Publications by authors named "Shoji Kubo"

321 Publications

Postoperative direct-acting antiviral treatment after liver resection in patients with hepatitis C virus-related hepatocellular carcinoma.

Hepatol Res 2021 Sep 2. Epub 2021 Sep 2.

Department of Hepato-Biliary-Pancreatic Surgery and.

Aim: We investigated effects of direct-acting antiviral (DAA)-induced sustained virological response (SVR) after liver resection in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) for postoperative recurrence and survival.

Methods: Surgical outcomes in 18 patients with postoperative DAA-induced SVR (HCC-DAA group) were compared with those in 23 patients with preoperative DAA-induced SVR (DAA-HCC group) and those in 10 patients who did not receive DAA therapy (control group). Patients who received DAA therapy >1 year after surgery and those with recurrence <1 year after surgery were excluded.

Results: Serum concentrations of aminotransferases improved 1 year after surgery in both the HCC-DAA and DAA-HCC groups. The number of HCC-DAA patients with albumin-bilirubin (ALBI) grade 1 increased from 11 to 15. The disease-free survival rate did not differ between HCC-DAA group (3 year, 60%) and the other 2 groups (DAA-HCC group, 92% and control group, 60%). The 3-year overall survival rates were better in the DAA-HCC group (84%) and HCC-DAA group (100%) than in the control group (46%; all ps < 0.05 according to Holm's test). Multivariable analysis revealed that tumor stage was an independent risk factor for postoperative recurrence, and ALBI grade at 1 year after surgery was predictive of postoperative survival, but DAA-induced SVR was neither.

Conclusions: Although postoperative DAA-induced SVR itself may not suppress postoperative recurrence, improvement in liver function as a result of DAA administration after surgery may prolong postoperative survival. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/hepr.13709DOI Listing
September 2021

Impact of alcohol abstinence on survival after hepatic resection for hepatocellular carcinoma in patients with alcohol-related liver disease.

Ann Med Surg (Lond) 2021 Aug 29;68:102644. Epub 2021 Jul 29.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

Background: This study aimed to evaluate the prognostic impact of alcohol abstinence on survival after hepatic resection for hepatocellular carcinoma (HCC) in patients with alcohol-related liver disease (ALD).

Patients And Methods: In total, 92 patients with ALD-HCC who underwent initial and curative hepatic resection were identified, including 56 and 36 patients with and without alcohol abstinence, respectively.

Results: The 3-, 5-, and 7-year recurrence-free survival (RFS) were 46%, 43%, and 37% in the abstinence group, and 61%, 36%, and 36% in the non-abstinence group, respectively (p = 0.71). The 3-, 5-, and 7-year overall survival (OS) were 91%, 76%, and 66% in the abstinence group, and 87%, 57%, and 44% in the non-abstinence group, respectively (p = 0.023). Multivariate analysis revealed that non-abstinence was an independent prognostic factor for OS (P = 0.026). The incidence rate of liver-related death including HCC-specific death, liver failure, and renal failure in cirrhosis (hepatorenal syndrome) between the non-abstinence and abstinence groups were 41.7% vs. 19.6% (p = 0.032). Worsening of the Child-Pugh grade at intrahepatic recurrence was more frequently observed in the non-abstinence (33.3%) than that in the abstinence group (6.5%) (p = 0.039).

Conclusions: Alcohol abstinence might improve the long-term survival of patients with ALD-HCC undergoing hepatic resection.
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http://dx.doi.org/10.1016/j.amsu.2021.102644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346358PMC
August 2021

Impact of Advancing Age on the Status and Risk of Postoperative Infections After Liver Resection.

World J Surg 2021 Jul 9. Epub 2021 Jul 9.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan.

Background: Despite the recently increasing number of elderly patients undergoing liver resection, the impact of advancing age on postoperative infections (PIs) incidence and risk remains unclear. This study aimed to investigate the impact of advancing age on PIs incidence and status.

Methods: This retrospective study included 744 patients undergoing liver resection without biliary reconstruction or combined resection of other organs. Multivariable analysis with a restricted cubic spline was used to evaluate the impact of advancing age on PIs and to determine its association with PIs risk in patients undergoing open and laparoscopic liver resection (OLR and LLR, respectively).

Results: Multivariable analysis demonstrated that advancing age was significantly associated with increased PIs risk (P = 0.017). The spline curve showed that the odds ratio for PIs sharply increased starting approximately at 65 years of age. Unadjusted restricted cubic splines assessing the subcategories of PIs demonstrated that advancing age was associated with increased risks of organ/space surgical site infection and sepsis (P = 0,064 and 0.048, respectively). Multivariable analysis revealed that LLR was associated with the lower PIs risk compared with OLR (P = 0.025), whereas the lower PIs risk with LLR was not significantly obscured by advancing age (P = 0.29).

Conclusions: Advancing age was associated with increased risk of PIs, including organ/space surgical site infections and sepsis, after liver resection especially in patients aged ≥ 65 years.
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http://dx.doi.org/10.1007/s00268-021-06236-8DOI Listing
July 2021

Superiority of CRP-albumin-lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma.

HPB (Oxford) 2021 Jun 22. Epub 2021 Jun 22.

Department of Hepato-Biliary-Pancreatic Surgery Osaka City University Graduate School of Medicine, Japan.

Background: We aimed to investigate whether a novel biomarker incorporating albumin, lymphocytes, and CRP can predict the prognosis for hepatocellular carcinoma (HCC) after hepatectomy.

Methods: Between January 2011 and December 2013, 384 patients who underwent hepatectomy in four university hospitals in Japan were investigated as a discovery cohort. The CRP-Albumin-Lymphocyte (CALLY index) was defined as (Albumin × Lymphocyte)/(CRP × 10). Patients with a CALLY index ≥5 (n = 200) were compared to those with an index <5 (n = 184). Next, validation was performed using 267 patients from three other university hospitals (external validation cohort).

