Publications by authors named "Soichiro Kiyono"

42 Publications

Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma.

J Cancer 2021 5;12(9):2694-2701. Epub 2021 Mar 5.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Hepatocellular carcinoma (HCC) is typically accompanied by abundant arterial blood flow. Although angiogenic growth factors such as Angiopoietin 2 (Ang2) play a central role in tumor angiogenesis in HCC, the role of serum Ang2 as a biomarker in HCC remains unclear. In this study, we aimed to investigate the potential of Ang2 as a diagnostic and prognostic biomarker in HCC using a sandwich enzyme-linked immunosorbent assay (ELISA). The median Ang2 levels in controls (n=20), chronic liver disease patients (n=98), and HCC patients (n=275) were 1.58, 2.33, and 3.53 ng/mL, respectively. The optimal cut-off value of Ang2 was determined as 3.5 ng/mL by receiver operating curve analysis. The sensitivity, specificity, and accuracy of Ang2 for HCC detection were 50.9, 83.7, and 59.5%, respectively. Spearman's rank correlation coefficient analysis demonstrated only a weak correlation between Ang2 serum levels and alpha-fetoprotein (AFP) or des-gamma-carboxy prothrombin (DCP) serum levels. The diagnostic value of Ang2 was comparable to those of other existing markers. In addition, 24 out of 73 patients with normal AFP and DCP levels (32.9%) demonstrated abnormally high Ang2 levels (≥3.5 ng/mL). Although no significant difference in overall survival was found between Ang2 and Ang2 patients with curative ablation therapy, recurrence-free survival (RFS) in Ang2 patients was observed to be significantly shorter than those in Ang2 patients. Multivariate analysis demonstrated that high serum Ang2 levels (≥3.5 ng/mL) and the presence of multiple tumors were poor prognostic factors. In conclusion, our findings indicate that serum Ang2 is a potential novel biomarker for both diagnosis and prognosis in HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.56436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040723PMC
March 2021

Percutaneous Two-Dimensional Shear Wave Elastography for Diagnosis of Pancreatic Tumor.

Diagnostics (Basel) 2021 Mar 11;11(3). Epub 2021 Mar 11.

Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1 Inohan, Chuo-ku Chiba City 260-8670, Japan.

Background: To investigate the efficacy of two-dimensional shear wave elastography (2D-SWE) for the diagnosis of pancreatic mass lesions.

Methods: This ethics committee-approved cross-sectional study included 52 patients with histologically-proven pancreatic tumors (pancreatic ductal adenocarcinoma (PDAC), 36; tumor-forming pancreatitis (TFP), 15; neuroendocrine tumor, 1) and 33 control subjects. The 2D-SWE was performed for the tumor/non-tumor tissues, and SWE-mapping patterns and propagation quality were assessed.

Results: Three mapping patterns were detected based on the size and distribution of the coloring areas. Pattern A (whole coloring) was detected in all non-tumor tissues and TFP, whereas pattern C (multiple small coloring spots) was detected in PDAC only. Pattern B (partial coloring with smaller spots) was detected in other lesions. The specificity and positive predictive value of pattern A for non-PDAC and those of pattern C for PDAC were 100%. The SWE value was higher in tumor lesions than in the non-tumor tissues (38.1 vs. 9.8 kPa; < 0.001) in patients with PDAC. The SWE value in the non-tumor lesion was higher in patients with PDAC than in control (9.8 vs. 7.5 kPa; < 0.001).

Conclusions: 2D-SWE may play a role as a novel diagnostic tool for PDAC to detect a specific mapping pattern with quantitative assessment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11030498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001884PMC
March 2021

The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma.

Sci Rep 2021 Mar 5;11(1):5303. Epub 2021 Mar 5.

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.

FGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19 (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19 (n = 105) patients, there were no significant differences between FGF19 (n = 21) and FGF19 (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-84117-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935880PMC
March 2021

Propofol midazolam for sedation during radiofrequency ablation in patients with hepatocellular carcinoma.

JGH Open 2021 Feb 22;5(2):273-279. Epub 2020 Dec 22.

Departmetn of Anesthesiology, Graduate School of Medicine Chiba University Chiba Japan.

Background And Aim: Standardization of the sedation protocol during radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) is needed. This randomized, single-blind, investigator-initiated trial compared clinical outcomes during and after RFA using propofol and midazolam, respectively, in patients with HCC.

Methods: Few- and small-nodule HCC patients (≤3 nodules and ≤3 cm) were randomly assigned to either propofol or midazolam. Patient satisfaction was assessed using a 100-mm visual analog scale (VAS) (1 mm = not at all satisfied, 100 mm = completely satisfied). Sedation recovery rates 1, 2, 3, and 4 h after RFA were evaluated based on Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores; full recovery was defined as a MOAA/S score of 5.

Results: Between July 2013 and September 2017, 143 patients with HCC were enrolled, and 135 patients were randomly assigned to the treatment group. Compared with midazolam, propofol exhibited similar median procedural satisfaction (propofol: 73.1 mm, midazolam: 76.9 mm, = 0.574). Recovery rates 1 and 2 h after RFA were higher in the propofol group than in the midazolam group. Meanwhile, recovery rates observed 3 and 4 h after RFA were similar in the two groups. The safety profiles during and after RFA were almost identical in the two groups.

