Preoperative Immunonutrition Significantly Reduced Surgical Site Infection After Urinary Diversion for Invasive Bladder Cancer: A Retrospective Cohort Study.

BACKGROUND: Radical cystectomy and ileal conduit have a high incidence of surgical site infection. In this study, we evaluated the effects of preoperative immunonutrition on its incidence following these procedures. MATERIALS AND METHODS: We retrospectively enrolled 86 patients who underwent radical cystectomy and ileal conduit at our hospital between 2014 October and 2021 July. They were sequentially divided into the Immunonutrition group (n = 43) and Control group (n = 43). Patients in the Immunonutrition group drank 4 packs of IMPACT (Nestle, Japan) per day for 5 days before surgery. IMPACT contains arginine and eicosapentaenoic acid. We compared levels of plasma arginine and eicosapentaenoic acid before and after surgery and the rate of surgical site infection between the groups. Factors related to surgical site infection were analyzed using univariate and multivariable logistic regression analysis. RESULTS: No statistically significant differences were observed in patient characteristics between the groups except for surgical operative method (P < .001) and transfusion (P = .009). Levels of plasma arginine and eicosapentaenoic acid were significantly increased the day before surgery in the immunonutrition group (P < .001). However, the levels of plasma arginine on the day after surgery did not vary significantly between the groups. The incidence of surgical site infection was significantly lower in the immunonutrition group (P = .014). Multivariate analyses showed a significant association of surgical site infection with immunonutrition (OR = 0.14, CI 0.03-0.72, P = .019) and with ASA classification (OR = 4.76, CI 1.23-18.40, P = .024). CONCLUSIONS: Preoperative immunonutrition significantly reduced the incidence of surgical site infection following radical cystectomy and ileal conduit.

Relationship between preoperative nitrogen balance and energy and protein intake in patients with esophageal cancer.

BACKGROUND & AIMS: Nitrogen balance (NB) is an important indicator of protein utilization in the body, and a positive NB is essential for maintaining and improving nutritional status. However, information is lacking on the target values of the energy and protein levels required to maintain positive NB in cancer patients. This study aimed to verify the energy and protein requirements for positive NB in preoperative esophageal cancer patients. METHODS: This study included patients for esophageal cancer surgery who were admitted for radical surgery. Urine urea nitrogen (UUN) levels were measured based on 24-h urine storage. Energy and protein intakes were calculated from the dietary intake during hospitalization and the amount administered from enteral and parenteral nutrition. The characteristics of the positive and negative NB groups were compared, and patients' characteristics related to UUN excretion were analyzed. RESULTS: Seventy-nine patients with esophageal cancer were included, and 46% of patients were negative NB. All patients with energy intake ≥30 kcal/kg/day and protein intake ≥1.3 g/kg/day had positive NB. Whereas, in the group with energy intake ≥30 kcal/kg/day and protein intake <1.3 g/kg/day, 67% of patients were positive NB. There was a significant positive relation between UUN excretion and retinol-binding protein in multiple regression analyses adjusted for several patients' characteristics (ß = 0.28, p = 0.048). CONCLUSION: In preoperative esophageal cancer patients, 30 kcal/kg/day of energy and 1.3 g/kg/day of protein were the guideline values for positive NB. Good short-term nutritional status was a factor associated with increased UUN excretion.

Effects of body composition on early postoperative discharge and postoperative complications in patients with esophageal cancer.

BACKGROUND: Patients with esophageal cancer are prone to nutrition deterioration during the perioperative period and have a high incidence of postoperative complications, prolonging hospitalization. Decreased muscle mass is a known contributor to this deterioration, but there is insufficient evidence on the effects of preoperative maintenance and improvement of muscle mass. In this study, we evaluated the relationship between body composition, early postoperative discharge, and postoperative complications in patients with esophageal cancer. METHODS: This was a retrospective cohort study. Patients were divided into an early discharge group and a control group, who were discharged ≤21 days postoperatively and >21 days, respectively. The relationship of body composition to postoperative complications and discharge time in patients was evaluated via multivariate logistic regression using isotemporal substitution (IS) models. RESULTS: The early discharge group comprised 31 of the 117 patients (26%) included. This group had significantly lower incidences of sarcopenia and postoperative complications than the control group. In logistic regression analyses estimating the effect of changes in body composition using the IS models, preoperative replacement of 1 kg of body fat with 1 kg of muscle mass was associated with significantly higher odds of early discharge (odds ratio [OR], 1.28; 95% CI, 1.03-1.59) and lower odds of postoperative complications (OR, 0.81; 95% CI, 0.66-0.98). CONCLUSION: In patients with esophageal cancer, a preoperative increase in muscle mass may reduce postoperative complications and hospital stay duration.

