Low geriatric nutritional risk index predicts poor prognosis in patients with cirrhosis: a retrospective study.

Aim: Malnutrition, which increases the risk of liver disease-related events and mortality, is a serious complication in cirrhosis. This study aimed to investigate whether the geriatric nutritional risk index (GNRI) could predict the long-term prognosis in patients with cirrhosis. Methods: We retrospectively evaluated 266 patients with cirrhosis and classified them into two groups based on baseline GNRI scores: risk (≤98, n = 104) and no-risk groups (>98, n = 162). The cumulative survival rates were compared between the two groups in patients with compensated and decompensated cirrhosis, respectively. Cox proportional hazards regression analysis was used to identify significant and independent factors associated with mortality. Results: The median observation period was 54.9 (33.6-61.7) months and 65 (24.4%) liver disease-related deaths occurred during the follow-up period. The GNRI scores significantly and inversely correlated with Child-Pugh score (r = -0.579), model for end-stage liver disease score (r = -0.286), and Mac-2 binding protein glycosylation isomer (r = -0.494). Multivariate analysis identified low GNRI as a significant and independent factor associated with mortality [overall cohort: hazard ratio (HR), 0.926; p < 0.001; compensated cirrhosis: HR, 0.947; p = 0.003; decompensated cirrhosis: HR, 0.923; p < 0.001]. The risk group demonstrated significantly lower cumulative survival rates than the no-risk group in overall cohort, and patients with compensated and decompensated cirrhosis (p < 0.001, <0.001, and = 0.013, respectively). Conclusion: Low GNRI was associated with poor long-term prognosis in both patients with compensated and decompensated cirrhosis. Therefore, the GNRI is a simple and useful tool for predicting prognosis and modifying the nutritional status in patients with cirrhosis.

Insulin-like growth factor 1 predicts decompensation and long-term prognosis in patients with compensated cirrhosis.

Aim: Insulin-like growth factor 1 (IGF-1), which is primarily produced in hepatocytes and is associated with liver functional reserve, plays a crucial role in the pathological condition of cirrhosis. This study aimed to investigate the usefulness of serum IGF-1 levels for predicting the long-term prognosis and decompensation development in patients with cirrhosis. Methods: We retrospectively evaluated 148 patients with cirrhosis and divided them into three groups according to baseline IGF-1 levels: low (L)-, intermediate (I)-, and high (H)-IGF-1 groups. The cumulative survival rates were compared among these groups in compensated and decompensated cirrhosis, respectively. Significant and independent factors associated with mortality and decompensation development were identified using Cox proportional hazards regression analysis. Results: The median observation period was 57.1 (41.7-63.2) months. Thirty (20.3%) patients died of liver disease-related events and 21 (22.3%) patients with compensated cirrhosis developed decompensation. Multivariate analysis identified low serum IGF-1 levels as a significant and independent factor associated with mortality (all patients: hazard ratio [HR], 0.967; p = 0.004; patients with compensated cirrhosis: HR, 0.927; p = 0.002). The cumulative survival rates were significantly lower in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (all patients: p < 0.001 and = 0.009; patients with compensated cirrhosis: p = 0.012 and 0.003, respectively). However, in decompensated cirrhosis, the cumulative survival rates demonstrated no significant differences among the three groups. The cumulative decompensation incidence rates were significantly higher in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (p < 0.001 and = 0.009, respectively). Low serum IGF-1 levels were significantly and independently associated with decompensation development (HR, 0.939; p < 0.001). Conclusion: Low serum IGF-1 levels were significantly and independently associated with decompensation development and poor long-term prognosis in patients with compensated cirrhosis. Therefore, IGF-1 may be useful for predicting decompensation-related events and should be regularly monitored in the management of compensated phase.

Osteosarcopenia predicts poor survival in patients with cirrhosis: a retrospective study.