Conclusion: Patient satisfaction was almost identical in patients receiving propofol and midazolam sedation during RFA. Propofol sedation resulted in reduced recovery time compared with midazolam sedation in patients with HCC. The safety profiles of both propofol and midazolam sedation during and after RFA were acceptable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgh3.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857294PMC
February 2021

Analyses of Intermediate-Stage Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization prior to Designing Clinical Trials.

Liver Cancer 2020 Sep 22;9(5):596-612. Epub 2020 Jul 22.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden.

Aims: The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs.

Methods: We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC.

Results: Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC.

Conclusions: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000508809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548915PMC
September 2020

Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma.

Liver Cancer 2020 Aug 5;9(4):382-396. Epub 2020 May 5.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: The present study aimed to assess the efficacy and safety of lenvatinib and verify the possibility of lenvatinib for the expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma (HCC) in real-world practice, primarily focusing on the population that was excluded in the REFLECT trial.

Methods: We retrospectively collected data on patients with advanced HCC who were administered lenvatinib in 7 institutions in Japan.

Results: Of 152 advanced HCC patients, 95 and 57 patients received lenvatinib in first-line and second- or later-line systemic therapies, respectively. The median progression-free survival in Child-Pugh class A patients was nearly equal between first- and second- or later-line therapies (5.2 months; 95% CI 3.7-6.9 for first line, 4.8 months; 95% CI 3.8-5.9 for second or later line, = 0.933). According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate of 27 patients (18%) who showed a high burden of intrahepatic lesions (i.e., main portal vein and/or bile duct invasion or 50% or higher liver occupation) at baseline radiological assessment was 41% and similar with that of other population. The present study included 20 patients (13%) with Child-Pugh class B. These patients observed high frequency rates of liver function-related adverse events due to lenvatinib. The 8-week dose intensity of lenvatinib had a strong correlation with liver function according to both the Child-Pugh and albumin - bilirubin scores.

Conclusion: Lenvatinib had potential benefits for patients with advanced HCC with second- or later-line therapies and a high burden of intrahepatic lesions. Dose modification should be paid increased attention among patients with poor liver function, such as Child-Pugh class B patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000507022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506220PMC
August 2020

Long-term administration of Tolvaptan to patients with decompensated cirrhosis.

Int J Med Sci 2020 15;17(7):874-880. Epub 2020 Mar 15.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

: Tolvaptan, an oral vasopressin-2 antagonist, sometimes improves hepatic edema including ascites in patients with decompensated cirrhosis. In this study, we examined the effectiveness and survival advantage in patients with the long-term administration of tolvaptan. : A total of 115 patients with refractory ascites who were treated with tolvaptan were retrospectively analyzed based on their clinical records. Patients with a decrease in body weight of ≥1.5 kg from the baseline on day 7 were determined as responders. Re-exacerbation was defined as a return to the baseline BW, dose escalation of conventional diuretics, or abdominal drainage. : Of the 115 patients, 84 were included in this analysis. Response to tolvaptan treatment was observed in 55 out of the 84 patients (65.5%), with a mean weight reduction of 2.52 kg. Multivariate analyses demonstrated that body mass index (≥24) and urinary specific gravity (≥1.018) were significant predictors of the response to tolvaptan. However, cumulative re-exacerbation rates in responders at 6 and 12 months were 42.4 and 60.1%, respectively. Child-Pugh (classification C), HCC complication, and serum sodium levels (≥133 mEq/L) were determined as independent prognostic factors impacting overall survival (OS). Although there were no significant differences in OS between tolvaptan responders and non-responders, the responders without re-exacerbation within 3 months showed significantly longer OS than those with re-exacerbation within 3 months. : A persistent therapeutic response, but not early response to tolvaptan, was associated with favorable survival of decompensated cirrhotic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.41454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163362PMC
February 2021

Free fatty acid-based low-impedance liver image: a characteristic appearance in nonalcoholic steatohepatitis (NASH).

Eur Radiol Exp 2020 01 23;4(1). Epub 2020 Jan 23.

Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: To examine in vitro acoustic property of nonalcoholic fatty disease in mouse and human liver to identify nonalcoholic steatohepatitis (NASH).

Methods: The acoustic impedance (× 10 kg/m/s) was measured in 35 free fatty acids (FFAs, 500 mmol/L) and histologically-diagnosed liver samples of twelve mice (four control, four simple steatosis [SS], and four NASH) and eight humans (two control, three SS, and three NASH), using 80-MHz acoustic microscopy. The sum of percentage (SP) composition of FFAs (SP-FFAs) was also assessed.

Results: Median impedance of all FFAs was 0.7 (5 FFAs with impedance 0.7); 17 FFAs with impedance < 0.7 were classified as low-impedance group; and, 13 FFAs with impedance > 0.7 were classified as high-impedance group. The median impedance of the mouse liver decreased from control (1.715), to SS (1.68), to NASH (1.635) (control versus NASH, p = 0.039 without significant differences for the other comparisons, p ≥ 0.1). Similarly, the median impedance of human liver showed decreased from control (1.825), to SS (1.788), to NASH (1.76) (control versus SS, p = 0.023; control versus NASH, p = 0.003; SS versus NASH, p = 0.050). The ratio of SP-FFAs between the low-impedance and high-impedance groups showed an increase in both mice and humans, with significant differences in mice (control versus SS, p < 0.001; control versus NASH, p < 0.001; SS versus NASH, p = 0.003), without significant differences in humans (p ≥ 0.671).