Results: The number of TNM Stage III and IV patients was significantly higher in the CALLY <5 group than the ≥5 group (p = 0.003). There was a significant difference in the 5-year survival rate (CALLY ≥5: 71% vs. <5: 46%; p < 0.001). Multivariate analysis identified the CALLY index as an independent factor of overall survival. Similarly, there was a significant difference in the 5-year survival rate between the CALLY ≥5 (73%) and <5 (48%) groups (p < 0.001), and the CALLY index was identified as an independent prognostic factor in the external validation cohort.

Conclusion: The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.
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http://dx.doi.org/10.1016/j.hpb.2021.06.414DOI Listing
June 2021

Multicenter Propensity Score-Based Study of Laparoscopic Repeat Liver Resection for Hepatocellular Carcinoma: A Subgroup Analysis of Cases with Tumors Far from Major Vessels.

Cancers (Basel) 2021 Jun 25;13(13). Epub 2021 Jun 25.

Department of Hepato-Biliary Surgery and Transplantation, Hepatobiliary Centre, Paul Brousse Hospital, Villejuif 94800, France.

Less morbidity is considered among the advantages of laparoscopic liver resection (LLR) for HCC patients. However, our previous international, multi-institutional, propensity score-based study of emerging laparoscopic repeat liver resection (LRLR) failed to prove this advantage. We hypothesize that these results may be since the study included complex LRLR cases performed during the procedure's developing stage. To examine it, subgroup analysis based on propensity score were performed, defining the proximity of the tumors to major vessels as the indicator of complex cases. Among 1582 LRLR cases from 42 international high-volume liver surgery centers, 620 cases without the proximity to major vessels (more than 1 cm far from both first-second branches of Glissonian pedicles and major hepatic veins) were selected for this subgroup analysis. A propensity score matching (PSM) analysis was performed based on their patient characteristics, preoperative liver function, tumor characteristics and surgical procedures. One hundred and fifteen of each patient groups of LRLR and open repeat liver resection (ORLR) were earned, and the outcomes were compared. Backgrounds were well-balanced between LRLR and ORLR groups after matching. With comparable operation time and long-term outcome, less blood loss (283.3±823.0 vs. 603.5±664.9 mL, = 0.001) and less morbidity (8.7 vs. 18.3 %, = 0.034) were shown in LRLR group than ORLR. Even in its worldwide developing stage, LRLR for HCC patients could be beneficial in blood loss and morbidity for the patients with less complexity in surgery.
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http://dx.doi.org/10.3390/cancers13133187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268302PMC
June 2021

Report of the 22nd Nationwide Follow-Up Survey of Primary Liver Cancer in Japan (2012-2013).

Hepatol Res 2021 May 29. Epub 2021 May 29.

Follow-up Survey Committee, Liver Cancer Study Group of Japan, Japan.

In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21,155 newly registered patients and 43,041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from 1 January 2012 to 31 December 2013. Basic statistics compiled for patients newly registered in the 22nd survey was cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/hepr.13675DOI Listing
May 2021

Impact of hepatitis C virus on survival in patients undergoing resection of intrahepatic cholangiocarcinoma: Report of a Japanese nationwide survey.

Hepatol Res 2021 Aug 16;51(8):890-901. Epub 2021 Jun 16.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Aim: We reviewed the data of a nationwide follow-up survey to determine the impact of hepatitis C virus (HCV) infection on the outcomes of hepatectomy for mass-forming (MF) type, and combined mass-forming and periductal infiltrating (MF + PI) type intrahepatic cholangiocarcinoma (ICC).

Methods: In total, 956 patients with ICC who underwent curative hepatic resection were included in this cohort study, and patients were classified according to virus status. Patients were classified according to virus status as follows: HCV-related ICC (n = 138, 14.4%), hepatitis B virus (HBV)-related ICC (n = 43, 4.5%) and non-virus-related ICC (n = 775, 81.1%). To control for variables, we used 1:1 propensity score-matching to compare outcomes after surgery between HCV-related (n = 102) and non-virus-related ICC cases (n = 102).

Results: We successfully matched HCV-related and non-virus-related ICC cases with similar liver function and tumor characteristics. Patients with HCV-related ICC had significantly shorter recurrence-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, p = 0.016) and overall survival (hazard ratio: 0.57, 95% confidence interval: 0.37-0.88, p = 0.011) than patients with non-virus-related ICC. Cox proportional hazard analysis showed that HCV-related ICC offered a worse prognosis than non-virus-related ICC.

Conclusions: HCV infection increases the risk of recurrence and worsens overall survival in patients after curative resection for MF and combined MF + PI type ICC.
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http://dx.doi.org/10.1111/hepr.13676DOI Listing
August 2021

Identification of microRNA-96-5p as a postoperative, prognostic microRNA predictor in nonviral hepatocellular carcinoma.

Hepatol Res 2021 May 26. Epub 2021 May 26.

Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Aim: The microRNA (miR) clusters miR-183/96/182 and miR-217/216a/216b are significantly upregulated in nonviral hepatocellular carcinoma (NBNC-HCC). Here, we investigate the impact of each member of these clusters on the clinical outcome of NBNC-HCC and analyze the antitumor effects of miR-96-5p.

Methods: The association between recurrence-free survival of 111 NBNC-HCC patients and the levels of miR-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, miR-216a-5p, and miR-216b-5p in tumor and adjacent tissues was investigated. The impact of miR-96-5p on apoptosis and invasion of a hepatoma cell line, HepG2, was investigated by cell counting, Transwell assay, and flow cytometry, respectively.