BACKGROUND: Osteosarcopenia, defined as the coexistence of sarcopenia and osteoporosis, is associated with adverse clinical outcomes. The present study investigated the prognostic significance of osteosarcopenia in patients with cirrhosis. METHODS: This retrospective study evaluated 126 patients with cirrhosis. Participants were classified into three groups based on the presence or absence of (1) sarcopenia and/or osteoporosis; and (2) Child-Pugh (CP) class B/C cirrhosis and/or osteosarcopenia, and the cumulative survival rates were compared between the groups. Cox proportional hazards model was used to identify independent factors associated with mortality. Sarcopenia and osteoporosis were diagnosed according to the Japan Society of Hepatology and the World Health Organization criteria, respectively. RESULTS: Among the 126 patients, 24 (19.0%) had osteosarcopenia. Multivariate analysis identified osteosarcopenia as a significant and independent prognostic factor. The cumulative survival rates were significantly lower in patients with osteosarcopenia than in those without (1/3/5-year survival rates = 95.8%/73.7%/68.0% vs. 100%/93.6%/86.5%, respectively; p = 0.020). Patients with osteosarcopenia, but not sarcopenia or osteoporosis alone, had significantly lower cumulative survival rates than those without both conditions (p = 0.019). Furthermore, patients with both CP class B/C and osteosarcopenia had significantly lower cumulative survival rates than those without both (p < 0.001) and with either condition (p < 0.001). CONCLUSIONS: Osteosarcopenia was significantly associated with mortality in patients with cirrhosis. The cumulative survival rates were lower in patients with osteosarcopenia than in those without both conditions. Additionally, comorbid osteosarcopenia worsened the prognosis of patients with CP class B/C. Therefore, simultaneous evaluation of both sarcopenia and osteoporosis is crucial to better predict the prognosis.

Prognostic significance of sarcopenia and severe vitamin D deficiency in patients with cirrhosis.

Background and Aim: Sarcopenia and severe vitamin D deficiency are associated with malnutrition and poor prognosis. We investigated the impact of the comorbidity of Child-Pugh (CP) class B/C cirrhosis and the aforementioned complications on the prognosis of patients with cirrhosis. Methods: We retrospectively evaluated 104 patients with cirrhosis. The cumulative survival rates were compared between patients with and without both or either of these disease conditions: CP class B/C and complications (sarcopenia or severe vitamin D deficiency). Sarcopenia was diagnosed according to the Japan Society of Hepatology criteria. Severe vitamin D deficiency was defined as levels of 25-hydroxyvitamin D <10 ng/mL in serum. Results: The prevalence of CP class B/C, sarcopenia, and severe vitamin D deficiency was 26.9%, 38.5%, and 24.0%, respectively. Patients with both CP class B/C and sarcopenia had significantly lower survival rates than those without both (hazard ratio [HR] = 6.101; P < 0.001) and with either condition (HR = 6.137; P = 0.001). Similarly, patients with both CP class B/C and severe vitamin D deficiency or with either condition had significantly lower survival rates than those without both conditions (HR = 8.135 or 3.189; P < 0.001 or =0.025, respectively). CP class B/C (HR = 3.354; P = 0.006) and severe vitamin D deficiency (HR = 2.445; P = 0.044) were independent prognostic factors. Conclusions: The coexistence of CP class B/C and sarcopenia or severe vitamin D deficiency worsened the prognosis of patients with cirrhosis. Nutritional assessments such as sarcopenia and vitamin D status should be considered to better evaluate disease conditions and patient prognosis.

The Geriatric Nutritional Risk Index predicts sarcopenia in patients with cirrhosis.

