Details of a Researcher - Hasegawa, Yasushi

Papers - Hasegawa, Yasushi

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Safety and efficacy of pancreaticogastrostomy for hepatopancreatoduodenectomy compared to pancreaticojejunostomy for perihilar cholangiocarcinoma

Nakano Y., Abe Y., Udagawa D., Kitago M., Hasegawa Y., Hori S., Tanaka M., Uemura S., Odaira M., Mihara K., Nishiyama R., Chiba N., Hayatsu S., Kawachi S., Kitagawa Y.

World Journal of Surgical Oncology 23 ( 1 ) 2025.12

Background: Hepatopancreatoduodenectomy (HPD) is one of the most challenging surgeries for perihilar cholangiocarcinoma. Postoperative pancreatic fistula (POPF) is a critical and fatal complication. The safety and efficacy of pancreaticogastrostomy (PG) for HPD compared to pancreaticojejunostomy (PJ) remain unclear. In this study, we aimed to investigate and compare the short-term outcomes of PG and PJ for HPD in terms of the POPF rate. Methods: Two groups of patients (PG group vs. PJ group) were retrospectively compared between January 2013 and January 2024. The reconstruction method was changed from PJ to PG in March 2021. Results: A total of 50 patients were enrolled in this study. The PG and PJ groups comprised 15 (30.0%) and 35 (70.0%) patients, respectively. In the PJ group, three (8.6%) patients died after surgery because of clinically relevant POPF (CR-POPF), intraabdominal bleeding, and post-hepatectomy liver failure. The operative time was longer in the PG group (909 min vs. 706 min, P = 0.020); however, the CR-POPF rate was lower in the PG group than in the PJ group (0 [0%] vs. 19 [54.3%], P < 0.001). Moreover, the number of patients who developed massive postoperative ascites (≥ 1,500 mL/day) was lower in the PG group than in the PJ group (3 [20.0%] vs. 16 [45.7%] patients, P = 0.028). Conclusions: Changing the method of pancreatic reconstruction for HPD from PJ to PG improved the short-term outcomes of patients at our institution. PG reconstruction is safe and effective for HPD as it reduces the incidence of CR-POPF.

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Laparoscopic cholecystectomy with synchronous navigation of ICG fluorescence and Yellow Enhance mode

Sonoda K., Abe Y., Kitago M., Yagi H., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Kojima H., Kitagawa Y.

Asian Journal of Surgery 48 ( 7 ) 4186 - 4187 2025.07

ISSN 10159584

Technique: Laparoscopic cholecystectomy (LC), widely performed for gallbladder (GB) diseases poses risks of severe complications. To minimize these risks, Tokyo Guidelines 2018 advocated for “safe steps in LC for acute cholecystitis (AC)” including “maintaining the plane of dissection on the GB surface throughout LC”. Moreover, the dissection along the inner layer of the subserosa (SS-inner) of GB helps surgeons avoid bile duct or vascular injury. This step occasionally becomes challenging when distinguishing the GB surface from adjacent fat. ICG, injected into biliary tract, illuminates in green under Infra-red (IR) mode and facilitates the identification of biliary tract. Otherwise, Yellow Enhance (YE) mode developed by Olympus Corporation, which highlights yellow-colored tissues by converting orange-yellow tissues to a clearer yellow, improves the contrast between anatomical structures. Results: In a case of AC following percutaneous transhepatic gallbladder drainage (PTGBD), we applied both ICG fluorescence and YE mode. The ICG injected from PTGBD illuminated the GB surface in green, while YE mode highlighted the fatty tissue in a clearer yellow, facilitating the distinction between these two tissues and the accurate dissection along the SS-inner. An additional advantage of injecting ICG from PTGBD, or from the cannulation tube intraoperatively inserted to GB, over intravenous administration is that the GB surface can be illuminated in cases of GB stone incarceration. Conclusion: The combination of ICG fluorescence and YE mode encourages surgeons to identify the boundary between the GB surface and the surrounding fatty tissues, which assists the accurate dissection along the SS-inner.

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Potential Impact of Screening Examinations on Prognosis of De Novo Malignancies in Adult Patients After Liver Transplantation

Uemura S., Hasegawa Y., Obara H., Kitago M., Yagi H., Abe Y., Hori S., Tanaka M., Nakano Y., Kitagawa Y.

Livers 5 ( 2 ) 2025.06

Background: De novo malignancies (DNMs) after liver transplantation (LT) are a major cause of long-term mortality. However, no definitive screening protocol has been established due to their diversity. This study aimed to evaluate DNM diagnosis methods, screening protocols, and prognoses. Methods: This retrospective study included 231 adult LT recipients from April 1997 to March 2021. Disease-specific survival (DSS) was analyzed to assess the impact of screening on prognosis. Most recipients underwent serum tests every three months, annual gastrointestinal endoscopy, and chest-abdominal CT as part of routine surveillance. Results: Twenty-five DNMs were diagnosed in 22 patients, with median age of 61 years (range, 23–72), of whom 13 (59.1%) were female. The duration from transplantation to DNM diagnosis of DNM was 88 months (range, 4–195). DNM was diagnosed as follows: seven patients (31.8%) through screening (screening group) and 15 patients (68.2%) by other means (non-screening group). Curative treatment was achieved in all of the patients diagnosed by screening, whereas it was possible in only 60.0% of patients diagnosed by other means (p = 0.026). DSS in the screening group was significantly longer than that in the non-screening group (p = 0.024). Conclusions: While screening was associated with earlier-stage diagnosis and improved outcomes in some patients, the overall efficacy of the protocol requires further validation in larger studies.

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A case of hepatic epithelioid hemangioendothelioma with features resembling those of acute-onset autoimmune hepatitis that was undiagnosed before liver transplantation

Usui S., Chu P.S., Hirano M., Hasegawa Y., Ueno A., Nomura R., Obara H., Kitagawa Y., Kanai T., Nakamoto N.

Clinical Journal of Gastroenterology 18 ( 3 ) 514 - 519 2025.06

ISSN 18657257

Hepatic epithelioid hemangioendothelioma (HEHE), which is extremely rare, is considered to have a malignant grade between that of hepatic hemangioma and that of hepatic hemangiosarcoma; however, some cases progress so quickly that they present with portal hypertension. We report the case of a woman with findings similar to those of acute-onset autoimmune hepatitis (AIH) that was not diagnosed before liver transplantation. The patient presented with jaundice and ascites. A hematological examination revealed negative tumor markers, high IgG levels, and negative hepatitis virus markers. Computed tomography findings of the liver showed map-like signs characteristic of acute-onset AIH. Despite some response, immunosuppressive drugs such as prednisolone, cyclosporine, and mycophenolate mofetil did not improve liver failure, and she underwent liver transplantation after 200 days of treatment. The explanted liver exhibited white areas that extended in a map-like manner and were occupied by fibrous stroma. Tumors with WWTR1-CAMTA1 gene fusion were recognized and diagnosed as HEHE. Although a histological examination is essential, a percutaneous liver biopsy could not be performed preoperatively because of the presence of ascites. Furthermore, the rarity of the disease, similarity of imaging findings with non-neoplastic patterns, and serological findings made it difficult to differentiate this case from acute-onset autoimmune hepatitis.

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Chronological changes in etiology, pathological and imaging findings in primary liver cancer from 2001 to 2020

Tsuzaki J., Ueno A., Masugi Y., Tamura M., Yamazaki S., Matsuda K., Kurebayashi Y., Sakai H., Yokoyama Y., Abe Y., Hayashi K., Hasegawa Y., Yagi H., Kitago M., Jinzaki M., Sakamoto M.