Results: MicroRNA-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, and miR-216b-5p were significantly upregulated in tumor tissues compared to the adjacent tissues (p = 0.0005, p = 0.0030, p = 0.0002, p = 0.0011, and p = 0.0288, respectively). By multivariate Cox regression analysis, high tumor/adjacent ratios of miR-182-5p (p = 0.007) and miR-217-5p (p = 0.008) were associated with poor recurrence-free survival. In contrast, a low tumor/adjacent ratio of miR-96-5p (p < 0.001) was associated with poor recurrence-free survival. It suggested that further upregulation of miR-96-5p in tumors might have an inhibitory effect on recurrence. Transfection of miR-96-5p mimic significantly induced apoptosis of HepG2 cells, in association with downregulation of Nucleophosmin 1 (NPM1) and a decrease of phosphorylated AKT protein. Interestingly, simultaneous knockdown of the NPM1 and AKT genes induced apoptosis. MicroRNA-96-5p also suppressed proliferation and invasion, which inhibited epithelial-to-mesenchymal transition of HCC cells.

Conclusion: MicroRNA-96-5p as a tumor suppressor would be valuable to stratify NBNC-HCC patients at high risk of recurrence.
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http://dx.doi.org/10.1111/hepr.13674DOI Listing
May 2021

Effect of Diameter and Number of Hepatocellular Carcinomas on Survival After Resection, Transarterial Chemoembolization, and Ablation.

Am J Gastroenterol 2021 Apr 21. Epub 2021 Apr 21.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan; Department of Biostatistics, School of Public Health, the University of Tokyo, Tokyo, Japan; Department of Surgery, Division of General and Hepatobiliary Surgery, G.B. Rossi Hospital, University of Verona Medical School, Verona, Italy; School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Department of Surgery, San Gerardo Hospital, Monza, Italy; Hepatobiliary Surgery Unit, Foundation "Policlinico Universitario A. Gemelli" IRCCS, Catholic University of the Sacred Heart, Rome, Italy; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Diagnostic Radiology, Saitama Medical University International Medical Center, Saitama, Japan; Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan; Departments of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan; Department of Pathology, Keio University School of Medicine, Tokyo, Japan; Department of Gastroenterology, The Juntendo University, Tokyo, Japan; Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan; Department of Clinical Laboratory Medicine, Kurume University Hospital, Fukuoka, Japan; Department of Radiology, Kobe University Graduate School of Medicine, Hyogo, Japan; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; General and Transplant Surgery Unit, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan; National Center for Global Health and Medicine, Tokyo, Japan.

Introduction: Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables.

Methods: The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort.

Results: Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures decreased with progressive incremental increases in diameter and number of HCCs. For patients undergoing resection, the inverse probability of treatment-weighted-adjusted 5-year OS probabilities were 10%-20% higher compared with patients undergoing TACE for 1-6 HCC lesions <10 cm and were also 10%-20% higher compared with patients undergoing ablation when the HCC diameter was 2-3 cm. For patients undergoing resection and TACE, the model performed well in the external cohort.

Discussion: Our novel prognostic model performed well in predicting OS after resection and TACE for HCC and demonstrated that resection may have a survival benefit over TACE and ablation based on the diameter and number of HCCs.
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http://dx.doi.org/10.14309/ajg.0000000000001256DOI Listing
April 2021

Fibroblast growth factor receptor 2 (FGFR2) fusions in Japanese patients with intrahepatic cholangiocarcinoma.

Jpn J Clin Oncol 2021 May;51(6):911-917

Department of Surgery, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan.

Objective: Fibroblast growth factor receptor gene alterations have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer that has a poor prognosis. This study evaluated the frequency of fibroblast growth factor receptor 2 fusions in clinical specimens from Japanese patients with iCCA.

Methods: This study enrolled 116 patients who had histologically or cytologically confirmed adenocarcinoma and been diagnosed as relapsing after resection or with unresectable intrahepatic cholangiocarcinoma. We evaluated the frequency of fibroblast growth factor receptor 2 fusions-positive cells in their specimens using break-apart fluorescent in situ hybridization 'for 114 patients who met the study protocol'.

Results: Of a total of 114 cases, six (5.3%) were identified as fibroblast growth factor receptor 2 fusions-positive with a high frequency (87% or more) of fibroblast growth factor receptor 2 fusions-positive tumour cells whereas the remainder, with the exception of three cases with indeterminate results, were identified as fibroblast growth factor receptor 2 fusions-negative. The patients' baseline characteristics as well as their objective response rates, disease control rates, times to progression, and times to treatment failure with previous or ongoing first-line chemotherapy did not have any obvious relationship to the proportion of fibroblast growth factor receptor 2 fusions-positive case.

Conclusions: Further detailed elucidation of fibroblast growth factor receptor 2 fusion status is expected to contribute to the development of promising therapeutic options for patients suffering from recurrent or unresectable intrahepatic cholangiocarcinoma.
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http://dx.doi.org/10.1093/jjco/hyab029DOI Listing
May 2021

Durable response after discontinuation of pembrolizumab therapy for intrahepatic cholangiocarcinoma: a case report.

Clin J Gastroenterol 2021 Jun 2;14(3):858-865. Epub 2021 Apr 2.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

Although it has recently been reported that immune checkpoint inhibitors (ICIs) constitute effective treatment for solid tumors, the success rate in patients with intrahepatic cholangiocarcinoma is limited. We administered pembrolizumab to a patient as treatment for liver and lymph node metastases of intrahepatic cholangiocarcinoma. The patient had abundant infiltration of programmed death ligand 1-positive macrophages, cytotoxic T cells (CD8-positive lymphocytes), and programmed death 1-positive lymphocytes as well as a high combined positive score of 33.1, high-frequency microsatellite instability, and mismatch repair deficiency. These characteristics are predictive biomarkers of the efficacy of ICIs. After pembrolizumab was administered four times (triweekly administration), the carbohydrate antigen 19-9 serum level fell within the normal range, and computed tomography revealed that the size of the metastatic liver tumors and enlarged hilar lymph node had markedly decreased. However, the patient developed pruritus and exanthema on the trunk and limbs after 14 administrations and was diagnosed with bullous pemphigoid. We discontinued pembrolizumab therapy and started treatment for bullous pemphigoid. Nine months after discontinuation of pembrolizumab therapy, the patient remains alive without tumor relapse. This patient had durable response even after discontinuation of pembrolizumab therapy for multiple metastases of intrahepatic cholangiocarcinoma.
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http://dx.doi.org/10.1007/s12328-021-01396-5DOI Listing
June 2021

Change in antimicrobial susceptibility of pathogens isolated from surgical site infections over the past decade in Japanese nation-wide surveillance study.