Patients with cirrhosis are at high risk for sarcopenia and malnutrition, which are associated with reduced quality of life and increased mortality. We investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) and sarcopenia/gait speed and assessed the usefulness of the GNRI for predicting sarcopenia in patients with cirrhosis. We evaluated 202 patients with cirrhosis and divided them into three groups based on baseline GNRI values: low (L)-GNRI (< 94.0, n = 49), intermediate (I)-GNRI (between 94.0 and 109.5, n = 103), and high (H)-GNRI groups (> 109.5, n = 50). Sarcopenia was diagnosed according to the criteria of the Japan Society of Hepatology. The prevalence of sarcopenia and slow gait speed was the lowest in the H-GNRI group (8.0% and 26.0%, respectively) and the highest in the L-GNRI group (49.0% and 44.9%, respectively). They increased stepwise with a decline in the GNRI group (p < 0.001 and p = 0.05, respectively). The GNRI values were significantly and positively correlated with handgrip strength, skeletal muscle mass index, and gait speed. Multivariate analysis identified lower GNRI as an independent risk factor for sarcopenia. The optimal cutoff value of the GNRI for predicting sarcopenia was 102.1 (sensitivity/specificity, 0.768/0.630). The GNRI was significantly associated with sarcopenia and physical performance and could be a helpful screening tool for predicting sarcopenia in patients with cirrhosis.

Potential significance of uncovered self-expandable metal stents for distal malignant biliary obstruction: A propensity score-adjusted competing risk regression analysis.

Objectives: Selection criteria for self-expandable metal stents (SEMSs) with or without cover during palliative treatment of distal malignant biliary obstruction (DMBO) remain unclear. We evaluated factors associated with time to recurrent biliary obstruction (TRBO) in fully covered SEMSs (FCSEMSs) and uncovered SEMSs (UCSEMSs). Methods: We retrospectively analyzed consecutive patients with DMBO who received a SEMS. TRBO was determined using the Kaplan-Meier analysis, and complications were compared between the FCSEMS and UCSEMS groups. After TRBO-associated factors were extracted using multivariate competing-risks regression (CRR), propensity score-adjusted CRRs were performed to verify their robustness. Results: There were 180 patients (66 FCSEMSs and 114 UCSEMSs) enrolled in this study. There was no significant difference between median TRBO in the FCSEMS and UCSEMS groups (275 vs. 255 days, p = 0.67). Complications were more frequent in the FCSEMS than UCSEMS group (21.2% vs. 8.8%; p = 0.023). Multivariate CRR for TRBO-associated factors revealed that "pancreatic ductal carcinoma (PDAC) treated with UCSEMS" was the only independent predictor of TRBO (p = 0.03). Similarly, the propensity score-adjusted CRRs showed no significant difference in TRBO in "FCSEMS" vs "UCSEMS" (p = 0.96); however, there was a significant difference in "PDAC using UCSEMS" vs "other" (p = 0.043). In the palliative care group including any DMBO without chemotherapy, the first quartile of the TRBO of UCSEMS was 100 days. Conclusions: UCSEMSs are a possible option for both patients with DMBO arising from PDAC and for patients with any DMBO receiving palliative care who should avoid SEMS-related complications.

Safety and efficacy of pentazocine-midazolam combination for pain and anxiety relief in radiofrequency ablation therapy for hepatocellular carcinoma.

Background and Aim: Radiofrequency ablation (RFA) therapy is frequently used as first-line treatment for small hepatocellular carcinoma (HCC). RFA is often associated with pain; however, no definitive solution has been established for its relief. We retrospectively analyzed the safety and efficacy of the combination of pentazocine and midazolam to relieve pain experienced by HCC patients undergoing RFA. Methods: We studied 77 patients with 98 HCCs treated with RFA between January 2015 and August 2019. Patients were divided into two groups: the sedative-free group, which included those who received pentazocine alone, and the pentazocine-midazolam group, which included those who received a combination of pentazocine and midazolam. The degrees of analgesia and sedation were evaluated using the numerical rating scale (NRS) and the Richmond Agitation-Sedation Scale (RASS), respectively. Other parameters such as treatment time, awakening time, midazolam dosage, vital signs, local recurrence rate, and time to recurrence were also examined. Results: The median NRS score and RASS score were significantly lower in the pentazocine-midazolam group. Ninety-five percent of patients in the pentazocine-midazolam group had no memory of the RFA session. The treatment time and awakening time were prolonged for the pentazocine-midazolam group. No significant differences in oxygen saturation, recurrence rates, and time to local recurrence were observed between groups. Conclusion: A combination of pentazocine and midazolam is safe and effective for pain and anxiety relief experienced by patients undergoing RFA for local treatment of HCC.

