Publications by authors named "Masaru Miyazaki"

521 Publications

Clinical implication of ICG test in major hepatectomy for biliary tract cancer.

Minerva Surg 2021 Apr 23. Epub 2021 Apr 23.

Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Major hepatectomy with bile duct resection (BDR) is associated with severe postoperative complications; therefore, evaluation of preoperative liver function is important. However, little is known about mechanisms of increased severe complications in patients with poor liver function. The aim of this study was to evaluate whether ICG-R15 is useful for predicting the risk of severe postoperative complications in this operation, and to reveal the mechanisms of increasing severe complications by focusing on immune function and liver regeneration after hepatectomy.

Methods: Patients receiving major hepatectomy with BDR between 2000 and 2017 were retrospectively reviewed. Severe postoperative complications were defined as Clavien-Dindo grade >IV.

Results: In 284 patients undergoing major hepatectomy with BDR, ICG-R15 was correlated with severe postoperative complications, with cut-off value of 11.8%. In brief, the incidences of hyperbilirubinemia, coagulopathy, liver failure, respiratory failure, severe complications, and mortality were higher in the high ICG-R15 group. Moreover, high ICG-R15 (>11.8%) was an independent factor for predicting severe complications after major hepatectomy with BDR. Immune dysfunction in the early phase after operation, prolonged postoperative immunosuppression, and delayed liver regeneration were reasons for increasing severe postoperative complications in patients with high ICG-R15.

Conclusions: High ICG-R15 is an independent risk factor for severe complications after major hepatectomy with BDR, and its cut-off value is 11.8%. Compromised condition and delayed liver regeneration induced by immune dysfunction are reasons of increased severe postoperative complications in patients with high ICG-R15.
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http://dx.doi.org/10.23736/S2724-5691.21.08580-1DOI Listing
April 2021

Mortality, morbidity, and failure to rescue in hepatopancreatoduodenectomy: An analysis of patients registered in the National Clinical Database in Japan.

J Hepatobiliary Pancreat Sci 2021 Apr 20;28(4):305-316. Epub 2021 Mar 20.

Japanese Society of Hepato-Biliary-Pancreatic Surgery, Tokyo, Japan.

Background: The high operative mortality rate after hepatopancreatoduodenectomy (HPD) is still a major issue. The present study explored why operative mortality differs significantly due to hospital volume.

Method: Surgical case data were extracted from the National Clinical Database (NCD) in Japan from 2011 to 2014. Surgical procedures were categorized as major (≥2 sections) and minor (<2 sections) hepatectomy. Hospitals were categorized according to the certification system by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) based on the number of major hepato-biliary-pancreatic surgeries performed per year. The FTR rate was defined as death in a patient with at least one postoperative complication.

Results: A total of 422 patients who underwent HPD were analyzed. The operative mortality rates in board-certified A training institutions, board-certified B training institutions, and non-certified institution were 7.2%, 11.6%, and 21.4%, respectively. Multiple logistic regression showed that certified A institutions, major hepatectomy, and blood transfusion were the predictors of operative mortality. Failure to rescue rates were lowest in certified A institutions (9.3%, 17.0%, and 33.3% in certified A, certified B, and non-certified, respectively).

Conclusions: To reduce operative mortality after HPD, further centralization of this procedure is desirable. Future studies should clarify specific ways to improve the failure-to-rescue rates in certified institutions.
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http://dx.doi.org/10.1002/jhbp.918DOI Listing
April 2021

Proposal of a novel H category-based classification of colorectal liver metastases based on a Japanese nationwide survey.

J Hepatobiliary Pancreat Sci 2021 Apr 16;28(4):317-326. Epub 2021 Mar 16.

Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Japan.

Background: The conventional H category-based classification for colorectal liver metastases (CRLM) was created by equal weighting of tumor number and tumor size; however, our previous nomogram to predict postoperative disease-free survival demonstrated that CRLM ≥5 as a parameter provided 4.5 times greater impact compared with a largest CRLM size >5 cm.

Methods: A total of 3815 patients newly diagnosed with CRLM between 2005 and 2007, including 2220 resectable cases, were investigated. Six groups were created based on largest lesion size (≤ 5 vs >5 cm) and lesion number (1, 2-4, and ≥5).

Results: The novel (n) H1, nH2, and nH3 categories were defined as solitary lesions with a size ≤5 cm; lesions other than nH1 or nH3; and ≥5 lesions with any lesion size, respectively. In the resectable cohort, the 5-year cumulative overall survival rates were 64.0%, 53.5%, and 42.6% in the nH1, nH2, and nH3 groups, respectively (P < .001), and no significant differences were observed between the conventional H2 and H3 categories. In the overall cohort, the discrimination ability of the two classifications were comparable.

Conclusion: The novel H category-based classification might be beneficial in predicting overall survival in patients with CRLM independent of their resectability.
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http://dx.doi.org/10.1002/jhbp.920DOI Listing
April 2021

Prognostic Significance of Systemic Inflammatory Response in Cases of Temporal Bone Squamous Cell Carcinoma.

