Publications by authors named "Hideko Ohama"

49 Publications

Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study.

Sci Rep 2021 Aug 17;11(1):16663. Epub 2021 Aug 17.

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.

It was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child-Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.
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http://dx.doi.org/10.1038/s41598-021-96089-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370989PMC
August 2021

Dysbiosis and liver diseases (Review).

Int J Mol Med 2021 Sep 30;48(3). Epub 2021 Jul 30.

The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka 569‑8686, Japan.

Dysbiosis, a qualitative and quantitative aberrancy of gut microbiota, has attracted marked attention. At present, advances in molecular biological techniques have made it possible to analyze gut microbiota at the DNA and RNA levels without culturing, and methods such as 16S ribosomal RNA targeting analysis and metagenomic analysis using next‑generation sequencers have been developed. The relationship between gut microbiota and various diseases has been extensively examined. Gut microbiota are essential for the immune system, energy intake and fat storage, and humans use them to build complex immune regulatory mechanisms and to obtain energy from food. The liver is the first organ to be nourished by the portal blood flow of intestinal origin, and liver diseases can be strongly influenced by various factors of intestinal origin, such as intestinal bacteria, bacterial components, and intestinal bacterial metabolites. Rigorous research has revealed that the composition of the gut microbiota is altered and the diversity of bacteria is reduced in liver diseases. Significance of various factors transported to the liver by portal vein blood flow from the intestine has been extensively investigated. Gut microbiota in liver disease can be associated with disease progression regardless of disease etiology and even with carcinogenesis. The relationship between gut microbiota and liver diseases (hepatitis virus‑related diseases, autoimmune liver diseases, alcoholic liver disease, non‑alcoholic fatty liver disease, non‑alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma) and the treatments of dysbiosis (antibiotics, prebiotics, probiotics and fecal microbiota transplantation) in liver disease are outlined based on the current evidence.
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http://dx.doi.org/10.3892/ijmm.2021.5016DOI Listing
September 2021

Impact of modified albumin-bilirubin grade on survival in patients with HCC who received lenvatinib.

Sci Rep 2021 Jul 14;11(1):14474. Epub 2021 Jul 14.

Hepato-Biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan.

We investigated the impact on survival of modified albumin-bilirubin (mALBI) grade versus Child-Pugh classification in patients with hepatocellular carcinoma (HCC) who received lenvatinib. A total of 524 patients with HCC who received lenvatinib were included. Univariate analysis showed that mALBI grade 2b/3 and Child-Pugh class B/C were significantly associated with survival [hazard ratio (HR), 2.471; 95% confidence interval (CI), 1.944-3.141 and HR, 2.178; 95%CI, 1.591-2.982]. In patients with a Child-Pugh score of 5, multivariate analysis showed that mALBI grade 2b/3 was independently associated with survival (HR, 1.814; 95%CI, 1.083-3.037). Conversely, among patients with mALBI grade 1/2a, there was no difference in survival between those with a Child-Pugh class of 5 or 6 (p = 0.735). Time-dependent receiver operating characteristic analysis showed that the ALBI score predicted survival better than the Child-Pugh score. The optimal cut-off value of the ALBI score for predicting survival was nearly the same as the value separating mALBI grades 2a and 2b. In conclusion, the mALBI grade was a better predictor of survival than the Child-Pugh classification in patients with unresectable HCC who received lenvatinib therapy.
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http://dx.doi.org/10.1038/s41598-021-93794-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280227PMC
July 2021

Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib.

Liver Int 2021 Jul 12. Epub 2021 Jul 12.

Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan.

Background And Aim: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome.

Methods: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS).

Results: The appearance of arterial hypertension G ≥ 2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.93, P = .0188], whereas decreased appetite G ≥ 2 independently predicted decreased OS (HR 1.70, 95% CI 1.25-2.32, P = .0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56-0.93, P = .0149), whereas decreased appetite G ≥ 2 predicted decreased PFS (HR 1.36, 95% CI 1.04-1.77, P = .0277).

Conclusions: Our main findings are that the occurrence of arterial hypertension G ≥ 2 is a predictor of longer survival, whereas decreased appetite G ≥ 2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients' quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.
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http://dx.doi.org/10.1111/liv.15014DOI Listing
July 2021

Association between Administration of Antithrombotics and Intraperitoneal Hemorrhage in Patients Undergoing Percutaneous Interventions for Liver Diseases.

J Clin Med 2021 Jun 7;10(11). Epub 2021 Jun 7.

2nd Department of Internal Medicine, Osaka Medical College, Takatsuki 5698686, Japan.

Currently, percutaneous interventions are essential for diagnosis and treatment of liver diseases. The most frequent complication of percutaneous interventions is intraperitoneal hemorrhage. Recently, the number of patients with liver diseases on antithrombotics has been increasing. This retrospective cohort study aimed to evaluate the risk factors for intraperitoneal hemorrhage in patients after percutaneous interventions for liver diseases. This study included 1025 patients who underwent percutaneous interventions for liver diseases from April 2015 to March 2020. All interventions were performed using an ultrasound-guided approach. The influence of antithrombotic drug administration in patients, who underwent percutaneous interventions according to the guidelines for the American Association for the Study of Liver Disease, was evaluated. Intraperitoneal hemorrhage after percutaneous interventions was detected by computed tomography. Intraperitoneal hemorrhage occurred in nine patients (0.88%); however, these adverse events were not severe. We compared clinical characteristics between the patients with and without intraperitoneal hemorrhage. Although, there was no difference based on the administration of antithrombotics ( = 0.1961), seven of nine patients who showed intraperitoneal hemorrhage received percutaneous treatments (radio frequency ablation or microwave ablation). Therefore, we divided patients who underwent treatments and liver biopsy and then investigated the influence of antithrombotics on the intraperitoneal hemorrhage. After propensity score matching in each patient group, the administration of antithrombotics was not identified as a risk factor for hemorrhage in patients who underwent interventional treatments and patients who underwent liver biopsy. When the antithrombotics were discontinued, according to the guidelines, it may not increase the risk factor for hemorrhage in patients of liver disease who underwent percutaneous interventions.
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http://dx.doi.org/10.3390/jcm10112527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201393PMC
June 2021

Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma: Early clinical experience.