J Infect Chemother 2021 Jul 29;27(7):931-939. Epub 2021 Mar 29.

Department of Infection Control and Prevention, Kagoshima University Hospital, Kagoshima, Japan.

Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2018 to 2019 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in 2010 and 2014-2015 surveillance studies. Although the rate of detection of extended-spectrum β-lactamase producing strains of Escherichia coli was increased from 9.5% in 2010 to 23% in 2014-2015, the incidence decreased to 8.7% in 2018-2019. Although high susceptibility rates were detected to piperacillin/tazobactam (TAZ), the geometric mean MICs were substantially higher than to meropenem (2.67 vs 0.08 μg/mL). By contrast, relatively low geometric mean MICs (0.397 μg/mL) were demonstrated for ceftolozane/TAZ. Although the MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second, no further decrease was detected in 2018-2019. For the Bacteroides fragilis group species, low levels of susceptibility were observed for moxifloxacin (65.3%), cefoxitin (65.3%), and clindamycin (CLDM) (38.9%). In particular, low susceptibility against cefoxitin was demonstrated in non-fragilis Bacteroides, especially B. thetaiotaomicron. By contrast, low susceptibility rates against CLDM were demonstrated in both B. fragilis and non-fragilis Bacteroides species, and a steady decrease in susceptibility throughout was observed (59.3% in 2010, 46.9% in 2014-2015, and 38.9% in 2018-2019). In conclusion, Japanese surveillance data revealed no significant lowering of antibiotic susceptibility over the past decade in organisms commonly associated from SSIs, with the exception of the B. fragilis group.
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http://dx.doi.org/10.1016/j.jiac.2021.03.010DOI Listing
July 2021

Association between the confluent form of pancreatic and bile duct and histopathological findings in pancreaticobiliary maljunction: A case series study.

Ann Med Surg (Lond) 2021 Mar 23;63:102180. Epub 2021 Feb 23.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

Introduction: Pancreaticobiliary maljunction (PBM) is a congenital anomaly wherein the persistent reflux of the pancreatic juice into the biliary tract induces biliary tract cancer. The prediction criteria for gallbladder carcinogenesis have been reported previously through results obtained from examining carcinogenic and non-carcinogenic cases with the parameters that classified each confluent form in PBM. This study aimed to validate these previous study results and provide new recommendations for gallbladder carcinogenesis prevention.

Methods: Twenty-four patients with PBM underwent hepaticojejunostomy. The prediction criteria for gallbladder carcinogenesis consist of three elements. The confluent forms that satisfied none or one of the three criteria were defined as a low score group, and those that satisfied two or three were defined as the high score group. Immunohistology and pathological search were performed on the gallbladders' sections in both groups to evaluate chronic inflammation.

Results: The cases with dysplasia, positive Ki67 labeling index, and gallbladder cancer were more common in the high score group and tended to have more lymphocyte infiltration. These findings indicate that the degree of inflammation and cell proliferation might be more severe in the high score group than in the low score group.

Conclusions: There is a close relationship between the confluent form and the histopathological findings of the gallbladder in patients with PBM. The confluent forms observed in the high score group might have an additional correlation with increased proliferation activity and subsequent malignant transformation of the gallbladder epithelium.
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http://dx.doi.org/10.1016/j.amsu.2021.102180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920799PMC
March 2021

Clinical benefit for clinical sequencing using cancer panel testing.

PLoS One 2021 26;16(2):e0247090. Epub 2021 Feb 26.

Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background: Clinical sequencing using a panel of genes has recently been applied worldwide for patients with refractory solid tumors, but the significance of clinical sequencing using gene panel testing remains uncertain. Here we sought to clarify the feasibility and utility of clinical sequencing in the treatment of refractory tumors at our hospital.

Methods: A total of 39 patients with advanced solid tumors treated at our hospital between 2018 and 2020 were enrolled in the clinical sequencing. Among them, we identified 36 patients whose tissue samples were of suitable quality for clinical sequencing, and we analyzed the genomic profiles of these tumors.

Results: Pathogenic alterations were detected in 28 (78%) of the 36 patients. The most common mutation was TP53 (55%), followed by KRAS (22%), and the highest frequency of gene amplification was ERBB2 (17%). Nine of the 36 patients were identified as candidates for novel molecular-targeted therapy based on their actionable gene alterations, but only one case ended up receiving novel targeted therapy following the genetic tests.

Conclusions: Our current results suggested that clinical sequencing might be useful for the detection of pathogenic alterations and the management of additional cancer treatment. However, molecular target based on actionable genomic alteration does not always bridge to subsequent therapy due to clinical deterioration, refusal for unapproved drug, and complexity of clinical trial access. Both improved optimal timing of clinical sequencing and a consensus about its off-label use might help patients receive greater benefit from clinical sequencing.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247090PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909652PMC
August 2021

Should Lymph Nodes Be Retrieved in Patients with Intrahepatic Cholangiocarcinoma? A Collaborative Korea-Japan Study.

Cancers (Basel) 2021 Jan 25;13(3). Epub 2021 Jan 25.

Department of Surgery, Sungkyunkwan University School of Medicine, Seoul 16419, Korea.

Background: This study was performed to investigate the oncologic role of lymph node (LN) management and to propose a surgical strategy for treating intrahepatic cholangiocarcinoma (IHCC).

Methods: The medical records of patients with resected IHCC were retrospectively reviewed from multiple institutions in Korea and Japan. Short-term and long-term oncologic outcomes were analyzed according to lymph node metastasis (LNM). A nomogram to predict LNM in treating IHCC was established to propose a surgical strategy for managing IHCC.