Laryngoscope 2021 Feb 4. Epub 2021 Feb 4.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective/hypothesis: Squamous cell carcinoma (SCC) of the temporal bone is an extremely rare condition. This rarity has led to a delay in the establishment of a standard treatment protocol and adequate staging system. Identification of prognostic markers of this disease from a variety of fields is desirable in the establishment of treatment guidelines for temporal bone SCC. The aim of this study is to assess the prognostic role of inflammation-based prognostic scores in cases of temporal bone SCC.

Study Design: Case reries with chart review.

Methods: A total of 71 cases of primary malignancy eligible for curative treatment at a single tertiary medical institute were retrospectively analyzed. Univariate and multivariate regression analyzes were used to investigate the association between the inflammation-based scores and 5-year overall survival.

Results: Univariate Cox regression analyzes showed that a high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, low lymphocyte-to-monocyte ratio, a Glasgow prognostic score of 2, and the systemic inflammation score of 2 were significantly associated with a poor prognosis, as well as a classification of T4 stage, presence of cervical lymph node metastasis, high white blood cell counts, and high C-reactive protein levels. The multivariate analysis showed that a clinical stage of T4 and a systemic inflammation score of 2 were independent prognostic markers.

Conclusions: Inflammation-based prognostic markers are associated with the survival of patients with temporal bone SCC, as well as other head and neck SCCs.

Level Of Evidence: 4 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29421DOI Listing
February 2021

[Ⅱ.Carbon Ion Radiation Therapy as Perioperative Treatment for Pancreatic Cancer].

Gan To Kagaku Ryoho 2020 Oct;47(10):1428-1432

Dept. of Surgery, Dokkyo Medical University, Saitama Medical Center.

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October 2020

[Liver, Pancreas, Biliary Tract Cancer Current Progress in Radiotherapy with Heavy-Charged Particles for Hepatobiliary-Pancreatic Cancers: Its History and Perspective].

Authors:
Masaru Miyazaki

Gan To Kagaku Ryoho 2020 Oct;47(10):1421-1422

International University of Health and Welfare, Narita Hospital.

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October 2020

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

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

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

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

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

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

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

Conclusions: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.
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http://dx.doi.org/10.1159/000508809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548915PMC
September 2020

Prognostic Impact of Tumor Extension in Patients With Advanced Temporal Bone Squamous Cell Carcinoma.

Front Oncol 2020 7;10:1229. Epub 2020 Aug 7.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. Our objective here was to explore anatomical factors associated with the prognosis of T4 TB-SCC cases. Case series with chart review. Two academic tertiary care medical centers. The medical records of all TB-SCC cases were retrospectively reviewed in two institutions. The resulting data set contained 30 cases of primary T4 cancer eligible for initial definitive (curative) treatment. Disease-specific survival was calculated according to the Kaplan-Meier method. Cox proportional hazards model was used to identify anatomical prognosis factors. The disease-specific 5-years survival rate of 30 cases of T4 TB-SCC was 53.9%. The tumor invasion to the pterygoid muscle, posterior fossa dura, and sigmoid sinus and destruction of the ossicles were associated with poor prognosis in univariate analysis. The multivariate analysis reveals that the invasion of the ossicles, posterior fossa dura, and sigmoid sinus is an independent prognostic factor [hazard ratio (HR): 4.528 (95% CI: 1.161-17.658), p = 0.030; HR: 5.135 (95% CI: 1.616-16.315), p = 0.006; HR: 4.292 (95% CI: 1.385-13.303), p = 0.012]. The invasion of the carotid canal, petrous apex, middle fossa dura, otic capsule, pterygoid muscle, and middle ear had a high HR (HR > 2). The more invaded anatomical factors present in patients resulted in a poorer patient disease-specific prognosis, with a statistically significant difference. Assessing which anatomical structures are susceptible to invasion by tumors may be important for predicting TB-SCC patient prognosis and selecting appropriate treatment planning, especially surgical intervention. In addition to previously reported factors, the destruction of the ossicles in the middle ear cavity can be an anatomical prognosis factor.
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http://dx.doi.org/10.3389/fonc.2020.01229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427636PMC
August 2020

Long-term outcome of liver resection for colorectal metastases in the presence of extrahepatic disease: A multi-institutional Japanese study.

J Hepatobiliary Pancreat Sci 2020 Nov 17;27(11):810-818. Epub 2020 Aug 17.

Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Background/purpose: The purpose of the present study was to assess long-term outcomes following liver resection for colorectal liver metastases (CRLM) with concurrent extrahepatic disease and to identify the preoperative prognostic factors for selection of operative candidates.

Methods: In this retrospective, multi-institutional study, 3820 patients diagnosed with CRLM during 2005-2007 were identified using nationwide survey data. Data of identified patients with concurrent extrahepatic lesions were analyzed to estimate the impact of liver resection on overall survival (OS) and to identify preoperative, prognostic indicators.