Clinical Usefulness of FRAX Score for Predicting Sarcopenia in Patients with Chronic Liver Disease.

We investigated the usefulness of the Fracture Risk Assessment tool (FRAX) for predicting sarcopenia in chronic liver disease (CLD). In this cross-sectional study, we evaluated 321 patients with CLD. The FRAX with and without bone mineral density (BMD) was employed to calculate the 10-year risks of major osteoporotic and hip fractures. The FRAX score for high fracture risk was defined as a 10-year major osteoporotic fracture probability of ≥20% or a 10-year hip fracture probability of ≥3%. The diagnosis of sarcopenia was based on the Japan Society of Hepatology criteria. According to the FRAX, with and without BMD, 134 (41.7%) and 193 (60.1%) patients had a high fracture risk, respectively. The high fracture risk group had a significantly higher frequency of sarcopenia than the non-high fracture risk group. FRAX scores of major osteoporotic and hip fractures were negatively correlated with handgrip strength and muscle mass. Using the FRAX with BMD, the cutoff scores of major osteoporotic and hip fractures for predicting sarcopenia were 8.55% (sensitivity/specificity, 0.847/0.568) and 3.35% (0.729/0.746), respectively. Using the FRAX without BMD, they were 18.5% (0.635/0.725) and 7.65% (0.729/0.758), respectively. The FRAX is a simple and convenient screening tool for predicting sarcopenia in patients with CLD.

Clinical characteristics of sarcopenia in patients with alcoholic liver cirrhosis.

BACKGROUND AND AIM: Sarcopenia frequently develops in patient with liver cirrhosis (LC). Ethanol reduces muscle protein synthesis and accelerates proteolysis. However, the relationship between heavy alcohol consumption and sarcopenia remains controversial. This study aimed to investigate the characteristics and prevalence of sarcopenia among patients with alcoholic LC (ALC) in real-world clinical settings. METHODS: This cross-sectional study included 181 patients with LC. Heavy alcohol consumption was defined as >60 g/day. Sarcopenia was diagnosed according to the Japan Society of Hepatology criteria. RESULTS: Among the 181 patients, 64 (35.4%) were diagnosed with ALC. Patients with ALC were younger (median, 61.5 vs 72.0 years; P < 0.001) and had a lower prevalence of sarcopenia (18.8 vs 32.5%; P = 0.048) than those with non-ALC. Conversely, the former had a higher prevalence of Child-Pugh class B/C (P = 0.015), higher total bilirubin (P = 0.017), and lower prothrombin time (P < 0.001) than the latter. The prevalence of sarcopenia increased alongside advancing age in patients with ALC (P = 0.007). Multivariate analysis identified older age (but not disease stage/liver function reserve and alcohol consumption) as an independent factor associated with sarcopenia (P = 0.002) in patients with ALC. CONCLUSION: Patients with ALC were younger and had a lower prevalence of sarcopenia, despite advanced disease stage/impaired liver function reserve, compared to those with non-ALC in real-world clinical settings. However, older age was strongly associated with sarcopenia, even in patients with ALC. There was no significant influence of heavy alcohol consumption on the development of sarcopenia.

Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease.