Cancer Rep (Hoboken) 2021 Jun 11:e1464. Epub 2021 Jun 11.

Department of Internal Medicine, Himeji Red Cross Hospital, Hyogo, Japan.

Background: Although atezolizumab plus bevacizumab (Atez/bev) treatment has been developed for unresectable hepatocellular carcinoma (u-HCC), changes in hepatic function during therapy have yet to be reported.

Aim: This retrospective clinical study aimed to elucidate early responses to Atez/Bev.

Methods: From September 2020 to April 2021, 171 u-HCC patients undergoing Atez/Bev treatment were enrolled (BCLC stage A:B:C:D = 5:68:96:2). Of those, 75 had no prior history of systemic treatment. Relative changes in hepatic function and therapeutic response were assessed using albumin-bilirubin (ALBI) score and Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1, respectively.

Results: In initial imaging examination findings, objective response rates for early tumor shrinkage and disease control after 6 weeks (ORR-6W/DCR-6W) were 10.6%/79.6%. Similar response results were observed in patients with and without a past history of systemic treatment (ORR-6W/DCR-6W = 9.7%/77.8% and 12.2%/82.9%), as well as patients in whom Atez/Bev was used as post-progression treatment following lenvatinib (ORR-6W/DCR-6W = 7.7%/79.5%), for which no known effective post-progression treatment has been established. In 111 patients who underwent a 6-week observation period, ALBI score was significantly worsened at 3 weeks after introducing Atez/Bev (-2.525 ± 0.419 vs -2.323 ± 0.445, p < .001), but then recovered at 6-weeks (-2.403 ± 0.452) as compared to 3-weeks (p = .001). During the observation period, the most common adverse events were appetite loss (all grades) (12.3%), general fatigue/hypertension (all grades) (11.1%, respectively), and urine protein (all grades) (10.5%).

Conclusion: Atez/Bev might have therapeutic potential not only as first but also later-line treatment of existing molecular target agents. In addition, this drug combination may have less influence on hepatic function during the early period, as the present patients showed a good initial therapeutic response.
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http://dx.doi.org/10.1002/cnr2.1464DOI Listing
June 2021

Therapeutic efficacy of ramucirumab after lenvatinib for post-progression treatment of unresectable hepatocellular carcinoma.

Gastroenterol Rep (Oxf) 2021 Apr 10;9(2):133-138. Epub 2020 Oct 10.

Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan.

Background: Lenvatinib is used for unresectable hepatocellular carcinoma (u-HCC) as first-line, as well as second- and third-line therapy in Japan. We evaluated the therapeutic efficacy of newly developed ramucirumab when given after lenvatinib for post-progression treatment.

Methods: Of 385 patients with u-HCC and treated with lenvatinib at 16 different institutions in Japan between May 2018 and January 2020, 28 who received ramucirumab as the next treatment were enrolled and therapeutic responses were evaluated in a retrospective manner.

Results: The median age of the 28 patients given ramucirumab was 70 years and the median albumin-bilirubin score was -2.19. Of the 28 patients, 23 were male, 21 were classified as Child-Pugh A and 7 as Child-Pugh B, and 25 were Barcelona Clinic Liver Cancer Stage C. Ramucirumab was given as second-line therapy in 14, third-line in 9, and fourth-line in 5. Therapeutic response was obtained in only 26 patients; the objective response rate was 3.8% (1/26) and the disease-control rate was 42.3% (11/26), with a median period to progression of 2.0 months. The reasons for discontinuation of ramucirumab were progression of disease in 16 and Grade 3 adverse events (gastrointestinal bleeding, ascites) in 2.

Conclusions: The anticipated therapeutic efficacy of ramucirumab for post-progression treatment following lenvatinib was not seen in our early experience.
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http://dx.doi.org/10.1093/gastro/goaa042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128005PMC
April 2021

What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure?

Liver Cancer 2021 Apr 25;10(2):115-125. Epub 2021 Feb 25.

Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan.

Background/aim: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD).

Methods: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], = 26; continued LEN beyond PD [B group], = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score.

Results: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, = 0.004), appearance of new extrahepatic metastasis (HR 2.396, = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, < 0.001), and continuing LEN beyond PD (HR 0.297, < 0.001).

Conclusion: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.
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http://dx.doi.org/10.1159/000513355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077500PMC
April 2021

Impact of Early Lenvatinib Administration on Survival in Patients with Intermediate-Stage Hepatocellular Carcinoma: A Multicenter, Inverse Probability Weighting Analysis.

Oncology 2021 27;99(8):518-527. Epub 2021 Apr 27.

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan.

Aim/background: Transarterial chemoembolization (TACE) is recommended for patients with intermediate-stage hepatocellular carcinoma (HCC). In this study, we investigated the impact of early lenvatinib administration in patients with intermediate-stage HCC, especially those with tumors beyond the up-to-7 criteria.

Materials/methods: A total of 208 patients with intermediate-stage HCC whose initial treatment was early lenvatinib administration or TACE were enrolled. Multivariate overall survival analysis was performed in this cohort. In addition, the impact of early lenvatinib administration on survival in patients with HCC beyond the up-to-7 criteria was clarified using inverse probability weighting (IPW) analysis.

Results: The overall cumulative survival rates at 6, 12, 18, and 24 months were 94.4, 79.9, 65.8, and 50.1%, respectively. Multivariate analysis with Cox proportional hazards modeling showed that HCC treatment with lenvatinib (hazard ratio [HR], 0.199; 95% confidence interval [CI], 0.077-0.517; p < 0.001), α-fetoprotein ≥100 ng/mL (HR, 1.687), Child-Pugh class B disease (HR, 1.825), and beyond the up-to-7 criteria (HR, 2.016) were independently associated with overall survival. The 6-, 12-, 18-, and 24-month cumulative survival rates were 96.0, 90.4, 65.7, and 65.7%, respectively, in patients treated with lenvatinib, and 94.1, 78.5, 65.3, and 48.4%, respectively, in patients who received TACE (p < 0.001). In addition, univariate analysis with Cox proportional hazards modeling adjusted by IPW showed that lenvatinib therapy was significantly associated with overall survival in patients with HCC beyond the up-to-7 criteria (HR, 0.230; 95% CI, 0.059-0.904; p = 0.035).