Relationship between GLIM criteria and disease-specific symptoms and its impact on 5-year survival of esophageal cancer patients.

BACKGROUND & AIMS: Malnutrition is common in patients with esophageal cancer, which affects their prognosis. The global leadership initiative on malnutrition (GLIM) criteria was recently proposed as the world's first diagnostic criteria for malnutrition. However, the association between esophageal cancer patients and the GLIM criteria is unclear. The purpose of this study was to evaluate the percentage of patients diagnosed with malnutrition preoperatively using the GLIM criteria, assess the impact of disease-specific symptoms on the severity of malnutrition, and assess the prognostic relevance of GLIM defined malnutrition in patients with esophageal cancer. METHODS: This was a retrospective single-center cohort study. Preoperative nutritional status of patients with esophageal cancer hospitalized between June 2009 and July 2011 was evaluated according to the GLIM criteria. Factors related to severe malnutrition as per the GLIM criteria were analyzed using multivariable logistic regression analysis. The association between the severity of malnutrition based on the GLIM criteria and 5-year survival was assessed using a multivariable Cox proportional hazard model. RESULTS: Overall, 117 esophageal cancer patients were nutritionally assessed. The percentage of moderate malnutrition and severe malnutrition was 21% and 23%, respectively. Subjective dysphagia [odds ratio (OR): 7.39, 95% confidence interval (CI): 1.46-37.52] and subjective esophageal obstruction (OR: 10.49, 95% CI: 3.47-31.70) were independent risk factors for severe malnutrition. The hazard ratio (HR) for 5-year mortality tended to be higher for moderate malnutrition (HR: 2.12, 95% CI: 0.91-4.95); however, it was not significantly associated with either moderate malnutrition or severe malnutrition (HR: 1.30, 95% CI: 0.52-3.27). Cases that were censored during the follow-up period probably affected the survival results. CONCLUSION: Subjective feelings of dysphagia and esophageal obstruction might be related to malnutrition severity in esophageal cancer patients. Malnutrition assessed by the GLIM criteria was not significantly associated with 5-year survival.

Change in skeletal muscle mass is associated with lipid profiles in female rheumatoid arthritis patients -TOMORROW study.

BACKGROUND & AIMS: To examine the relationship between changes in skeletal muscle mass and lipid metabolism and glycometabolism in patients with rheumatoid arthritis (RA). METHODS: Data were analyzed from 148 female RA patients and 145 age-matched non-RA (control) female subjects from a prospective cohort study (TOMORROW; TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality study). Appendicular skeletal muscle mass (ASM) was assessed using dual-energy x-ray absorptiometry and skeletal muscle mass index (SMI) was calculated as ASM divided by the square of height. The reference value for SMI in Asian women, 5.4 kg/m2, was used to define low SMI. Data were assessed using cross-sectional (2010 baseline data) and longitudinal (change in value from 2010 to 2013) methods from the retrospective cohort. RESULTS: At baseline in RA patients, the low SMI group showed significantly higher low-density lipoprotein cholesterol (LDL-chol) (p = 0.015), apolipoprotein (Apo)B (p = 0.046), and ApoB-to-A1 (ApoB/A1) (p = 0.025) than the normal SMI group. In multiple regression analysis of RA patients, sequential changes from 2010 to 2013 (Δ) in SMI and ApoB and ApoC2 showed significant negative relationships (ß = -0.19, -0.18, respectively) even after adjusting for age, RA duration, exercise habits, medication for RA, disease severity, activities of daily living (ADL) and body fat mass. No significant relation was evident between ΔSMI and various glycometabolism parameters in RA patients. CONCLUSIONS: Skeletal muscle mass might be related to lipid metabolism in RA patients. This relationship is independent of factors such as disease severity and body fat mass.