AIM: Osteoporotic fractures negatively impact health-related quality of life and prognosis. Advanced glycation end products (AGEs) impair bone quality and reduce bone strength. The aim of this study was to determine the relationship between plasma levels of pentosidine, a surrogate marker for AGEs, and prevalent fractures in patients with chronic liver disease (CLD). METHODS: This cross-sectional study included 324 patients with CLD. Vertebral fractures were evaluated using lateral thoracolumbar spine radiographs. Information on prevalent fractures was obtained through a medical interview, medical records, and/or radiography. The patients were classified into low (L), intermediate (I), and high (H) pentosidine (Pen) groups based on baseline plasma pentosidine levels. RESULTS: Of the 324 patients, 105 (32.4%) had prevalent fractures. The prevalence of liver cirrhosis (LC) and prevalent fractures significantly increased stepwise with elevated pentosidine levels. The H-Pen group had the highest prevalence of LC (88.6%, p < 0.001) and prevalent fractures (44.3%, p = 0.007), whereas the L-Pen group had the lowest prevalence of LC (32.1%, p < 0.001) and prevalent fractures (21.0%, p = 0.007). Multiple logistic regression analysis identified pentosidine as a significant independent factor related to prevalent fractures (odds ratio = 1.069, p < 0.001). Pentosidine levels increased stepwise and correlated with liver disease severity. They were markedly high in patients with decompensated LC. In multiple regression analysis, liver functional reserve factors (total bilirubin, albumin, and prothrombin time-international normalized ratio) significantly and independently correlated with pentosidine levels. CONCLUSIONS: Plasma pentosidine was significantly associated with prevalent fractures and liver functional reserve in patients with CLD. Pentosidine may be useful in predicting fracture risk and should be closely followed in CLD patients with advanced disease.

Relationship between osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia in patients with primary biliary cholangitis.

AIM: Bone disorders are serious complications in patients with primary biliary cholangitis (PBC), especially in postmenopausal female patients. Given that osteoporosis interrelates closely with sarcopenia, the concept of osteosarcopenia (coexistence of the two complications) has been established. This study aimed to investigate the relationship between osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia in PBC patients. METHODS: This study involved 117 consecutive PBC patients (21 males and 96 females). Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. Sarcopenia was diagnosed according to the Japan Society of Hepatology assessment criteria. RESULTS: Of the 117 patients, 33 (28.2%), 27 (23.1%), 21 (17.9%), and 18 (15.4%) had osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia, respectively. Multivariate analysis identified sarcopenia as a significant, independent risk factor associated with osteoporosis in all and female patients [odds ratio (OR) = 4.126, P = 0.018; OR = 6.510, P = 0.001, respectively], and vice versa (OR = 3.420, P = 0.040; OR = 4.012, P = 0.026, respectively). The skeletal muscle mass index and handgrip strength were significantly correlated with the BMD of the lumbar spine, femoral neck, and total hip (r = 0.46-0.59, P < 0.001). Patients with osteosarcopenia had significantly higher prevalence of vertebral fracture (10/18; 55.6%) than those without both osteoporosis and sarcopenia (5/75; 6.7%). CONCLUSION: We demonstrated the prevalence of osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia in PBC, and noted that these complications interrelated closely with each other. Comprehensive assessment and treatment strategies for bone and muscle disorders are essential for PBC patients.

Low Serum 25-Hydroxyvitamin D Levels Are Related to Frailty and Sarcopenia in Patients with Chronic Liver Disease.

Low vitamin D status is related to frailty and/or sarcopenia in elderly individuals. However, these relationships are unclear in patients with chronic liver disease (CLD). This study aimed at exploring the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and frailty or sarcopenia in 231 patients with CLD. Frailty was determined based on five factors (weight loss, low physical activity, weakness, slowness, and exhaustion). Sarcopenia was diagnosed by applying the Japan Society of Hepatology criteria. The patients were classified into three groups according to baseline 25(OH)D levels: low (L), intermediate (I), and high (H) vitamin D (VD) groups. Of the 231 patients, 70 (30.3%) and 66 (28.6%) had frailty and sarcopenia, respectively. The prevalence rate of frailty and sarcopenia significantly increased stepwise with a decline in the vitamin D status. The L-VD group showed the highest prevalence rates of frailty and sarcopenia (49.1% (28/57), p < 0.001 for both), whereas the H-VD group showed the lowest prevalence rates of frailty (15.3% (9/59)) and sarcopenia (18.6% (11/59)) (p < 0.001 for both). Multivariate analysis identified serum 25(OH)D levels as a significant independent factor related to frailty and sarcopenia. Serum 25(OH)D levels significantly correlated with handgrip strength, skeletal muscle mass index, and gait speed. In conclusion, low serum vitamin D level, especially severe vitamin D deficient status, is closely related to frailty and sarcopenia in patients with CLD.

