Changes in characteristics of gastroenterology center inpatients in Japan because of rapidly aging society.

BACKGROUND AND AIM: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue. METHODS: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data. RESULTS: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001). CONCLUSION: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.

Clinical features of patients with hepatocellular carcinoma treated with radiofrequency ablation therapy: developing a simple score to determine the need for immune-adjuvant therapy.

BACKGROUND/AIM: Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy. METHODS: From 2000 to 2022, 528 patients with Child-Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated. RESULTS: Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05). CONCLUSION: HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC.

Simple Scoring System for Esophagogastric Varices Prediction in Hepatocellular Carcinoma Patients without Liver Stiffness Evaluation.

INTRODUCTION: For predicting esophagogastric varices (EGVs), the Virtual Baveno VII Consensus Workshop has proposed a combination of liver stiffness determination and platelet count measurement using a FibroScan®. However, FibroScan® is not available at all institutions. The present study aimed to develop a simple method to predict development of EGV using only general blood examination results. MATERIALS AND METHODS: A total of 1,090 hepatocellular carcinoma patients were enrolled, after excluding 956 with major portal vein tumor thrombus (Vp3/Vp4) or without upper gastrointestinal endoscopy examination results available. Those with EGV (≥ grade F2) or a history of treatment for the condition were defined as positive for significant EGV, and then clinical factors were retrospectively evaluated to determine indicators of occurrence. RESULTS: Logistic multivariate analysis showed platelet count (≤12 × 104/µL) (odds ratio [OR] 3.79, p < 0.001), mALBI grade 2a (OR 1.52, p = 0.036), and mALBI 2b or 3 (OR 3.46, p < 0.001) as significant predictive factors. Based on the OR values, platelet count (≤12 × 104/µL) and mALBI grade 2b/3 were each assigned 2 points and mALBI 2a was given 1 point, with the result termed recommendation for EGV screening (REGS) score. Significant EGV occurrence was noted in 2.9% (9/311) of the patients with a REGS score 0, 11.0% (13/118) with a score 1, 19.3% (53/274) with a score 2, 29.5% (39/132) with a score 3, and 38.0% (97/255) with a score 4 (p < 0.001). CONCLUSION: The findings indicate that REGS score can provide useful predictive information for development of significant EGV without the need for special equipment such as a FibroScan®.

Endoscopic Submucosal Dissection Using EndoTrac, a Novel Traction Device.

BACKGROUND: Endoscopic submucosal dissection (ESD) is recognized as a minimally invasive and curative treatment for superficial gastrointestinal (GI) cancers. However, ESD is still challenging and time-consuming with a high risk of adverse events such as bleeding and perforation. Various traction methods have been explored for maintaining good visualization of the submucosal layer during ESD. We developed a novel traction device (the EndoTrac) which can easily tie the thread and has the ability to change the towing direction. The aim of this study is to evaluate safety and feasibility of ESD using the EndoTrac for GI neoplasms. PATIENTS AND METHODS: We retrospectively analyzed 44 patients (45 lesions) with esophageal, gastric, duodenal, and colorectal neoplasms who had undergone ESD using the EndoTrac device between June 2018 and May 2019. Primary outcome measures were preparation time, procedural success using the EndoTrac device, and ease of ability to change towing direction. RESULTS: Mean preparation time was 2 (2-5) min in esophagus, 3 (1-5) min in stomach, 6 (5-9) min in duodenum, and 4 (2-8) min in colorectum. The procedural success rate was 100% (8/8) in esophagus, 100% (21/21) in stomach, 100% (4/4) in duodenum, and 100% (12/12) in colorectum. The rate of successful towing to both proximal and distal sides was 100% (8/8) in esophagus, 100% (21/21) in stomach, 0% (0/4) in duodenum, and 100% (12/12) in colorectum. CONCLUSIONS: Use of the EndoTrac device appears to be a feasible approach to ESD for GI neoplasms.

Exacerbation of psoriasis vulgaris by sorafenib treatment for hepatocellular carcinoma.