Effect of Postoperative Oral Intake on Prognosis for Esophageal Cancer.

BACKGROUND: Patients undergoing surgery for esophageal cancer are at risk of prolonged hospital stay for postoperative malnutrition. Postoperative early oral feeing is a part of the "enhanced recovery after surgery protocol" for coping with this risk. However, the usefulness of early oral intake during perioperatively is questionable. METHODS: In total, 117 patients treated surgically for esophageal cancer were analyzed in the study. We assessed the oral energy sufficiency rate per nutritional requirement (oral-E/NR) at the fourth week postoperatively and classified the patients into two groups: Poor oral intake group (POI group; <25% oral-E/NR) and the control group (≥25% oral-E/NR). We analyzed the relationship among postoperative oral intake and prognoses. RESULTS: The POI group had worse postoperative nutritional status and a lower survival rate than the control group. In a multivariate analysis, <25% oral-E/NR was one of the independent factors contributing to negative outcomes postoperatively (adjusted hazard ratio: 2.70, 95% confidence interval: 1.30-5.61). CONCLUSIONS: In patients undergoing surgery for esophageal cancer, poor postoperative oral intake negatively affected not only on their postoperative nutritional status but also their overall prognosis. It is necessary to improve the adequacy of oral intake postoperatively for patients with esophageal cancer.

Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus-related liver cirrhosis.

AIM: Hypozincemia is associated with the progression of chronic liver diseases, but it is unknown whether hypozincemia promotes human hepatocarcinogenesis. Our aim is to evaluate the serum zinc levels in liver cirrhosis (LC) patients and clarify the relationship between the serum zinc levels and the development of hepatocellular carcinoma (HCC). METHODS: Cirrhotic patients without HCC (n = 299) were enrolled from 14 medical institutes in Japan as a multicenter prospective study (No. 2028). Of the 299 patients, 157 were included in the present study based on reliable and consistent serum zinc levels and no history of oral zinc supplementation. Clinical parameters associated with the development of HCC were determined. Furthermore, the cumulative incidence of HCC was analyzed using Kaplan-Meier methods and was calculated using the log-rank test. A Cox regression analysis was utilized for the multivariate analysis to evaluate the predictors of hepatocarcinogenesis. RESULTS: Thirty of 157 patients (19.1%) developed HCC during an observation period of 3 years. Serum zinc levels were significantly decreased in hepatitis C virus-related LC (C-LC) patients with HCC (0.0180). The risk factors for incidence of HCC were hypozincemia (0.0014), high α-fetoprotein (0.0080), low branched chain amino acids-to-tyrosine ratio (0.0128), or female sex (0.0228). Hypozincemia (hazard ratio 1.61, 0.0324) was the only significant predictor of hepatocarcinogenesis by multivariate Cox regression analysis. CONCLUSIONS: Hypozincemia is associated with hepatocarcinogenesis in C-LC patients.

Preoperative Depressive Mood of Patients With Esophageal Cancer Might Delay Recovery From Operation-Related Malnutrition.

BACKGROUND: We investigated the relationship between the preoperative psychological state and the perioperative nutritional conditions of patients with esophageal cancer. METHODS: Seventy-three participants underwent operations for esophageal cancer in our hospital. Depressive state was evaluated using the Self-Rating Depression Scale (SDS). General quality of life (QOL) was assessed using the SF-8™, and the nutritional assessments were evaluated through anthropometric analysis, bioelectrical impedance analysis (BIA) and some biochemical assessments. RESULTS: In the preoperative stage, patients with higher SDS scores, representing a more depressive state, had low arm circumference, grip strength, serum albumin levels and prognostic nutritional index. Patients with higher SDS scores also had a tendency for a lower physical component summary, representing physical QOL by the Eight-Item Short Form Health Survey (SF-8™). At 3 months after surgery, patients with higher preoperative SDS scores had significantly lower body mass indexes (BMIs) and had a lower tendency of body fat masses. In the univariate and multivariate analyses on the recovery of BMI at 3 months after surgery, preoperative SDS score was the only independent risk factor (odd ratio (OR): 4.07, 95% confidence interval (CI): 1.15 - 14.35) in this study. CONCLUSION: Preoperative depressive mood, as evaluated by the SDS, was the sole relevant factor for postoperative body weight recovery of patients with esophageal cancer. Preoperative depressive mood of patients with esophageal cancer might delay recovery from operation-related malnutrition. Some measures against preoperative depressive mood might be necessary for early recovery from postoperative malnutrition in patients with esophageal cancer.