Results: A total of 1138 patients were enrolled. Of these, 413 patients underwent LN management and 725 did not. A total of 293 patients were found to have LNM. The No. 12 lymph node (36%) was the most frequent metastatic node, and the No. 8 lymph node (21%) was the second most common. LNM showed adverse long-term oncologic impact in patients with resected IHCC (14 months, 95% CI (11.4-16.6) vs. 74 months, 95% CI (57.2-90.8), < 0.001), and the number of LNM (0, 1-3, 4≤) was also significantly related to negative oncologic impacts in patients with resected IHCC (74 months, 95% CI (57.2-90.8) vs. 19 months, 95% CI (14.4-23.6) vs. 11 months, 95% CI (8.1-13.8)), < 0.001). Surgical retrieval of more than four (≥4) LNs could improve the survival outcome in resected IHCC with LNM (13 months, 95% CI (10.4-15.6)) vs. 30 months, 95% CI (13.1-46.9), = 0.045). Based on preoperatively detectable parameters, a nomogram was established to predict LNM according to the tumor location. The AUC was 0.748 (95% CI: 0.706-0.788), and the Hosmer and Lemeshow goodness of fit test showed = 0.4904.

Conclusion: Case-specific surgical retrieval of more than four LNs is required in patients highly suspected to have LNM, based on a preoperative detectable parameter-based nomogram. Further prospective research is needed to validate the present surgical strategy in resected IHCC.
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http://dx.doi.org/10.3390/cancers13030445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865580PMC
January 2021

PD-L1 positive macrophages were increased in a case of pembrolizumab-induced bullous pemphigoid.

J Dermatol 2021 Mar 13;48(3):e146-e148. Epub 2021 Jan 13.

Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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http://dx.doi.org/10.1111/1346-8138.15756DOI Listing
March 2021

Intrahepatic cholangiocarcinoma with a tumor thrombus extending from the inferior vena cava to the right atrium: a case report.

Surg Case Rep 2021 Jan 6;7(1). Epub 2021 Jan 6.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

Background: Vascular invasion involving a tumor thrombus in the inferior vena cava and/or right atrium is an unfavorable prognostic factor after intrahepatic cholangiocarcinoma resection. We report an intrahepatic cholangiocarcinoma case with a tumor thrombus extending from the left hepatic vein via the inferior vena cava to the right atrium.

Case Presentation: A 58-year-old man with epigastralgia was referred to our hospital after an emergent transcatheter arterial embolization was done following the radiological diagnosis of a ruptured hepatic tumor. The serum concentrations of carcinoembryonic antigen, carbohydrate 19-9, duke pancreatic monoclonal antigen type 2, and cytokeratin-19 fragments were elevated; meanwhile those of alfa-fetoprotein and des-γ-carboxy prothrombin were within normal ranges. A contrast-enhanced computed tomography scan showed a heterogeneously enhanced tumor, 13 cm in diameter, in the left lobe of the liver, enlarged lymph nodes along the lesser curvature of the stomach, and a tumor thrombus extending from the left hepatic vein via the inferior vena cava to the right atrium. We performed a left hemihepatectomy and tumor thrombectomy under total hepatic vascular exclusion to reduce the risk of sudden death. After dissection of the liver parenchyma along the left side of the middle hepatic vein, except for the left hepatic vein, the inferior vena cava just below the right atrium could be clamped by pulling down the left lobe of the liver toward the caudal side. The thrombus could be removed by incising the inferior vena cava under total hepatic vascular exclusion. Microscopic examination showed a tubular adenocarcinoma. Immunohistochemical staining was positive for cytokeratin-7, cytokeratin-19, and epithelial membrane antigen, but negative for arginase-1, glypican-3, and hepatocyte. The patient was pathologically diagnosed with an intrahepatic cholangiocarcinoma with a tumor thrombus in the inferior vena cava. Adjuvant chemotherapy with tegafur/gimeracil/oteracil was administered for 1 year. The patient remained in good health without cancer recurrence for over 4 years after the operation.

Conclusion: An aggressive surgical approach may be indicated for intrahepatic cholangiocarcinoma with a tumor thrombus in the inferior vena cava and/or right atrium to avoid the risk of impending death.
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http://dx.doi.org/10.1186/s40792-020-01085-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788148PMC
January 2021

Report of the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan (2010-2011).

Hepatol Res 2021 Apr 4;51(4):355-405. Epub 2021 Mar 4.

Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.

In the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 22,134 new patients and 41,956 previously followed patients were compiled from 546 institutions over a 2-year period from 1 January 2010 to 31 December 2011. Basic statistics compiled for patients newly registered in the 21st survey were cause of death, medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 20th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy and with radiofrequency ablation. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 1998 and 2011 whose final outcome was survival or death (excluding unknown). Cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, and Child-Pugh grade) and by treatment type (hepatectomy, local ablation therapy, transcatheter arterial chemoembolization, and hepatic arterial infusion chemotherapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2011 into four time-period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer.
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http://dx.doi.org/10.1111/hepr.13612DOI Listing
April 2021

Precancerous Lesions and Liver Atrophy as Risk Factors for Hepatolithiasis-Related Death after Liver Resection for Hepatolithiasis.

Asian Pac J Cancer Prev 2020 Dec 1;21(12):3647-3654. Epub 2020 Dec 1.

Department of Hepato-Biliary-Pancreatic Surgery Osaka City University Graduate School of Medicine 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.

Background: Cholangiocarcinoma and secondary biliary cirrhosis can develop after liver resection for hepatolithiasis and are causes of hepatolithiasis-related death. We determined potential risk factors for hepatolithiasis-related death and subsequent cholangiocarcinoma, including precancerous lesions such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct, in patients undergoing liver resection for hepatolithiasis.