We treated a 66-year-old Japanese male with unresectable hepatocellular carcinoma (u-HCC) for multiple (>5) liver tumors (maximum 2.6 cm in size, Child-Pugh B score 7) in September 2018. The patient had a history of psoriasis vulgaris and sorafenib (SOR) was introduced (800 mg/day) because of transcatheter arterial chemoembolization (TACE) refractoriness. However, psoriasis vulgaris exacerbation and a high fever were observed 2 weeks later, and the patient was admitted, after which improvement of psoriasis vulgaris was obtained with external medicine administration and SOR intake discontinuation. Few reports have noted exacerbation of psoriasis vulgaris caused by SOR treatment.

SARC-F combined with a simple tool for assessment of muscle abnormalities in outpatients with chronic liver disease.

AIM: An easily performed method for examination of muscle abnormalities is anticipated. We aimed to elucidate the clinical usefulness of simple assessments for muscle abnormality including a simple five-item questionnaire (SARC-F) in chronic liver disease patients. METHODS: From February to July 2019, 383 outpatients (median age 71 years, 259 men; chronic hepatitis (CH) : liver cirrhosis Child-Pugh A : liver cirrhosis Child-Pugh B : liver cirrhosis Child-Pugh C = 157:176:39:11) who underwent a computed tomography examination were enrolled. SARC-F, previously reported cut-off values for muscle strength decline (MSD; handgrip), pre-muscle volume loss (pre-MVL), calf circumference and finger-circle test results were used, and these results were analyzed retrospectively. RESULTS: A high SARC-F score (≥4) was observed in 25 patients, and a low score (<4) in 358 patients. The frequency of high SARC-F increased significantly with progression of chronic liver disease (chronic hepatitis : liver cirrhosis Child-Pugh A : liver cirrhosis Child-Pugh B/C = 2.5%:8.0%:14.0%, P=0.010). MSD frequency was 22.4% in men and 41.1% in women. Muscle volume loss and pre-MVL were noted in 22% and 30.5%, respectively, of the male patients, and 9.7% and 32.3%, respectively, of the female patients. In cases with high SARC-F and MSD, calf circumference and finger-circle abnormalities were found in 56% and 40.0% of patients, respectively, whereas those values for patients with low SARC-F and MSD were 14.5% and 10.6%, respectively (P < 0.001, for each; positive/negative predictive values: 0.560/0.855 and 0.400/0.894, respectively). Each SARC-F item showed a good area under the curve for MSD, but not pre-MVL. CONCLUSION: SARC-F score in combination with MSD and calf circumference or finger-circle test results may be an easy and simple method for surveillance of chronic liver disease patients with a high risk of sarcopenia and decline of quality of life.

Zinc deficiency as an independent prognostic factor for patients with early hepatocellular carcinoma due to hepatitis virus.

AIM: Although a reduced serum zinc level is often observed in patients with chronic liver disease due to hepatitis virus, its prognostic importance has not been adequately investigated. This study aimed to elucidate the association of zinc deficiency with prognosis, especially in early hepatocellular carcinoma (HCC) patients. METHODS: From 2005 to 2018, 466 patients with naïve HCC due to hepatitis virus were enrolled (327 men, 139 women; median age 70 years; hepatitis C virus [HCV] n = 389, hepatitis B virus [HBV] n = 69, hepatitis C virus and hepatitis B virus n = 8; Child-Pugh A n = 367, Child-Pugh B n = 82; Child-Pugh C n = 17; TNM-LCSGJ stage I n = 150, stage II n = 181, stage III n = 91, stage IVa n = 26, state IVb n = 18). Of the 466 patients, 287 were within the Milan criteria (early HCC) and treated curatively. Zinc deficiency was defined as <60 µg/dL. Clinical records and prognostic factors were retrospectively evaluated. RESULTS: The levels of serum zinc became lower with chronic liver disease progression (Child-Pugh A, B, C: 64.3 ± 14.3, 52.3 ± 15.7, 48.4 ± 13.5 µg/dL, respectively; P < 0.001). In early HCC patients treated curatively, overall survival and recurrence rates were better in patients treated curatively and without zinc deficiency as compared with patients with zinc deficiency (3-year overall survival 86.5% vs. 77.2%, 5-year overall survival 73.5% vs. 43.8%, P < 0.001; 3-year recurrence 44.8% vs. 58.3%, 5-year recurrence 56.8% vs. 77.5%, P = 0.002). Not only infection control of hepatitis virus (sustained virological response in HCV or nucleos(t)ide analogs in HBV; HR 0.078, P < 0.001), but also zinc deficiency (HR 1.773, P = 0.041) were significant prognostic factors for death. CONCLUSION: Serum levels of zinc were reduced in association with chronic liver disease grade progression. In addition to infection control of hepatitis virus, zinc deficiency might be a significant prognostic factor for survival in patients with early HCC due to viral hepatitis treated curatively.