Loss of skeletal muscle mass in patients with chronic liver disease is related to decrease in bone mineral density and exercise tolerance.

AIM: This study aimed to identify the relationship between loss of skeletal muscle mass and clinical factors such as osteoporosis in patients with chronic liver disease. METHODS: The subjects were 112 patients (85 men and 27 women) with hepatocellular carcinoma who were scheduled to undergo hepatectomy. Skeletal muscle reduction was diagnosed according to the cut-off level of the skeletal mass index (SMI) for Asians (men <7.0 kg/m2 , women <5.4 kg/m2 ). Osteoporosis was diagnosed according to T-score ≤-2.5 standard deviation. The SMI and T-score were assessed using the results of dual-energy X-ray absorption. Peak oxygen consumption (PeakVO2 ), an index of exercise tolerance, was evaluated using the cardiopulmonary exercise test. The characteristics of patients with low SMI (low SMI group) were compared with those of patients whose SMI was not low (control group). Outcomes are presented as median (interquartile range). RESULTS: The T-score was significantly lower in the low SMI group (control vs. low SMI -1.1 [1.8] vs. -1.6 [1.9], P = 0.049). T-score positively correlated with SMI (r = 0.409, P < 0.0001). PeakVO2 was significantly decreased in the low SMI group (17.7 [6.3] vs. 14.4 [4.5], P = 0.006). In multivariate logistic regression analysis, T-score (odds ratio [OR], 3.508; 95% confidence interval [CI], 1.074-11.456; P = 0.038) and PeakVO2 (OR, 3.512; 95% CI, 1.114-11.066; P = 0.032) were significantly related to SMI, independent of age and sex. CONCLUSIONS: Skeletal muscle reduction in chronic liver disease is closely related to exercise tolerance and osteoporosis, and these factors are believed to be associated with physical inactivity in daily life.

Correction: Validation of Skeletal Muscle Volume as a Nutritional Assessment in Patients With Gastric or Colorectal Cancer Before Radical Surgery.

[This corrects the article DOI: 10.14740/jocmr3129w.].

Validation of Skeletal Muscle Volume as a Nutritional Assessment in Patients With Gastric or Colorectal Cancer Before Radical Surgery.

BACKGROUND: Recently, some studies have reported the importance of sarcopenia as a prognostic factor in patients with gastrointestinal cancer who have undergone surgery. We aimed to examine skeletal muscle volume for use in nutritional assessment of preoperative patients, and to compare the results with those of other conventional methods of nutritional assessment, such as biochemical or body composition values. METHODS: This was an open cohort study which examined skeletal muscle volume for use in nutritional assessment of preoperative patients. A total of 121 patients with gastrointestinal cancer who underwent radical surgery were enrolled in this study between June 1, 2008 and December 31, 2012. There were 39 and 82 patients with gastric and colorectal cancer, respectively. The primary outcome of this study was postoperative overall survival. The secondary outcomes were postoperative survival from cancer-related deaths, recurrences of cancer after surgery, postoperative complications, and postoperative hospital inpatient stay (measured in days). Univariate and multivariate analyses were used to identify the relevant factors for postoperative outcomes mentioned above. RESULTS: Skeletal muscle volume was a significant (hazard ratio (HR): 3.34, 95% confidence interval (CI): 1.21 - 9.17, P = 0.020) independent prognostic factor for cancer-related deaths in patients with gastric or colorectal cancer who had undergone surgery, and a marginally independent (HR: 2.48, 95% CI: 0.91 - 6.81, P = 0.077) factor that negatively contributed to overall survival in these patients. In contrast, the preoperative skeletal muscle volume was not correlated with the recurrence of cancer, and was not significantly correlated with the occurrence of severe complications after surgery or prolongation of hospitalization. CONCLUSIONS: The preoperative skeletal muscle volume was a significant prognostic factor in patients with gastric or colorectal cancers. Therefore, the estimation of skeletal muscle volume may be important for stable, long-term nutritional assessment in patients with gastrointestinal cancers.