Methods: The study cohort included 62 patients who underwent liver resection for hepatolithiasis without concomitant cholangiocarcinoma and had surgical specimens available for pathological examination. Univariate and multivariate analyses were conducted to examine risk factors associated with subsequent cholangiocarcinoma after hepatolithiasis and hepatolithiasis-related death. In 28 patients with BilIN lesions, the specimens were immunohistochemically stained for γ-H2AX and S100P.

Results: In the study cohort, the causes of death were subsequent cholangiocarcinoma, biliary cirrhosis, and other diseases in 5, 3, and 7 patients, respectively. Liver atrophy, precancerous lesions, postoperative repeated cholangitis, and jaundice for ≥1 week during the follow-up period were risk factors for hepatolithiasis-related death. Multivariate analysis showed that liver atrophy and precancerous lesions were independent risk factors for hepatolithiasis-related death. Liver atrophy or precancerous lesions were also risk factors for subsequent cholangiocarcinoma by univariate analysis. The positive expression of γ-H2AX and S100P was observed in 18 and 14 of the 28 BilIN lesions, respectively.

Conclusions: Liver atrophy and precancerous lesions with malignant transformation were risk factors not only for subsequent cholangiocarcinoma but also hepatolithiasis-related death after liver resection for hepatolithiasis, indicating that long-term follow-up is necessary even after liver resection in patients harboring these risk factors.
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http://dx.doi.org/10.31557/APJCP.2020.21.12.3647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046297PMC
December 2020

Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma.

Surgery 2021 04 13;169(4):922-928. Epub 2020 Nov 13.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Japan.

Background: Extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection.

Methods: The participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping.

Results: Extrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3-5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively.

Conclusion: We have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon's selection of treatment strategies for hepatocellular carcinoma patients.
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http://dx.doi.org/10.1016/j.surg.2020.10.012DOI Listing
April 2021

New Hepatic Resection Criteria for Intermediate-Stage Hepatocellular Carcinoma Can Improve Long-Term Survival: A Retrospective, Multicenter Collaborative Study.

Asian Pac J Cancer Prev 2020 Oct 1;21(10):2903-2911. Epub 2020 Oct 1.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background: Hepatic resection (HR) is not recommended for intermediate-stage hepatocellular carcinoma (HCC) by the Barcelona Clinic Liver Cancer criteria. We examined the prognostic factors of HR for intermediate-stage HCC and developed new HR criteria for intermediate-stage HCC.

Methods: A total of 110 patients who underwent HR without any prior treatment for intermediate-stage HCC between January 2007 and December 2012 were enrolled at eight university hospitals. The outcomes and prognostic factors of HR were evaluated to develop new HR criteria.

Results: In terms of tumor size and number, the most significant prognostic factors were within the up-to-seven criteria. Furthermore, serum albumin level ≥35 g/L and serum alpha-fetoprotein (AFP) level.
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http://dx.doi.org/10.31557/APJCP.2020.21.10.2903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798158PMC
October 2020

Analysis of Patient Outcome after Non-curative Resection for Hepatocellular Carcinoma Using Nationwide Survey Data in Japan.

World J Surg 2021 Feb 26;45(2):607-614. Epub 2020 Oct 26.

Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan.

Background: Non-curative (debulking) hepatic resection for hepatocellular carcinoma (HCC) is occasionally applied for selected cases with bulky tumors or for oncologic emergency cases; however, the clinical usefulness of this procedure has not yet been fully evaluated. The aim of the present study was to evaluate the patient outcomes of non-curative hepatic resections for HCC using data from bi-annual nationwide surveys conducted in Japan.

Method: Data of 1084 non-curative hepatic resections for HCC were collected. The patient outcomes were compared with those of curative resections, transcatheter arterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy (HAIC).

Results: Patient survival after the non-curative resection was poorer than that after curative resection (P < 0.001) and was especially dismal in cases with extrahepatic tumor spread (lymph node metastasis, peritoneal seeding, or distant metastasis). As compared to cases receiving TACE without surgery, non-curative resections for multiple intrahepatic tumors were applied to cases with advanced tumors with good liver functional reserve. The survival outcomes were significantly more favorable in the TACE group, but the results became similar after propensity score matching of the patients. The survival outcome of patients receiving non-curative resections was better than that of cases treated by HAIC, with median survival times of 26.0 months and 10.0 months, respectively.

Conclusion: The indications for non-curative hepatic resection in patients with HCC should be judged cautiously, especially in patients with extrahepatic tumor spread. This treatment approach may be beneficial for selected patients with intermediate- or advanced-stage HCC limited in liver and with good liver functional reserve.
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http://dx.doi.org/10.1007/s00268-020-05830-6DOI Listing
February 2021

Risk factors for hepatocellular carcinoma in treated chronic hepatitis C patients-Relationship to smoking and alcohol.

JGH Open 2020 Oct 16;4(5):867-875. Epub 2020 Apr 16.

Department of Public Health Osaka City University Graduate School of Medicine Osaka Japan.

Background And Aim: The purpose of this study was to identify lifestyle risk factors, such as cigarette smoking and alcohol consumption, in relation to the development of hepatocellular carcinoma (HCC) among chronic hepatitis C patients who have achieved a sustained virologic response (SVR).

Methods: This cross-sectional study was conducted between 2014 and 2017 using self-administered questionnaires and medical information at two tertiary hospitals in Osaka, Japan. Study subjects were chronic hepatitis C patients who had achieved SVR without HCC following antiviral treatment that was completed more than 1 year earlier. A logistic regression model was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the development of post-SVR HCC for each factor.

Results: Of 202 participants, 18 patients were diagnosed with post-SVR HCC. After considering potential confounders, former drinkers at the time of SVR (OR, 9.51; 95% CI, 1.08-83.90) and patients with a history of gastric or duodenal ulcer (OR, 4.14; 95% CI, 1.37-12.46) were significantly associated with HCC. In addition, among patients with severe fibrosis, current smokers at the time of SVR had an increased OR for HCC compared with never smokers, with marginal significance (OR, 5.61; 95% CI, 0.97-32.63).