Conclusion: Lower acoustic impedance based on the intrahepatic composition of FFAs may be characteristic of NASH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s41747-019-0137-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977798PMC
January 2020

Switching to systemic therapy after locoregional treatment failure: Definition and best timing.

Clin Mol Hepatol 2020 04 15;26(2):155-162. Epub 2020 Jan 15.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

In patients with unresectable hepatocellular carcinoma (HCC) without both macrovascular invasion and extrahepatic metastasis, the initial treatment choice recommended is transarterial chemoembolization (TACE). Before sorafenib came into wide use, TACE had been pointlessly carried out repeatedly. It was in the early 2010s that the concept of TACE refractory was advocated. Two retrospective studies from Japan indicated that conversion from TACE to sorafenib the day after patients were deemed as TACE refractory improved overall survival compared with continued TACE, according to the definition by the Japan Society of Hepatology. Nowadays, phase 3 trials have shown clinical benefits of several novel molecular target agents. Compared with the era of sorafenib, sequential treatments with these molecular target agents have gradually prolonged patients' survival and have become major strategies in patients with HCC. Taking these together, conversion from TACE to systemic therapies at the time of TACE refractory, compared with before, may have a greater impact on survival and may be considered deeper in the decisions-making process in patients with unresectable HCC who are candidate for TACE. Up-to-date information on the concept of TACE refractory is summarized in this review. We believe that the survival of patients with unresectable HCC without both macrovascular invasion and extrahepatic metastasis may be dramatically improved by optimal timing of TACE refractory and switching to systemic therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3350/cmh.2019.0021nDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160341PMC
April 2020

Incidence and hemodynamic feature of risky esophageal varices with lower hepatic venous pressure gradient.

Int J Med Sci 2019 9;16(12):1614-1620. Epub 2019 Nov 9.

Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

To examine the incidence of cirrhosis patients with high-risk esophageal varices (EV) who show hepatic venous pressure gradient (HVPG) < 10 mmHg and to identify their hemodynamic features. This prospective study consisted of 110 cirrhosis patients with EV, all with the candidate for primary or secondary prophylaxis. Sixty-one patients had red sign, and 49 patients were bleeders. All patients underwent both Doppler ultrasound and HVPG measurement. There were 18 patients (16.4%) with HVPG < 10 mmHg. The presence of venous-venous communication (VVC) was more frequent in patients with HVPG < 10 mmHg (10/18) than in those with HVPG ≥ 10 mmHg (19/92; p = 0.0021). The flow volume in the left gastric vein (LGV) and the incidence of red sign were higher in the former (251.9 ± 150.6 mL/min; 16/18) than in the latter (181 ± 100.5 mL/min, p = 0.02; 45/92; p = 0.0018). The patients with red sign had lower HVPG (13.3 ± 4.5) but advanced LGV hemodynamics (velocity 13.2 ± 3.8 cm/s; flow volume 217.5 ± 126.6 mL/min), whereas those without red sign had higher HVPG (16.2 ± 4.6, p = 0.001) but poorer LGV hemodynamics (10.9 ± 2.3, p = 0.002; 160.1 ± 83.1, p = 0.02). Patients with high-risk EV with HVPG < 10 mmHg showed 16.4% incidence. Although low HVPG may be underestimated by the presence of VVC, the increased LGV hemodynamics compensates for the severity of portal hypertension, which may contribute to the development of red sign.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.37040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909812PMC
April 2020

Serum fibroblast growth factor 19 serves as a potential novel biomarker for hepatocellular carcinoma.

BMC Cancer 2019 Nov 12;19(1):1088. Epub 2019 Nov 12.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background: Abnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the potential of serum FGF19 as a novel tumor marker of HCC based on a sandwich enzyme-linked immunosorbent assay (ELISA).

Methods: The serum FGF19 levels of 304 patients with HCC was measured by ELISA. The serum levels of existing markers, including alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were determined by chemiluminescence enzyme immunoassay. Both diagnostic value of FGF19 and its changes after curative ablation therapy was further examined.

Results: The median FGF19 levels in controls, chronic liver disease patients, and primary HCC patients, were 78.8 pg/mL, 100.1 pg/mL, and 214.5 pg/mL, respectively. The subsequent receiver operating characteristic curves (ROC) successfully determined an optimal cut-off value of 200.0 pg/mL. The area under the ROC curve (AUC) of FGF19 for HCC detection was comparable to those of AFP and DCP. Of importance, FGF19 showed higher sensitivity for the detection of small HCC (solitary cancer with diameter < 20 mm) than those of existing markers. In addition, 43 out of 79 cases (54.4%) with normal AFP and DCP (so-called "double negative HCC") exhibited serum FGF19 level ≥ 200 pg/mL. In 45 HCC patients treated with curative ablation therapy, serum FGF19 levels changed from 257.4 pg/mL to 112.0 pg/mL after the treatment.

Conclusion: Our findings reveal that FGF19 can be a potential novel biomarker for HCC. Although FGF19 is not necessarily a substitute for existing markers, it may help improve the prognosis in HCC patients owing to its resourceful use in various aspects of HCC management and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-019-6322-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849282PMC
November 2019

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Invest New Drugs 2020 02 6;38(1):172-180. Epub 2019 Jun 6.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-019-00801-8DOI Listing
February 2020

Long-Term Prognosis of Patients with Obscure Gastrointestinal Bleeding: A Retrospective Cohort Study.