Enteral Diet Enriched with ω-3 Fatty Acid Improves Oxygenation After Thoracic Esophagectomy for Cancer: A Randomized Controlled Trial.

BACKGROUND: Although the anti-inflammatory effects of immunomodulating diets (IMDs) have recently attracted attention, the efficacy of enteral feeding of such diets after radical surgery remains controversial. Thus, we conducted a new prospective, randomized controlled study to elucidate any beneficial effect of an IMD containing eicosapentaenoic acid (EPA) and γ-linolenic acid (GLA) in patients undergoing radical esophagectomy for thoracic esophageal cancer. METHODS: From November 2009 to July 2011, 87 consecutive patients were randomized to receive either an IMD enriched with EPA, GLA, and antioxidants (n = 42) or a standard isocaloric, isonitrogenous diet (control group, n = 45) after esophagectomy with radical lymphadenectomy. The primary outcome measure was changes in the oxygenation status (PaO2/FIO2 ratio), and the secondary outcome measures were body composition, inflammation-related factors, coagulation markers, cholesterol concentrations, and major clinical outcomes. RESULTS: Oxygenation was significantly better on postoperative days (PODs) 4, 6, and 8 in the IMD than control group (366.5 ± 63.3 vs. 317.3 ± 58.8, P = 0.001; 361.5 ± 52.6 vs. 314.0 ± 53.2, P < 0.001; 365.4 ± 71.2 vs. 315.2 ± 56.9, P = 0.001, respectively). Changes in the ratio of body weight on PODs 14 and 21 and lean body weight on POD 21 were significantly greater in the IMD than control group. No significant differences were observed in other measures. CONCLUSIONS: An enteral IMD enriched with EPA and GLA improved oxygenation and maintained the body composition of patients undergoing radical esophagectomy, indicating the potential efficacy of such a diet after esophagectomy.

Effect of Intramuscular Adipose Tissue Content on Prognosis in Patients Undergoing Hepatocellular Carcinoma Resection.

BACKGROUND: It has recently been reported that myosteatosis, the infiltration of fat in skeletal muscle, is associated with insulin resistance and type 2 diabetes mellitus. The present study investigated the effect of skeletal muscle fat accumulation on short- and long-term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC) and aimed to identify prognostic factors. METHODS: The records of 141 HCC patients who underwent hepatectomy were retrospectively reviewed. Clinicopathological and outcome data from 71 patients with high intramuscular adipose tissue content (IMAC) were compared with those from 70 patients with low IMAC. RESULTS: The 5-year overall survival rate was 46% among patients with high IMAC and 75% among those with low IMAC. The 5-year disease-free survival rates in these groups were 18 and 38%, respectively. Multivariate analysis revealed that high IMAC was predictive of an unfavorable prognosis. High IMAC was significantly correlated with liver dysfunction, higher intraoperative blood loss, the need for blood transfusion, and comorbid diabetes mellitus. CONCLUSIONS: Greater fat accumulation in skeletal muscle was predictive of worse overall survival after partial hepatectomy in patients with HCC, even with adjustment for other known predictors. The identification of patients with greater skeletal muscle fat accumulation before hepatectomy could permit early preventive strategies to maintain muscle quality and thus improve prognosis and patient selection for hepatectomy.

Utility of a web-based weight loss program with auto-extraction of behavioural objectives and recording of daily weight and steps in pre-obese outpatients.