Low Serum Branched-Chain Amino Acid and Insulin-Like Growth Factor-1 Levels Are Associated with Sarcopenia and Slow Gait Speed in Patients with Liver Cirrhosis.

Branched-chain amino acid (BCAA) and insulin-like growth factor 1 (IGF-1) are essential for muscle protein synthesis. We investigated the association of serum BCAA and IGF-1 levels with sarcopenia and gait speed in 192 patients with liver cirrhosis (LC). Sarcopenia was diagnosed according to the Japan Society of Hepatology criteria. Slow gait speed was defined as <1.0 m/s. Subjects were divided into three groups based on baseline BCAA or IGF-1 levels: low (L), intermediate (I), and high (H) groups. The L-BCAA group had the highest prevalence of sarcopenia (60.4%, p < 0.001) and slow gait speed (56.3%, p = 0.008), whereas the H-BCAA group had the lowest prevalence of sarcopenia (8.5%, p < 0.001). The L-IGF-1 group showed the highest prevalence of sarcopenia (46.9%, p < 0.001), whereas the H-IGF-1 group had the lowest prevalence of sarcopenia (10.0%, p < 0.001) and slow gait speed (18.0%, p = 0.003). Using the optimal BCAA and IGF-1 cutoff values for predicting sarcopenia (372 µmol/L and 48.5 ng/mL, respectively), the sensitivity and specificity were 0.709 and 0.759 for BCAA and 0.636 and 0.715 for IGF-1, respectively. Low serum BCAA and IGF-1 levels were associated with sarcopenia and slow gait speed in patients with LC.

Relationship between Osteosarcopenia and Frailty in Patients with Chronic Liver Disease.

Osteosarcopenia and frailty have a negative health impact on an aging society. This cross-sectional study aimed to investigate the clinical characteristics and relationship of osteosarcopenia and frailty in 291 patients with chronic liver disease (CLD), who comprised 137 males and 154 females, with a median age of 70.0 years. Sarcopenia was diagnosed according to the Japan Society of Hepatology criteria. Bone mineral density was measured using dual-energy X-ray absorptiometry. Frailty was defined by five parameters (exhaustion, slowness, weakness, low physical activity, and weight loss). Among the 291 patients, 49 (16.8%) and 81 (27.8%) had osteosarcopenia and frailty, respectively. Frailty and vertebral fracture were more frequently noted in patients with osteosarcopenia than in those without osteosarcopenia (79.6% vs. 17.4% and 59.2% vs. 20.2%, respectively; p < 0.001 for both). Meanwhile, osteosarcopenia and vertebral fracture were more frequently observed in patients with frailty than in those without frailty (48.1% vs. 4.8% and 49.4% vs. 18.1%, respectively; p < 0.001 for both). On multivariate analysis, frailty was an independent factor associated with osteosarcopenia (odds ratio (OR), 9.837; p < 0.001), and vice versa (OR, 10.069; p < 0.001). Osteosarcopenia and frailty were prevalent, closely interrelated, and increased the risk of vertebral fracture in patients with CLD.

Comparative assessment of sarcopenia using the JSH, AWGS, and EWGSOP2 criteria and the relationship between sarcopenia, osteoporosis, and osteosarcopenia in patients with liver cirrhosis.