Conclusions: Lenvatinib may be a suitable first-line treatment for patients with intermediate-stage HCC beyond the up-to-7 criteria.
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http://dx.doi.org/10.1159/000515896DOI Listing
August 2021

Hepatic F4/80 CD11b CD68 cells influence the antibacterial response in irradiated mice with sepsis by Enterococcus faecalis.

J Leukoc Biol 2021 05;109(5):943-952

2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan.

Gut-associated sepsis is a major problem in patients undergoing abdominal radiation therapy; the majority of pathogens causing this type of sepsis are translocated from the gut microbiota. While treating sepsis, bacterial clearance must be achieved to ensure patient survival, and the hepatic immune response is responsible for this process. In particular, Kupffer cells play a crucial role in the hepatic immune response against infectious agents. Recently, two populations of Kupffer cells have been described: liver-resident macrophages (Mϕ) (F4/80 CD11b CD68 cells) and hepatic Mϕ derived from circulating monocytes (F4/80 CD11b CD68 cells). We examined the properties of both types of hepatic Mϕ obtained from irradiated and normal mice and their role in sepsis. Hepatic F4/80 CD11b CD68 cells from both normal and irradiated mice did not show any antibacterial activity. However, F4/80 CD11b CD68 cells from normal mice behaved as effector cells against sepsis by Enterococcus faecalis, although those from irradiated mice lost this ability. Moreover, hepatic F4/80 CD11b CD68 cells from normal infected mice were shown to be IL-12 IL-10 CD206 CCL1 (considered M1Mϕ), and hepatic F4/80 CD11b CD68 cells from the same mice were shown to be IL-12 IL-10 CD206 CCL1 (considered M2aMϕ). When normal mice were exposed to radiation, hepatic F4/80 CD11b CD68 cells altered their phenotype to IL-12 IL-10 CD206 CCL1 (considered M2bMϕ), independent of infection, but hepatic F4/80 CD11b CD68 cells remained IL-12 IL-10 CD206 CCL1 (M2aMϕ). In addition, hepatic F4/80 CD11b CD68 cells from irradiated mice acquired antibacterial activity upon treatment with CCL1 antisense oligodeoxynucleotides. Therefore, the characteristics of hepatic F4/80 CD11b CD68 cells play a key role in the antibacterial response against gut-associated sepsis.
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http://dx.doi.org/10.1002/JLB.4A0820-550RRDOI Listing
May 2021

Therapeutic efficacy of lenvatinib as third-line treatment after regorafenib for unresectable hepatocellular carcinoma progression.

Hepatol Res 2021 Aug 5;51(8):880-889. Epub 2021 May 5.

Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.

Aim: Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma. This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after regorafenib failure.

Methods: From June 2017 to October 2020, 63 patients with Child-Pugh A and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, Barcelona Clinic Liver Cancer B:C = 23:40). They were divided into two groups, those treated with lenvatinib after regorafenib treatment (R-L group, n = 47) and those who did not receive lenvatinib after regorafenib (non-R-L group, n = 16). Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting.

Results: Serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the R-L and non-R-L groups, whereas the albumin-bilirubin score, Child-Pugh class, and tumor burden were not. Progression-free survival was also not significantly different (median 4.1 vs. 3.8 months, p = 0.586). As for overall survival, the R-L group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (MST 19.7 vs. 10.3 months, 33.8 vs. 15.3 months, p < 0.001 and p = 0.022, respectively). Modified albumin-bilirubin grade 2b (score >-2.27) at the start of regorafenib (HR 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (HR 0.355, p = 0.004) were found to be significant prognostic factors in Cox proportional hazards multivariate analysis, after inverse probability weighting adjustment.

Conclusion: These results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinoma patients with better hepatic reserve function.
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http://dx.doi.org/10.1111/hepr.13644DOI Listing
August 2021

Diabetes mellitus does not influence results of hepatectomy in hepatocellular carcinoma: case control study.

Contemp Oncol (Pozn) 2020 4;24(4):211-215. Epub 2021 Jan 4.

Department of General and Gastroenterological Surgery, Osaka Medical College Mishima-Minami Hospital, Takatsuki City, Osaka, Japan.

Introduction: Patients with diabetes mellitus undergoing hepatectomy for hepatocellular carcinoma (HCC) are at high risk of acquiring perioperative infections. Herein, we investigate the peri-operative impact of diabetes on hepatectomy.

Material And Methods: The surgical outcomes in 363 patients who underwent laparoscopic and open hepatic resection for HCC, with or without diabetes mellitus, were reviewed retrospectively. The association of diabetes mellitus with surgical outcomes and remnant liver regeneration was analyzed. The Student's and χ tests, Mann-Whitney's U test, Wilcoxon's signed-rank test, or Fisher's exact test were used in the statistical analysis.

Results: Of the 363 patients, 136 (37.5%) had diabetes, while 227 (62.5%) did not. After propensity score matching, there were no significant differences between the groups in surgical outcomes such as surgery duration, bleeding amount, and postoperative complication rate. No significant differences were observed between the groups in terms of incidence rates of not only infectious complications, including surgical site infection and remote site infection, but also postoperative complication (Clavien-Dindo grade > IIIA), post-hepatectomy liver failure, and massive ascites. There were no differences in the remnant liver regeneration at 7 days and 1, 2, 5, and 12 months following the surgery between the groups ( = 0.076, 0.368, 0.864, 0.288, and 0.063, respectively). No significant differences between the groups in the overall and recurrence-free survival were observed ( = 0.613 and 0.937).

Conclusions: Remnant liver regeneration in diabetic patients was not morphologically and functionally delayed compared to that in non-diabetic patients. Moreover, diabetes has no effect on the short- and long-term prognosis.
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http://dx.doi.org/10.5114/wo.2020.102825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836278PMC
January 2021

The Management of Recurrence of Hepatocellular Carcinoma Occurring Within 6 Months After Hepatic Resection: A Comparative Study Using a Propensity Score Matching Analysis.

J Gastrointest Cancer 2021 Jan 20. Epub 2021 Jan 20.

Department of General and Gastroenterological Surgery, Osaka Medical College Mishima-Minami Hospital, 8-1 Tamagawa-shinmachi, Takatsuki City, Osaka, 569-0856, Japan.

Background: Hepatectomy is currently recommended as the most reliable treatment for hepatocellular carcinoma. However, the association between the choice of treatment for recurrence and the timing of recurrence remains controversial.

Methods: Three-hundred thirty-nine patients who underwent hepatectomy were retrospectively analyzed using a propensity score matching analysis for the risk factors and outcomes for early recurrences within 6 months. The remnant liver volumes and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after surgery. The Student's t test and chi-square test, the likelihood-ratio test, Fisher's exact test, Mann-Whitney U test, or Wilcoxon signed-rank test were used in the statistical analyses.

Results: Early recurrence developed in 41/312 patients (13.1%). Vascular invasion and non-curative resection were independent risk factors for the occurrence of early recurrence (P < 0.001 and < 0.001, respectively). Patients with early recurrence had a poorer prognosis than patients who developed later recurrences (P < 0.001). Patients who underwent surgery or other local treatments had better outcomes (P < 0.001). The changes in remnant liver volumes and laboratory data after postoperative month 2 were not significantly different between the two groups.

Conclusion: Patients with early recurrence within 6 months had a poorer prognosis than patients who developed a later recurrence. However, patients who underwent repeat hepatectomy for recurrences had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival.
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http://dx.doi.org/10.1007/s12029-021-00585-2DOI Listing
January 2021

Safety and Efficacy of Laparoscopic Liver Resection for Colorectal Liver Metastasis With Obesity.

Am Surg 2021 Jun 7;87(6):919-926. Epub 2020 Dec 7.

Department of Internal Medicine, Osaka Medical College Mishima-Minami Hospital, Japan.

Introduction: Laparoscopic liver resection (LLR) in obese patients has been reported to be particularly challenging owing to technical difficulties and various comorbidities.

Methods: The safety and efficacy outcomes in 314 patients who underwent laparoscopic or open nonanatomical liver resection for colorectal liver metastases (CRLM) were analyzed retrospectively with respect to the patients' body mass index (BMI) and visceral fat area (VFA).

Results: Two hundred and four patients underwent LLR, and 110 patients underwent open liver resection (OLR). The rate of conversion from LLR to OLR was 4.4%, with no significant difference between the BMI and VFA groups ( = .647 and .136, respectively). In addition, there were no significant differences in terms of operative time and estimated blood loss in LLR ( = .226 and .368; .772 and .489, respectively). The incidence of Clavien-Dindo grade IIIa or higher complications was not significantly different between the BMI and VFA groups of LLR ( = .877 and .726, respectively). In obese patients, the operative time and estimated blood loss were significantly shorter and lower, respectively, in LLR than in OLR ( = .003 and < .001; < .001 and < .001, respectively). There was a significant difference in the incidence of postoperative complications, organ/space surgical site infections, and postoperative bile leakage between the LLR and OLR groups ( = .017, < .001, and < .001, respectively).

Conclusion: LLR for obese patients with CRLM can be performed safely using various surgical devices with no major difference in outcomes compared to those in nonobese patients. Moreover, LLR has better safety outcomes than OLR in obese patients.
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http://dx.doi.org/10.1177/0003134820952448DOI Listing
June 2021

Analysis of efficacy of lenvatinib treatment in highly advanced hepatocellular carcinoma with tumor thrombus in the main trunk of the portal vein or tumor with more than 50% liver occupation: A multicenter analysis.

Hepatol Res 2021 Feb 5;51(2):201-215. Epub 2021 Jan 5.

Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.

Aims: To assess the safety, efficacy, and prognostic impact of clinical factors associated with lenvatinib treatment in highly advanced hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein trunk (VP4) or tumor with more than 50% liver occupation (tm50%LO).

Methods: A total of 61 highly advanced HCC patients (41 patients with tm50%LO and 20 patients with VP4) who were treated with lenvatinib at multicenter were enrolled and retrospectively analyzed for treatment outcomes according to their clinical status, including tumor morphology.

Results: The most frequent grade ≥3 adverse event in tm50%LO HCC was elevated aspartate aminotransferase (17.1%). Objective response rates were 37.5% and 0% in tm50%LO HCC patients with Child-Pugh grade (CP)-A and CP-B, respectively, and 26.7% and 0% in VP4 HCC patients with CP-A and CP-B, respectively. Estimated median progression-free survival and overall survival were 132 days and 229 days, and 101 days and 201 days in patients with tm50%LO and VP4, respectively. In multivariate analysis, modified albumin-bilirubin grade (hazard ratio 0.372, 95% CI 0.157-0.887; p = 0.0241) and tumor morphology (hazard ratio 0.322, 95% CI 0.116-0.889; p = 0.0287) were independently associated with progression-free survival in patients with tm50%LO HCC. In VP4 HCC, median progression-free survival was worse in CP-B (57 days) than in CP-A patients (137 days, p = 0.0462).

Conclusions: Lenvatinib treatment offers a benefit in highly advanced HCC (tm50%LO or VP4) patients with good liver function or nodular-type tumor. The various characteristics identified in this study might be useful as indicators of lenvatinib treatment in highly advanced HCC with tm50%LO or VP4, which are considered very refractory cancers.
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http://dx.doi.org/10.1111/hepr.13592DOI Listing
February 2021

Hepatectomy and liver regeneration in the results of treatment of colorectal liver metastasis.

Contemp Oncol (Pozn) 2020 30;24(3):172-176. Epub 2020 Oct 30.

Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Takatsuki City, Osaka, Japan.

Introduction: Hepatectomy is currently the most reliable treatment modality for colorectal liver metastases (CRLM). This paper describes and discusses the outcomes of initial versus repeat hepatic resection for CRLM.

Material And Methods: Between January 2008 and December 2018, we retrospectively analyzed the data of 385 patients who underwent initial and repeat hepatic resection for CRLM at a single institution with respect to surgical outcomes and remnant liver regeneration. The remnant liver volume was postoperatively measured via computed tomography on postoperative day 7 and at 1, 2, 5, 12, and 24 months postoperatively.

Results: The liver regeneration rate peaked at 1 week postoperatively, and gradually decreased thereafter. Remnant liver volume plateaued around 1-2 months postoperatively, when regeneration was almost complete. There was no difference in the rate of liver volume regeneration during the entire postoperative period between initial and repeat hepatic resection ( 0.708, 0.511, 0.055, 0.053, 0.102, and 0.110, respectively). After 2 months postoperatively, the laboratory data showed recovery toward near normal levels, and none of the data exhibited significant differences. There were also no significant differences in morbidity rate, mortality rate, overall survival, and recurrence-free survival after hepatic resection ( 0.488, 0.124, 0.071 and 0.387, respectively).

Conclusions: Initial and repeat hepatectomy showed similar outcomes of remnant liver regeneration and short- and long-term prognoses.
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http://dx.doi.org/10.5114/wo.2020.100272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670187PMC
October 2020

Clinical importance of muscle volume in lenvatinib treatment for hepatocellular carcinoma: Analysis adjusted with inverse probability weighting.

J Gastroenterol Hepatol 2021 Jul 29;36(7):1812-1819. Epub 2020 Nov 29.

Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan.

Background And Aim: This study aimed to elucidate the clinical importance of muscle volume loss (pre-sarcopenia) in patients receiving lenvatinib as treatment for unresectable hepatocellular carcinoma (u-HCC).

Methods: Of 437 u-HCC patients treated with lenvatinib at specific institutions in Japan between March 2018 and May 2020, 151 with available computed tomography imaging data from the time of lenvatinib introduction were enrolled. Pre-sarcopenia was diagnosed based on a previously reported cut-off value calculation formula [psoas muscle area at level of middle of third lumbar vertebra (cm )/height (m) ]. Clinical features and prognostic factors for overall survival (OS) with inverse probability weighting were investigated retrospectively for their relationship with pre-sarcopenia.

Results: Cox hazard multivariate analysis showed alpha-fetoprotein (≥400 ng/mL) (hazard ratio [HR] 2.271, P < 0.001), Barcelona Clinic Liver Cancer stage (C and D) (HR 1.625, P = 0.018), and positive for pre-sarcopenia (HR 1.652, P = 0.042) to be significant prognostic factors. OS rates for the pre-sarcopenia group (n = 41) were worse than those for the non-pre-sarcopenia group (n = 110) (0.5-, 1-, and 1.5-year OS: 72.5%, 27.9%, and 7.0% vs 80.7%, 56.7%, and 46.1%, respectively; P < 0.001), as was progression-free survival (P = 0.025). Time to stopping lenvatinib or disease progression was better in the non-pre-sarcopenia group (0.5-, 1-, and 1.5-year OS: 48.0%, 24.5%, and 8.4% vs 20.0%, 10.3%, and 4.2%, respectively; P < 0.001). Also, the frequency of the adverse event appetite loss (any grade) was greater in the pre-sarcopenia group (43.9% vs 18.2%, P = 0.003).

Conclusion: Pre-sarcopenia was shown to be a significant prognostic factor in patients treated with lenvatinib for u-HCC.
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http://dx.doi.org/10.1111/jgh.15336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359359PMC
July 2021

Efficacy and safety of laparoscopic hepatectomy for hepatocellular carcinoma comorbid with cirrhosis.

Prz Gastroenterol 2020 19;15(3):225-233. Epub 2020 Sep 19.

Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan.

Introduction: Laparoscopic hepatectomy (LH) is very difficult to perform in patients with cirrhosis because of the haemorrhagic and fibrotic nature of the liver, although there are various advantages to laparoscopic surgery.

Aim: To investigate the surgical outcomes, and efficacy and safety of LH versus open hepatectomy (OH) for hepatocellular carcinoma (HCC) resection.

Material And Methods: A total of 112 patients with cirrhosis, who underwent hepatectomy, were analysed retrospectively. We investigated the safety and efficacy of LH for HCC with cirrhosis. Student's and χ tests, Mann-Whitney's test, Wilcoxon's signed-rank test, and Fisher's exact test were used in the statistical analysis.

Results: Seventy-one patients underwent LH, and 41 underwent OH. The conversion rate from LH to OH was 12.7%. After propensity score matching, the estimated blood loss was significantly lower in the LH group than in the OH group (25 vs. 310 ml; < 0.001), and there was a significant difference between the groups in the operative time ( = 0.091). The LH group had complication rates of 3.6% and 0% for refractory ascites and pleural effusion, respectively, while those were 17.9% and 10.7%, respectively, in the OH group ( = 0.019 and = 0.005, respectively). The LH group had no mortality, whereas the OH group had a mortality rate of 10.7% ( = 0.038). The postoperative length of stay was significantly longer in the LH group than in the OH group (9 days vs. 14 days) ( = 0.002).

Conclusions: LH can be performed safely for HCC with cirrhosis. More favourable results are achieved with LH than with OH in terms of surgical outcomes.
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http://dx.doi.org/10.5114/pg.2020.99039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509897PMC
September 2020

The Effects of Allogeneic Blood Transfusion in Hepatic Resection.

Am Surg 2021 Feb 15;87(2):228-234. Epub 2020 Sep 15.

13010 Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.

Background: Hepatectomy has a high risk of perioperative bleeding due to the underlying disease. Here, we investigated the postoperative impact of allogeneic blood transfusion during hepatectomy.

Methods: The surgical outcomes in 385 patients who underwent hepatic resection for hepatocellular carcinoma were retrospectively reviewed. The association of allogeneic blood transfusion with surgical outcomes and remnant liver regeneration data was analyzed.