The epidemic of obesity is now a major public health concern in many parts of the world. Face-to-face tailored lifestyle modification therapy is one of the major approaches used for weight loss. However, the lack of time for multiple visits and the lack of resources for administering therapy hinder its implementation. We administered a web-based weight loss program for obese patients from July 2010 to January 2012 that required only 2 personal interviews over 6 months. The program used a system of auto-extraction of behavioural objectives and auto recording of daily weight and number of steps taken. The subjects included 3 obese men (mean age, 35.7 ± 2.3 years; mean body mass index (BMI), 30.4 ± 0.8 kg/m²) and 17 obese women (mean age, 39.3 ± 9.5 years; mean BMI, 28.1 ± 1.8 kg/m2) who volunteered to participate in this weight loss program. Weight loss achieved through this program was significant (mean, 2.7%, p=0.047). Abdominal visceral fat area (VFA) decreased significantly (mean, 12.6%, p=0.017), and the serum cholinesterase and alanine aminotransferase levels improved (mean, 33 U/L, p=0.003; mean, 7 IU/L, p=0.033 respectively). Metabolic syndrome criteria number had a tendency to decrease. Dietary and nutrient intake levels on the food frequency questionnaire improved. Weight loss ratio after 6 months and initial weight loss ratio were strongly significantly correlated. A web-based weight loss program with auto-extraction of behavioural objectives and recording of daily weight and steps can achieve weight loss, as determined by VFA reduction, on low manpower.

Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis.

BACKGROUND & AIMS: Although a low plasma level of branched-chain amino acids (BCAAs) is a marker of cirrhosis, it is not clear whether BCAA supplements affect disease progression. We performed a multicenter study to evaluate the effects of BCAA supplementation on hepatocarcinogenesis and survival in patients with cirrhosis. METHODS: We enrolled 299 patients from 14 medical institutions in Japan in a prospective, multicenter study in 2009; 267 patients were followed through 2011. Patients were given BCAA supplements (5.5-12.0 g/day) for more than 2 years (n = 85) or no BCAAs (controls, n = 182). The primary end points were onset of hepatocellular carcinoma (HCC) and death. Factors associated with these events were analyzed by competing risk analysis. RESULTS: During the study period, 41 of 182 controls and 11 of 85 patients given BCAAs developed HCC. On the basis of the Cox and the Fine and Gray models of regression analyses, level of α-fetoprotein, ratio of BCAA:tyrosine, and BCAA supplementation were associated with development of HCC (relative risk for BCAAs, 0.45; 95% confidence interval, 0.24-0.88; P = .019). Sixteen controls and 2 patients given BCAAs died. Factors significantly associated with death were Child-Pugh score, blood level of urea nitrogen, platelet count, male sex, and BCAA supplementation (relative risk of death for BCAAs, 0.009; 95% confidence interval, 0.0002-0.365; P = .015) in both regression models. CONCLUSIONS: On the basis of a prospective study, amino acid imbalance is a significant risk factor for the onset of HCC in patients with cirrhosis. BCAA supplementation reduces the risk for HCC and prolongs survival of patients with cirrhosis.

Assessment of preoperative exercise capacity in hepatocellular carcinoma patients with chronic liver injury undergoing hepatectomy.

BACKGROUND: Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy. METHODS: Sixty-one HCC patients underwent preoperative cardiopulmonary exercise testing to determine their anaerobic threshold (AT). The AT was defined as the break point between carbon dioxide production and oxygen consumption per unit of time (VO2). Postoperative events including recurrence of HCC, death, liver failure, and complications of cirrhosis were recorded. Univariate and multivariate analyses were performed to evaluate associations between 35 clinical factors and outcomes, and identify independent prognostic indicators of event-free survival and maintenance of Child-Pugh class. RESULTS: Multivariate analyses identified preoperative branched-chain amino acid/tyrosine ratio (BTR) <5, alanine aminotransferase level ≥42 IU/l, and AT VO2 <11.5 ml/min/kg as independent prognostic indicators of event-free survival. AT VO2 <11.5 ml/min/kg and BTR <5 were identified as independent prognostic indicators of maintenance of Child-Pugh class. CONCLUSIONS: This study identified preoperative exercise capacity as an independent prognostic indicator of event-free survival and maintenance of Child-Pugh class in HCC patients with chronic liver injury undergoing hepatectomy.