BACKGROUND: Sarcopenia and osteoporosis reduce life quality and worsen prognosis in patients with liver cirrhosis (LC). When these two complications coexist, a diagnosis of osteosarcopenia is made. We aimed to investigate the actual situations of sarcopenia, osteoporosis, osteosarcopenia, and vertebral fracture, and to clarify the relationship among these events in patients with LC. METHODS: We describe a cross-sectional study of 142 patients with LC. Sarcopenia was defined according to the Japan Society of Hepatology (JSH) criteria, Asian Working Group for Sarcopenia (AWGS) criteria, and European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. The skeletal muscle mass index (SMI) and handgrip strength were assessed using bioelectrical impedance analysis and a digital grip strength dynamometer, respectively. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and vertebral fracture was evaluated using spinal lateral X-rays. The severity of LC was assessed using the Child-Pugh classification. RESULTS: Among the 142 patients, the prevalence of sarcopenia was 33.8% (48/142) according to the JSH and AWGS criteria and 28.2% (40/142) according to the EWGSOP2 criteria. The number of patients with osteoporosis, osteosarcopenia, and vertebral fracture was 49 (34.5%), 31 (21.8%), and 41 (28.9%), respectively. Multivariate analysis revealed a close association between sarcopenia and osteoporosis. Osteoporosis was independently associated with sarcopenia [odds ratio (OR) = 3.923, P = 0.010]. Conversely, sarcopenia was independently associated with osteoporosis (OR = 5.722, P < 0.001). Vertebral fracture occurred most frequently in patients with osteosarcopenia (19/31; 61.3%) and least frequently in those without both sarcopenia and osteoporosis (12/76; 15.8%). The SMI and handgrip strength values were significantly correlated with the BMD of the lumbar spine (r = 0.55 and 0.51, respectively; P < 0.001 for both), femoral neck, (r = 0.67 and 0.62, respectively; P < 0.001 for both), and total hip (r = 0.67 and 0.61, respectively; P < 0.001 for both). CONCLUSIONS: Sarcopenia, osteoporosis, osteosarcopenia, and vertebral fracture were highly prevalent and closely associated with one another in patients with LC. Specifically, patients with osteosarcopenia had the highest risk of vertebral fractures. Early diagnosis of these complications is essential for treatment intervention.

Characterisation of blood microbiota in patients with liver cirrhosis.

BACKGROUND AND AIMS: Bacterial infections arising in patients with liver cirrhosis are associated with life-threatening complications such as hepatic encephalopathy and spontaneous bacterial peritonitis in relation to bacterial translocation. To investigate the state of bacterial translocation, we surveyed the peripheral blood microbiota by 16S rRNA gene sequencing and analysed the blood microbial profiles. METHODS: Sixty-six patients with liver cirrhosis were enrolled in this study, whereas 14 healthy individuals were also analysed as controls. Total RNA was purified from the peripheral blood, and an approximately 430 base pair genomic locus which included the V3-V4 region of the 16s rRNA gene was amplified and assessed using bacterial pyrosequencing. RESULTS: At the genus level, a total of 183 operational taxonomic units were identified in cirrhotic patients, whereas 123 units in controls. Intergroup differences in gut microbiota were analysed by the linear discriminant analysis effect size, which showed that the abundance of Enterobacteriaceae was significantly higher in cirrhotics. On the contrary, the abundance of Akkermansia, Rikenellaceae and Erysipelotrichales were significantly lower in cirrhotics (relative abundance of Akkermansia in cirrhotics and controls: 0% and 0.2%, respectively; Rikenellaceae: 0.1% and 0.92%; Erysipelotrichales: 0.58% and 1.21%). CONCLUSION: The present study has demonstrated that various circulating bacteria are present in cirrhotic patients, and the diversity of such bacteria is consistent with the presence of dysbiosis in cirrhotics. Although the clinical significance of the findings remains to be clarified, the findings may potentially facilitate diagnostic and therapeutic attempts to comprehend and furthermore to manipulate bacterial infections in cirrhotic patients.

Prognostic significance of Wilms' tumor 1 expression in patients with pancreatic ductal adenocarcinoma.