Results: Eighty-six patients (24.0%) received an allogeneic blood transfusion and 272 patients (76.0%) did not. After propensity score matching, the incidence rates of postoperative complication (Clavien-Dindo grade >IIIA), posthepatectomy liver failure, and massive ascites were significantly higher for the group that received a blood transfusion than for the group that did not receive blood transfusion ( < .001, = .001, and <.001, respectively). Postoperative measures of total bilirubin, albumin, platelet count, prothrombin time, aspartate aminotransferase, and alanine aminotransferase were significantly more favorable in patients without blood transfusion until day 7 after surgery. There were no correlations in the remnant liver regeneration at 7 days, and 1, 2, 5, and 12 months postoperatively between the 2 groups ( = .585, .383, .507, .261, and .430, respectively). Regarding prognosis, there was no significant difference in overall and recurrence-free survival between the 2 groups ( = .065 and .166, respectively).

Conclusion: Allogeneic transfusion during hepatectomy strongly affected remnant liver function in the early postoperative period; however, this was not related to the remnant liver regeneration volume. Despite that the allogeneic transfusion resulted in poorer postoperative laboratory test results and increased postoperative complication and mortality rates, it had no effect on the long-term prognosis.
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http://dx.doi.org/10.1177/0003134820950285DOI Listing
February 2021

Liver dysfunction is associated with poor prognosis in patients after immune checkpoint inhibitor therapy.

Sci Rep 2020 09 2;10(1):14470. Epub 2020 Sep 2.

Second Department of Internal Medicine, Osaka Medical College, 2-7, Daigakumachi, Takatsuki, Osaka, 569-8686, Japan.

Immune-related adverse events (irAEs) are induced by immune checkpoint inhibitors (ICIs). Liver is one of the main target organs which irAEs occur and we investigated the influence of liver dysfunction on prognosis of patients after ICIs. From July 2014 to December 2018, 188 patients with diverse cancers who received ICIs (nivolumab or pembrolizumab) were enrolled. Twenty-nine patients experienced liver dysfunction of any grades after ICIs. Progression-free survival (PFS) was significantly shorter in the liver dysfunction-positive group than in the liver dysfunction-negative group, and a similar result was obtained for Overall survival (OS). Multiple logistic regression analysis revealed liver metastasis and alanine aminotransferase before ICIs were associated with a higher incidence of liver dysfunction after ICIs. Regardless of liver metastasis, PFS and OS were significantly shorter in the liver dysfunction-positive group. In conclusion, this study suggests liver dysfunction is associated with poor prognosis in patients after ICIs with diverse cancers.
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http://dx.doi.org/10.1038/s41598-020-71561-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468148PMC
September 2020

Increased both PD-L1 and PD-L2 expressions on monocytes of patients with hepatocellular carcinoma was associated with a poor prognosis.

Sci Rep 2020 06 25;10(1):10377. Epub 2020 Jun 25.

2nd Department of Internal Medicine, Osaka Medical College, 2-7, Daigakumachi, Takatsuki, Osaka, 569-8686, Japan.

Anti-programmed cell death-1 (PD-1) antibodies has been approved to treat HCC. Some PD-1 ligands (PD-L1 and PD-L2) negative tumors respond to treatment of anti-PD-1 antibodies, and this fact may be caused by the expression of PD-1 ligands on non-tumor cells. PD-L1 was recently found to be expressed on CD14 cells from cancer patients. We investigate PD-1 ligands expression on CD14 cells of patients with HCC and the role of CD14 cells in an antitumor response. In this study, 87 patients diagnosed with HCC were enrolled. CD14 cells from patients with HCC expressed PD-L1 (4.5-95.5%) and PD-L2 (0.2-95.0%). According to cut-off values, we classified patients as those either with PD-L1PD-L2CD14 cells or other types of CD14 cells. The overall survival of patients with PD-L1PD-L2CD14 cells was shorter than that of patients with other types of CD14 cells (p = 0.0023). PD-L1PD-L2CD14 cells produced IL-10 and CCL1, and showed little tumoricidal activity against HepG2 cells. The tumoricidal activity of CD8 cells from patients with PD-L1PD-L2CD14 cells were suppressed by co-cultivation with CD14 cells from the syngeneic patient. Furthermore, anti-PD-1 antibody restored their tumoricidal activity of CD8 cells. In conclusion, some patients with HCC have PD-L1PD-L2CD14 cells that suppress their antitumor response. These inhibitory functions of CD14 cells may be associated with a poor prognosis in these patients.
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http://dx.doi.org/10.1038/s41598-020-67497-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316832PMC
June 2020

Platelet-lymphocyte ratio predicts survival in patients with hepatocellular carcinoma who receive lenvatinib: an inverse probability weighting analysis.

Eur J Gastroenterol Hepatol 2021 02;32(2):261-268

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama.

Objective: Lenvatinib, a newly developed molecularly targeted agent, has become available as a first-line therapy in patients with unresectable hepatocellular carcinoma (HCC). The platelet-to-lymphocyte ratio (PLR) has been associated with poor outcome in various malignancies, including HCC. In this study, we investigated the ability of PLR to predict outcomes in patients with unresectable HCC who received lenvatinib.

Methods: Multivariate survival analysis was performed in 283 patients with unresectable HCC who received lenvatinib. In addition, the utility of PLR for predicting survival was clarified using an inverse probability weighting (IPW) analysis.

Results: Cumulative overall survival at 100, 200, 300, 400, and 500 days was 95.2, 83.8, 68.3, 60.3, and 49.9%, respectively. Multivariate analysis with Cox proportional hazards modeling showed that PLR (≥150) [hazard ratio, 1.588; 95% confidence interval (CI), 1.039-2.428; P = 0.033], α-fetoprotein level, and Barcelona clinic liver cancer stage were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high PLR (P = 0.029). In addition, univariate analysis with Cox proportional hazards modeling adjusted by IPW showed that PLR (≥150) (hazard ratio, 1.396; 95% CI, 1.051-1.855; P = 0.021) was significantly associated with overall survival. Conversely, univariate analysis with Cox proportional hazards modeling adjusted only by IPW showed that PLR (≥150) (hazard ratio, 1.254; 95% CI, 1.016-1.549; P = 0.035) was significantly associated with progression-free survival. PLR values were not independently associated with therapeutic responses before or after IPW-adjusted logistic regression analysis.

Conclusions: PLR predicted overall survival in patients with unresectable HCC who received lenvatinib.
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http://dx.doi.org/10.1097/MEG.0000000000001734DOI Listing
February 2021

Nutritional Index as Prognostic Indicator in Patients Receiving Lenvatinib Treatment for Unresectable Hepatocellular Carcinoma.