Results: Three- and 5-year OS rates after liver resection in 251 CRLM patients with extrahepatic disease (lung, n = 116; lymph node, n = 51; peritoneal, n = 37; multiple sites, n = 23) were 50.2% and 32.0%, respectively. Multivariate analysis revealed that a primary tumor in the right colon, lymph node metastasis from the primary tumor, serum carbohydrate antigen (CA) 19-9 level >37 UI/mL, the site of extrahepatic disease, and residual liver tumor after hepatectomy were associated with higher mortality. We proposed a preoperative risk scoring system based on these factors that adequately discriminated 5-year OS after liver resection in training and validation datasets.

Conclusions: Performing R0 liver resection for colorectal liver metastases with treatable extrahepatic disease may prolong survival. Our proposed scoring system may help select appropriate candidates for liver resection.
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http://dx.doi.org/10.1002/jhbp.810DOI Listing
November 2020

Splenic enlargement induced by preoperative chemotherapy is a useful indicator for predicting liver regeneration after resection for colorectal liver metastases.

World J Surg Oncol 2020 Jun 23;18(1):139. Epub 2020 Jun 23.

Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan.

Background: Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection.

Methods: We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty-one patients had conversion chemotherapy. The other 67 patients underwent up-front liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed.

Results: A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration.

Conclusions: Splenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.
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http://dx.doi.org/10.1186/s12957-020-01918-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313099PMC
June 2020

Clinicopathological characteristics of intraductal papillary neoplasm of the bile duct: a Japan-Korea collaborative study.

J Hepatobiliary Pancreat Sci 2020 Sep 2;27(9):581-597. Epub 2020 Jul 2.

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

Background: The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location.

Methods: IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid-tubular components. Medical data were evaluated.

Results: Among 694 IPNB patients, 520 and 174 had Type 1 and Type 2, respectively. The levels of AST, ALT, ALP, T. Bil, and CEA were significantly higher in patients with Type 2 than in those with Type 1. Type 1 IPNB was more frequently located in the intrahepatic bile duct than Type 2, whereas Type 2 was more frequently located in the distal bile duct than Type 1 IPNB (P < 0.001). There were significant differences in 5-year cumulative survival rates (75.2% vs 50.9%; P < 0.0001) and 5-year cumulative disease-free survival rates (64.1% vs 35.3%; P < 0.0001) between the two groups.

Conclusion: Type 1 and Type 2 IPNBs differ in their clinicopathological features and prognosis. This classification may help to further understand IPNB.
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http://dx.doi.org/10.1002/jhbp.785DOI Listing
September 2020

Highly expressed tumoral emmprin and stromal CD73 predict a poor prognosis for external auditory canal carcinoma.

Cancer Sci 2020 Aug 22;111(8):3045-3056. Epub 2020 Jun 22.

Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.

Squamous cell carcinoma of the external auditory canal (SCC-EAC) is rare and has a poor prognosis. The SCC-EAC cases with high-grade tumor budding (TB) or poorly differentiated clusters (PDCs) are associated with shorter survival than those with low-grade TB or PDCs. Extracellular matrix metalloproteinase inducer (emmprin) is a protein expressed in tumor cells that stimulates the production of MMP-2 by stromal fibroblasts to facilitate tumor invasion. Recently, we reported that emmprin forms a complex with CD73 to regulate MMP-2 production from fibroblasts in vitro. Here, we examined the association of emmprin and CD73 expression with TB or PDCs as well as with survival in 34 biopsy specimens of SCC-EAC patients. High tumoral emmprin expression was associated with high-grade TB, whereas high stromal CD73 expression was associated with high-grade PDCs. Furthermore, concurrent elevated expression of tumoral emmprin and stromal CD73 was determined to be an independent poor prognostic factor. In immunoprecipitation analyses, complex formation between emmprin and CD73 was demonstrated in vitro. Production of MMP-2 from fibroblasts was more abundant when cocultured with tumor cells than from fibroblasts cultured alone. Furthermore, MMP-2 production was reduced by the transfection of CD73 siRNA in fibroblasts cocultured with tumor cells. The colocalization of emmprin and CD73 was enhanced in not only the peripheral cells of the tumor cell clusters that interact with fibroblasts but also in the cells of intratumor clusters. Overall, this study provides novel insights into the roles of emmprin, CD73, and MMP-2 in tumor invasiveness.
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http://dx.doi.org/10.1111/cas.14508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419056PMC
August 2020

Effect of immunonutrition on infectious complications in low skeletal muscle mass patients after pancreaticoduodenectomy.

Clin Nutr 2021 Jan 28;40(1):103-109. Epub 2020 Apr 28.

Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.

Background & Aims: Sarcopenia is considered a risk factor of postoperative complications among patients undergoing abdominal surgery. However, few studies have demonstrated an effective strategy for reducing complications in sarcopenic patients. This study aimed to examine retrospectively the effect of preoperative immunonutrition on postoperative complications, especially infectious complications, in low skeletal muscle mass patients undergoing pancreaticoduodenectomy (PD).