Conclusions: In chronic hepatitis C patients with severe fibrosis, continuing smoking after achieving SVR could be a risk factor for post-SVR HCC. The relationship between gastric or duodenal ulcer history and post-SVR HCC should be investigated further.
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http://dx.doi.org/10.1002/jgh3.12331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578324PMC
October 2020

Successful temporary resection of a ruptured hepatoblastoma without preoperative chemotherapy: A case report presenting a novel surgical strategy.

Int J Surg Case Rep 2020 10;76:431-434. Epub 2020 Oct 10.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abenoku, Osaka, 545-8585, Japan.

Introduction: Although spontaneous tumor rupture is a serious complication of hepatoblastoma, there is no consensus regarding the treatment strategy in infants. We report a patient with lung metastases who had a ruptured hepatoblastoma prior to the start of the scheduled chemotherapy and was successfully treated with a combined treatment including liver resection, lung resection, and chemotherapy.

Presentation Of Case: A 22-month-old boy with a ruptured hepatoblastoma and lung metastases underwent an emergency laparotomy with complete tumor resection, followed by chemotherapy. Moreover, a barely detectable metastatic lung lesion shown by a chest CT scan was resected after the fifth chemotherapy treatment. Both postoperative and chemotherapy courses were uneventful. The patient survived without any recurrent hepatoblastoma 2 years after the emergency surgery despite the poor prognosis indicated by distant metastases at the time of diagnosis.

Discussion: Because rupture itself can be the main cause of death in patients with hepatoblastoma, emergency tumor hemostasis is essential. However, there are no reports comparing the prognosis of the treatment method performing tumor hemostasis alone, tumor resection after chemotherapy, and tumor hemostasis and resection at the same time. The clinical course of the patient indicates that performing tumor hemostasis and resection simultaneously and lung resection after chemotherapy is an effective option to treat a ruptured hepatoblastoma with disseminated tumors and lung metastases if the patient's condition is stable.

Conclusion: Aggressive treatment with surgery and chemotherapy is an effective option for ruptured hepatoblastoma with disseminated tumors and lung metastases in infants.
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http://dx.doi.org/10.1016/j.ijscr.2020.09.202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585050PMC
October 2020

Lenvatinib-Induced Tumor-Related Hemorrhages in Patients with Large Hepatocellular Carcinomas.

Oncology 2021 8;99(3):186-191. Epub 2020 Oct 8.

Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.

Introduction: Lenvatinib has been approved as a systemic therapy for patients with unresectable hepatocellular carcinoma (HCC). We recently experienced lenvatinib-induced tumor-related hemorrhage in patients with HCC. The full details of tumor-related hemorrhage as a lenvatinib-related adverse event have not been elucidated.

Methods: This was a retrospective single-center study that enrolled consecutive patients treated with lenvatinib for unresectable HCC from April 2018 to February 2020.

Results: Sixty-eight consecutive patients were enrolled in this study. Among them, 5 cases developed intraperitoneal or intratumoral hemorrhages. The patients with hemorrhage had larger tumors (maximum tumor size, 97.5 ± 46.4 and 38.2 ± 28.8 mm, respectively; p = 0.009) than the patients without hemorrhage. The dosing period of lenvatinib (median, 3 and 93 days, respectively; p < 0.001) and the survival time from initial administration of lenvatinib (median, 77 and 495 days, respectively; p < 0.001) of the patients with hemorrhage were shorter than those of the patients without hemorrhage. Especially, in 4 cases with large HCCs (maximum tumor diameter was >90 mm), tumor hemorrhage with vascular lake-like phenomenon was evident, although most tumor blood flow was suppressed.

Discussion/conclusion: It becomes clear that lenvatinib treatment brings about tumor-related hemorrhages despite rapid suppression of tumor blood flow. We speculate that lenvatinib quickly blocks the feeding circulation, resulting in tumor hemorrhage by necrosis. Clinicians should pay careful attention to the development of life-threatening hemorrhages when treating large HCCs with lenvatinib.
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http://dx.doi.org/10.1159/000510911DOI Listing
March 2021

Impact of the Preoperative C-reactive Protein to Albumin Ratio on the Long-Term Outcomes of Hepatic Resection for Intrahepatic Cholangiocarcinoma.

Asian Pac J Cancer Prev 2020 Aug 1;21(8):2373-2379. Epub 2020 Aug 1.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan.

Objective: The present study aimed to investigate the impact of preoperative C-reactive protein to albumin (CRP/Alb) ratio on the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC).

Methods: 82 patients who underwent hepatic resection for mass-forming type of ICC were evaluated. The relationship between preoperative CRP/Alb ratio and survival outcomes was investigated.

Results: The optimal cutoff value of CRP/Alb ratio for assessing overall survival (OS) was determined as 0.089. Univariate analysis for recurrence-free survival (RFS) showed that CRP/Alb ratio >0.089, carbohydrate antigen 19-9 (CA 19-9) >37 U/mL, lymph node metastasis, vascular invasion, and multiple tumors were significantly associated with postoperative recurrence. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.006), and multiple tumors (p < 0.001). Univariate analysis for OS showed that CRP/Alb ratio >0.089, CA 19-9 >37 U/mL, lymph node metastasis, vascular invasion, multiple tumors, and positive surgical margin were significantly associated with overall death. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.01), and multiple tumors (p = 0.005).

Conclusion: Preoperative CRP/Alb ratio may predict poor long-term outcomes after hepatic resection in patients with ICC.
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http://dx.doi.org/10.31557/APJCP.2020.21.8.2373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771946PMC
August 2020

Surgical outcomes for hepatocellular carcinoma detected after hepatitis C virus eradiation by direct-acting antivirals.

J Surg Oncol 2020 Dec 27;122(8):1543-1552. Epub 2020 Aug 27.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Objective: To investigate the postoperative recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after liver resection in patients with and without the achievement of sustained virologic response (SVR) through the administration of direct-acting antivirals (DAA).