Ultrasonography surveillance improves prognosis of patients with hepatocellular carcinoma.

To examine the effectiveness of ultrasonography (US) for hepatocellular carcinoma (HCC) surveillance, the prognosis of HCC patients who underwent such screening at an expert medical institution or at general clinics were analyzed, as well as those without US surveillance. From October 2006 to December 2014, 872 patients with naïve HCC were enrolled and divided into the surveillance (S)-group (n=398), who underwent follow-up examinations with US, and the non-S group (n=474). The S-group was further subdivided into patients who underwent follow-up surveillance at Ehime Prefectural Central Hospital, an expert medical institution (SE-group, n=189), and those who received surveillance at general clinics (SG-group, n=209). Prognosis and clinical characteristics were analyzed. In the non-S group, the frequency of patients without viral hepatitis (NBNC-HCC) and Tumor, Node, Metastasis stage was greater. As a result, the median survival time (MST) of the non-S group was reduced, compared with the S group (non-S group, 34.1 vs. S group, 68.2 months; P<0.001). Tumor size was significantly different between the SE- and SG-groups (SE-group, 2.0±1.0 vs. SG-group, 2.5±1.3 cm; P<0.001), whereas tumor number (SE-group: 1.5±1.1 vs. SG-group, 1.7±1.2; P=0.164) and MST (SE-group, 72.1 vs. SG-group, 67.1 months; P=0.931) were not significantly different. Surveillance performed at either an expert medical institution or general clinic improved the prognosis of HCC patients. Dissemination of findings demonstrating the importance of surveillance for HCC to all clinicians as well as patients with chronic liver disease is important, and establishment of an effective surveillance strategy for NBNC-HCC is required.

[Marked improvement in renal tubular markers after switching from adefovir to tenofovir alafenamide in a case of Fanconi syndrome diagnosed through high ALP levels].

A woman in her 60s visited our hospital due to elevation of ALP (1357U/L). The patient had been treated with lamivudine (LAM) in 2005, LAM+adefovir (ADV) in 2009, and ADV+entecavir in 2015 for chronic hepatitis B (CH-B). The ALP isozyme was predominantly bone type. Urinary ß-2 microglobulin (MG) and α-1MG increased to 49635µg/L and 64.1mg/L, respectively. Though no fractures were found during bone scintigraphy, the patient was diagnosed with Fanconi syndrome. However, 3 months after switching from ADV to tenofovir alafenamide (TAF), ALP decreased to 856U/L, and urinary ß-2MG and α-1MG decreased to 624µg/L and 6.0mg/L, respectively. Fanconi syndrome should be considered when an increase in ALP is observed in patients treated with ADV, and urinary ß-2MG and α-1MG assays are useful for establishing a diagnosis. Switching from ADV to TAF was an effective therapeutic option.

Combination of Resection and Ablative Treatment for Hepatocellular Carcinoma: Usefulness of Complementary Radiofrequency Ablation.