Methods: This was a retrospective, consecutive cohort study conducted in our institution. Skeletal muscle mass was assessed using preoperative computed tomography images in 298 consecutive patients who underwent PD between May 2009 and May 2016. Cross-sectional areas at the third lumbar vertebrae normalized for stature (cm/m) were defined as the skeletal muscle mass index (SMI). Low SMI was defined as the lowest sex-specific quartile of SMI. Risk factors for postoperative infectious complications and the effect of preoperative immunonutrition on low SMI patients who underwent PD were evaluated.

Results: Results of multivariate analysis showed that the presence of low SMI and absence of preoperative immunonutrition were independent risk factors for postoperative infectious complications after PD (odds ratio [OR], 3.17 and 3.10, respectively; P < 0.001). In high SMI patients, the rate of postoperative infectious complications was significantly lower in those who received immunonutrition than in those who did not receive immunonutrition (31.9 vs. 46.1%, respectively; OR, 1.82; P = 0.045). Further, similar findings were exhibited in low SMI patients (26.3 vs. 83.6%, respectively; OR, 14.31; P < 0.001), even though OR was markedly higher in low vs. high SMI patients.

Conclusion: There is a stronger association with reduced infectious complications in patients who have low SMI and receive immunonutrition (UMIN-CTR Identifier: UMIN000035775.).
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http://dx.doi.org/10.1016/j.clnu.2020.04.032DOI Listing
January 2021

Comprehensive data of 3525 patients newly diagnosed with colorectal liver metastasis between 2013 and 2014: 2nd report of a nationwide survey in Japan.

J Hepatobiliary Pancreat Sci 2020 Aug 9;27(8):555-562. Epub 2020 Jun 9.

Tokyo Medical and Dental University, Tokyo, Japan.

Background: To collect large-scale data for further research to improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese society of Hepato-Biliary-Pancreatic Surgery. The joint committee was initiated to collect data since 2014 and has already reported data including the prognostic data of 3820 patients newly diagnosed with CRLM between 2005 and 2007.

Methods: The data of patients newly diagnosed with CRLM after 2013 are continuously being registered prospectively, and herein, we report the data of the patients newly diagnosed with CRLM in 2013 and 2014.

Results: The data of 3839 patients newly diagnosed with CRLM in 2013 and 2014 were registered from 156 departments (75%) of 152 institutions among 209 departments (from 201 institutions) that agreed to participate in this database system at its initiation. Finally, 3525 patients were enrolled in this study after a quality management process conducted by the joint committee. We report the comprehensive data obtained from 3525 patients, including clinicopathological findings, treatment strategies, and implementation status of chemotherapy.

Conclusion: The joint committee will provide these raw data while updating prognostic data to researchers who will conduct meaningful studies that meet the aim of the joint committee.
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http://dx.doi.org/10.1002/jhbp.738DOI Listing
August 2020

Long-Term Results of High-Dose 2-Fraction Carbon Ion Radiation Therapy for Hepatocellular Carcinoma.

Adv Radiat Oncol 2020 Mar-Apr;5(2):196-203. Epub 2019 Sep 27.

International University of Health and Welfare, Mita Hospital, Tokyo, Japan.

Purpose: Carbon ion beams have several physical and biological advantages compared with conventional radiation for cancer therapy. The objective of this study is to evaluate the safety and effectiveness of 2-fraction carbon ion radiation therapy (CIRT) in patients with hepatocellular carcinoma (HCC).

Methods And Materials: Between December 2008 and March 2013, 57 patients with localized HCC were treated with CIRT at a total dose of 45 Gy (relative biological effectiveness) in 2 fractions and retrospectively analyzed after long-term observation. The main endpoints of this study were treatment-related toxicity and local tumor control. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Changes in the Child-Pugh score from before to after CIRT were also examined to evaluate hepatic toxicity. Local control was defined as no progression of the irradiated lesion according to the modified Response Evaluation Criteria in Solid Tumors.

Results: The median age of the patients was 75 years (range, 49-89 years). Of these patients, 41 had a newly diagnosed lesion, and 16 had residual or recurrent lesions after previous treatments. The median follow-up duration was 54 months (range, 7-103 months). All surviving patients were followed for more than 51 months. Two patients experienced grade 3 acute skin reactions, but no other grade 3 or higher toxicities were observed in any organ. No patient exhibited an increase in the Child-Pugh score of 2 or more points after CIRT. The local tumor control rates at 1, 3, and 5 years were 98%, 91%, and 91% after CIRT, respectively. All lesions that failed to respond to previous treatments were successfully controlled by CIRT. The 1-, 3-, and 5-year overall survival rates were 97%, 67%, and 45%, respectively.

Conclusions: Two-fraction CIRT was a well-tolerated and effective treatment for patients with HCC.
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http://dx.doi.org/10.1016/j.adro.2019.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136623PMC
September 2019

Primary Advanced Squamous Cell Carcinoma of the Temporal Bone: A Single-Center Clinical Study.