Oncology 2020 25;98(5):295-302. Epub 2020 Feb 25.

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.

Background/aim: Few studies have examined the details of nutritional status in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing systemic chemotherapy with lenvatinib. We evaluated the prognostic/predictive value of nutritional status using Onodera's prognostic nutritional index (O-PNI) for overall survival among patients with u-HCC treated with lenvatinib.

Methods: Three-hundred and seventy-five u-HCC patients treated with lenvatinib were enrolled (median age 72 years; Child-Pugh class A/B/C: n = 312/60/3; BCLC stage A/B/C/D: n = 2/159/212/2). We examined median survival time (MST) and time to progression (TTP) in all patients (n = 375), prognosis according to the O-PNI (high/low: >40/≤40) in 298 patients with lymphocyte findings, and the prognostic/predictive values of Child-Pugh stage, albumin-bilirubin (ALBI)/modified ALBI (mALBI) grade, and O-PNI for Chemotherapy grade (OPNIC grade 1/2/3: O-PNI >40/≤40 to >36/≤36).

Results: The MST and TTP were 16.6 and 8.0 months, respectively. The MST and TTP according to the O-PNI (>40/≤40) were "not reached" (NR)/12.4 months (p < 0.001) and 10.0/6.1 months (p = 0.012), respectively. There was a good correlation noted between ALBI score and O-PNI (r = -0.939, p < 0.001). The predictive value of the O-PNI for mALBI grade 2a was 36.0 (specificity/sensitivity = 0.894/0.942; area under the curve [AUC] = 0.978), while that for mALBI grade 1 was 39 (specificity/sensitivity = 0.920/0.929; AUC = 0.972), which was very similar to a high O-PNI. The MST analyzed with the OPNIC in the 298 patients was NR/16.2/10.4 months for OPNIC grade 1/2/3 (p < 0.001), respectively, and the c-index was 0.632, the same as that for mALBI grade (0.632), while that for Child-Pugh class was 0.571.

Conclusions: OPNIC grading might have a potential for easy substitution of mALBI grading. A good nutritional status (OPNIC grade 1) or mALBI grade 1 is the best indication for lenvatinib use, while with an OPNIC grade 3, lenvatinib might be not suitable.
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http://dx.doi.org/10.1159/000506293DOI Listing
May 2020

Neutrophil-to-lymphocyte ratio is associated with survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib.

Liver Int 2020 04 1;40(4):968-976. Epub 2020 Mar 1.

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan.

Background And Aims: Lenvatinib, a newly developed molecularly targeted agent, has become available for patients with unresectable hepatocellular carcinoma (HCC). Neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor outcomes in numerous malignancies. In this study, we investigated the impact of NLR on associating outcomes in patients with HCC treated with lenvatinib.

Methods: A total of 237 patients with HCC treated with lenvatinib were included. We performed univariate and multivariate analyses in this cohort. In addition, we clarified appropriate cut-off NLR levels for associating overall survival using hazard ratio (HR) spline curves.

Results: Cumulative overall survival at 100, 200 and 300 days was 95.2%, 83.4% and 66.6% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.874; 95% confidence interval [CI], 1.097-3.119), α-foetoprotein ≥ 400 ng/mL (HR, 1.969; 95% CI, 1.188-3.265) and modified albumin-bilirubin grade 2b or 3 (HR, 2.123; 95% CI, 1.267-3.555) were independently associated with overall survival. Cumulative progression-free survival at 100, 200 and 300 days was 72.4%, 49.8% and 38.7% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.897; 95% CI, 1.268-2.837) and BCLC stage ≥ C (HR, 1.516; 95% CI, 1.028-2.236) were independently associated with progression-free survival. Disease control rate was significantly different between the patients with low NLR (<4) (85.5%) and high NLR (≥4) (67.3%) (P = .007). Spline curve analysis revealed that NLR of approximately 3.0-4.5 is an appropriate cut-off for associating overall survival.

Conclusions: NLR can be associated with outcomes in patients with HCC treated with lenvatinib.
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http://dx.doi.org/10.1111/liv.14405DOI Listing
April 2020

The Relationship Between the Number of Ports and Surgical Outcomes in Laparoscopic Hepatectomy.

Surg Laparosc Endosc Percutan Tech 2020 Feb;30(1):85-90

Department of General and Gastroenterological Surgery.

Introduction: Reduced port surgery (RPS) has been garnering interest as a novel minimally invasive surgery lately.

Aim: The authors examined the relationship between the number of ports and surgical outcomes after laparoscopic hepatectomy (LH).

Materials And Methods: Between January 2012 and April 2019, 209 patients who underwent laparoscopic partial resection and lateral sectionectomy were retrospectively analyzed with respect to operative variables and surgical outcomes. Patients were divided into 5 groups by the number of ports used. Student's t test, the χ test, the likelihood-ratio test, Fisher exact test, or Mann-Whitney U test were used to analyze the data.

Results: Operative duration was significantly longer in patients with a larger number of ports than in those with a smaller number of ports. Chronological pain scores according to the visual analog scale (VAS) on postoperative days 1, 2, 4, and 7 were not associated with the number of ports and wound length in the umbilical region. The frequency of using additional analgesic agents was not significantly different between the groups. VAS scores and the number of additional analgesic agents used were smaller in patients in whom non-steroidal anti-inflammatory drugs were regularly administered postoperatively than in those in whom the drug was not regularly administered postoperatively. LH had a 3.4% complication rate (Clavien-Dindo classification >IIIA); however, this was not significantly different between the groups.

Conclusions: No significant difference in postoperative pain was observed between RPS and conventional methods, although operative durations were shorter with RPS. However, RPS for LH may be associated with excellent cosmetic results compared with conventional methods.
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http://dx.doi.org/10.1097/SLE.0000000000000750DOI Listing
February 2020

Endoscopic Ultrasound-Guided Pancreatic Transmural Stenting and Transmural Intervention.

Clin Endosc 2020 Jul 27;53(4):429-435. Epub 2019 Nov 27.