AIM/BACKGROUND: In HCC patients with multiple tumors in separate segments, monotherapy with surgical resection is often difficult when the estimated residual liver volume after surgery is thought to be inadequate. We evaluated the usefulness of resection combined with low invasive radiofrequency ablation (RFA) for treatment of such cases. MATERIALS/METHODS: We analyzed 115 HCC patients with countable multiple tumors (≤5) without vascular invasion and/or extrahepatic metastasis, and treated solely with resection (SR group: n = 82), or with both resection and RFA (Comb group: n = 33) from January 2000 to December 2017. Clinical characteristics, overall survival rate (OSR), and disease-free survival rate (DFSR) were analyzed in a retrospective manner. RESULTS: There were 88 males (76.5%) and the average age of all patients was 67.8 ± 8.9 years. The average number of tumors and average maximum tumor size were 2.4 ± 0.7 and 4.1 ± 2.1 cm, respectively. Forty-two (36.5%) patients were classified as beyond up-to-7 criteria. The 3- and 5-year OSRs in the SR group were 82.0 and 67.0%, respectively, and in the Comb group were 75.2 and 65.6%, respectively (p = 0.244), while the 3- and 5-year DFSRs in the SR group were 45.2 and 28.0%, respectively, and those in the Comb group were 37.3 and 23.3%, respectively (p = 0.257). CONCLUSION: The combination of surgical resection and complementary RFA may be an effective strategy for treating HCC patients with countable multiple tumors, who are otherwise difficult to treat with surgical resection or RFA alone.

Easy surveillance of muscle volume decline in chronic liver disease patients using finger-circle (yubi-wakka) test.

BACKGROUND: Muscle atrophy (MA) and muscle strength decline are important clinical features in chronic liver disease (CLD) patients. An easy to perform MA screening method without need for special equipment would be helpful. We evaluated the usefulness of the previously reported finger-circle test as screening for MA in CLD patients. METHODS: We retrospectively enrolled 358 Japanese CLD outpatients (70.8 ± 10.2 years, male/female = 234/124) who had undergone a computed tomography examination from December 2017 to March 2018, of whom 137 had chronic hepatitis, 169 had liver cirrhosis Child-Pugh A, and 52 had liver cirrhosis Child-Pugh B/C. Bilateral psoas muscle area at the middle of the third lumber vertebra (L3) was evaluated with computed tomography findings, which was performed as a screening of hepatocellular carcinoma, using a previously reported parameter for MA [psoas index (PI): total psoas muscle area (cm2 )/height (m)2 ] [mean PI ± standard deviation (SD) of male patients: 6.50 ± 1.13 cm2 /m2 and those of female patients: 4.30 ± 0.90 cm2 /m2 ]. We then evaluated the correlation between MA and finger-circle test results in these patients. RESULTS: The mean PI values for finger-circle test results Bigger, Just-fits, and Smaller were 5.64 ± 1.34, 5.00 ± 1.25, and 4.83 ± 1.46 cm2 /m2 , respectively, in male patients (P < 0.001) and 4.31 ± 1.06, 3.93 ± 0.97, and 3.42 ± 0.94 cm2 /m2 , respectively, in female patients (P = 0.001). We found that a finger-circle test result in male patients other than Bigger (Just-fits and Smaller) predicted a decline in psoas muscle area of L3 to PI 5.25 cm2 /m2 (sensitivity/specificity 0.619/0.667, area under the curve 0.654, 95% confidence interval 0.583-0.724), which was approximately mean minus 1 SD (5.37 cm2 /m2 ). On the other hand, a Smaller test result in female patients predicted a decline in psoas muscle area of L3 to PI 3.33 cm2 /m2 (sensitivity/specificity 0.740/0.583, area under the curve 0.698, 95% confidence interval 0.583-0.813), approximately mean minus 1 SD (3.40 cm2 /m2 ). CONCLUSIONS: The finger-circle test is an easy to perform and effective screening method for predicting earlier stage of MA in CLD patients without the need for special equipment.

Prediction of risk of falls based on handgrip strength in chronic liver disease patients living independently.