Nutritional status in relation to lifestyle in patients with compensated viral cirrhosis.

AIM: To assess the nourishment status and lifestyle of non-hospitalized patients with compensated cirrhosis by using noninvasive methods. METHODS: The subjects for this study consisted of 27 healthy volunteers, 59 patients with chronic viral hepatitis, and 74 patients with viral cirrhosis, from urban areas. We assessed the biochemical blood tests, anthropometric parameters, diet, lifestyle and physical activity of the patients. A homeostasis model assessment-insulin resistance (HOMA-IR) value of ≥ 2.5 was considered to indicate insulin resistance. We measured height, weight, waist circumference, arm circumference, triceps skin-fold thickness, and handgrip strength, and calculated body mass index, arm muscle circumference (AMC), and arm muscle area (AMA). We interviewed the subjects about their dietary habits and lifestyle using health assessment computer software. We surveyed daily physical activity using a pedometer. Univariate and multivariate logistic regression modeling were used to identify the relevant factors for insulin resistance. RESULTS: The rate of patients with HOMA-IR ≥ 2.5 (which was considered to indicate insulin resistance) was 14 (35.9%) in the chronic hepatitis and 17 (37.8%) in the cirrhotic patients. AMC (%) (control vs chronic hepatitis, 111.9% ± 10.5% vs 104.9% ± 10.7%, P = 0.021; control vs cirrhosis, 111.9% ± 10.5% vs 102.7% ± 10.8%, P = 0.001) and AMA (%) (control vs chronic hepatitis, 128.2% ± 25.1% vs 112.2% ± 22.9%, P = 0.013; control vs cirrhosis, 128.2% ± 25.1% vs 107.5% ± 22.5%, P = 0.001) in patients with chronic hepatitis and liver cirrhosis were significantly lower than in the control subjects. Handgrip strength (%) in the cirrhosis group was significantly lower than in the controls (control vs cirrhosis, 92.1% ± 16.2% vs 66.9% ± 17.6%, P < 0.001). The results might reflect a decrease in muscle mass. The total nutrition intake and amounts of carbohydrates, protein and fat were not significantly different amongst the groups. Physical activity levels (kcal/d) (control vs cirrhosis, 210 ± 113 kcal/d vs 125 ± 74 kcal/d, P = 0.001), number of steps (step/d) (control vs cirrhosis, 8070 ± 3027 step/d vs 5789 ± 3368 step/d, P = 0.011), and exercise (Ex) (Ex/wk) (control vs cirrhosis, 12.4 ± 9.3 Ex/wk vs 7.0 ± 7.7 Ex/wk, P = 0.013) in the cirrhosis group was significantly lower than the control group. The results indicate that the physical activity level of the chronic hepatitis and cirrhosis groups were low. Univariate and multivariate logistic regression modeling suggested that Ex was associated with insulin resistance (odds ratio, 6.809; 95% CI, 1.288-36.001; P = 0.024). The results seem to point towards decreased physical activity being a relevant factor for insulin resistance. CONCLUSION: Non-hospitalized cirrhotic patients may need to maintain an adequate dietary intake and receive lifestyle guidance to increase their physical activity levels.

Guidelines on nutritional management in Japanese patients with liver cirrhosis from the perspective of preventing hepatocellular carcinoma.

AIM: The Japanese Nutritional Study Group for Liver Cirrhosis (JNUS) was assembled in 2008 with the support of a Health Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare of Japan. The goal of the study group was to propose new nutritional guidelines for Japanese patients with liver cirrhosis (LC), with the aim of preventing hepatocellular carcinoma. METHODS: Between 2008 and 2010, the member investigators of JNUS conducted various clinical and experimental studies on nutrition on LC. These included anthropometric studies, a questionnaire study on daily nutrient intake, clinical trials, experimental studies using animal models, re-evaluation of previous publications and patient education. Over this 3-year period, the group members regularly discussed the nutritional issues related to LC, and a proposal was finally produced. RESULTS: Based on the results of JNUS projects and discussions among the members, general recommendations were made on how Japanese patients with LC should be managed nutritionally. These recommendations were proposed with a specific regard to the prevention of hepatocarcinogenesis. CONCLUSION: The new JNUS guidelines on nutritional management for Japanese patients with LC will be useful for the actual nutritional management of patients with LC. The JNUS members hope that these guidelines will form the basis for future discussions and provide some direction in nutritional studies in the field of hepatology.