Methods: Among 28 patients with HCC detected after DAA-SVR (DAA group) and 197 patients with HCC who did not receive treatment for HCV infection or who did not achieve an SVR (control group) between January 2000 and July 2019, we performed propensity score matching (PSM) to avoid confounding differences between the two groups.

Results: After PSM, 28 patients in each group were selected for analysis. The DAA-SVR patients showed improved liver function at operation and at recurrence in comparison to the control group. The disease-free survival rate at 3 years after surgery was 69% in the DAA group and 35% in the control group, respectively (P = .021). In the DAA group, all three patients with recurrence met the Milan criteria and could be managed by curative treatments and none died of liver failure during the follow-up period.

Conclusions: SVR status suppresses postoperative recurrence of HCV-related HCC detected after DAA-SVR. Improved liver function may contribute to the successful treatment and prevention of liver failure.
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http://dx.doi.org/10.1002/jso.26184DOI Listing
December 2020

A case of primary hepatic mixed neuroendocrine-non-neuroendocrine tumor (MiNEN) associated with gallbladder carcinosarcoma.

Clin J Gastroenterol 2020 Dec 10;13(6):1280-1288. Epub 2020 Aug 10.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

A woman in her seventies visited our hospital because of abdominal pain. Multiple hepatic tumors were detected and a liver biopsy revealed mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), which was composed of cholangiocellular carcinoma and neuroendocrine tumor (NET). Diagnostic imaging ruled out primary malignancies other than the liver and identified that the tumor originated from the liver. Because a predominant and aggressive part of the tumor was considered to be cholangiocellular carcinoma, gemcitabine and S-1 were used as first-line treatment. After the treatment, octreotide acetate was administered for the NET component, followed by transcatheter arterial embolization. Subsequently, her gallbladder (GB) rapidly swelled with biliary tract obstruction, and cholecystectomy revealed carcinosarcoma of the GB. She is still undergoing treatment at 44 months after diagnosis. Herein we report this case of primary hepatic MiNEN consisting of cholangiocarcinoma and NET, followed by GB carcinosarcoma. This is the first case illustrating that a multidisciplinary treatment approach for MiNEN accompanied with carcinosarcoma, involving assessment and treatment targeting the most aggressive component, can result in a long survival time.
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http://dx.doi.org/10.1007/s12328-020-01202-8DOI Listing
December 2020

Lifestyles Associated with Prognosis After Eradication of Hepatitis C Virus: A Prospective Cohort Study in Japan.

Dig Dis Sci 2021 06 27;66(6):2118-2128. Epub 2020 Jul 27.

Department of Public Health, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka, 545-8585, Japan.

Background: Hepatocellular carcinoma develops in some patients with hepatitis C virus (HCV), even after achieving sustained virological response (SVR).

Aims: We examined factors associated with liver disease progression in a prospective cohort study of SVR patients.

Methods: Participants were patients who had visited a hospital for clinical follow-up of chronic HCV infection in 2005 and had reached SVR as a result of subsequent antiviral treatment. Baseline information including lifestyle and dietary habits before SVR was collected in 2005 using self-administered questionnaires, and clinical information before SVR was collected from medical records in 2005. Study outcome was liver disease progression such as liver cirrhosis, hepatocellular carcinoma, and/or liver disease-related death after SVR. Proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals for each variable.

Results: Of 180 SVR patients, 27 patients (15%) showed liver disease progression after SVR: 26 (14%) were diagnosed with liver cirrhosis, two (1%) with hepatocellular carcinoma, and/or one (0.6%) with liver-disease-related death. Besides older age at SVR (HR = 11.9, P < 0.01) and aspartate aminotransferase-to-platelet ratio index score ≥ 1.0 before SVR (HR = 2.63, P = 0.03), alcohol drinkers before SVR (HR = 2.82, P = 0.06) were suggested to be associated with liver disease progression after SVR, whereas higher consumption of vitamin B12 before SVR showed a decreased HR for liver disease progression (HR = 0.41, P = 0.09).

Conclusions: Alcohol drinking might be associated with liver disease progression, whereas vitamin B12 intake might have protective effects against liver disease progression after eradication of HCV. Further studies are needed to confirm these findings.
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http://dx.doi.org/10.1007/s10620-020-06475-0DOI Listing
June 2021

Mortality analysis of Aeromonas hydrophila infection in hepato-biliary pancreatic surgery: Multicenter retrospective observational study.

J Hepatobiliary Pancreat Sci 2020 Oct 16;27(10):747-755. Epub 2020 Aug 16.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka City, Japan.

Background/purpose: Aeromonas hydrophila can cause lethal infectious complications after surgery. There have been no large cohort studies of this specific to the hepato-biliary-pancreatic (HBP) field. We investigate the postoperative influence of A hydrophila infection after HBP surgery.

Methods: We retrospectively reviewed patients who underwent HBP surgery between 2008 and 2017 at eight university hospitals. Patients with A hydrophila isolation during perioperative management were extracted, and their postoperative courses were investigated.

Results: Bacterial culture examination of 10 074 patients was performed as perioperative management. Among them, 76 patients (0.75%) had A hydrophila isolation, most of whom underwent pancreatoduodenectomy (n = 38) or hepatectomy with biliary reconstruction (n = 14). There were seven mortalities after these two procedures (13.5%), five within 3 days after the onset of infection. Bile (n = 48) and abdominal drainage fluid (n = 29) were major sites of A hydrophila isolation. Typical prophylactic antibiotics, cefazolin or flomoxef, were mostly resistant. There was no mortality among patients that received sensitive antibiotics prophylactically.

Conclusions: Isolation of A hydrophila was low in our cases of HBP surgery, but the condition of some patients deteriorated rapidly by this infection. Although there could be several bacterial infections during management of HBP surgery, A hydrophila should not be overlooked. Preparation of appropriate prophylactic antibiotics may prevent or reduce mortality.
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http://dx.doi.org/10.1002/jhbp.805DOI Listing
October 2020
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