AIM: Falling is known to be associated with cognitive function. We evaluated the relationship between muscle function and falls in patients with chronic liver disease (CLD). METHODS: We enrolled 100 sequential CLD patients without dementia who were admitted to our institution for scheduled treatment from July 2017 to May 2018 (age 71.0 ± 10.2 years; 76 men). All subjects were self-reliant in regard to activities of daily living. On admission, handgrip strength was determined and falls within 1 month of admission were noted. For determining handgrip strength decline (HSD), previously reported values were used (men, <26 kg; women, <18 kg). The relationship between HSD and falls in CLD patients was evaluated in a retrospective manner. RESULTS: Thirty-two patients had chronic hepatitis and 49 had liver cirrhosis (LC) Child-Pugh A, 17 had LC Child-Pugh B, and 2 had LC Child-Pugh C. Twelve (12.0%) had a history of falling, including 8 (26.7%) of 30 with and 4 (5.7%) of 70 without HSD (P = 0.006). The cut-off value for age in relationship to falling was 69.0 years old (area under the receiver operating characteristic curve, 0.668; 95% confidence interval, 0.514-0.821). A fall during hospitalization was noted more often in patients with a history of falling than in those without (16.7% [2/12] vs. 2.3% [2/88], P = 0.018). CONCLUSION: In CLD patients, the presence of HSD and older age might be independent risk factors for predicting a fall. Assessment of handgrip strength could be an effective clinical tool for easily assessing the risk of falling, especially in elderly CLD patients.

Proposed a simple score for recommendation of scheduled ultrasonography surveillance for hepatocellular carcinoma after Direct Acting Antivirals: multicenter analysis.

BACKGROUND AND AIM: To develop a scoring method using with common clinical data for predicting hepatocellular carcinoma (HCC) development after sustained virological response at 24 weeks (SVR24) after treatment with direct acting antivirals (DAAs), we retrospectively evaluated clinical features of patients who obtained SVR24. METHODS: From October 2014 to December 2017, 1069 hepatitis C virus patients without a past history of HCC, who obtained SVR24 by DAAs at two different areas, were enrolled (the training [n = 484, ChuShikoku-group] and validation [n = 585, Chubu-group] sets). All were examined by ultrasonography as surveillance for HCC at the time of starting DAAs and twice a year after SVR24. We identified three parameters at SVR24, male gender, FIB-4 index > 3.25, and α-fetoprotein level > 5.0 ng/mL, as risk factors for HCC development and gave them point values, with the sum used as After DAAs Recommendation for Surveillance (ADRES) score. RESULTS: In the ChuShikoku-group, the respective 1-/2-year rates for HCC incidence rates ADRES score 0 were 0.0%/0.0%, for a score 1 were 1.1%/2.1%, score 2 were 8.8%/15.9%, and score 3 were 17.1%/28.1%. On the other hand, those respective scores for the Chubu-group were 0.0%/0.0%, 0.0%/0.7%, 7.9%/10.6%, and 19.5%/not available. The c-index of the predictive value for HCC development in the training set after SVR24 was 0.835 while 0.899 in the validation set. Finally, those of the entire cohort were 0.0%/0.0%, 0.5%/1.6%, 8.4%/13.4%, and 18.0%/32.8%. CONCLUSION: The present ADRES score was simple and easy to use and may be useful for predicting risk of HCC development in short term after reaching SVR24 by DAAs.

Relative changes in handgrip strength and skeletal muscle volume in patients with chronic liver disease over a 2-year observation period.

AIM: There are few reports regarding relative changes in muscle function of patients with chronic liver disease (CLD). We examined CLD patients to evaluate relative changes in handgrip strength and muscle volume. METHODS: We enrolled 413 CLD outpatients who underwent handgrip strength measurements in both 2015 and 2017 (age 67.9 ± 10.0 years; male / female = 242/171; hepatitis C virus [HCV] / hepatitis B virus [HBV] / HBV and HCV / alcohol / others = 239/92/4/22/56; Child-Pugh score [CPS] in 2015 [5/6/7/8/9/≥10 = 335/51/12/11/3/1]). Relative change in muscle volume (ΔPI) from 2015 to 2017 was evaluated using computed tomography findings in 230 of the patients, using a previously reported method. Clinical characteristics, as well as relative changes of handgrip strength (ΔHGS) and ΔPI were analyzed. RESULTS: For the patient cohort as a whole, CPS became significantly worse in 2017 (5/6/7/8/9/≥10 = 319/56/13/11/5/9; P = 0.002). In individual patients with CPS decline, serum albumin level was significantly decreased (3.78 ± 0.50 to 3.33 ± 0.61 g/dL; P < 0.001), whereas no decrease was seen in those without such a decline (4.16 ± 0.48 to 4.20 ± 0.44 g/dL; P = 0.028). Furthermore, ΔHGS (-1.4 ± 4.8 [n = 59] vs. 0.7 ± 4.8 kg [n = 354]; P = 0.002) and ΔPI (-0.44 ± 0.88 [n = 38] vs. 0.03 ± 0.64 cm2 /m2 [n = 192]; P = 0.003) were worse in patients with, compared to those without, a decline in CPS. Age was not significantly different between patients with and without handgrip strength decline (66.5 ± 10.3 vs. 65.3 ± 9.9 years; P = 0.256). There was a significant relationship between ΔHGS, ΔPI and relative change in serum albumin (r = 0.161, P = 0.001 and r = 0.225, P < 0.001, respectively). CONCLUSION: Decline in CPS, especially decreasing serum albumin level, showed a significant relationship with muscle function reduction and muscle volume loss.

