatment. METHODS: The effects of TACE and of the combined therapies (TACE + PEI or TACE + RFA) on the long-term survival rates were evaluated in 268 untreated HCC patients by various statistical analyses. RESULTS: The cumulative survival rates in the TACE alone group were significantly superior to those in the palliative treatment group. Further, the cumulative survival rates in the combined TACE + PEI/RFA group were significantly superior to those in the TACE alone group. When the comparison among the groups was restricted to patients with two or three tumors fulfilling the Milan criteria, significantly greater prolongation of survival was observed in the combined TACE + PEI/RFA group than in the PEI/RFA alone group. CONCLUSIONS: The aforementioned treatment modalities yielded greater improvements of the survival rate and survival duration as compared to palliative treatment in HCC patients. Furthermore, in terms of the effect on the survival period, combined TACE + PEI/RFA therapy was more effective than TACE monotherapy, and also more effective than PEI or RFA monotherapy in cases with multiple tumors fulfilling the Milan criteria.

Abdominal surgery affects small bowel transit time and completeness of capsule endoscopy.

The aim of the study was to evaluate bowel dysmotility in patients with a history of abdominal surgery by measuring both gastric transit time and small bowel transit time during capsule endoscopy and assessing the completeness of the examination. The study included 26 patients who had undergone abdominal surgery (postoperative group) and 52 patients who had not (control group). The capsule reached the cecum in 50.0% of the postoperative group and 80.8% of the control group (P=0.005). While there was no significant difference in gastric transit time between the two groups (P=0.882), small bowel transit time was significantly longer in the postoperative group (338.3+/-119.2 min) than in the control group (266.4+/-110.8 min, P=0.010). This is the first study to report that the small bowel transit time during capsule endoscopy is prolonged in patients who had a history of abdominal surgery, resulting in a lower frequency of complete examination.