2nd Department of Internal Medicine, Osaka Medical College, Osaka, Japan.

Endoscopic ultrasound (EUS)-guided pancreatic access is an emergent method that can be divided into the two main techniques of EUS-guided rendezvous and pancreatic transmural stenting (PTS). While many reports have described EUS-guided procedures, the indications, technical tips, clinical effects, and safety of EUS-guided pancreatic duct drainage (EUS-PD) remain controversial. This review describes the current status of and problems associated with EUS-PD, particularly PTS. We reviewed clinical data derived from a total of 334 patients. Rates of technical and clinical success ranged from 63% to 100% and 76% to 100%, respectively. In contrast, the rate of procedure-related adverse events was high at 26.7% (89/334). The most frequent adverse events comprised abdominal pain (n=38), acute pancreatitis (n=15), bleeding (n=9), and issues associated with pancreatic juice leakage such as perigastric fluid, pancreatic fluid collection, or pancreatic juice leaks (n=8). In conclusion, indications for EUS-PTS are limited, as is the evidence of its viability, due to the scarcity of expert operators. Despite improvements made to various devices, EUS-PTS remains technically challenging. Therefore, a long-term, large-scale, multicenter study is required to establish this technique as a viable alternative drainage method.
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http://dx.doi.org/10.5946/ce.2019.130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403024PMC
July 2020

The Management of Recurrence within Six Months after Hepatic Resection for Colorectal Liver Metastasis.

Dig Surg 2020 9;37(4):282-291. Epub 2019 Oct 9.

Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.

Background: Hepatectomy is currently recommended as the most reliable treatment for colorectal liver metastases. However, the association between the choice of treatment for recurrence and the timing of recurrence remains controversial.

Methods: Two-hundred ninety-five patients who underwent hepatectomy were retrospectively analyzed for the risk factors and the outcomes for early recurrence within 6 months. The remnant liver volumes (RLVs) and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after the operation.

Results: Early recurrence developed in 88/295 patients (29.8%). Colorectal cancer lymph node metastasis, synchronous liver metastasis, and multiple liver metastases were independent risk factors for the occurrence of early recurrence (p < 0.001, 0.032, and 0.019, respectively). Patients with early recurrence had a poorer prognosis than did patients who developed later recurrence (p < 0.001). Patients who underwent surgery or other local treatment had better outcomes. The changes in RLV and laboratory data after postoperative month 2 were not significantly different between the 2 groups.

Conclusion: Patients with early recurrence within 6 months had a poorer prognosis than did patients who developed later recurrence. However, patients who underwent repeat hepatectomy for recurrence had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival.
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http://dx.doi.org/10.1159/000503420DOI Listing
April 2021

Efficacy and Safety of Deep Sedation in Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma.

Adv Ther 2019 02 3;36(2):344-354. Epub 2019 Jan 3.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Introduction: Radiofrequency ablation (RFA) has been accepted as safe and effective for treating early-stage hepatocellular carcinoma (HCC). However, it often causes severe pain. Therefore, in this study, we performed RFA under deep sedation and investigated its efficacy and safety.

Methods: We conducted a retrospective study including 511 HCC patients who received approximately 886 RFA treatments between December 2014 and November 2016 at our institution. Respiratory depression was defined as oxygen saturation of below 90%; and severe body movement was defined as movement caused by pain, which was managed by lowering the power of the generator. Factors associated with respiratory depression and severe body movement were examined via univariate and multivariate regression analyses.

Results: Respiratory depression occurred in 15.3% of the patients and severe body movement in 26.5% of the patients. In the multivariate analysis, BMI (≥ 25 kg/m, odds ratio [OR] = 1.75, P = 0.035) and longer ablation (≥ 10 min, OR = 2.59, P = 0.002) were significant respiratory depression-related factors. Male sex (OR = 2.02, P = 0.005), Child-Pugh class A (odds ratio = 1.96, P = 0.018), and longer ablation (≥ 10 min, OR = 3.03, P < 0.001) were significant factors related to severe body movement.

Conclusion: Deep sedation for RFA can be performed safely and effectively. Higher BMI and longer ablation were risk factors for respiratory depression and male sex, Child-Pugh class A, and longer ablation were independent predictors of severe body movement during RFA under deep sedation.
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http://dx.doi.org/10.1007/s12325-018-0865-zDOI Listing
February 2019

Percutaneous Ablation for Hepatocellular Carcinoma: Comparison of Various Ablation Techniques and Surgery.

Can J Gastroenterol Hepatol 2018 3;2018:4756147. Epub 2018 Jun 3.

Department of Gastroenterology, Juntendo University School of Medicine, Japan.

Image-guided percutaneous ablation is considered best in the treatment of early-stage hepatocellular carcinoma (HCC). Ablation is potentially curative, minimally invasive, and easily repeatable for recurrence. Ethanol injection used to be the standard in ablation. However, radiofrequency ablation has recently been the most prevailing ablation method for HCC. Many investigators have reported that radiofrequency ablation is superior to ethanol injection, from the viewpoints of treatment response, local tumor curativity, and overall survival. New-generation microwave ablation can create a larger ablation volume in a shorter time period. Further comparison studies are, however, mandatory between radiofrequency ablation and microwave ablation, especially in terms of complications and long-term survival. Irreversible electroporation, which is a non-thermal ablation method that delivers short electric pulses to induce cell death due to apoptosis, requires further studies, especially in terms of long-term outcomes. It is considerably difficult to compare outcomes in ablation with those in surgical resection. However, radiofrequency ablation seems to be a satisfactory alternative to resection for HCC 3 cm or smaller in Child-Pugh class A or B cirrhosis. Furthermore, radiofrequency ablation may be a first-line treatment in HCC 2 cm or smaller in Child-Pugh class A or B cirrhosis. Various innovations would further improve outcomes in ablation. Training programs may be effective in providing an excellent opportunity to understand basic concepts and learn cardinal skills for successful ablation. Sophisticated ablation would be more than an adequate alternative of surgery for small- and possibly middle-sized HCC.
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http://dx.doi.org/10.1155/2018/4756147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008833PMC
February 2019
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