Muscle volume loss a prognostic factor for death in liver cirrhosis patients and special relationship to portal hypertension.

AIM: We examined the prognosis of liver cirrhosis (LC) patients with and without portal hypertension (PHT) and muscle volume loss (MVL). METHODS: From 2006 to 2016, 346 LC outpatients (PHT/non-PHT = 173/173) were enrolled (median age, 69 years; men / women, 204/142; Child-Pugh A / B, 230/116; and presence of MVL 15.6% in each group) after propensity matching, following exclusion of those with hepatocellular carcinoma (HCC) beyond the Milan criteria and Child-Pugh C. Portal hypertension was defined as positive for significant esophagogastric varices; MVL was diagnosed based on a previously reported index using CT imaging. Overall survival rate (OSR) was evaluated from the viewpoints of PHT and MVL. RESULTS: There were no significant differences in clinical background (age, gender, etiology, presence of HCC [within Milan criteria], or Child-Pugh class) between the groups. Although there was no significant difference regarding OSR between patients with and without MVL in the non-PHT group (P = 0.076, Holm's method), the OSR of patients with MVL in the PHT group was lower compared to those without MVL in both groups (P = 0.017 and P = 0.012, respectively, Holm's method). As a result, the OSR of patients with MVL (n = 54) was lower than the other patients (n = 292) (3- and 5-year OSR, 69.0% vs. 86.4% and 35.8% vs. 74.1%, respectively; P < 0.001). Multivariate Cox hazard analysis showed that positive for HCC (hazard ratio [HR], 2.028; 95% confidence interval [CI], 1.189-3.460; P = 0.009) and positive for MVL (HR, 2.768; 95% CI, 1.575-4.863; P < 0.001) were significant independent prognostic factors for death. CONCLUSION: Muscle volume loss and HCC, but not PHT, were found to be independent prognostic factors for death in LC patients.

Impact of muscle volume and muscle function decline in patients undergoing surgical resection for hepatocellular carcinoma.

BACKGROUND AND AIM: This study investigated the prognostic impact of muscle volume loss (MVL) and muscle function decline in patients undergoing resection for hepatocellular carcinoma (HCC). METHODS: This study enrolled 171 naïve HCC patients treated with resection from 2007 to 2015, after excluding those lacking spirometry or computed tomography findings, who had received non-curative treatments, or with restrictive or obstructive lung disorders. The median peak expiratory flow rate (%PEF) was set as the cut-off value for muscle function decline, and MVL was diagnosed using a previously reported value. Clinical backgrounds and prognosis were retrospectively evaluated. RESULTS: Overall survival rate was lower in the MVL (n = 35) as compared with the non-MVL (n = 136) group (1/3/5-year overall survival rate = 88.2%/81.6%/55.6% vs 91.0%/81.5%/74.8%, respectively; P = 0.0083), while there were no differences regarding hepatic function or tumor burden between the groups. Child-Pugh class B (hazard ratio [HR] 3.510, 95% confidence interval [CI]: 1.558-7.926, P = 0.0025), beyond Milan criteria (HR 1.866, 95%CI: 1.024-3.403, P = 0.042), and presence of MVL (HR 1.896, 95%CI: 1.052-3.416, P = 0.033) were significant prognostic factors. The decreased %PEF group (n = 84) showed a higher rate of postoperative delirium than the others (n = 87) (27.4% vs 11.5%, P = 0.0088). The cut-off values for %PEF and age for postoperative delirium were 63.3% (area under receiver operating characteristic [AUROC] 0.697) and 73 years old (AUROC 0.734), respectively. Delirium was observed in 50.0% (14/28) of patients with both factors, 23.8% (15/63) of those with 1 factor, and 5.0% (4/80) of those without either factor. CONCLUSION: Muscle volume loss is an independent prognostic factor in HCC patients treated with surgical resection, while advanced age and decreased muscle function might indicate high risk for postoperative delirium.

Validation of Newly Proposed Time to Transarterial Chemoembolization Progression in Intermediate-Stage Hepatocellular Carcinoma Cases.

BACKGROUND/AIM: Determination of failure of transarterial chemoembolization (TACE) for treatment of Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) has become important because of the development of tyrosine kinase inhibitor (TKI) treatment. We evaluated the usefulness and efficacy of the newly proposed time to TACE progression (TTTP). PATIENTS AND METHODS: From 2006 to 2016, 192 BCLC-B HCC patients [median age 72 years, male/female ratio = 149/43, Child-Pugh score 5/6/7 = 106/56/30, albumin-bilirubin (ALBI) grade 1/2 = 64/128, Kinki criteria B1/B2 = 64/128] were enrolled. TTTP was defined based on a previous report and first imaging performed 3 months after initial TACE had been used to obtain baseline images. The patients were divided into three groups according to TTTP (<5, 5-10, and ≥10 months; group I, II, and III, respectively). We evaluated the relationship between TTTP and overall survival (OS) as well as the prognostic factors for death. RESULTS: The median number of TACE procedures was 4 (interquartile range 3-7). There was a moderate correlation between TTTP and OS (r = 0.527, 95% CI 0.416-0.622, p < 0.001). The median survival for group I (n = 78), II (n = 49), and III (n = 65) was 24.6, 34.7, and 49.5 months, respectively (group I vs. group II, p = 0.023; group I vs. group III, p < 0.001; group II vs. group III, p = 0.037; Holm's method). ALBI grade 2 (HR 1.548, 95% CI 1.004-2.388, p = 0.048), alpha-fetoprotein (>100 ng/mL) (HR 1.540, 95% CI 1.035-2.291, p = 0.033), and TTTP (<5 months) (HR 2.157, 95% CI 1.447-3.215, p < 0.001) were significant prognostic factors for death in multivariate Cox hazard analysis. CONCLUSION: In patients with reduced TTTP, especially <5 months, it might be difficult to improve prognosis with a repeated TACE procedures. In such cases, reconsideration of the therapeutic strategy might be needed when possible.

Abdominal Ultrasound Findings of Tumor-Forming Hepatic Malignant Lymphoma.

AIM/BACKGROUND: Evaluations of abdominal ultrasonography (US) findings of primary and secondary tumor-forming hepatic malignant lymphoma (HML) have not been adequately reported. In this study, we elucidated US and contrast-enhanced US (CEUS) findings in patients with HML. MATERIALS/METHODS: From January 2006 to March 2017, 25 patients with HML were enrolled (primary 7, secondary 18), each of whom was diagnosed pathologically. They were divided into 2 groups based on tumor diameter (cutoff, 30 mm). US imaging findings were retrospectively analyzed. RESULTS: All tumors in patients with a small HML (<30 mm in diameter, small group, n = 14) were revealed as homogeneous hypo-echoic type (100%), with penetrating sign observed in only 1 patient. Tumors in 11 patients in the small group, examined with CEUS, showed homogeneous enhancement in the early vascular phase (91%) and a washout pattern in the portal phase (100%), and they were revealed as defective in the post-vascular phase (100%). In the large group (≥30 mm; n = 11), tumors were revealed as a heterogeneous hypo-echoic lesion in 10 (91%) and penetrating sign was observed in 8 (73%). Dilatation of the distal intrahepatic bile duct by the tumor was observed in 4 patients in the large group. In 7 large group patients examined with CEUS, imaging findings in the early vascular phase varied, with 5 (71%) showing a washout pattern in the portal phase and 5 (71%) revealed as defective in the post-vascular phase. CONCLUSION: We found that US imaging features of HML differ depending on the tumor diameter.