Usefulness of transient elastography for assessment of liver fibrosis in chronic hepatitis B: Regression of liver stiffness during entecavir therapy.

AIM: The usefulness of transient elastography remains to be validated in chronic hepatitis B, particularly as a tool for monitoring the degree of liver fibrosis during treatment. METHODS: The subjects were 50 patients with chronic hepatitis B virus infection. Liver biopsy was performed in 38 patients, and in 12 patients with platelet counts of 50 × 10(9)/L or less, cirrhosis was clinically diagnosed on the basis of specific signs of portal hypertension. Liver stiffness was measured by transient elastography at baseline and after 12 months of treatment in 20 nucleos(t)ide-naïve patients who started entecavir within 3 months after study entry. RESULTS: Twenty (40%) patients were classified as F1, 10 (20%) as F2, 5 (10%) as F3, and 15 (30%) as F4 (cirrhosis). Median liver stiffness (interquartile range) was 7.0 kPa (5.6-9.4), 9.8 kPa (5.6-14.7), 9.8 kPa (7.6-12.9), and 17.3 kPa (8.2-27.6) in fibrosis stages F1 to F4, respectively. Liver stiffness significantly correlated with fibrosis stage (r = 0.46; P = 0.0014). Of the patients who started entecavir, median liver stiffness significantly decreased from 11.2 kPa (7.0-15.2) to 7.8 kPa (5.1-11.9; P = 0.0090) during 12 months of treatment. Median levels of amino-terminal peptide of type III procollagen and type IV collagen 7S domain in serum significantly decreased from 0.9 (0.6-1.3) to 0.6 (0.5-0.7) U/mL (P = 0.0010) and from 5.0 (4.4-6.7) to 3.9 (3.2-4.4) ng/mL (P = 0.015), respectively. CONCLUSION: Liver stiffness measurement can be useful for monitoring regression of liver fibrosis during entecavir treatment in patients with chronic hepatitis B virus infection.

Differences in molecular alterations of hepatocellular carcinoma between patients with a sustained virological response and those with hepatitis C virus infection.

BACKGROUND/AIMS: The mechanism of hepatocarcinogenesis remains unclear in patients in whom hepatitis C virus (HCV) disappears after interferon (IFN) therapy. We compared molecular alterations in hepatocellular carcinoma (HCC) between patients with a sustained virological response (SVR) to IFN and patients with HCV. METHODS: The study group comprised 44 patients with HCV and 13 patients with SVR. One patient in the SVR group had two tumour nodules, both of which were examined. Mitochondrial DNA (mtDNA) mutations in displacement-loop lesions were directly sequenced. Mutation of the TP53 gene was examined by direct sequencing. The methylation status of p16, p15, p14, RB and PTEN genes was evaluated by a methylation-specific polymerase chain reaction. RESULTS: The average number of mtDNA mutations was 4.2 in 44 HCCs with HCV and 2.0 in 14 HCCs with SVR (P=0.0021). mtDNA mutation was less frequently detected in HCCs from patients with SVR than in patients with HCV. TP53 mutations were detected in 12 (27%) of 44 HCCs with HCV and 2 (14%) of 14 SVR-HCCs. Hypermethylation of the p16, p15, p14, RB and PTEN promoters was, respectively, detected in 34, 13, 8, 12 and 11 of 44 HCCs from patients with HCV and 14, 0, 0, 2 and 2 of 14 HCCs from patients with SVR (P=0.049, 0.021, 0.085, 0.322 and 0.402). Hypermethylation of p16 was one of the most important alterations in SVR-HCC. CONCLUSIONS: Molecular alterations in hepatocarcinogenesis of patients with SVR-HCC were different from those of patients with continuous HCV infection.