Publications by authors named "Junichi Arita"

138 Publications

High-performance Collective Biomarker from Liquid Biopsy for Diagnosis of Pancreatic Cancer Based on Mass Spectrometry and Machine Learning.

J Cancer 2021 4;12(24):7477-7487. Epub 2021 Nov 4.

Department of Anatomy and Cell Biology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.

Most pancreatic cancers are found at progressive stages when they cannot be surgically removed. Therefore, a highly accurate early detection method is urgently needed. This study analyzed serum from Japanese patients who suffered from pancreatic ductal adenocarcinoma (PDAC) and aimed to establish a PDAC-diagnostic system with metabolites in serum. Two groups of metabolites, primary metabolites (PM) and phospholipids (PL), were analyzed using liquid chromatography/electrospray ionization mass spectrometry. A support vector machine was employed to establish a machine learning-based diagnostic algorithm. Integrating PM and PL databases improved cancer diagnostic accuracy and the area under the receiver operating characteristic curve. It was more effective than the algorithm based on either PM or PL database, or single metabolites as a biomarker. Subsequently, 36 statistically significant metabolites were fed into the algorithm as a collective biomarker, which improved results by accomplishing 97.4% and was further validated by additional serum. Interestingly, specific clusters of metabolites from patients with preoperative neoadjuvant chemotherapy (NAC) showed different patterns from those without NAC and were somewhat comparable to those of the control. We propose an efficient screening system for PDAC with high accuracy by liquid biopsy and potential biomarkers useful for assessing NAC performance.
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http://dx.doi.org/10.7150/jca.63244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8734412PMC
November 2021

MNX1-HNF1B axis is indispensable for intraductal papillary mucinous neoplasm lineages.

Gastroenterology 2021 Dec 21. Epub 2021 Dec 21.

Division of Advanced Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Background And Aims: Chromatin architecture governs cell lineages by regulating the specific gene expression; however, its role in the diversity of cancer development remains unknown. Among pancreatic cancers, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMN) with an associated invasive carcinoma (IPMNinv) arise from two distinct precursors, and their fundamental differences remain obscure. Here, we aimed to assess the difference of chromatin architecture regulating transcriptional signatures or biological features in pancreatic cancers.

Methods: We established 28 human organoids from distinct subtypes of pancreatic tumors, including IPMN, IPMNinv, and PDAC. We performed exome-seq, RNA-seq, ATAC-seq, ChIP-seq, Hi-C, and phenotypic analyses with shRNA or CRISPR interference.

Results: Established organoids successfully reproduced the histology of primary tumors. IPMN and IPMNinv organoids harbored GNAS, RNF43, or KLF4 mutations and showed the distinct expression profiles compared to PDAC. Chromatin accessibility profiles revealed the gain of stomach-specific open regions in IPMN and the pattern of diverse gastrointestinal tissues in IPMNinv. In contrast, PDAC presented an impressive loss of accessible regions in comparison with normal pancreatic ducts. Transcription factor footprint analysis and functional assays identified that MNX1 and HNF1B were biologically indispensable for IPMN lineages. The upregulation of MNX1 was specifically marked in the human IPMN lineage tissues. The MNX1-HNF1B axis governed a set of genes including MYC, SOX9, and OLFM4, which are known to be essential for gastrointestinal stem cells. Hi-C analysis suggested the HNF1B target genes to be three-dimensionally connected in the genome of IPMNinv.

Conclusion: Our organoid analyses identified the MNX1-HNF1B axis to be biologically significant in IPMN lineages.
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http://dx.doi.org/10.1053/j.gastro.2021.12.254DOI Listing
December 2021

Artificial intelligence enhances the accuracy of portal and hepatic vein extraction in computed tomography for virtual hepatectomy.

J Hepatobiliary Pancreat Sci 2021 Nov 14. Epub 2021 Nov 14.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background/purpose: Current conventional algorithms used for 3-dimensional simulation in virtual hepatectomy still have difficulties distinguishing the portal vein (PV) and hepatic vein (HV). The accuracy of these algorithms was compared with a new deep-learning based algorithm (DLA) using artificial intelligence.

Methods: A total of 110 living liver donor candidates until 2017, and 46 donor candidates until 2019 were allocated to the training group and validation groups for the DLA, respectively. All PV or HV branches were labeled based on Couinaud's segment classification and the Brisbane 2000 Terminology by hepato-biliary surgeons. Misclassified and missing branches were compared between a conventional tracking-based algorithm (TA) and DLA in the validation group.

Results: The sensitivity, specificity, and Dice coefficient for the PV were 0.58, 0.98, and 0.69 using the TA; and 0.84, 0.97, and 0.90 using the DLA (P < .001, excluding specificity); and for the HV, 0.81, 087, and 0.83 using the TA; and 0.93, 0.94 and 0.94 using the DLA (P < .001 to P = .001). The DLA exhibited greater accuracy than the TA.

Conclusion: Compared with the TA, artificial intelligence enhanced the accuracy of extraction of the PV and HVs in computed tomography.
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http://dx.doi.org/10.1002/jhbp.1080DOI Listing
November 2021

[Ⅰ.Treatment Strategy for Intrahepatic Recurrence of Hepatocellular Carcinoma after Surgical Resection].

Gan To Kagaku Ryoho 2021 Oct;48(10):1218-1222

Hepato-Biliary-Pancreatic Surgery Division, Dept. of Surgery, Graduate School of Medicine, The University of Tokyo.

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October 2021

Understanding conditional cumulative incidence of complications following liver resection to optimize hospital stay.

HPB (Oxford) 2021 Jul 8. Epub 2021 Jul 8.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address:

Background: After liver resection, the in-hospital observation periods associated with minimal risks for complications and unplanned readmission remains unclear. This study aimed to assess changes in risks of complications over time.

Methods: Surgical complexity of liver resection was stratified into grades I (low complexity), II (intermediate), and III (high). The cumulative incidence rate and risk factors for complication ≥ Clavien-Dindo grade II (defined as treatment-requiring complications) were assessed.

Results: Of 581 patients, grade I, II, and III resections were performed in 81 (13.9%), 119 (20.5%), and 381 patients (65.6%). Complexity grades (I vs. III, hazard ratio [HR] 0.45, P = 0.007; II vs. III, HR 0.60, P = 0.011) and background liver status (HR 1.76, P = 0.004) were risk factors for treatment-requiring complications. The cumulative incidence rate of treatment-requiring complications was higher after grade III resection than grade I resection (38.1% vs. 16.1%, P < 0.001) or grade II resection (38.1% vs. 25.2%, P = 0.019). Without cirrhosis/chronic hepatitis, the cumulative incidence rate of treatment-requiring complications decreased to less than 10% on postoperative day (POD) 3 after grade I resection, POD 5 after grade II resection, and POD 10 after grade III resection.

Conclusion: Conditional complication risk analysis stratified by surgical complexity may be useful for optimizing in-hospital observation.
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http://dx.doi.org/10.1016/j.hpb.2021.06.419DOI Listing
July 2021

Management of neuroendocrine liver metastasis: Searching for new prognostic factor and appraising repeat hepatectomy.

Hepatobiliary Surg Nutr 2021 Jun;10(3):410-412

Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.21037/hbsn-21-88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188123PMC
June 2021

A safe sequential treatment approach for patients who have acute cholecystitis with severe inflammation: Transmural gallbladder drainage followed by laparoscopic cholecystectomy under the guidance of fluorescence imaging.

Asian J Endosc Surg 2022 Jan 30;15(1):230-234. Epub 2021 May 30.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

Introduction: For patients who have acute severe cholecystitis, urgent/early biliary drainage followed by delayed/elective laparoscopic cholecystectomy is recommended according to the Tokyo Guidelines 2018. Percutaneous transhepatic gallbladder drainage is an established technique. Recently, transmural gallbladder drainage under the guidance of endoscopic ultrasonography (EUS-GBD) was reported as a safe alternative. During surgery, fluorescence imaging using indocyanine green (ICG) has been increasingly used for visualizing the bile ducts. Herein, we report a sequential treatment approach which ensures safety without impairing normal activities before cholecystectomy: EUS-GBD followed by laparoscopic cholecystectomy using ICG fluorescence imaging.

Materials And Surgical Technique: A 66-year-old man with acute cholecystitis underwent urgent EUS-GBD and had the drainage tube placement through the duodenum into the gallbladder. During 2.5 months of the waiting period, he had no clinical troubles. After insertion of a laparoscope, we found a structure between the gallbladder and the duodenum. We injected 0.025 mg/mL of ICG into the nasobiliary drainage tube (placed in the gallbladder through the duodenum) and confirmed that the structure was a fistula. After removing the tube, the fistula was divided using a surgical stapler under the guidance of fluorescence imaging. The cystic and common bile ducts were also clearly visualized as fluorescence.

Discussion: We reported a safe sequential treatment approach for the patient who required biliary drainage: EUS-GBD followed by laparoscopic cholecystectomy under the guidance of ICG fluorescence imaging. This sequential approach may improve patients' satisfaction with respect to quality of life during the waiting period and may ensure the safety of laparoscopic cholecystectomy.
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http://dx.doi.org/10.1111/ases.12955DOI Listing
January 2022

Impact of board certification system and adherence to the clinical practice guidelines for liver cancer on post-hepatectomy risk-adjusted mortality rate in Japan: A questionnaire survey of departments registered with the National Clinical Database.

J Hepatobiliary Pancreat Sci 2021 Oct 7;28(10):801-811. Epub 2021 Jul 7.

The Japanese Society of Gastroenterological Surgery, Tokyo, Japan.

Background: It is unclear to what extent a board certification system and implementation of clinical guidelines improves the quality of hepatectomy.

Methods: A web-based questionnaire survey was administered to departments registered with the National Clinical Database (NCD) in Japan between 1 October 2014 and 31 January 2015. Quality indicators (QIs), including affiliations with academic societies, numbers of board-certified doctors affiliated with each institute, and adherence to clinical practice guidelines for hepatocellular carcinoma, were evaluated by calculating risk-adjusted odds ratios (AORs) for 90-day postoperative mortality of patients who had undergone hepatectomy in 2013 and 2014.

Results: Of 1255 departments that had registered at least one hepatectomy in NCD, 592 departments, performing 8601 hepatectomies in total, responded to the questionnaire. AORs were significantly lower in departments that were certified as training hospitals by the Japanese Society of Gastroenterological Society, Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), and Japan Society of Hepatology than in non-certified departments. Affiliation of three or more JSHBPS-certified experts or instructors with an institution also contributed to low AORs. None of the QIs regarding implementation of guidelines significantly impacted on the AOR.

Conclusions: Quality indicator measurements may improve quality of post-hepatectomy outcomes in Japan.
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http://dx.doi.org/10.1002/jhbp.1000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597098PMC
October 2021

Survey of surgical resections for neuroendocrine liver metastases: A project study of the Japan Neuroendocrine Tumor Society (JNETS).

J Hepatobiliary Pancreat Sci 2021 Jun 20;28(6):489-497. Epub 2021 Apr 20.

Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.

Background/purpose: Hepatic resection is considered the treatment of choice for neuroendocrine liver metastases (NELM). However, the safety and efficacy of resection have not been fully evaluated using a large cohort. The aim of the present study was to collect real-world data regarding hepatic resections for NELM.

Methods: A retrospective, multicenter survey was conducted. The background characteristics of patients undergoing an initial hepatic resection for NELM, the operative details, pathological findings, and patient outcomes were investigated.

Results: A total of 222 patients were enrolled from 30 institutions. The primary tumor site was the pancreas in 58.6%, and the presentation of NELM was synchronous in 63.1% of the cases. Concomitant resection of the primary tumor and liver metastases was performed for 66.4% of the synchronous metastases, and the 90-day morbidity and mortality rates were 12.6% and 0.9%, respectively. The operations resulted in R2 resections in 26.1% of the cases, and 83.4% of the patients experienced recurrence after R0/1 resections. However, the patients were treated using multiple modalities after R2 resection or recurrence, and the overall survival rate was relatively favorable, with 5-year and 10-year survival rates of 70.2%, and 43.4%, respectively. Univariable and multivariable analyses identified the tumor grading (G3) of the primary tumor as a significant prognostic factor for both the recurrence-free and overall survivals.

Conclusions: The present data confirmed the safety of the surgical resection of NELM. Although recurrences were frequent, the survival outcomes after resection were favorable when a multi-disciplinary treatment approach was used.
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http://dx.doi.org/10.1002/jhbp.956DOI Listing
June 2021

Open and/or laparoscopic one-stage resections of primary colorectal cancer and synchronous liver metastases: An observational study.

Medicine (Baltimore) 2021 Mar;100(11):e25205

Department of Surgical Oncology.

Abstract: One-stage resections of primary colorectal cancer and liver metastases have been reported to be feasible and safe. Minimally invasive approaches have become more common for both colorectal and hepatic surgeries. This study aimed to investigate outcomes of these combined surgical procedures among different approaches.We retrospectively analyzed patients diagnosed as having primary colorectal cancer with synchronous liver metastases and who underwent 1-stage primary resection and hepatectomy with curative intent in our hospital. According to the surgical approach for the primary tumor and hepatic lesions, namely open laparotomy (Op) or laparoscopic approach (Lap), patients were classified into Op-Op, Lap-Op (laparoscopic colorectal resection plus open hepatectomy), and Lap-Lap groups, respectively. Clinicopathological factors were reviewed, and short- and long-term outcomes were compared among the groups.The Op-Op, Lap-Op, and Lap-Lap groups comprised 36, 18, and 17 patients, respectively. The superior/posterior hepatic segments were more frequently resected via an open approach. There was no laparoscopic major hepatectomy. The median volume of intraoperative blood loss was smaller in the Lap-Lap and Lap-Op groups (290 and 270 mL) than in the Op-Op group (575 mL, P = .008). The hospital stay after surgery was shorter in the Lap-Lap and Lap-Op groups (median: 17 days and 15 days, vs 19 days for the Op-Op group, P = .033). The postoperative complication rates and survivals were similar among the groups.Application of laparoscopy to 1-stage resections of primary colorectal cancer and liver metastases may offer advantages of enhanced recovery from surgical treatment, given appropriate patient selection.
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http://dx.doi.org/10.1097/MD.0000000000025205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982201PMC
March 2021

A new rapid diagnostic system with ambient mass spectrometry and machine learning for colorectal liver metastasis.

BMC Cancer 2021 Mar 10;21(1):262. Epub 2021 Mar 10.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Probe electrospray ionization-mass spectrometry (PESI-MS) can rapidly visualize mass spectra of small, surgically obtained tissue samples, and is a promising novel diagnostic tool when combined with machine learning which discriminates malignant spectrum patterns from others. The present study was performed to evaluate the utility of this device for rapid diagnosis of colorectal liver metastasis (CRLM).

Methods: A prospectively planned study using retrospectively obtained tissues was performed. In total, 103 CRLM samples and 80 non-cancer liver tissues cut from surgically extracted specimens were analyzed using PESI-MS. Mass spectra obtained by PESI-MS were classified into cancer or non-cancer groups by using logistic regression, a kind of machine learning. Next, to identify the exact molecules responsible for the difference between CRLM and non-cancerous tissues, we performed liquid chromatography-electrospray ionization-MS (LC-ESI-MS), which visualizes sample molecular composition in more detail.

Results: This diagnostic system distinguished CRLM from non-cancer liver parenchyma with an accuracy rate of 99.5%. The area under the receiver operating characteristic curve reached 0.9999. LC-ESI-MS analysis showed higher ion intensities of phosphatidylcholine and phosphatidylethanolamine in CRLM than in non-cancer liver parenchyma (P < 0.01, respectively). The proportion of phospholipids categorized as monounsaturated fatty acids was higher in CRLM (37.2%) than in non-cancer liver parenchyma (10.7%; P < 0.01).

Conclusion: The combination of PESI-MS and machine learning distinguished CRLM from non-cancer tissue with high accuracy. Phospholipids categorized as monounsaturated fatty acids contributed to the difference between CRLM and normal parenchyma and might also be a useful diagnostic biomarker and therapeutic target for CRLM.
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http://dx.doi.org/10.1186/s12885-021-08001-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945316PMC
March 2021

ABO Blood Group and Risk of Pancreatic Carcinogenesis in Intraductal Papillary Mucinous Neoplasms.

Cancer Epidemiol Biomarkers Prev 2021 05 2;30(5):1020-1028. Epub 2021 Mar 2.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: ABO blood group has been associated with risks of various malignancies, including pancreatic cancer. No study has evaluated the association of ABO blood group with incidence of pancreatic carcinogenesis during follow-up of patients with intraductal papillary mucinous neoplasms (IPMN).

Methods: Among 3,164 patients diagnosed with pancreatic cysts at the University of Tokyo (Tokyo, Japan) from 1994 through 2019, we identified 1,815 patients with IPMN with available data on ABO blood group. We studied the association of ABO blood group with incidence of pancreatic carcinoma, overall and by carcinoma types [IPMN-derived carcinoma or concomitant pancreatic ductal adenocarcinoma (PDAC)]. Utilizing competing-risks proportional hazards models, we estimated subdistribution hazard ratios (SHR) for incidence of pancreatic carcinoma with adjustment for potential confounders, including cyst characteristics.

Results: During 11,518 person-years of follow-up, we identified 97 patients diagnosed with pancreatic carcinoma (53 with IPMN-derived carcinoma and 44 with concomitant PDAC). Compared with patients with blood group O, patients with blood groups A, B, and AB had multivariable SHRs (95% confidence intervals) for pancreatic carcinoma of 2.25 (1.25-4.07; = 0.007), 2.09 (1.08-4.05; = 0.028), and 1.17 (0.43-3.19; = 0.76), respectively. We observed no differential association of ABO blood group with pancreatic carcinoma incidence by carcinoma types.

Conclusions: In this large long-term study, patients with IPMN with blood group A or B appeared to be at higher risk of pancreatic carcinoma compared with those with blood group O.

Impact: ABO blood group can be a biomarker for pancreatic cancer risk among patients with IPMNs.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1581DOI Listing
May 2021

Impact of Abdominal Incision Type on Postoperative Pain and Quality of Life Following Hepatectomy.

World J Surg 2021 06 17;45(6):1887-1896. Epub 2021 Feb 17.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: The aim of this prospective study was to analyze the impact of abdominal incision type on postoperative pain and quality of life (QOL) in hepatectomy.

Methods: In patients undergoing hepatectomy by open, hybrid, or pure laparoscopic approaches, we classified abdominal incisions as: pure laparoscopic (LAP), midline (MID), J-shaped (J), and J-shaped incision plus thoracotomy (TRC). Postoperative pain was measured on postoperative day (POD) 3, 7, 30, and 90 using a visual analog scale (VAS). QOL was evaluated using the short-form-36 questionnaire preoperatively and on POD 30 and 90.

Results: We categorized 165 patients into LAP (n = 9, 5%), MID (n = 21, 13%), J (n = 95, 58%), and TRC (n = 40, 24%) groups. Median VAS scores on PODs 3/7/30/90 were: LAP, 27.5/7.5/10/10; MID, 30/10/15/5; J, 50/27.5/20/10, and TRC, 50/30/30/19. The J and TRC groups had significantly higher VAS scores vs. MID on PODs 3 and 7; the LAP and MID groups did not differ significantly. No significant positive correlations were observed between incision length and postoperative VAS, when we stratified patients into two groups according to the presence or absence of a transverse incision. Physical QOL summary scores did not return to preoperative levels even on POD 90, in patients with an additional transverse incision. Mental QOL summary scores worsened with postoperative complications rather than with abdominal incision type.

Conclusions: Transverse incisions, rather than incision length, led to worse midline incision pain and poorer QOL recovery post-hepatectomy. A hybrid approach may be a considerable option when pure laparoscopic hepatectomy is technically difficult.

Trial Registration: This study was registered in the UMIN Clinical Trials Registry (registration number: UMIN000017467; http://www.umin.ac.jp/ctr/index.htm ).
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http://dx.doi.org/10.1007/s00268-021-05992-xDOI Listing
June 2021

An aberrant right hepatic artery arising from the gastroduodenal artery: a pitfall encountered during pancreaticoduodenectomy.

Surg Today 2021 Oct 11;51(10):1577-1582. Epub 2021 Feb 11.

Department of Visceral Surgery, University Hospital of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland.

Purpose: Among the variations of the right hepatic artery (RHA), the identification of an aberrant RHA arising from the gastroduodenal artery (GDA) is vital for avoiding damage to the RHA during surgery, since ligation of the GDA is necessary during pancreaticoduodenectomy (PD). However, this variation is not frequently reported. The purpose of this study was to focus on an aberrant RHA arising from the GDA, which was not noted in the classifications reported by Michels and Hiatt.

Methods: A total of 574 patients undergoing a PD between Jan 2001 and Dec 2015 at a tertiary care hospital in Switzerland (n = 366) and between Jan 2009 and May 2015 at a hospital in Japan (n = 208) were included in the analysis. Of these, preoperative CT angiography or/and MRI angiography findings were available for 532 patients. We retrospectively analyzed the hepatic artery variations, patient demographics, and surgical outcomes.

Results: Among the 532 patients who received a PD, an RHA originating from the GDA was observed in 19 cases (3.5%). Eleven patients (2.1%) had both an aberrant RHA and an aberrant left hepatic artery (LHA) (Hiatt Type 4). Six patients (1.2%) had a replaced CHA arising from the SMA (Hiatt Type 5). We could, therefore, correctly identify the aberration in all cases.

Conclusions: We observed rarely reported but important aberrant RHA variations arising from the GDA. To prevent injury during PD in patients with this type of aberrant RHA, intensive preparations using CT and/or MRI imaging before surgery and intraoperative liver Doppler ultrasonography are considered to be essential.
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http://dx.doi.org/10.1007/s00595-021-02242-4DOI Listing
October 2021

Axin2 Peribiliary Glands in the Periampullary Region Generate Biliary Epithelial Stem Cells That Give Rise to Ampullary Carcinoma.

Gastroenterology 2021 05 16;160(6):2133-2148.e6. Epub 2021 Jan 16.

Department of Gastroenterology, The University of Tokyo, Tokyo, Japan.

Background & Aims: Peribiliary glands (PBGs), clusters of epithelial cells residing in the submucosal compartment of extrahepatic bile ducts, have been suggested as biliary epithelial stem/progenitor cell niche; however, evidence to support this claim is limited because of a lack of PBG-specific markers. We therefore sought to identify PBG-specific markers to investigate the potential role of PBGs as stem/progenitor cell niches, as well as an origin of cancer.

Methods: We examined the expression pattern of the Wnt target gene Axin2 in extrahepatic bile ducts. We then applied lineage tracing to investigate whether Axin2-expressing cells from PBGs contribute to biliary regeneration and carcinogenesis using Axin2-Cre mice.

Results: Wnt signaling activation, marked by Axin2, was limited to PBGs located in the periampullary region. Lineage tracing showed that Axin2-expressing periampullary PBG cells are capable of self-renewal and supplying new biliary epithelial cells (BECs) to the luminal surface. Additionally, the expression pattern of Axin2 and the mature ductal cell marker CK19 were mutually exclusive in periampullary region, and fate tracing of CK19 luminal surface BECs showed gradual replacement by CK19 cells, further supporting the continuous replenishment of new BECs from PBGs to the luminal surface. We also found that Wnt signal enhancer R-spondin3 secreted from Myh11-expressing stromal cells, corresponding to human sphincter of Oddi, maintained the periampullary Wnt signal-activating niche. Notably, introduction of PTEN deletion into Axin2 PBG cells, but not CK19 luminal surface BECs, induced ampullary carcinoma whose development was suppressed by Wnt inhibitor.

Conclusion: A specific cell population receiving Wnt-activating signal in periampullary PBGs functions as biliary epithelial stem/progenitor cells and also the cellular origin of ampullary carcinoma.
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http://dx.doi.org/10.1053/j.gastro.2021.01.028DOI Listing
May 2021

Identification of Glisson's Capsule Invasion During Hepatectomy for Colorectal Liver Metastasis by Contrast-Enhanced Ultrasonography Using Perflubutane.

World J Surg 2021 Apr 3;45(4):1168-1177. Epub 2021 Jan 3.

Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Glisson invasion by CLM is associated with a risk of margin-positive resection, leading to poor long-term outcomes after hepatectomy. This study was performed to evaluate the efficacy of intraoperative ultrasonography (IOUS) for the diagnosis of Glisson's capsule invasion by colorectal liver metastasis (CLM).

Methods: This prospective study involved 50 consecutive patients undergoing hepatectomy for CLM. Preoperatively, all patients had undergone gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). During hepatectomy, a contrast agent (perflubutane) was intravenously injected and Glisson invasion was estimated based on three characteristic findings: a tumor thrombus, peripheral dilatation, and border irregularity/caliber change. The diagnostic abilities of the preoperative and intraoperative imaging studies were evaluated based on pathological examinations of resected specimens.

Results: Among 187 CLMs resected, pathological examinations proved Glisson invasion in 24 tumors (13%). IOUS revealed a tumor thrombus in 3 tumors (1.6%), peripheral dilatation in 4 (2.1%), and border irregularity and/or caliber change in 24 (12.8%). The sensitivity and specificity of IOUS with any of the above three findings for diagnosis of Glisson invasion was 79% and 96%, respectively, while preoperative EOB-MRI detected Glisson invasion in only four tumors (sensitivity/specificity, 17%/100%). The cutoff value of caliber change for diagnosis of Glisson invasion was set at 140% by receiver operating characteristic analysis. The R0 resection rates were not significantly different between patients with (82%) and without (85%) Glisson invasion.

Conclusions: Identification of characteristic findings (tumor thrombus, peripheral dilatation, and border irregularity/caliber change) by contrast-enhanced IOUS is useful for the prediction of Glisson invasion by CLM.
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http://dx.doi.org/10.1007/s00268-020-05883-7DOI Listing
April 2021

Simulation and navigation liver surgery: an update after 2,000 virtual hepatectomies.

Glob Health Med 2020 Oct;2(5):298-305

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.

The advent of preoperative 3-dimensional (3D) simulation software has made a variety of unprecedented surgical simulations possible. Since 2004, we have performed more than 2,000 preoperative simulations in the University of Tokyo Hospital, and they have enabled us to obtain a great deal of information, such as the detailed shape of liver segments, the precise volume of each segment, and the volume of hepatic venous drainage areas. As a result, we have been able to perform more aggressive and complicated surgery safely. The next step is to create a navigation system that will accurately reproduce the preoperative plan. Real-time virtual sonography (RVS) is a navigation system that provides fusion images of ultrasonography and reconstructed computed tomography images or magnetic resonance images. The RVS system facilitates the surgeon's understanding of interpretation of ultrasound images and the detection of tumors that are difficult to find by ultrasound alone. In the near future, surgical navigation systems may evolve to the point where they will be able to inform surgeons intraoperatively in real time about not only intrahepatic structures, such as vessels and tumors, but also the portal territory, hepatic vein drainage areas, and resection lines that have been planned preoperatively.
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http://dx.doi.org/10.35772/ghm.2020.01045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731191PMC
October 2020

Intestinal-type histology is associated with better prognosis in patients undergoing liver resection for gastric/esophagogastric-junction liver metastasis.

Glob Health Med 2019 Dec;1(2):101-109

Gastrointestinal Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

The indication for resection of gastric/esophagogastric-junction liver metastasis (GELM) has yet to be established. This study aimed to investigate prognostic factors in patients undergoing GELM resection. From 2001 to 2015, 31 consecutive patients underwent resection for GELM; and factors for poor prognosis were evaluated. Of the 31 patients, 23 (74.2%) developed multiple liver metastases. The histology of gastric cancer was intestinal-type adenocarcinoma in 21 patients (67.7%). Median overall survival (OS) was 3.2 years. The 1-, 3-, and 5-year OS rates were 92.8%, 56.2%, and 42.2%, respectively. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 58.5%, 31.3%, and 31.3%, respectively. Multivariate analysis indicated that intestinal-type adenocarcinoma was associated with a significantly lower risk of OS (hazard ratio [HR], 0.26; =0.022) and RFS (HR, 0.25; = 0.008). In multiple logistic regression analysis, intestinal-type adenocarcinoma (odds ratio, 0.14; = 0.012) reduced incidence of extra-hepatic recurrence after GELM resection. In conclusion, GELM resection in patients with intestinal-type histology is preferable because intestinal-type adenocarcinoma is associated with better prognosis and a lower incidence of extra-hepatic recurrence than diffuse/other-type adenocarcinoma.
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http://dx.doi.org/10.35772/ghm.2019.01012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731421PMC
December 2019

Silk fibroin vascular graft: a promising tissue-engineered scaffold material for abdominal venous system replacement.

Sci Rep 2020 12 3;10(1):21041. Epub 2020 Dec 3.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

No alternative tissue-engineered vascular grafts for the abdominal venous system are reported. The present study focused on the development of new tissue-engineered vascular graft using a silk-based scaffold material for abdominal venous system replacement. A rat vein, the inferior vena cava, was replaced by a silk fibroin (SF, a biocompatible natural insoluble protein present in silk thread), tissue-engineered vascular graft (10 mm long, 3 mm diameter, n = 19, SF group). The 1 and 4 -week patency rates and histologic reactions were compared with those of expanded polytetrafluoroethylene vascular grafts (n = 10, ePTFE group). The patency rate at 1 and 4 weeks after replacement in the SF group was 100.0% and 94.7%, and that in the ePTFE group was 100.0% and 80.0%, respectively. There was no significant difference between groups (p = 0.36). Unlike the ePTFE graft, CD31-positive endothelial cells covered the whole luminal surface of the SF vascular graft at 4 weeks, indicating better endothelialization. SF vascular grafts may be a promising tissue-engineered scaffold material for abdominal venous system replacement.
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http://dx.doi.org/10.1038/s41598-020-78020-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713399PMC
December 2020

Risk factors for hepatitis B virus recurrence after living donor liver transplantation: A 22-year experience at a single center.

Biosci Trends 2021 Jan 25;14(6):443-449. Epub 2020 Nov 25.

Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan.

The factors associated with hepatitis B virus (HBV) recurrence after living donor liver transplantation (LDLT) have not been fully clarified. The aim of this study was to determine the risk factors associated with HBV recurrence after LDLT. From January 1996 to December 2018, a total of 609 LDLT operations were performed at our center. A retrospective review was performed of 70 patients (male, n = 59; female, n = 11; median age = 54 years) who underwent LDLT for HBV-related liver disease. The virologic and biochemical data, tumor burden, antiviral and immunosuppressive therapy were evaluated and compared between the HBV recurrence and non-recurrence groups. Eleven of 70 patients (16%) developed post-LDLT HBV recurrence. The overall actuarial rates of HBV recurrence at 1, 3, 5, 10, and 20 years were 0%, 13%, 16.7%, 18.8%, and 18.8%, respectively. The median interval between LDLT and HBV recurrence was 57 months (range, 18-124 months). Based on the univariate and multivariate analyses, a serum HBV DNA level of ≥ 4 log copies/mL (hazard ratio [HR], 4.861; 95% confidence interval [95% CI], 1.172-20.165; P = 0.029), and hepatocellular carcinoma (HCC) beyond the Milan criteria (HR, 10.083; 95% CI, 2.749-36.982; P < 0.001) were independent risk factors for HBV recurrence after LDLT. In LDLT patients, high pre-LT HBV DNA levels and HCC beyond the Milan criteria were risk factors for HBV recurrence. With the current expansion of the LT criteria for HCC, we should remain cautious regarding the risk of HBV recurrence, particularly in these groups.
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http://dx.doi.org/10.5582/bst.2020.03336DOI Listing
January 2021

5-Aminolevulinic acid-mediated photodynamic activity in patient-derived cholangiocarcinoma organoids.

Surg Oncol 2020 Dec 21;35:484-490. Epub 2020 Oct 21.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Accurate diagnosis of the disease extension of cholangiocarcinoma (CCA) is often difficult in clinical practice. The diagnostic yield of conventional pre-operative imaging or endoscopic procedures is sometimes insufficient for the evaluation of longitudinal spreading of CCA. Here we investigated the usefulness of 5-aminolevulinic acid (5-ALA) for the pre- or intra-operative diagnosis of CCA, using patient-derived organoids.

Methods: Four CCA- and two adjacent tissue-derived organoids were established. After 5-ALA treatment, we assessed their photodynamic activity using fluorescence microscopy.

Results: CCA organoids established from different patients showed diverse morphology in contrast to monolayer structures of non-tumor organoids, and had the ability to form subcutaneous tumors in immunodeficient mice. CCA organoids demonstrated remarkably high photodynamic activity based on higher accumulation of protoporphyrin IX as a metabolite of 5-ALA compared to non-tumor organoids (40-71% vs. < 4%, respectively). Importantly, cancer cell-specific high photodynamic activity distinguished the organoids originated from biliary stenotic lesions from those of non-stenotic lesions in a CCA patient. The high photodynamic activity did not depend on the expression profile of heme biosynthesis genes.

Conclusions: Distinct 5-ALA-based photodynamic activity could have diagnostic potential for the discrimination of CCA from non-tumor tissues.
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http://dx.doi.org/10.1016/j.suronc.2020.10.011DOI Listing
December 2020

Indocyanine green administration a day before surgery may increase bile duct detectability on fluorescence cholangiography during laparoscopic cholecystectomy.

J Hepatobiliary Pancreat Sci 2021 Feb 17;28(2):202-210. Epub 2020 Nov 17.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: The optimal indocyanine green (ICG) administration protocol for fluorescence cholangiography during laparoscopic cholecystectomy (LC) has yet to be determined.

Methods: A prospective study including 20 cases of ICG fluorescence-navigated LC was conducted. Accordingly, the first 10 patients were administered 2.5 mg of ICG on the day of surgery after intubation (surgery-day group), while the remaining 10 consecutive patients were administered 0.25 mg/kg of ICG on the evening before surgery (one-day-before group). Fluorescence intensity (FI) of each tissue and FI ratios were then compared between both groups.

Results: The median interval between observation and ICG administration was 27 minutes and 16 hours 24 minutes in the surgery-day and one-day-before group, respectively. Although FI values for the common bile duct (CBD), liver, and hepatoduodenal ligament (HDL) were significantly lower in the one-day-before group than in the surgery-day group, CBD- , 0.6-1.2 vs 2.5, 0.9 = -4.8; P < .001), and CBD-HDL contrast (1.7, 1.4-2.4 vs 2.3, 1.5-13.3; P = .038) were significantly higher in the one-day-before group than in the surgery-day group.

Conclusion: ICG administration a day before LC may offer better CBD background contrast compared to administration just prior to surgery.
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http://dx.doi.org/10.1002/jhbp.855DOI Listing
February 2021

Drain Placement After Uncomplicated Hepatic Resection Increases Severe Postoperative Complication Rate: A Japanese Multi-institutional Randomized Controlled Trial (ND-trial).

Ann Surg 2021 02;273(2):224-231

Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan.

Objective: To assess the clinical impact of a no-drain policy after hepatic resection.

Summary Of Background Data: Previous randomized controlled trials addressing no-drain policy after hepatic resection seem inconclusive because they did not adopt appropriate study design to validate its true clinical impact.

Methods: This unblinded, randomized controlled trial was done at 7 Japanese institutions. Patients undergoing hepatic resection without biliary reconstruction were randomized to either D group or ND group. When the risk of postoperative bile leakage or hemorrhage were considered high, the patients were excluded during the operation. Primary endpoint was the postoperative complication of C-D grade 3 or higher within 90 postoperative days. A noninferiority of ND group to D group was assessed, and if it was confirmed, a superiority was assessed.

Results: Between May 2015 and July 2017, a total of 400 patients were finally included in the per-protocol set analysis: 199 patients in D group and 201 patients in ND group. Intraoperatively, 37 patients were excluded from the final enrollment because of high risk of bile leakage or hemorrhage. Postoperative complication rate of C-D grade 3 or higher was 8.0% (16/199) in the D group and 2.5% (5/201) in the ND group. The risk difference was -5.5% (95% confidence interval: -9.9% to -1.2%) and fulfilled the prescribed noninferiority margin of 4%. No postoperative mortality was experienced in both groups. Bile leakage was diagnosed in 8.0% (16/199) of the D group and none in the ND group (P < 0.001). In none of the subgroups classified based on 8 potentially relevant factors, drain placement was favored in terms of C-D grade 3 or higher complication.

Conclusions: Drains should not be placed after uncomplicated hepatic resections.
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http://dx.doi.org/10.1097/SLA.0000000000004051DOI Listing
February 2021

MRI Findings of Liver Parenchyma Peripheral to Colorectal Liver Metastasis: A Potential Predictor of Long-term Prognosis.

Radiology 2020 12 6;297(3):584-594. Epub 2020 Oct 6.

From the Department of Radiology (Y. Nakai, W.G., R.K., O.A.), Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery (Y. Nishioka, J.A., K.H.), and Department of Pathology (H.A., T.U.), Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Background Gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI is superior to CT in the detection of colorectal liver metastases (CRLMs) smaller than 10 mm. However, few studies have used MRI findings to predict patients' long-term prognosis. Purpose To investigate the relationship between Gd-EOB-DTPA-enhanced MRI findings in the liver parenchyma peripheral to CRLM and both pathologic vessel invasion and long-term prognosis. Materials and Methods This retrospective study included patients who underwent Gd-EOB-DTPA-enhanced MRI before curative surgery for CRLM, without neoadjuvant chemotherapy, between July 2008 and June 2015. Early enhancement, reduced Gd-EOB-DTPA uptake, and bile duct dilatation peripheral to the CRLM at MRI were evaluated by three abdominal radiologists. All tumor specimens were reevaluated for the presence or absence of portal vein, hepatic vein, and bile duct invasion. Predictors of recurrence-free survival (RFS) and overall survival (OS) after surgery were identified with Cox proportional hazard model with the Bayesian information criterion. Previously reported prognosticators were selected for multivariable analyses. The median follow-up period was 60 months (range, 9-127 months). Results Overall, 106 patients (mean age, 65 years ± 12 [standard deviation]; 68 men) with 148 CRLMs were evaluated. Bile duct dilatation peripheral to the tumor was associated with pathologic portal vein invasion (sensitivity, 12 of 50 [24%]; specificity, 89 of 98 [91%]; = .02), bile duct invasion (sensitivity, eight of 19 [42%]; specificity, 116 of 129 [90%]; = .001), poor RFS ( = .03; hazard ratio [HR] = 2.4 [95% confidence interval {CI}: 1.3, 4.2]), and poor OS ( = .01; HR = 2.4 [95% CI: 1.2, 4.9]). For RFS and OS, early enhancement and reduced Gd-EOB-DTPA uptake peripheral to the CRLM were eliminated by means of variable selection in the multivariable analysis, but the combination of these findings with bile duct dilatation provided a predictor of poor OS ( = .001; HR = 3.3 [95% CI: 1.6, 6.8]). Conclusion MRI signal intensity changes peripheral to the colorectal liver metastasis were predictors of long-term prognosis after curative surgery without neoadjuvant chemotherapy. © RSNA, 2020 See also the editorial by Bashir in this issue.
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http://dx.doi.org/10.1148/radiol.2020202367DOI Listing
December 2020

The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid.

J Med Ultrasound 2020 Apr-Jun;28(2):59-82. Epub 2020 May 25.

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

The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
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http://dx.doi.org/10.4103/JMU.JMU_124_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446696PMC
May 2020

Identification of liver lesions using fluorescence imaging: comparison of methods for administering indocyanine green.

HPB (Oxford) 2021 Feb 13;23(2):262-269. Epub 2020 Jul 13.

Hepato-Pancreatico-Biliary Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Japan. Electronic address:

Background: Fluorescence imaging using indocyanine green (ICG) enables intraoperatively visualizing liver tumors as fluorescent. This study evaluated the doses and timing of ICG administration for visualizing tumors via fluorescence using near-infrared light camera systems.

Methods: Consecutive patients who underwent open liver resection for liver tumors from 2016 to 2017 were included. ICG was intravenously injected one-day before surgery at 0.25 mg-intravenous injection (IV), 1.25 mg-IV, 2.5 mg-IV, or 3.75 mg-IV. No additional ICG was administered when patients underwent ICG (0.5 mg/kg) retention test within 10 preoperative days. The ability of fluorescence imaging to enable identifying liver tumors was compared using the PDE-NEO and PINPOINT.

Results: 154 lesions in 82 patients were assessed. The tumor identification rate of PDE-NEO did not differ significantly among dosages. The positive predictive values of PDE-NEO were significantly lower at 3.75 mg-IV (69.0%) than in the control group (92.0%) (p = 0.036) and at 1.25 mg-IV (88.9%) (p = 0.033). The tumor identification rate of PINPOINT was significantly higher at 3.75 mg-IV (82.4%) than at 1.25 mg-IV (60.0%) (p = 0.035). The positive predictive values of PINPOINT did not significantly differ among dosages.

Conclusion: Administering 2.5 mg of ICG one-day before surgery can enable identifying tumors via fluorescence imaging when the ICG test was not performed within 10 preoperative days.
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http://dx.doi.org/10.1016/j.hpb.2020.06.006DOI Listing
February 2021

Therapeutic effect of portal vein stenting for portal vein stenosis after upper-abdominal surgery.

HPB (Oxford) 2021 Feb 27;23(2):238-244. Epub 2020 Jun 27.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address:

Background: The therapeutic effect of portal vein (PV) stenting for PV stenosis following nontransplant hepato-pancreato-biliary (HPB) surgery has not been fully investigated.

Methods: Changes in portal venous pressure (PVP) gradient before and after stenting, complications, symptomatic improvement, and stent patency were evaluated.

Results: We identified 14 consecutive patients undergoing PV stenting for malignant (n = 8) and benign (n = 6) PV stenosis. Signs of PV stenosis were composed of refractory ascites in 6 patients, varices with hemorrhagic tendencies in 5, and abnormal liver function in 5. The median PVP gradient after PV stenting was 3.0 cm HO (range, 1.5-3.0), which was significantly smaller than that before PV stenting (median, 15 cm HO [range, 2.5-25]; P < 0.01). Thirteen out of 14 (93%) achieved clinical success with symptomatic improvement, except one patient with sustained refractory ascites because of peritoneal seeding. During the median follow-up time of 7.3 months (range, 1.0-87), stent occlusion occurred in two patients (14%) because of intrastent tumor growth. The 1-year cumulative stent patency rate was 76% in the entire cohort.

Conclusions: Based on durable effect on patency, we deemed PV stenting for PV stenosis after HPB surgery to be safe and beneficial for improving symptoms.
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http://dx.doi.org/10.1016/j.hpb.2020.06.003DOI Listing
February 2021

Germline MICA Polymorphism Is Associated with the Long-Term Outcomes in Patients Undergoing Hepatectomy for Colorectal Liver Metastases.

J Gastrointest Surg 2020 09 10;24(9):2137-2139. Epub 2020 Jun 10.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8654, Japan.

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http://dx.doi.org/10.1007/s11605-020-04659-7DOI Listing
September 2020

Sex differences in postsurgical skeletal muscle depletion after donation of living-donor liver transplantation, although minimal, should not be ignored.

BMC Surg 2020 Jun 3;20(1):119. Epub 2020 Jun 3.

Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Donor safety is the top priority in living-donor liver transplantation. Splenic hypertrophy and platelet count decrease after donor surgery are reported to correlate with the extent of hepatectomy, but other aftereffects of donor surgeries are unclear. In this study, we evaluated the surgical effects of donor hepatectomy on skeletal muscle depletion and their potential sex differences.

Methods: Among a total of 450 consecutive donor hepatectomies performed from April 2001 through March 2017, 277 donors who completed both preoperative and postoperative (60-119 days postsurgery) evaluation by computed tomography were the subjects of this study. Donors aged 45 years or older were considered elderly donors. Postoperative skeletal muscle depletion was assessed on the basis of the cross-sectional area of the psoas major muscle. Postoperative changes in the spleen volume and platelet count ratios were also analysed to evaluate the effects of major hepatectomy.

Results: The decrease in the postoperative skeletal muscle mass in the overall donor population was slight (99.4 ± 6.3%). Of the 277 donors, 59 (21.3%) exhibited skeletal muscle depletion (i.e., < 95% of the preoperative value). Multivariate analysis revealed that elderly donor (OR:2.30, 95% C.I.: 1.27-4.24) and female donor (OR: 1.94, 95% C.I. 1.04-3.59) were independent risk factors for postoperative skeletal muscle depletion. Stratification of the subjects into four groups by age and sex revealed that the elderly female donor group had significantly less skeletal muscle mass postoperatively compared with the preoperative values (95.6 ± 6.8%), while the other three groups showed no significant decrease. Due to their smaller physical characteristics, right liver donation was significantly more prevalent in the female groups than in the male groups (112/144, 77.8% vs 65/133, 48.9%; p < 0.001). The estimated liver resection rate correlated significantly with the splenic hypertrophy ratio (r = 0.528, p < 0.001) and the extent of the platelet count decrease (r = - 0.314, p < 0.001), but donor age and sex did not affect these parameters.

Conclusion: Elderly female donors have a higher risk of postoperative skeletal muscle depletion. Additionally, female donors are more likely to donate a right liver graft, whose potential subclinical risks include postoperative splenic enlargement and a platelet count decrease.
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http://dx.doi.org/10.1186/s12893-020-00781-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268651PMC
June 2020

The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid.

Ultrasonography 2020 Jul 27;39(3):191-220. Epub 2020 Apr 27.

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

The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
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http://dx.doi.org/10.14366/usg.20057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315291PMC
July 2020
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