Efficacy of branched-chain amino acid supplementation and walking exercise for preventing sarcopenia in patients with liver cirrhosis.

BACKGROUND/AIM: Sarcopenia is recognized as a condition related to quality of life and prognosis in patients with chronic liver disease, although no useful strategy for improving muscle volume and strength has been established. Here, we evaluated the efficacy of supplementation with branched-chain amino acid (BCAA) administration and walking exercise. PATIENTS AND METHODS: From December 2015 to July 2016, 33 Japanese outpatients with liver cirrhosis were enrolled (median: 67 years, HCV : HBV : alcohol : others=26 : 2 : 2 : 3, male : female=13 : 20, Child-Pugh A : B=30 : 3). None had a history of BCAA supplementation. After calculating the average number of daily steps using a pedometer for a 2-3-week period, BCAA supplementation (protein 13.5 g, 210 kcal/day) as a late evening snack and walking exercise (additional 2000 steps/day prescribed) were started. Body composition including muscle volume was analyzed using a bioelectrical impedance analysis method, and serological data and muscle strength (leg, handgrip) were evaluated at enrollment, and then 1, 2, and 3 months after starting the protocol. RESULTS: The median average number of daily steps was 3791 (interquartile range: 2238-5484). The average period of BCAA supplementation was 2.7±0.7 months. During the period from enrollment to 3 months after starting the protocol, HbA1c and NH3 were not significantly changed, whereas the BCAA/tyrosine ratio improved (4.3±1.35 to 5.24±2.04, P=0.001). In addition, the ratios for average daily steps (1.595, P=0.02) as well as muscle volume, leg strength, and handgrip strength (1.013, 1.110, and 1.056, respectively; all P<0.01) were increased at 3 months. CONCLUSION: BCAA supplementation and walking exercise were found to be effective and easily implemented for improving muscle volume and strength in liver cirrhosis patients.

Muscle volume loss as a prognostic marker in hepatocellular carcinoma patients treated with sorafenib.

AIM: To elucidate the clinical significance of muscle wasting in regard to survival of hepatocellular carcinoma (HCC) patients undergoing sorafenib treatment, we evaluated prognostic factors including muscle wasting at the start of sorafenib treatment. METHODS: We enrolled 93 patients with unresectable HCC (68.3 ± 9.4 years old, 81 men, 12 women, Child-Pugh score 5:6:7 = 69:22:2) who were treated with sorafenib. Muscle wasting was evaluated based on psoas muscle area index (psoas muscle area at level of middle of third lumbar vertebra [cm2 ] / height [m]2 ) calculated from computed tomography findings. Previously reported cut-off values for muscle wasting in men and women (4.24 and 2.50 cm2 /m2 , respectively) were used. Patients were divided into those with (muscle-atrophy group, n = 20) and without (non-atrophy group, n = 73) muscle wasting. RESULTS: There were no significant differences in regard to etiology, Child-Pugh classification, and tumor-node-metastasis stage between the groups. In contrast, body mass index in the muscle-atrophy group was lower (20.9 ± 2.4 vs. 23.5 ± 3.4, P = 0.003). Although time to progression was not different (median 2.1 vs. 2.8 months, P = 0.242), the 6-, 12-, and 18-month survival rates were worse in the muscle-atrophy group (62.7%, 32.3%, and 32.3% vs. 78.3%, 64.7% and 48.1%, respectively, P = 0.042). In multivariate Cox hazard analysis, des-γ-carboxy prothrombin level (≥100 mAU/mL) (hazard ratio, 2.540; P = 0.018) and positive for muscle wasting (hazard ratio, 2.158; P = 0.032) were significant prognostic factors at the start of sorafenib treatment. CONCLUSION: Muscle wasting is an important prognostic factor in patients treated with sorafenib.