Digestion 2019 11;100(1):37-44. Epub 2019 Jan 11.

Department of Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Aims: We evaluated the long-term prognosis of patients with obscure gastrointestinal bleeding (OGIB) who underwent capsule endoscopy (CE).

Methods: In our hospital, 429 patients underwent CE between November 2007 and March 2012. Among them, 259 patients underwent CE as the first examination for OGIB and were then followed at 77 clinics and hospitals. The clinical characteristics were investigated, including age, gender, overt/occult bleeding, the use of antithrombotic drugs and NSAIDs, complications (liver cirrhosis and hemodialysis), and CE. We asked the medical institutions for their survival data as of August 2017 (> 5 years after CE).

Results: The prognoses of 240 patients (92.6%) were analyzed. The average follow-up period was 55.7 (1-115) months. During the follow-up period, 57 patients (23.8%) died and the survival rates were 90.5% at 1 year, 81.7% at 3 years, and 74.7% at 5 years. Age 65 years or older and liver cirrhosis were predictive factors for a poor prognosis. Rebleeding occurred in 42 patients (17.9%) and small bowel cancer and gastrointestinal stromal tumor were found at 12 and 21 months after CE, respectively.

Conclusions: Patients with OGIB showed a poor prognosis, especially those who were elderly or who had liver cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000493854DOI Listing
December 2019

Left gastric vein-based noninvasive test for esophageal varices: a same-day comparison of portal hemodynamic assessment with endoscopic appearance.

Clin Transl Gastroenterol 2018 05 25;9(5):154. Epub 2018 May 25.

Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuo-ku, 260-8670, Japan.

Objective: To examine the effect of hemodynamic assessment of the left gastric vein (LGV) as a noninvasive test to diagnose esophageal varices (EV) in cirrhosis patients.

Methods: This cross-sectional study consisted of 229 cirrhosis patients (62.7 ± 11.8 years; Child-Pugh score 5-14). One hundred fifty-four patients had EV (67.2%; small, 53; medium, 71; large, 30). All patients underwent a blood test and Doppler ultrasound followed by upper gastrointestinal endoscopy on the same day. The diagnostic ability for EV was compared between LGV-related findings and the platelet count/spleen diameter ratio (Plt/Spl).

Results: The detectability of the LGV was higher in patients with EV (129/144, 89.6%) than in those without (35/75, 46.7%; p < 0.0001), and was higher in those with large EV (30/30, 100%) than in those without (134/199, 67.3%; p = 0.0002). The positive detection of the LGV showed 100% sensitivity and negative predictive value (NPV) to identify large EV in the whole cohort and compensated group (n = 127). The best cutoff value in the LGV diameter was 5.35 mm to identify large EV, showing 0.753 area under the receiver operating characteristic curve (AUROC) with 90% sensitivity and 96.5% NPV. The Plt/Spl showed 62.1% sensitivity and 87.1% NPV, and the best cutoff value was 442.9 to identify large EV with 0.658 AUROC, which was comparable to LGV-based assessment (p = 0.162).

Conclusions: This same-day comparison study demonstrated the value of LGV-based noninvasive test to identify large EV with high sensitivity and NPV in cirrhosis patients at a lower cost.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41424-018-0021-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968022PMC
May 2018

Successful retreatment with grazoprevir and elbasvir for patients infected with hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A inhibitor-including regimens due to adverse events.

Oncotarget 2018 Mar 23;9(22):16263-16270. Epub 2018 Mar 23.

Department of Gastroenterology, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.

Background: Sustained virologic response (SVR) by interferon and interferon-free treatment can results in the reduction of advanced liver fibrosis and the occurrence of hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). Recent interferon-free treatment for HCV shortens the duration of treatment and leads to higher SVR rates, without any serious adverse events. However, it is important to retreat patients who have had treatment-failure with HCV non-structural protein 5A (NS5A) inhibitor-including regimens. Combination of sofosbuvir and ledipasvir only leads to approximately 100% SVR rates in HCV genotype (GT1b), NS5A inhibitor-naïve patients in Japan. This combination is not an indication for severe renal disease or heart disease, and these patients should be treated or retreated with a different regimen.

Case Summary: Retreatment with HCV non-structural protein 3/4A inhibitor, grazoprevir, and HCV NS5A inhibitor, elbasvir, successfully eradicated HCV RNA in three patients with HCV genotype 1b infection who discontinued prior interferon-free treatments including HCV NS5A inhibitors due to adverse events within 2 weeks.

Conclusion: Retreatment with the 12-week combination regimen of grazoprevir and elbasvir is effective for HCV GT1b patients who discontinue the HCV NS5A inhibitor-including regimens within 2 weeks. The treatment response may be related to the short duration of initial treatment, which did not produce treatment-emergent RASs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.24620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882333PMC
March 2018

Interferon-free treatment for patients with chronic hepatitis C and autoimmune liver disease: higher SVR rates with special precautions for deterioration of autoimmune hepatitis.

Oncotarget 2018 Feb 3;9(14):11631-11637. Epub 2018 Feb 3.

Department of Gastroenterology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan.

Background: Interferon-free treatment can achieve higher sustained virological response (SVR) rates, even in patients in whom hepatitis C virus (HCV) could not be eradicated in the interferon treatment era. Immune restoration in the liver is occasionally associated with HCV infection. We examined the safety and effects of interferon-free regimens on HCV patients with autoimmune liver diseases.

Results: All 7 HCV patients with autoimmune hepatitis (AIH) completed treatment and achieved SVR. Three patients took prednisolone (PSL) at baseline, and 3 did not take PSL during interferon-free treatment. In one HCV patient with AIH and cirrhosis, PSL were not administered at baseline, but she needed to take 40 mg/day PSL at week 8 for liver dysfunction. She also complained back pain and was diagnosed with vasospastic angina by coronary angiography at week 11. However, she completed interferon-free treatment. All 5 HCV patients with primary biliary cholangitis (PBC) completed treatment and achieved SVR. Three of these HCV patients with PBC were treated with UDCA during interferon-free treatment.

Conclusions: Interferon-free regimens could result in higher SVR rates in HCV patients with autoimmune liver diseases. As interferon-free treatment for HCV may have an effect on hepatic immunity and activity of the autoimmune liver diseases, careful attention should be paid to unexpected adverse events in their treatments.

Methods: Total 12 patients with HCV and autoimmune liver diseases [7 AIH and PBC], who were treated with interferon-free regimens, were retrospectively analyzed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.24391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837765PMC
February 2018

Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment.

Invest New Drugs 2018 04 11;36(2):332-339. Epub 2017 Sep 11.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child-Pugh A and ECOG-PS ≤1 at the time of sorafenib failure. We also defined regorafenib candidate patients as follows: 1) continuing sorafenib at the time of radiological progression, 2) maintaining Child-Pugh A and ECOG-PS ≤ 1 at the time of sorafenib failure, and 3) continuing sorafenib 400 mg or more without intolerable adverse events at least 20 days of the last 28 days of treatment. Results Of 185 patients, 130 (70%) and 69 (37%) were candidates for second-line treatment and regorafenib. Child-Pugh score 6 and ECOG-PS 1 at the time of starting sorafenib were significantly lower in both second-line treatment and regorafenib candidate patients. Moreover, hand-foot skin reaction and liver failure during sorafenib treatment were associated with significantly low and high probabilities, respectively, of both Child-Pugh score > 6 and ECOG-PS > 1 at the time of sorafenib failure. Conclusion Regorafenib candidate patients after sorafenib failure are limited, and generally fewer than those who are candidates for second-line treatment. A lower Child-Pugh score and a better ECOG-PS were predictors of eligibility for second-line therapy and regorafenib treatment in sorafenib-treated patients with advanced HCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-017-0507-3DOI Listing
April 2018

Compensating effect of minor portal hypertension on the muscle mass loss-related poor prognosis in cirrhosis.

Int J Med Sci 2017 19;14(9):804-810. Epub 2017 Jul 19.

Department of Research Center for Frontier Medical Engineering, Chiba University, 1-33, Yayoicho, Inage-ku, Chiba, 263-8522, Japan.

To examine the influence of the severity of portal hemodynamic abnormality on the prognosis of cirrhosis with respect to the muscle mass loss (MML). The study involved a subgroup analysis in 98 cirrhosis patients (63.5 ± 11.8 years) who prospectively underwent both Doppler ultrasound and hepatic venous catheterization. The prognostic influence of MML diagnosed by computed tomography using the L3 skeletal muscle index was evaluated (median observation period, 32.7 months). The cumulative survival rate showed difference between patients with MML (n = 34; 82.2%/1year, 41.2%/3years and 36.1%/5years) and those without (n = 64; 92.1%/1year, 74.9%/3years and 69.4%/5years; P = 0.005). When divided with respect to the portal velocity, the survival rate showed differences between patients with and without MML in the cohort < 12.8 cm/s (n=52, p=0.009) and ≥ 12.8 cm/s (n=44, p=0.041). The survival rate also showed differences between patients with MML (n = 24; 78.8%/1year, 40.6%/3years and 34.8%/5years) and those without (n = 45; 91.1%/1year, 71.3%/3years and 63.1%/5years; P = 0.008) in the cohort with hepatic venous pressure gradient (HVPG) > 12 mmHg. However, in the cohort with HVPG ≤ 12 mmHg, survival rate showed no difference between patients with MML (n=10; 100%/1year, 61.9%/3years and 61.9%/5years) and those without (n=19; 93.8%/1year, 71.2%/3years and 59.4%/5years; p = 0.493) Lower HVPG has a compensating effect on the MML-induced poor prognosis of cirrhosis. Care should be taken in the evaluation of the influence of MML in consideration of the severity of portal hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.19847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562187PMC
May 2018

Application of transcutaneous ultrasonography for the diagnosis of muscle mass loss in patients with liver cirrhosis.

J Gastroenterol 2018 May 18;53(5):652-659. Epub 2017 Aug 18.

Center for Frontier Medical Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan.

Background: To propose an ultrasound-based parameter for the diagnosis of muscle mass loss (MML) in cirrhosis.

Methods: This is an IRB-approved cross-sectional study (October 2013 to January 2017) with written informed consent including 357 subjects-234 cirrhosis and 123 controls. MML was diagnosed using the skeletal muscle index at the L3 level (L3-SMI) on computed tomography (CT). Transcutaneous ultrasound was used to demonstrate a cross section of the right iliopsoas muscle, and the iliopsoas muscle index (IP index) was defined by the iliopsoas muscle area/height (mm/m). Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic ability of IP index for MML.

Results: The iliopsoas muscle was detected in all subjects. The IP index was lower in cirrhosis than in controls: males (211.2 ± 73.8 vs. 295.5 ± 139.4, P < 0.0001) and females (200.2 ± 72.5 vs. 284.4 ± 112.4, P < 0.0001). L3-SMI and IP index showed correlations in males (r = 0.699, P < 0.0001) and in females (r = 0.707, P < 0.0001). Independent factors for MML by multivariate analysis were body mass index and IP index in both males and females. Sensitivity, specificity, and area under the ROC curve by IP index to detect MML were 79.5%, 73.1%, and 0.835, respectively, with the best cut-off value of 189.2 for males, and 84.6%, 78.8%, and 0.874, respectively, with the best cut-off value of 180.6 for females.

Conclusions: Using transcutaneous ultrasound, the IP index may be a valuable diagnostic parameter for MML in cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00535-017-1378-2DOI Listing
May 2018

Histology-Based Assessment of Sonazoid-Enhanced Ultrasonography for the Diagnosis of Liver Metastasis.

Ultrasound Med Biol 2017 10 26;43(10):2151-2158. Epub 2017 Jul 26.

Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan.

This retrospective study aimed to assess the diagnostic performance of contrast-enhanced ultrasound with Sonazoid (S-CEUS) for liver metastasis. We enrolled in this study 98 patients with 148 histologically proven liver lesions, with 121 metastases and 27 non-metastases. The S-CEUS technique showed sensitivity in 95.0% (115 of 121), specificity in 44.4% (12 of 27) and accuracy in 85.8% (127 of 148) for the diagnosis of metastasis. Higher body mass index had a negative influence on the positive predictive value and accuracy, and a greater depth of the lesion had a negative influence on the accuracy. The management was changed in 8 patients (8.2%) because of S-CEUS findings. In conclusion, the addition of S-CEUS may offer a great benefit by improvement of the quality of diagnosis and management for patients with cancer who have a tentative diagnosis of liver metastasis by contrast-enhanced computed tomography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ultrasmedbio.2017.06.014DOI Listing
October 2017

Interrelationship between insulin resistance and portal haemodynamic abnormality in cirrhosis.

Int J Med Sci 2017 23;14(3):240-245. Epub 2017 Feb 23.

Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan.

There are only limited data regarding the effect of impaired portal circulation on the glucose metabolism. The study prospectively examined the interrelationship between insulin resistance (IR) and portal haemodynamic abnormality in cirrhosis. There were 53 cirrhosis patients (61.6 ± 13.0 years) all presenting gastroesophageal varices. Portal haemodynamics by both hepatic venous catheterisation and Doppler ultrasound were examined with respect to the homeostasis model assessment (HOMA)-IR and HOMA2-IR. The IR was defined by HOMA-IR > 3.0 or HOMA2-IR > 2.0. Forty-two patients (79.2%) had collateral vessels, 38 with left gastric vein, 12 with short/posterior gastric vein, 9 with splenorenal shunt, and 3 with inferior mesenteric vein. Multivariate analysis provided significant factors; wedged hepatic venous pressure (HR1.183, 95% CI 1.012-1.383, p=0.035) for HOMA-IR > 3.0, body mass index for HOMA2-IR > 2.0 (HR1.490, 95% CI 1.176-1.888, p=0.001), and collateral flow volume for both HOMA-IR > 3.0 (HR1.007, 95% CI 1.001-1.014, p=0.015) and HOMA2-IR > 2.0 (HR 1.007, 95% CI 1.002-1.013, p=0.009). The best cut-off value of collateral flow volume was 165 ml/min for detecting the HOMA-IR > 3.0 showing area under the receiver operating characteristic curve (AUROC) 0.688 (Odds ratio, 5.33) with sensitivity 70% and specificity 69.6%, and was 165 ml/min for detecting median value of HOMA2-IR > 2.0 showing AUROC 0.698 (odds ratio, 5.7) with sensitivity 75% and specificity 65.5%. There is a close linkage between the IR and impaired portal haemodynamics presented by the collateral development, suggesting the underlying pathogenesis of portal hypertension in cirrhosis patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.17738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370286PMC
July 2017

Endoscopic recovery of multiple migrated plastic stents during EUS-guided transmural drainage of pancreatic fluid collections.

Gastrointest Endosc 2017 04 21;85(4):860-861. Epub 2017 Feb 21.

Department of Gastroenterology, Mastudo City Hospital, Chiba, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2017.02.011DOI Listing
April 2017

Erratum to: Hemodynamic effect of the left gastric artery on esophageal varices in patients with cirrhosis.

J Gastroenterol 2016 12;51(12):1175

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00535-016-1248-3DOI Listing
December 2016

Two-dimensional shear wave elastography with propagation-based reliability assessment for grading hepatic fibrosis and portal hypertension.

J Hepatobiliary Pancreat Sci 2016 Sep 24;23(9):595-602. Epub 2016 Aug 24.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background: The aim of the present study was to examine the diagnostic ability of two-dimensional shear wave elastography (2D-SWE) with propagation-based reliability for grading of hepatic fibrosis and portal hypertension.

Methods: This prospective study (UMIN000022838) consisted of 135 subjects. Phase I (n = 40) examined the effect of standard deviation (SD)/median as the reliability criterion of 2D-SWE, and phase II (n = 95) compared the diagnostic ability of 2D-SWE under the best SD/median value and transient elastography (TE).

Results: Phase I reported 0.49 as a best cut-off SD/median value. In phase II, the elasticity showed a correlation between the 2D-SWE and TE (r = 0.88, P < 0.001). The area under the receiver operating characteristic curve (AUROC) was comparable between the 2D-SWE and TE (0.936 and 0.948 for chronic hepatitis, P = 0.34; 0.939 and 0.956 for cirrhosis, P = 0.25). The hepatic venous pressure gradient showed a positive correlation with the 2D-SWE (r = 0.435, P = 0.043) and TE (r = 0.378, P = 0.083) in 22 patients. The AUROC was comparable between the 2D-SWE (0.844 for ≥10 mmHg, 0.838 for ≥12 mmHg) and TE (0.781 for ≥10 mmHg, P = 0.484; 0.800 for ≥12 mmHg, P = 0.589).

Conclusions: 2D-SWE is promising for the assessment of the grade of hepatic fibrosis and portal hypertension, with the SD/median value as a reliability criterion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.379DOI Listing
September 2016

Non-Invasive Diagnosis of Portal Hypertensive Gastropathy: Quantitative Analysis of Microbubble-Induced Stomach Wall Enhancement.

Ultrasound Med Biol 2016 08 7;42(8):1792-9. Epub 2016 May 7.

Center for Frontier Medical Engineering, Chiba University, Inage-ku, Chiba, Japan.

The aim of the study described here was to elucidate the efficacy of contrast-enhanced ultrasound (CEUS) prospectively as a tool in the diagnosis of portal hypertensive gastropathy (PHG). The peak enhancement time at the upper stomach wall (PT) and intensity ratio at the upper stomach/the spleen (IR) between pre- and peak enhancement were evaluated by CEUS with perflubutane microbubble agent in 56 patients, 42 with cirrhosis (16 with PHG) and 14 controls. The IR was higher in patients with PHG (1.21 ± 0.11) than in those without (0.91 ± 0.15, p < 0.05) and the controls (0.78 ± 0.11, p < 0.01), although PT did not differ between these groups. The area under the receiver operating characteristic curve for IR was 0.8199 in the presence of PHG, with the best cutoff value of 0.94, sensitivity 65.9%, specificity 72.6%, positive predictive value 62.2%, negative predictive value 73.1% and accuracy 70.4%. CEUS may have potential as a less invasive tool for diagnosis of PHG in patients with cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ultrasmedbio.2016.03.011DOI Listing
August 2016

Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease.

Int J Med Sci 2016 11;13(3):169-78. Epub 2016 Feb 11.

Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan.

The aim was to examine the effect of free fatty acids on the regulation of PPARγ-PGC1α pathway, and the effect of PPARγ/PGC1α in NAFLD. The mRNA and protein expression of PGC1α and phospho/total PPARγ were examined in Huh7 cells after the palmitate/oleate treatment with/without the transfection with siRNA against PGC1a. The palmitate content, mRNA and protein expression of PGC1α and PPARγ in the liver were examined in the control and NAFLD mice. Palmitate (500 μM), but not oleate, increased protein expression of PGC1α and phospho PPARγ (PGC1α, 1.42-fold, P=0.038; phospho PPARγ, 1.56-fold, P=0.022). The palmitate-induced PPARγ mRNA expression was reduced after the transfection (0.46‑fold), and the protein expressions of PGC1α (0.52-fold, P=0.019) and phospho PPARγ (0.43-fold, P=0.011) were suppressed in siRNA-transfected cells. The palmitate (12325.8 ± 1758.9 μg/g vs. 6245.6 ± 1182.7 μg/g, p=0.002), and mRNA expression of PGC1α (11.0 vs. 5.5, p=0.03) and PPARγ (4.3 vs. 2.2, p=0.0001) in the liver were higher in high-triglyceride liver mice (>15.2 mg/g) than in low-triglyceride liver mice (<15.2 mg/g). The protein expressions of both PGC1α and PPARγ were higher in the NAFLD group than in the controls (PGC1α, 1.41-fold, P=0.035; PPARγ, 1.39-fold, P=0.042), and were higher in the high-triglyceride liver group (PGC1α, 1.52-fold, p=0.03; PPARγ, 1.22-fold, p=0.05) than in the low-triglyceride liver group. In conclusion, palmitate appear to up-regulate PPARγ via PGC1α in Huh7 cells, and both PGC1α and PPARγ are up-regulated in the NAFLD mice liver, suggesting an effect on lipid metabolism leading to intrahepatic triglyceride accumulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.13581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773281PMC
December 2016

Portal response related to shunt occlusion by balloon-occluded retrograde transvenous obliteration may determine the prognosis of cirrhosis.

Hepatol Res 2016 Dec 10;46(13):1321-1329. Epub 2016 May 10.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Aim: To determine the prognostic effect of portal hemodynamic responses after balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices (GV) in cirrhosis patients.

Methods: This retrospective study consisted of 37 cirrhosis patients (aged 62.5 ± 9.7 years) with medium- or large-grade GV treated with B-RTO. Portal hemodynamic response was assessed by the changes in flow volume in the portal trunk (PFV, mL/min) before and after the treatment. Group I showed increased PFV and group II showed no increase in PFV. The median observation period was 49.8 months (range, 4.7-150.3 months).

Results: All patients showed complete embolization of GV without any recurrence. There were 30 patients in group I and 7 patients in group II (decreased PFV in 6 and unchanged PFV in 1). The PFV at baseline was significantly lower in the former (583.5 ± 232.0 mL/min) than in the latter (880.7 ± 345.9 mL/min; P = 0.009). The survival rate was significantly lower in group II (83.3% at 1 year and 66.7% at 3 years) than in group I (96.7% at 1 year, 81.5% at 3 years, and 61.8% at 5 years; P = 0.012). The incidence of deterioration of the esophageal varices was 18/30 (60%) in group I and 5/7 (71.4%; P = 0.687) in group II. Multivariate analysis identified only no increase in portal response (hazard ratio, 8.086; P = 0.005) as an independent factor for poor prognosis.

Conclusion: Balloon-occluded retrograde transvenous obliteration for GV may result in a poor prognosis when portal hemodynamics shows no increase in portal response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.12690DOI Listing
December 2016

Hemodynamic effect of the left gastric artery on esophageal varices in patients with cirrhosis.

J Gastroenterol 2016 Sep 18;51(9):900-9. Epub 2016 Jan 18.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: To examine the hemodynamic effect of the left gastric artery (LGA) on the esophageal varices (EV) in cirrhosis.

Methods: This was a prospective study performed in 48 cirrhosis patients (35 men, 13 women; median age 61.6 ± 11.3 years, range 38-83 years) with EV (medium 35, large 13), who underwent selective LGA angiography, hepatic venous catheterization, endoscopic ultrasonography (EUS) and Doppler ultrasonography before endoscopic treatment for EV. Angiographic findings including diameter of the main trunk, detection time of EV, and mild/severe degree of peripheral staining were assessed. The median period of post-treatment observation was 17.1 months.

Results: LGA angiograms were successfully obtained in 45/48 patients. EV were demonstrated in 45/45 patients, with a mean detection time of 6.9 s (2-21), which was longer in patients with variceal recurrence (7.0 s) than in those without (5.6 s, P = 0.480). The staining was mild in 25 patients (55.6 %) and severe in 20 patients (44.4 %), and portal hypertensive gastropathy was more frequent in the latter (13/20, 65.0 %) than in the former (7/25, 28.0 %, P = 0.013). Multivariate analysis showed that pre-treatment detection time (P = 0.04) and post-treatment submucosal vascular area at the cardia wall by EUS (P = 0.036) were significant factors for variceal recurrence. No other factors, including hepatic venous pressure gradient and Doppler parameters, showed significant relationships with the variceal recurrence.

Conclusions: The hemodynamics in the LGA may act as an initiator of variceal formation, showing close linkage with variceal recurrence, and independent of portal pressure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00535-015-1157-xDOI Listing
September 2016

Eradication of esophageal varices by sclerotherapy combined with argon plasma coagulation: Effect of portal hemodynamics and longitudinal clinical course.

Dig Endosc 2016 Mar 26;28(2):152-61. Epub 2015 Nov 26.

Center for Frontier Medical Engineering, Chiba University, Chiba, Japan.

Background And Aim: To demonstrate the effect of endoscopic injection sclerotherapy (EIS) with argon plasma coagulation (APC) as a primary/secondary prophylaxis for esophageal varies (EV) on portal hemodynamics and long-term outcomes in cirrhosis.

Methods: This prospective study included 48 cirrhotic patients (64.5 ± 11.4 years; 26 bleeders, 22 non-bleeders). Post-treatment outcomes (EIS and APC; median observation period, 12.8 months for recurrence and 21.1 months for prognosis) were evaluated with respect to the findings of hepatic venous catheterization, Doppler ultrasound, and endoscopic ultrasonography (EUS).

Results: All patients showed EV eradication after endoscopic treatment, and a decreased frequency of a patent left gastric vein (pre: 83.3%, post: 27.1%, P < 0.001). However, hepatic venous pressure gradient (HVPG, mmHg) remained unchanged after the treatment, pre: 16.1 ± 3.6, post: 15.6 ± 3.8 (P = 0.269). Cumulative variceal recurrence/rebleeding rates were 25.5%/5.6% and 62.4%/23.1% at 1 and 3 years, respectively. Post-treatment EUS finding, area of submucosal vessels in the cardia ≥12 mm2 was the only significant factor for variceal recurrence (hazard ratio 9.769, 95% confidence interval 3.046-31.337; P < 0.001). Cumulative recurrence rate was significantly higher in patients with area of submucosal vessels in the cardia ≥12 mm2 (58.3% at 1 year and 100% at 3 years) than in those without (11.4% at 1 year and 40.9% at 3 years, P < 0.001). Cumulative overall survival rates were 95.2% and 71.9% at 1 and 3 years, respectively, showing no significant relationship with HVPG.

Conclusion: EIS with APC for EV is unlikely to have a significant influence on portal pressure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/den.12562DOI Listing
March 2016