Laryngoscope 2021 02 8;131(2):E583-E589. Epub 2020 Apr 8.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objectives/hypothesis: The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. For the purposes of retrospective meta-analysis in the future, a large dataset with information from various institutions would be ideal. Our objective here was to retrospectively review cases of TB-SCC encountered at a single tertiary referral center and explore survival outcomes and prognostic factors.

Study Design: Retrospective chart review.

Methods: The medical records of all TB-SCC cases were retrospectively reviewed. The resulting dataset contained 71 cases of primary cancer eligible for initial definitive (curative) treatment.

Results: T4 status was associated with lower disease-specific 5-year survival than T1 to T3 staging (T1: 100%, T2: 92%, T3: 86%, T4: 51%). Survival was significantly higher in operable than in inoperable cases, even when restricted to advanced (T3/T4) cancers. The tumor extension to the middle ear cavity was observed in 13/17 of T3 cases, but it was not associated with poor survival. In addition, among operable cases, negative surgical margins were associated with significantly higher survival than positive margins.

Conclusions: Definitive treatments can offer disease-specific 5-year survival of over 85% in T1 to T3 cases of TB-SCC. The tumor extension to the middle ear cavity is not associated with poor survival. T4 status, inoperability, nodal invasion, and positive surgical margin are identified as a predictor of poor prognosis. Still, the matter of how to deal with unresectable tumors remains an outstanding issue in the treatment of TB-SCC.

Level Of Evidence: 4 Laryngoscope, 131:E583-E589, 2021.
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http://dx.doi.org/10.1002/lary.28653DOI Listing
February 2021

Liver Transection-First Approach in Left Trisectionectomy for Perihilar Cholangiocarcinoma.

Ann Surg Oncol 2020 Jul 9;27(7):2381-2386. Epub 2020 Mar 9.

Mita Hospital, International University of Health and Welfare, Tokyo, Japan.

Left trisectionectomy [(LT) resection of segments 2, 3, 4, 5, 8, and 1] for perihilar cholangiocarcinoma is still a challenging procedure with high postoperative morbidity and mortality. To perform LT safely, the liver transection-first approach was developed. In this approach, liver transection is started without dividing the right anterior hepatic artery (RAHA) and right anterior portal vein (RAPV). After the completion of liver transection, the RAHA and RAPV, which run into the future resected liver, can be easily identified and divided under the wide surgical field at the hepatic hilus. The liver transection-first approach appears to be safer than the conventional LT, leading to less postoperative morbidity and mortality.
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http://dx.doi.org/10.1245/s10434-020-08306-yDOI Listing
July 2020

Long-term outcomes and significance of preoperative lymphocyte-to-monocyte ratio as a prognostic indicator in patients with invasive pancreatic neoplasms after repeat pancreatectomy.

BMC Cancer 2020 Feb 10;20(1):111. Epub 2020 Feb 10.

Department of General Surgery, Chiba University, Graduate School of Medicine, 1-8-1, Inohana, Chuo-ku, Chiba City, Chiba, 260-8677, Japan.

Background: Invasive pancreatic neoplasms have a high propensity for recurrence even after curative resection. Recently, patients who underwent pancreatectomy have an opportunity of undergoing secondary pancreatic resection, so-called "repeat pancreatectomy" to achieve curative operation and prolong their survival. We evaluated the long-term clinical outcomes and identified the prognostic factors, including systemic inflammation markers and the lymphocyte-to-monocyte ratio (LMR) of patients who underwent repeat pancreatectomy for invasive pancreatic tumors.

Methods: Twenty-eight consecutive patients with invasive pancreatic neoplasms (22 pancreatic ductal adenocarcinomas, 2 pancreatic acinar cell carcinomas, and 4 invasive intra-papillary mucinous carcinomas) with isolated local recurrence only in the remnant pancreas were analyzed retrospectively. To identify factors for the selection of optimal patients who should undergo repeat pancreatectomy, perioperative clinical parameters were analyzed by Cox proportional regression models.

Results: Of 28 patients, 12 patients experienced recurrence within 3 years after repeat pancreatectomy. Kaplan-Meier analysis showed that the median cancer-specific overall survival time of patients with invasive pancreatic neoplasms was 61 months, showing favorable outcomes. High preoperative LMR (LMR ≥ 3.3) (p = 0.022), no portal vein resection (p = 0.021), no arterial resection (p = 0.037), and pathological lymph node negative (p = 0.0057) were identified as favorable prognostic parameters on univariate analysis, and LMR ≥ 3.3 (p = 0.0005), and pathological lymph node negative (p = 0.018) on multivariate analysis.

Conclusions: Preoperative LMR is potentially a good indicator for selecting suitable patients to undergo repeat pancreatectomy in patients with isolated local recurrence of invasive pancreatic neoplasms.
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http://dx.doi.org/10.1186/s12885-020-6602-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011356PMC
February 2020

Ischemic Cholangiopathy Following Transcatheter Arterial Chemoembolization for Recurrent Hepatocellular Carcinoma After Hepatectomy: an Underestimated and Devastating Complication.

J Gastrointest Surg 2020 11 21;24(11):2517-2525. Epub 2019 Nov 21.

AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France.

Background: Ischemic cholangiopathy (IC) has a known poor prognosis. However, the risks and outcomes of this complication after transcatheter arterial chemoembolization (TACE) in hepatectomized patients are poorly documented. This study aimed to evaluate the incidence of and to identify the predictive factors for IC following TACE for recurrent hepatocellular carcinoma (HCC) after hepatectomy.

Method: From a cohort with a total of 486 patients who underwent resection for HCC, we included all consecutive patients who were treated with TACE for recurrent HCC after hepatectomy between 2000 and 2017. IC was defined by the coexistence of biological cholestasis and morphological lesions.

Results: A total of 156 patients underwent TACE for the treatment of HCC recurrence after hepatectomy. Of them, eight (5.1%) developed IC. Their prognosis was poor compared with patients without IC (3-year survival 23.4% vs 76.2%; P = 0.008). Two factors, namely, time between hepatectomy and TACE (4.8 months vs. 16.0 months, P = 0.001) and TACE for a remnant liver mobilized during hepatectomy (P = 0.001), were associated with IC. Receiver operating characteristic (ROC) curve analysis showed that 7 months was the more discriminant cutoff for the time period. IC occurred in 33.3% of the patients with the two factors, in 5.0% of those with one factor, and 0% in the absence of any factors.

Conclusion: TACE for treating HCC recurrence carries a high risk of IC when performed early after hepatectomy in a previously mobilized liver. Our results might aid in identifying candidates for TACE for recurrent HCC, considering the major effect on patient outcomes.
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http://dx.doi.org/10.1007/s11605-019-04409-4DOI Listing
November 2020

Clinicopathological features and prognosis of surgical resected cases of biliary cancer with pancreaticobiliary maljunction.

Hepatobiliary Pancreat Dis Int 2020 Feb 25;19(1):97-100. Epub 2019 Oct 25.

Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-0856, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.hbpd.2019.10.002DOI Listing
February 2020

Is hepatic artery coil embolization useful in distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic cancer?

World J Surg Oncol 2019 Jul 17;17(1):124. Epub 2019 Jul 17.

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

Background: The exact contribution of preoperative coil embolization in distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for the prevention of ischemic liver complication is not fully elucidated.

Methods: From January 2004 to July 2015, 31 patients underwent DP-CAR for the pancreatic body-tail cancer. Twenty-three patients received preoperative coil embolization. The characteristics and operative outcomes were analyzed retrospectively.

Results: The median survival time and 1- and 3-year overall survival rates were 23.7 months and 74.2% and 34.4%, respectively. No 30-day mortality occurred in any of the patients. Postoperative liver infarction developed only in 8 patients (25.8%) even though 7 of 8 patients had undergone preoperative coil embolization. Tumor contact with the gastroduodenal artery (GDA)/proper hepatic artery (PHA) on preoperative multi-detector computed tomography (MDCT), tumor size, operative time, portal vein resection, and stenosis of the GDA/PHA after DP-CAR are related to liver infarction. Among them, postoperative stenosis of the GDA/PHA on MDCT, which was observed in all 8 patients with liver infarction, was the most closely related factor to postoperative liver infarction. Tumor contact with the GDA/PHA did not worsen the R0 resection rate or overall survival rate.

Conclusion: Our data indicate that preoperative coil embolization of the common hepatic artery is not useful in DP-CAR as long as GDA is completely preserved during surgery.
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http://dx.doi.org/10.1186/s12957-019-1667-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637588PMC
July 2019

OLFM4 Enhances STAT3 Activation and Promotes Tumor Progression by Inhibiting GRIM19 Expression in Human Hepatocellular Carcinoma.

Hepatol Commun 2019 Jul 2;3(7):954-970. Epub 2019 May 2.

Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan.

Olfactomedin 4 (OLFM4) induces signal transducer and activator of transcription 3 (STAT3) activation by inhibiting gene associated with retinoid-interferon-induced mortality 19 (GRIM19), a strong STAT3 suppressor gene; however, the mechanisms of OLFM4 for regulating GRIM19-STAT3 cascade in hepatocellular carcinoma (HCC) remain unclear. The functions and regulations of OLFM4, GRIM19, and STAT3 activation in HCC progression were evaluated using surgical specimens collected from 111 HCC patients or 2 HCC cell lines . Moreover, the cancer stem cell-like property of OLFM4 mediated by leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), known as an intestinal stem cell marker, was investigated. OLFM4 was increased in HCC compared with adjacent liver tissue. The multivariate analysis revealed that high OLFM4 expression was an independent factor for poor prognosis. OLFM4 expression was negatively correlated with GRIM19 expression and positively correlated with STAT3 activation in HCC, thereby increasing cell cycle progression. OLFM4 knockdown in HCC cells increased GRIM19 expression and inhibited STAT3 activation; however, after double knockdown of GRIM19 and OLFM4, STAT3 activation decreased by OLFM4 knockdown was increased again. OLFM4 knockdown increased cell apoptosis, inhibited cell proliferation, and suppressed cancer stem cell-like property in HCC cells. The incidence of hematogenous recurrence was higher in HCC patients with high OLFM4 expression, suggesting that anoikis resistance of HCC was enhanced by OLFM4. In clinical cases, LGR5 expression and CD133 expression was correlated with OLFM4 expression in HCC, leading to poor patient prognosis. , LGR5 enhanced cancer stem cell-like property by up-regulating OLFM4 through the Wnt signaling pathway. : OLFM4 is induced by the LGR5-Wnt signaling pathway and is strongly associated with aggressive tumor progression and poor prognosis in HCC by regulating STAT3-induced tumor cell proliferation and cancer stem cell-like property. Therefore, OLFM4 is a novel prognostic predictor and a potential therapeutic target for patients with HCC.
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http://dx.doi.org/10.1002/hep4.1361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601327PMC
July 2019

The Expression of Yes-Associated Protein (YAP) Maintains Putative Cancer Stemness and Is Associated with Poor Prognosis in Intrahepatic Cholangiocarcinoma.

Am J Pathol 2019 09 18;189(9):1863-1877. Epub 2019 Jun 18.

Department of General Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan. Electronic address:

Intrahepatic cholangiocarcinoma (ICC) is resistant to most chemotherapeutic agents. Yes-associated protein (YAP) is related to tumor progression; however, its role in ICC remains unknown. We investigated the mechanism underlying YAP-mediated cancer progression by focusing on the property of cancer stem cells (CSCs) in ICC. Immunohistochemistry results revealed the positive YAP expression in 37 of 52 resected ICC cases. Those with positive YAP expression showed poor prognosis in Kaplan-Meier analysis (P = 0.023). YAP expression was associated with vimentin and the putative CSC marker, hepatic oval cell marker 6 (OV-6). The knockdown of YAP expression using specific siRNAs in ICC cells decreased octamer-binding transcription factor 4 (OCT4) expression in Western blot analyses and OV-6 and CD133 expression in flow cytometry analysis. Verteporfin, a YAP inhibitor, decreased N-cadherin and OCT4 expression in Western blot analyses. In vitro sphere formation and anoikis resistance assays revealed the impairment in CSC property and anoikis resistance in response to the decrease in YAP expression. Verteporfin treatment activated the protein kinase B/mechanistic target of rapamycin signaling pathway and dramatically impaired IL-6-stimulated STAT3 phosphorylation in ICC cells. The combination of verteporfin and rapamycin, an inhibitor of mechanistic target of rapamycin phosphorylation, inhibited cell proliferation and tumor growth. In conclusion, verteporfin regulates multiple signaling pathways and, in combination with rapamycin, might be a promising therapeutic strategy for ICC treatment.
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http://dx.doi.org/10.1016/j.ajpath.2019.05.014DOI Listing
September 2019

Survival Benefit of and Indications for Adjuvant Chemotherapy for Resected Colorectal Liver Metastases-a Japanese Nationwide Survey.

J Gastrointest Surg 2020 06 13;24(6):1244-1260. Epub 2019 Jun 13.

Tokyo Medical and Dental University, Tokyo, Japan.

Background: The survival benefit of and indications for adjuvant chemotherapy (AC) for colorectal liver metastases (CRLM) remain unclear.

Methods: Patients who were diagnosed with liver-limited CRLM between 2005 and 2007 and subsequently underwent R0 resection without preoperative chemotherapy were identified in a Japanese nationwide survey. This overall cohort was divided into synchronous and metachronous CRLM cohorts. In each of the three cohorts, the patients that were given AC were matched with those treated with surgery alone via 1:1 propensity score (PS) matching. Recurrence-free survival (RFS) and overall survival (OS) after the initial hepatectomy were compared.

Results: The median follow-up period was 79.4 months and the overall, synchronous, and metachronous cohorts included 1145, 498, and 647 patients, respectively. After the PS matching, the patients' demographics were well balanced. AC was effective in terms of both RFS and OS in the overall cohort (RFS hazard ratio [HR] 0.784, p = 0.045; OS HR 0.716, p = 0.028) and synchronous cohort (RFS HR 0.677, p = 0.027; OS HR 0.642, p = 0.036), whereas AC was not effective in the metachronous cohort (RFS HR 0.875, p = 0.378; OS HR 0.881, p = 0.496). However, in the metachronous cohort, AC was effective in terms of OS in the subgroup that exhibited disease-free intervals of ≤ 1 year after primary tumor resection (RFS HR 0.667, p = 0.068; OS HR 0.572, p = 0.042).

Conclusion: Adjuvant chemotherapy has a survival benefit for patients with resected CRLM. Synchronous CRLM is a favorable indication for AC, whereas in metachronous CRLM, the use of AC should be individualized according to each patient's risk factors.
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http://dx.doi.org/10.1007/s11605-019-04250-9DOI Listing
June 2020

Benchmarks in Pancreatic Surgery: A Novel Tool for Unbiased Outcome Comparisons.

Ann Surg 2019 08;270(2):211-218

Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland.

Objective: To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD).

Background: Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative.

Methods: This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches.

Results: Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases.

Conclusion: The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.
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http://dx.doi.org/10.1097/SLA.0000000000003223DOI Listing
August 2019

Adenoid cystic carcinoma with high-grade transformation forming spindle cell component of the submandibular gland.

Auris Nasus Larynx 2019 Dec 16;46(6):934-939. Epub 2019 Feb 16.

Department of Pathology, Fukuoka University, School of Medicine, Japan.

Adenoid cystic carcinoma (AdCC) with high-grade transformation (AdCC-HGT) is rare, and AdCC-HGT with spindle cell component is particularly rare. The patient was a 65-year-old man with a 5 cm sized swelling of the right submandibular gland. Submandibular sialoadenectomy was performed. Histopathological findings mainly showed conventional AdCC, and minorly showed two other components: (1) the pleomorphic component, a proliferation of atypical pleomorphic epithelial cells forming solid or small clusters and accompanied by necrosis; (2) the spindle cell component, containing atypical spindle cells invading the stroma. Postoperative chemoradiotherapy was performed. Multiple right lung nodular lesions were found on the contrast-enhanced chest CT one month after the surgery. Thoracoscopic pulmonary resection was performed. The lung tumors exhibited a proliferation of atypical spindle cells, accompanied by necrosis. We considered that the spindle cell component of the AdCC-HGT of the submandibular gland developed lung metastases. The patient died seven months after submandibular sialoadenectomy due to respiratory failure. Although rare, our case highlights the importance of recognising spindle cell components in conventional AdCC; even if the area is small, these high-grade transformation areas can metastasise and become prognostic factors.
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http://dx.doi.org/10.1016/j.anl.2019.01.014DOI Listing
December 2019

[Postoperative Recurrence of Pancreatic Cancer Successfully Treated with the Gemcitabine plus Oxaliplatin Regimen Resulting in Long-Term Survival-ACase Report].

Gan To Kagaku Ryoho 2019 Jan;46(1):142-144

Dept. of Surgery, Odawara Municipal Hospital.

A 38-year-old woman who presented with complaints of back pain was diagnosed with cancer of the pancreatic body. Since invasion of the celiac artery/superior mesenteric artery was suspected, she was referred to our department for chemotherapy. She received 4 courses of gemcitabine plus S-1(GS), and she underwent distal pancreatectomy with en bloc celiac axis resection/portal vein resection/reconstruction using a left renal vein graft(OP-CAR). Histopathological examination of the resected specimen revealed a positive margin(R1). She received 11 courses of GS as postoperative adjuvant chemotherapy. She developed marked abdominal distension due to metastatic ovarian enlargement, and bilateral salpingo-oophorectomy was performed. The intraoperative findings revealed multiple peritoneal dissemination. Peritoneocentesis was performed, and the patient was started on gemcitabine plus oxaliplatin(GEMOX)for control of the ascites. This treatment was followed by a rapid decrease in the size of the ascites and resolution of the symptoms of stenosis. The serum tumor marker levels decreased over the following 18months. She received a total of 35 courses of GEMOX. This patient showed long-term survival after the start of treatment: she survived for 5 years and 11 months after the initial examination and for 5 years and 6 months after the surgery. Our experience in this case suggests that GEMOX could be a useful treatment option to improve prognosis.
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January 2019

A case of successfully resected metachronous gastric and gallbladder metastases from pancreatic body cancer.

Surg Case Rep 2019 Feb 13;5(1):21. Epub 2019 Feb 13.

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

Background: Pancreatic ductal adenocarcinoma (PDAC) readily metastasizes to the lymph nodes, liver, lung, and peritoneum; however, gastric and gallbladder metastases are rare. We report a case of metachronous gastric and gallbladder metastases from PDAC.

Case Presentation: The patient is a 71-year-old man who underwent distal pancreatectomy for PDAC. Seventeen months after the surgery, a 30-mm nodule was detected at the lesser curvature of the stomach, which was diagnosed as recurrence of PDAC in the lymph nodes. He then received gemcitabine and S-1 combination chemotherapy for 6 months. Because tumor size remained approximately the same and tumor marker levels decreased, total gastrectomy and cholecystectomy were performed. Pathological examination showed well-differentiated tubular adenocarcinoma in the subserosa and muscularis propria of the stomach and gallbladder. The patient remains alive at 41 months after the second surgery with liver metastasis.

Conclusion: We reported a rare case of metachronous gastric and gallbladder metastases from pancreatic body cancer.
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http://dx.doi.org/10.1186/s40792-019-0581-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374494PMC
February 2019