The only current curative treatment for patients with pancreatic ductal adenocarcinoma (PDA) is surgical resection, and certain patients still succumb to disease shortly after complete surgical resection. Wilms' tumor 1 (WT1) serves an oncogenic role in various types of tumors; therefore, in the present study, WT1 protein expression in patients with PDA was analyzed and the association with overall survival (OS) and disease-free survival (DFS) time in patients with PDA was assessed following surgical resection. A total of 50 consecutive patients with PDA who received surgical resection between January 2005 and December 2015 at the Jikei University Kashiwa Hospital (Kashiwa, Chiba, Japan) were enrolled. WT1 protein expression in PDA tissue was measured using immunohistochemical staining. Furthermore, laboratory parameters were measured within 2 weeks of surgery, and systemic inflammatory response markers were evaluated. WT1 protein expression was detected in the nucleus and cytoplasm of all PDA cells and in tumor vessels. WT1 exhibited weak staining in the nuclei of all PDA cells; however, the cytoplasmic expression of WT1 levels was classified into four groups: Negative (n=0), weak (n=19), moderate (n=23) and strong (n=8). In patients with PDA, it was demonstrated that the OS and DFS times of patients with weak cytoplasmic WT1 expression were significantly prolonged compared with those of patients with moderate-to-strong cytoplasmic WT1 expression, as determined by log-rank test (P=0.0005 and P=0.0001, respectively). Furthermore, an association between the density of WT1-expressing tumor vessels and worse OS/DFS times was detected. Multivariate analysis also indicated a significant association between the overexpression of WT1 in PDA tissue and worse OS/DFS times. To the best of our knowledge, the present study is the first to demonstrate that moderate-to-strong overexpression of WT1 in the cytoplasm of PDA cells is significantly associated with worse OS/DFS times. Therefore, overexpression of WT1 in the cytoplasm of PDA cells may impact the recurrence and prognosis of patients with PDA following surgical resection. The results further support the development of WT1-targeted therapies to prolong survival in all patients with PDA.

Prognostic impact of carbohydrate sulfotransferase 15 in patients with pancreatic ductal adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDA) typically succumb to mortality early, even following surgical resection. Therefore, prognostic factors associated with early mortality are required to improve the survival of patients with PDA following surgical resection. Carbohydrate sulfotransferase 15 (CHST15) is responsible for the biosynthesis of sulfated chondroitin sulfate E (CS-E), which serves a pivotal function in cancer progression by cleaving CD44. CHST15 and CD44 expression in PDA tissue were assessed as a prognostic factor in patients with PDA following surgical resection. A total of 36 consecutive patients with PDA were enrolled following surgical resection between January 2008 and December 2014. The intensities of CHST15 and CD44 expression were analyzed by immunohistochemical staining. The recurrence period was significantly earlier in the strong CHST15 expression group compared with the negative-to-moderate CHST15 expression group. Overall survival (OS) was also significantly decreased in the strong CHST15 expression group compared with the negative-to-moderate CHST15 expression group. Multivariate analysis also indicated significant associations between CHST15 overexpression and disease-free survival (DFS) and OS. However, expression of CD44 in PDA tissue was not associated with DFS or OS. The present study has demonstrated for the first time that high CHST15 expression in PDA tissue may represent a potential predictive marker of DFS and OS in patients with PDA following surgical resection.

Hepatic Angiosarcoma Associated with Esophageal Variceal Hemorrhage.

Primary hepatic angiosarcoma is a very rare malignancy with a poor prognosis. Because patients present with no specific symptoms, the cancer can grow undetected and most cases are diagnosed too late for resection. We present the case of a 78-year-old Japanese man admitted to our hospital with massive hematemesis and melena. A total gastrectomy had previously been performed on the patient to treat gastric cancer. Endoscopic injection sclerotherapy was performed to control the bleeding from varices over the anastomosis. Computed tomography revealed the presence of multiple atypical liver nodules in the enhanced image. Histological diagnosis of hepatic angiosarcoma was obtained by percutaneous ultrasound-guided liver biopsy. To our knowledge, this is the first report of a patient with hepatic angiosarcoma and acute variceal hemorrhage.

Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer.

The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients.