Details of a Researcher - Hasegawa, Yasushi

Papers - Hasegawa, Yasushi

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Successful Case of Deceased Donor Liver Transplant for Polycystic Liver Disease

Sugimoto H., Oshima Y., Oba Y., Ikuma D., Sekine A., Mizuno H., Yamanouchi M., Hasegawa E., Suwabe T., Chu P.S., Hasegawa Y., Obara H., Sawa N., Ubara Y.

Transplantation Proceedings (Transplantation Proceedings) 54 ( 10 ) 2779 - 2783 2022.12

ISSN 00411345

A 58-year-old woman was admitted to hospital for deceased donor liver transplant. Her liver volume, measured by computed tomography, had reached 22,764 cm3 and she was bedridden with performance status 3 because of abdominal distention. The Model for End-Stage Liver Disease score was 24 with exception points. The final weight of the removed liver after cystic fluid puncture was 14 kg. The patient recovered well after transplant and was discharged on postoperative day 43 with a weight of 41 kg and performance status of 1.

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Development of a risk score model for 1-year graft loss after adult deceased donor liver transplantation in Japan based on a 20-year nationwide cohort

Takemura Y., Shinoda M., Takemura R., Hasegawa Y., Yamada Y., Obara H., Kitago M., Sakamoto S., Kasahara M., Umeshita K., Eguchi S., Ohdan H., Egawa H., Kitagawa Y.

Annals of Gastroenterological Surgery (Annals of Gastroenterological Surgery) 6 ( 5 ) 712 - 725 2022.09

Aim: Using nationwide data collected over the past 20 years, we aimed to investigate deceased donor liver transplantation (DDLT) outcomes to develop a unique risk model that can be used to establish a standard for organ acceptance in Japan. Methods: Data were collected for 449 recipients aged ≥18 years who underwent DDLT between 1999 and 2019. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to develop an original risk score model for 1-year graft loss (termed the Japan Risk Index [JRI]). We developed risk indices according to recipient, donor, and surgery components (termed JRI-R, D, and S, respectively). The JRI was validated via a 5-fold cross-validation. We also compared DDLT outcomes and risk indices among Era1 (−2011), Era2 (−2015), and Era3 (−2019). Results: The 1-year graft survival rate was 89.5% and improved significantly, reaching 84.7%, 87.6%, and 93.9% in Era1, Era2, and Era3, respectively. The JRI was calculated as JRI-R (re-transplantation, Model for End-Stage Liver Disease score, medical condition in intensive care unit) × JRI-D (age, catecholamine index, maximum sodium, maximum total bilirubin) × JRI-S (total ischemic time) × 0.84. The risk model achieved a mean C-statistic value of 0.81 in the validation analysis. The risk index was significantly lower in Era3 than in Era2. Conclusion: Changes in the risk index over time indicated that avoiding risks contributed to the improved outcomes in Era3. The JRI is unique to adult DDLT in Japan and may be useful as a reference for organ acceptance in the future.

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Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm

Fukushima G., Abe K., Kitago M., Iwasaki E., Hirata A., Takemura R., Ishii R., Yagi H., Abe Y., Hasegawa Y., Fukuhara S., Hori S., Tanaka M., Nakano Y., Yokose T., Shimane G., Kitagawa Y.

Pancreas (Pancreas) 51 ( 6 ) 617 - 623 2022.07

ISSN 08853177

Objectives Some intraductal papillary mucinous neoplasms (IPMNs) have malignant potential and can become pancreatic cancer. The mechanism behind the malignant progression of IPMN remains unknown. We aimed to identify the risk factors and interactions between backgrounds for IPMN. Methods We retrospectively enrolled 980 patients of pancreatic cancer or suspected IPMN (sIPMN) who underwent endoscopic ultrasound or retrograde cholangiopancreatography. We classified them into pancreatic cancer, high-risk sIPMN, and low-risk sIPMN, and investigated the risk factors for high-risk sIPMN. Results Smoking habits (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.04-6.85; P < 0.001), serum carbohydrate antigen 19-9 ≥37 U/mL (OR, 6.30; 95% CI, 2.88-13.80; P < 0.001), and family history of cancers (OR, 2.38; 95% CI, 1.30-4.37; P = 0.005) were independent risk factors for high-risk suspected IPMN. Odds ratios of diabetes and neutrophil-to-lymphocyte ratio of 2.45 or greater were significantly higher in patients with a family history of cancer than those without a family history of cancer (OR, 3.28; 95% CI, 0.52-20.80 vs 1.85; 95% CI, 0.78-4.41; OR, 2.44; 95% CI, 0.81-7.34 vs 1.24; 95% CI, 0.67-2.30, respectively). Conclusions Understanding the interactions between background factors can effectively prevent IPMNs' malignant transformation.

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Reappraisal of liver transplantation for erythropoietic protoporphyria: A deadly combination of disease recurrence and biliary complication

Endo Y., Hibi T., Shinoda M., Obara H., Kitago M., Yagi H., Abe Y., Hasegawa Y., Matsubara K., Hori S., Tanaka M., Makiuchi S., Nakano Y., Itano O., Kuroda T., Kitagawa Y.

Pediatric Transplantation (Pediatric Transplantation) 26 ( 4 ) 2022.06

ISSN 13973142

Background: Erythropoietic protoporphyria (EPP) is a rare inherited disorder that causes the accumulation of protoporphyrin in the erythrocytes, skin, and liver. Severe protoporphyric hepatopathy results in liver failure, requiring both liver and bone marrow transplantation as a life-saving procedure and to correct the underlying enzymatic defect, respectively. Case presentation: We report a 20-year-old man who underwent split liver transplantation using a right trisegment and caudate lobe graft for EPP-induced liver failure, but succumbed to a deadly combination of early relapse of EPP and subsequent, intractable, late-onset bile leakage from the cut surface of segment 4. EPP recurrence most likely created a high-risk situation for bile leakage from the non-communicating bile ducts of segment 4; therefore, this case shed light on the potential relationship between EPP recurrence and biliary complications. Conclusion: Physicians should recognize the potentially rapid and life-threatening progression of protoporphyric hepatopathy that leads to liver failure. For young patients with EPP, LT and sequential BMT should thoroughly be considered by a multidisciplinary team as soon as hepatic reserve deterioration becomes evident. Split liver transplantation should preferably be avoided and appropriate post-transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft.

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Genomic analysis of familial pancreatic cancers and intraductal papillary mucinous neoplasms: A cross-sectional study

Abe K., Kitago M., Kosaki K., Yamada M., Iwasaki E., Kawasaki S., Mizukami K., Momozawa Y., Terao C., Yagi H., Abe Y., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Kitagawa Y.

Cancer Science (Cancer Science) 113 ( 5 ) 1821 - 1829 2022.05

ISSN 13479032

Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follow a multistep process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole-exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who had intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first-degree relatives were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular, PDIA2 was identified as a novel candidate for one of the deleterious variants of familial pancreatic cancer.

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Standardized single-incision plus one-port laparoscopic left lateral sectionectomy: a safe alternative to the conventional procedure

Katagiri H., Nitta H., Takahara T., Hasegawa Y., Kanno S., Umemura A., Takeda D., Makabe K., Kikuchi K., Kimura T., Yanari S., Sasaki A.

Langenbeck's Archives of Surgery (Langenbeck's Archives of Surgery) 407 ( 3 ) 1277 - 1284 2022.05

ISSN 14352443

Purpose: Laparoscopic left lateral sectionectomy (LLLS) is a feasible and safe procedure with a relatively smooth learning curve. However, single-incision LLLS requires extensive surgical experience and advanced techniques. The aim of this study is to report the standardized single-incision plus one-port LLLS (reduced port LLLS, RPLLLS) technique and evaluate its safety, feasibility, and effectiveness for junior surgeons. Methods: Between January 2008 and November 2020, the clinical records of 49 patients who underwent LLLS, divided into the conventional LLLS (n = 37) and the RPLLLS group (n = 12), were retrospectively reviewed. The patient characteristics, pathologic results, and operative outcomes were evaluated. Results: A history of previous abdominal surgery in the RPLLLS group was significantly high (56.8% vs. 91.7%, p = 0.552). Notably, junior surgeons performed 62.2% of the conventional LLLSs and 58.4% of the standardized RPLLLSs. There were no significant differences between the two groups in terms of median operative time (121.0 vs. 113.5, p = 0.387), median blood loss (13.0 vs. 8.5, p = 0.518), median length of hospital stays (7.0 vs. 7.0, p = 0.408), and morbidity rate (2.7% vs. 0%, p = 0.565), respectively. Conclusion: This standardized RPLLLS is a feasible and safe alternative to conventional LLLS and may become the ideal training procedure for both junior surgeons and surgeons aiming to learn more complex procedures.

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Patients with liver cirrhosis due to nonalcoholic steatohepatitis have lesser chances for liver transplantation

Hasegawa Y., Obara H., Chu P.S., Shinoda M., Kitago M., Abe Y., Yagi H., Matsubara K., Nakamoto N., Kitagawa Y.

Journal of Hepato-Biliary-Pancreatic Sciences (Journal of Hepato-Biliary-Pancreatic Sciences) 29 ( 5 ) 562 - 569 2022.05

ISSN 18686974

Background: The main causes of liver cirrhosis have changed over the past decade. In Japan, the number of deceased donors is increasing but is still insufficient relative to the number of patients awaiting a liver transplant. In the present study we aimed to assess the outcomes of candidates for liver transplantation. Methods: This was a retrospective study of adult patients who visited our department for consultation regarding liver transplantation from January 2009 to December 2020. Of a total of 601 patients, 336 were followed-up. The following data were collected and analyzed: patient's characteristics, liver etiology, Child-Pugh and MELD scores, and the eventual outcome, that is, whether liver transplantation was performed. Results: Only 153 of 336 (45.5%) patients underwent liver transplantation, of which 42 (27.5%) received deceased donor liver transplantation, and 129 (38.4%) died without transplantation. The proportion of patients who underwent liver transplantation was low among patients with nonalcoholic steatohepatitis (NASH) (10.7%) (P <.001). The rate of qualified living donors was the lowest for patients with NASH (28.6%) and that for the other etiologies ranged from 55.6% to 67.4% (P =.050). Conclusion: Patients with liver cirrhosis due to NASH may have a lesser chance of undergoing liver transplantation from both living and deceased donors.

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Immunovascular classification of HCC reflects reciprocal interaction between immune and angiogenic tumor microenvironments

Kurebayashi Y., Matsuda K., Ueno A., Tsujikawa H., Yamazaki K., Masugi Y., Kwa W.T., Effendi K., Hasegawa Y., Yagi H., Abe Y., Kitago M., Ojima H., Sakamoto M.

Hepatology (Hepatology) 75 ( 5 ) 1139 - 1153 2022.05

ISSN 02709139

Background and Aims: Immune cells and tumor vessels constitute important elements in tumor tissue; however, their detailed relationship in human tumors, including HCC, is still largely unknown. Consequently, we expanded our previous study on the immune microenvironment of HCC and analyzed the relationship among the immune microenvironment, inflammatory/angiostatic factor expression, angiogenic factor expression, and tumor vessel findings, including vessels encapsulating tumor clusters (VETC) and macrotrabecular-massive (MTM) patterns. Approach and Results: We classified HCC into four distinct immunovascular subtypes (immune-high/angiostatic [IH/AS], immune-mid/angio-mid [IM/AM], immune-low/angiogenic [IL/AG], and immune-low/angio-low [IL/AL]). IH/AS, IM/AM, and IL/AG subtypes were associated with decreasing lymphocytic infiltration and increasing angiogenic factor expression and VETC/MTM positivity, reflecting their reciprocal interaction in the tumor microenvironment of HCC. IL/AG subtype was further characterized by CTNNB1 mutation and activation of Wnt/β-catenin pathway. IL/AL subtype was not associated with increased lymphocyte infiltration or angiogenic factor expression. Prognostically, IH/AS subtype and VETC/MTM positivity were independently significant in two independent cohorts. Increased angiogenic factor expression was not necessarily associated with VETC/MTM positivity and poor prognosis, especially when inflammatory/angiostatic milieu coexisted around tumor vessels. These results may provide insights on the therapeutic effects of immunotherapy, antiangiogenic therapies, and their combinations. The potential of evaluating the immunovascular microenvironment in predicting the clinical effect of these therapies in nonresectable HCC needs to be analyzed in the future study. Conclusions: HCC can be classified into four distinct immunovascular subtypes (IH/AS, IM/AM, IL/AG, and IL/AL) that reflect the reciprocal interaction between the antitumor immune microenvironment and tumor angiogenesis. In addition to its clinicopathological significance, immunovascular classification may also provide pathological insights on the therapeutic effect of immunotherapy, antiangiogenic therapy, and their combination.

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Decellularized Organ-Derived Scaffold Is a Promising Carrier for Human Induced Pluripotent Stem Cells-Derived Hepatocytes

Kojima H., Yagi H., Kushige H., Toda Y., Takayama K., Masuda S., Morisaku T., Tsuchida T., Kuroda K., Hirukawa K., Inui J., Nishi K., Nakano Y., Tanaka M., Hori S., Hasegawa Y., Abe Y., Kitago M., Adachi S., Tomi M., Matsuura K., Mizuguchi H., Kitagawa Y.

Cells (Cells) 11 ( 8 ) 2022.04

Human induced pluripotent stem cells (hiPSCs) are a promising cell source for elucidating disease pathology and therapy. The mass supply of hiPSC-derived cells is technically feasible. Carriers that can contain a large number of hiPSC-derived cells and evaluate their functions in vivo-like environments will become increasingly important for understanding disease pathogenesis or treating end-stage organ failure. hiPSC-derived hepatocyte-like cells (hiPSC-HLCs; 5 × 108) were seeded into decellularized organ-derived scaffolds under circumfusion culture. The scaffolds were implanted into immunodeficient microminiature pigs to examine their applicability in vivo. The seeded hiPSC-HLCs demonstrated increased albumin secretion and up-regulated cytochrome P450 activities compared with those in standard two-dimensional culture conditions. Moreover, they showed long-term survival accompanied by neovascularization in vivo. The decellularized organ-derived scaffold is a promising carrier for hiPSC-derived cells for ex vivo and in vivo use and is an essential platform for regenerative medicine and research.

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National survey of hepatobiliary and pancreatic surgery in hemophilia patients in Japan

Yoshimoto-Haramura T., Hidaka M., Hasegawa K., Suzumura K., Takemura N., Hama N., Mizuno T., Nomi T., Kobayashi T., Sano K., Yokomizo H., Nitta H., Kurata M., Hasegawa Y., Nagayama M., Tani M., Fukumoto T., Ohta M., Hayashi H., Taniguchi H., Ishino S., Aihara T., Murase T., Tsuchida A., Shimamura T., Marubashi S., Kaneko J., Hara T., Matsushima H., Soyama A., Endo T., Eguchi S.

Journal of Hepato-Biliary-Pancreatic Sciences (Journal of Hepato-Biliary-Pancreatic Sciences) 29 ( 3 ) 385 - 393 2022.03

ISSN 18686974

Background: Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan. Methods: The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications. Results: The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients. Conclusions: As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS.

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Dynamic contrast-enhanced CT at the early stage confirms two cases of acute liver failure due to acute-onset autoimmune hepatitis with extensive liver necrosis

Watanabe T., Chu P.S., Ehira T., Hasegawa Y., Hattori N., Shinoda M., Ikeda H., Tsujikawa H., Obara H., Hara M., Suzuki T., Matsunaga K., Okuse C., Itoh F.

Acta Hepatologica Japonica (Acta Hepatologica Japonica) 63 ( 3 ) 158 - 169 2022

ISSN 04514203

[Case 1] A 54-year-old female presented with severe liver damage. During diagnosis, contrast-enhanced CT enhanced the area of hypoattenuation on unenhanced CT in the arterial phase, after which the enhanced effect was prolonged to the equilibrium phase. Then, we started immunosuppressive therapy based on the results, including corticosteroid administration, and her hepatitis subsided. [Case 2] A 57-year-old female also presented with severe hepatitis. Contrast-enhanced CT findings were similar to those of Case 1. Since hepatic encephalo-pathy developed and worsened to degree IV, a brain-dead liver transplant was conducted on the 21st day. Nev-ertheless, histological diagnosis was challenging in both cases. Therefore, when unenhanced CT shows hetero-geneous hypoattenuation in the liver and contrast-enhanced CT shows a characteristic blood flow disorder, acute-onset autoimmune hepatitis and corticosteroid treatment should be considered, including in complex se-rological or histological case diagnoses.

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Intravenous administration of dehydroxymethylepoxyquinomicin with polymer enhances the inhibition of pancreatic carcinoma growth in mice

Fujisaki H., Nakano Y., Matsuda S., Suzuki K., Itano O., Tanaka M., Hori S., Hasegawa Y., Abe Y., Yagi H., Kitago M., Konno T., Ishihara K., Ohno K., Kishino S., Umezawa K., Kitagawa Y.

Anticancer Research (Anticancer Research) 41 ( 12 ) 6003 - 6012 2021.12

ISSN 02507005

Background/Aim: Pancreatic cancer, which exhibits resistance to cytotoxic and molecular targeted drugs, has an extremely poor prognosis. Nuclear factor-ĸB (NF-ĸB) is constitutively activated in many pancreatic cancer cases. Although the NF-ĸB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) has exhibited anti-cancer effects in pancreatic cancer models, its poor solubility limits its use to intraperitoneal administration. Materials and Methods: Poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) forms stable polymer aggregates with DHMEQ. The stability of DHMEQ aggregated with PMB in the human blood was measured by high-performance liquid chromatography–mass spectrometry (HPLC-MS) ex vivo. Anti-pancreatic cancer effects in AsPC-1 and MIA PaCa-2 pancreatic cancer cells were evaluated by cell growth inhibition assay in vitro and tumor growth inhibition assay in vivo. Results: DHMEQ aggregated with PMB (PMBDHMEQ) remained detectable after 60 min of incubation in the human blood, whereas DHMEQ aggregated with carboxymethyl cellulose (CMC-DHMEQ) was barely detectable. PMB-DHMEQ significantly inhibited AsPC-1 and MIA PaCa-2 cell growth in vitro compared to CMC-DHMEQ. Intravenous administration of PMB-DHMEQ reduced the tumor volume and liver metastasis compared to untreated or CMC-DHMEQ-treated mice. Conclusion: Aggregation with PMB improved the solubility of DHMEQ, and effectively inhibited pancreatic cancer cell growth both in vitro and in vivo.

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Pure Laparoscopic Donor Hepatectomy: Right Posterior Section Graft

Hasegawa Y., Nitta H., Takahara T., Katagiri H., Kanno S., Umemura A., Sasaki A.

Journal of Gastrointestinal Surgery (Journal of Gastrointestinal Surgery) 25 ( 10 ) 2718 - 2719 2021.10

ISSN 1091255X

Background: The use of laparoscopic liver resection (LLR) is widespread owing to its several advantages, especially smaller incision (Kaneko et al., Ann Gastroenterol Surg 1:33–43, 1; Ciria et al., Surg Endosc 34:349–360, 2). However, both posterior sectionectomy and donor hepatectomy are extremely difficult procedures to perform in LLR (Hasegawa et al., Ann Gastroenterol Surg 2:376–382, 3; Soubrane and Kwon, J Hepatobiliary Pancreat Sci 24:E1–E5, 4; Takahara et al., Transplantation 101:1628–1636, 5; Lee et al., Clin Transplant 33:e13683, 6; Hong et al., Surg Endosc 33:3741–3748, 7; Rhu et al., J Hepatobiliary Pancreat Sci 27:16–25, 8). Moreover, the right posterior section graft procurement is also difficult even in open laparotomy procedure (Sugawara et al., Transplantation 73:111–114, 9; Hwang et al., Liver Transpl 10:1150–1155, 10; Hori, Kirino, and Uemoto, Hepatol Res 45:1076–1082, 11; Kusakabe et al., Liver Transpl 26:299–303, 12). The pure laparoscopic donor posterior sectionectomy has not been reported yet. Therefore, we aimed to introduce a novel procedure through a video clip. Methods: The donor was placed in the semi-left lateral decubitus position with the reverse Trendelenburg position using a bean bag device. The right liver was mobilized, and the right hepatic vein was exposed. To adopt the liver hanging maneuver, a tape was inserted between the middle and right hepatic veins along the inferior vena cava. The posterior Glissonean pedicle was encircled and controlled, and the liver parenchyma was completely transected using the liver hanging maneuver. The vessels to the posterior section were respectively isolated. The posterior branches of the hepatic duct, hepatic artery, and portal vein were cut. The right hepatic vein was divided, and the graft liver was retrieved via a suprapubic incision. This study was approved by institutional ethics board (No. MH2019-119), and informed consent was taken from the patient. Results: The overall surgical time was 503 min, and the blood loss was 400 mL. No complications were observed, and the donor was discharged from the hospital on postoperative day 11. Conclusion: This is the first report of pure laparoscopic donor hepatectomy of the posterior section graft. This procedure is more difficult than other laparoscopic donor hepatectomies because it involves parenchymal transection in the right intersectional plane and dissection of the posterior branches of hilar vessels.

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Gamma-synuclein is a novel prognostic marker that promotes tumor cell migration in biliary tract carcinoma

Takemura Y., Ojima H., Oshima G., Shinoda M., Hasegawa Y., Kitago M., Yagi H., Abe Y., Hori S., Fujii-Nishimura Y., Kubota N., Masuda Y., Hibi T., Sakamoto M., Kitagawa Y.

Cancer Medicine (Cancer Medicine) 10 ( 16 ) 5599 - 5613 2021.08

Gamma-synuclein (SNCG) promotes invasive behavior and is reportedly a prognostic factor in a range of cancers. However, its role in biliary tract carcinoma (BTC) remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Using resected BTC specimens from 147 patients with adenocarcinoma (extrahepatic cholangiocarcinoma [ECC, n = 96]; intrahepatic cholangiocarcinoma [ICC, n = 51]), we immunohistochemically evaluated SNCG expression and investigated its correlation with clinicopathological factors and outcomes. Furthermore, cell lines with high SNCG expression were selected from 16 BTC cell lines and these underwent cell proliferation and migration assays by siRNAs. In the results, SNCG expression was present in 22 of 96 (22.9%) ECC patients and in 10 of 51 (19.6%) ICC patients. SNCG expression was significantly correlated with poorly differentiated tumor in both ECC and ICC (p = 0.01 and 0.03, respectively) and with perineural invasion and lymph node metastases in ECC (p = 0.04 and 0.003, respectively). Multivariate analyses revealed that SNCG expression was an independent poor prognostic factor in both OS and RFS in both ECC and ICC. In vitro analyses showed high SNCG expression in three BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing could suppress cell migration in NCC-BD1 and NCC-CC6-1 and downregulate cell proliferation in NCC-CC6-1 significantly. In conclusion, SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC.

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Invasive pulmonary aspergillosis after liver transplantation: lessons from successfully treated cases and review of the literature

Abe K., Shinoda M., Uno S., Obara H., Kitago M., Abe Y., Hishida T., Yagi H., Hasegawa Y., Kitagawa Y.

Surgery Today (Surgery Today) 51 ( 8 ) 1361 - 1370 2021.08

ISSN 09411291

Purpose: Invasive pulmonary aspergillosis (IPA) after liver transplantation (LT) is most often fatal. We analyzed the outcomes of IPA in a single center. Methods: We reviewed, retrospectively, the medical records of recipients of living donor LT (LDLT) or deceased donor LT (DDLT) performed between 1995 and 2019 at our institute. We analyzed the incidence of IPA and assessed the treatment courses of patients treated successfully and those not treatment successfully. Results: Among 326 recipients, IPA was diagnosed in 6 (1.8%). The incidence of IPA was significantly higher in patients with acute liver failure (ALF, 9.8%) than in those without ALF (0.4%), after DDLT (8.8%) than after LDLT (1.0%), and in recipients who received preoperative steroid pulse therapy (16.0%) than in those who did not (0.7%). Complete cure of IPA was achieved in the most recent three patients, by administering voriconazole immediately after the diagnosis of IPA and performing lung resection, while the IPA lesion was single and localized. Conclusions: Patients with risk factors for IPA must be monitored closely. Our three successfully treated cases demonstrate that initiating immediate voriconazole treatment and making a calculated decision about lung resection can contribute to a favorable outcome.

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Indication for resection and possibility of observation for intraductal papillary mucinous neoplasm with high-risk stigmata

Abe K., Kitago M., Masugi Y., Iwasaki E., Yagi H., Abe Y., Hasegawa Y., Fukuhara S., Hori S., Tanaka M., Nakano Y., Yokose T., Shimane G., Sakamoto M., Kitagawa Y.

Pancreatology (Pancreatology) 21 ( 4 ) 755 - 762 2021.06

ISSN 14243903

Background/Objectives: According to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs. Methods: We enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN. Results: Fifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45). Conclusions: Large nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.

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Pure laparoscopic living donor left lateral sectionectomy using glissonean approach and original bridging technique

Umemura A., Nitta H., Takahara T., Hasegawa Y., Katagiri H., Kanno S., Takeda D., Makabe K., Kobayashi M., Sasaki A.

Surgical Laparoscopy, Endoscopy and Percutaneous Techniques (Surgical Laparoscopy, Endoscopy and Percutaneous Techniques) 31 ( 3 ) 389 - 392 2021.06

ISSN 15304515

Background: Living donor liver transplantation (LDLT) is the final treatment for children with end-stage liver disease. Congenital biliary atresia (CBA) is the most common disease requiring LDLT in Japan, and a left lateral sector graft is preferably procured owing to its anatomic predictivity and identical graft volume for preschool recipients. Laparoscopic left lateral sectionectomy (L-LLS) for LDLT has been recently established; however, there is no report about the innovative technique in L-LLS. The aim of this study was to introduce our L-LLS using the Glissonean approach and bridging technique for pediatric LDLT. Materials and Methods: From September 2017 to September 2020, 5 cases of L-LLS for pediatric LDLT because of CBA were performed and we performed L-LLS using the original technique on their donors. In this novel procedure, the left Glissonean pedicle was encircled at the parenchymal side of the Laennec capsule after mobilization of the lateral sector and visualization of the left hepatic vein. Then, we passed 2 tapes through the encircled Glissonean pedicle at the hepatic side and the duodenal side, as the caudate lobe branch is enclosed like a bridge. By virtue of this bridging technique, we encircled the caudate lobe branch alone by switching the tape, and we clipped and divided it; this technique secured an adequately long hepatic duct on the graft side to perform a hepaticojejunostomy. The left hepatic duct was divided after indocyanine green fluorescence cholangiography, and the left hepatic artery and portal vein were divided as well. Finally, the left hepatic vein was transected and procured from an extended intraumbilical incision. Results: We achieved L-LLS by using the Glissonean approach and the bridging technique in the 5 donors. The median operating time and blood loss were 282 (268 to 332) minutes and 34 (25 to 75) mL, respectively. There was no conversion to hybrid or open LLS and no postoperative complications. Regarding recipient outcomes, hepatic artery thrombosis occurred on postoperative day 4 in a 5-year-old female. All grafts function well and all recipients are alive after discharge (range of observation period, 3 to 26 mo). Conclusions: We herein present standardized L-LLS using the Glissonean approach and bridging technique for pediatric LDLT. Our technique can secure a longer margin of the left hepatic duct for recipients' hepaticojejunotomy. Our results have demonstrated the advantage in pediatric LDLT, especially in patients with CBA after the Kasai procedure.

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Central hepatic bisectionectomy with hepatic artery and biliary tracts reconstruction for the patient with nodular type intrahepatic hilar cholangiocarcinoma: A case report

Umemura A., Nitta H., Takahara T., Hasegawa Y., Sugai T., Sasaki A.

International Journal of Surgery Case Reports (International Journal of Surgery Case Reports) 82 2021.05

ISSN 22102612

Introduction and importance: A central hepatic bisectionectomy (CHBS) for a hilar cholangiocarcinoma (CCA) is technically challenging because bilateral biliary reconstruction is required after resection. On the other hand, hepatic artery resection and reconstruction in a major liver resection are also technical procedures. In this report, we describe our radical CHBS with hepatic artery and biliary tracts reconstruction for a patient with nodular type intrahepatic hilar CCA. Case presentation: A 76-year-old man was referred for further investigation of an incidental hepatic tumor. The hepatic tumor was located from medial sector to anterior sector with encasement of the anterior branch of the right hepatic artery. Based on these findings, we performed a CHBS with right hepatic artery and biliary tracts reconstruction. The histopathological findings revealed that the tumor consisted of moderately differentiated tubular adenocarcinoma with tumor necrosis without a fibrous capsule. In this area, tumors cells had invaded branches of the hepatic vein; however, there was no destructive invasion to the hepatic artery. Consequently, he was diagnosed with a nodular type intrahepatic hilar CCA with pT2aN0M0. Clinical discussion: A CHBS is usually performed with the intent of anatomically preserving a patient's liver as much as possible. Concomitant resection and reconstruction of the hilar vessels and biliary tracts with CHBS is one of the most technically challenging procedures in liver resections. Conclusion: A CHBS with hepatic artery and biliary reconstruction may be a promising alternative if expert surgeons perform it on strictly selected patients.

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Peritoneal dissemination of pancreatic cancer caused by endoscopic ultrasound-guided fine needle aspiration: A case report and literature review

Kojima H., Kitago M., Iwasaki E., Masugi Y., Matsusaka Y., Yagi H., Abe Y., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Takemura Y., Fukuhara S., Ohara Y., Sakamoto M., Okuda S., Kitagawa Y.

World Journal of Gastroenterology (World Journal of Gastroenterology) 27 ( 3 ) 294 - 304 2021.01

ISSN 10079327

BACKGROUND Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a biopsy technique widely used to diagnose pancreatic tumors because of its high sensitivity and specificity. Although needle-tract seeding caused by EUS-FNA has been recently reported, dissemination of pancreatic cancer cells is generally considered to be a rare complication that does not affect patient prognosis. However, the frequency of dissemination and needle-tract seeding appears to have been underestimated. We present a case of peritoneal dissemination of pancreatic cancer due to preoperative EUS-FNA. CASE SUMMARY An 81-year-old man was referred to the Department of Surgery of our hospital in Japan owing to the detection of a pancreatic mass on computed tomography during medical screening. Trans-gastric EUS-FNA revealed that the mass was an adenocarcinoma; hence laparoscopic distal pancreatectomy with lymphadenectomy was performed. No intraoperative peritoneal dissemination and liver metastasis were visually detected, and pelvic lavage cytology was negative for carcinoma cells. The postoperative surgical specimen was negative for carcinoma cells at the dissected margin and the cut end margin; however, pathological findings revealed adenocarcinoma cells on the peritoneal surface proximal to the needle puncture site, and the cells were suspected to be disseminated via EUS-FNA. Hence, the patient received adjuvant therapy with S-1 (tegafur, gimeracil, and oteracil potassium); however, computed tomography performed 5 mo after surgery revealed liver metastasis and cancerous peritonitis. The patient received palliative therapy and died 8 mo after the operation. CONCLUSION The indications of EUS-FNA should be carefully considered to avoid iatrogenic dissemination, especially for cancers in the pancreatic body or tail.

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Efficacy of enhanced prehabilitation for patients with esophageal cancer undergoing esophagectomy

Akiyama Y., Sasaki A., Fujii Y., Fujisawa R., Sasaki N., Nikai H., Endo F., Baba S., Hasegawa Y., Kimura T., Takahara T., Nitta H., Otsuka K., Koeda K., Nishimura Y., Iwaya T.

Esophagus (Esophagus) 18 ( 1 ) 56 - 64 2021.01

ISSN 16129059

Background: Several studies have demonstrated that prehabilitation helps reduce the incidence of postoperative complications. In this study, we investigated the safety and efficacy of enhanced prehabilitation (EP) in the hospital for patients with esophageal cancer. Methods: We retrospectively reviewed the data of 48 consecutive patients who underwent radical esophagectomy with gastric tube reconstruction between September 2015 and June 2019. EP program had been introduced in August 2017. In the EP group, patients received the EP program during hospitalization 7 days before surgery in addition to conventional perioperative rehabilitation. The EP program consisted of aerobic exercise and muscle strength training in the morning and afternoon. Operative outcomes were compared between patients who received EP (EP group; 23 patients) and patients who did not receive EP (control group; 25 patients). Results: The preoperative (EP group vs. control group, 492.9 ± 79.7 vs. 418.9 ± 71.8 m, p < 0.001) and postoperative (EP group vs. control group, 431.5 ± 80 vs. 378 ± 68.7 m, p < 0.001) 6-min walk distance was significantly higher in the EP group than in the control group. The respiratory complications rate was significantly lower in the EP group (4.3%) than in the control group (36%) (p = 0.007). The incidence of atelectasis was particularly significantly lower in the EP group (0%) than in the control group (24%) (p = 0.012). Conclusions: EP was performed safely for patients before esophagectomy. EP improved the exercise tolerance of the patients before esophagectomy and might be useful in preventing respiratory complications.

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