Japanese Journal of Clinical Oncology 55 ( 4 ) 362 - 371 2025.04

ISSN 03682811

Purpose: To achieve a historical perspective, the chronological changes in primary liver cancer over a 20-year period were investigated at a single institution, focusing on shifts in etiology and the impact on imaging and pathological findings using The Liver Imaging Reporting and Data System. Materials and methods: A retrospective study of surgically resected primary liver cancer in 680 patients from 2001 to 2020 resulted in 434 patients with 482 nodules being analyzed. Dynamic contrast-enhanced computed tomography imaging and the Liver Imaging Reporting and Data System 2018 classification were employed. Two pathologists and two radiologists independently evaluated specimens and images. Results: This study highlighted a significant decline in cases of viral hepatitis and cirrhosis in primary liver cancer patients but an increase in intrahepatic cholangiocarcinoma and scirrhous hepatocellular carcinoma. Notably, there was a rise in non-viral hepatitis cases, potentially pointing toward an increase in steatohepatitic hepatocellular carcinoma cases in the future. Intrahepatic cholangiocarcinoma, scirrhous hepatocellular carcinoma and steatohepatitic hepatocellular carcinoma tumors exhibited slightly different distributions in the Liver Imaging Reporting and Data System classification compared with ordinary hepatocellular carcinoma, which may reflect the presence of fibrosis and lipid in tumor parenchyma. Conclusions: Consistent with past reports, this study demonstrated the emergence of primary liver cancer against a backdrop of non-viral and non-cirrhotic liver. Liver Imaging Reporting and Data System has been consistently useful in diagnosing primary liver cancer; however, among the histological subtypes of hepatocellular carcinoma, an increase is anticipated in scirrhous hepatocellular carcinoma and steatohepatitic hepatocellular carcinoma, which may present imaging findings different from those of ordinary hepatocellular carcinoma. This development may necessitate a reevaluation of the current approach for diagnosing and treating hepatocellular carcinoma based solely on imaging.

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Clinical Impact of Neoadjuvant Therapy for Resectable Pancreatic Ductal Adenocarcinoma: A Single-Center Retrospective Study

Shimane G., Kitago M., Yagi H., Abe Y., Hasegawa Y., Hori S., Tanaka M., Tsuzaki J., Yokoyama Y., Masugi Y., Takemura R., Kitagawa Y.

Annals of Surgical Oncology 32 ( 4 ) 2830 - 2840 2025.04

ISSN 10689265

Background: Neoadjuvant therapy is recommended for treating resectable pancreatic ductal adenocarcinoma (PDAC); however, its appropriate use in patients with resectable PDAC remains debatable. Objective: This study aimed to identify independent poor prognostic factors and evaluate the clinical significance of neoadjuvant therapy in patients with resectable PDAC. Methods: We retrospectively reviewed consecutive patients diagnosed with resectable PDAC at our institute between January 2003 and December 2022. We analyzed poor prognostic factors at the time of diagnosis in patients who underwent upfront surgery using the Cox proportional hazards model for overall survival (OS). The prognostic score was calculated by adding the individual prognostic factor scores. Results: Overall, 359 patients were included in this study, with 308 patients undergoing upfront surgery and the remaining 51 patients receiving neoadjuvant therapy. The R0 resection rate was significantly higher in the neoadjuvant therapy group (70.6%) than in the upfront surgery group (64.0%). Multivariate analysis in the upfront surgery group revealed the following independent poor prognostic factors: tumor size ≥ 35 mm, serum albumin level ≤.5 g/dL, neutrophil-to-lymphocyte ratio ≥ 3.5, carbohydrate antigen 19-9 level ≥ 250 U/mL, and Duke pancreatic monoclonal antigen type 2 level ≥ 750 U/mL. Among patients with prognostic scores of 0–1 (n = 263), the intention-to-treat OS did not significantly differ between the neoadjuvant therapy and upfront surgery groups. Among those patients with a prognostic score of ≥ 2 (n = 96), the neoadjuvant therapy group had significantly longer intention-to-treat OS than the upfront surgery group. Conclusions: Prognostic score-based stratification can help identify patients who could benefit from neoadjuvant therapy.

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New criteria for preoperative liver function assessment with safety margins to avoid postoperative mortality during liver resection for hilar cholangiocarcinoma

Kojima H., Abe Y., Udagawa D., Hayashi K., Chiba N., Imai S., Mihara K., Higashi H., Odaira M., Oshima G., Koizumi W., Kitago M., Yagi H., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Kawachi S., Kitagawa Y.

HPB 27 ( 2 ) 159 - 166 2025.02

ISSN 1365182X

Background: Despite recent medical advancements, surgery for hilar cholangiocarcinoma is associated with high complication and mortality rates. This may be partly attributed to the absence of established preoperative liver evaluation criteria for safe surgery. This study aimed to propose a reliable indicator for safe and well-planned management of major hepatectomy with extrahepatic bile duct resection. Methods: We included 150 patients who underwent major hepatectomy with extrahepatic bile duct resection between 2013 and 2021 in Japan. The risk factors for post-hepatectomy liver failure (PHLF) were retrospectively analyzed. Results: PHLF was observed in 24 (16.0 %) patients who underwent major hepatectomy with extrahepatic bile duct resection. In the multivariate analysis, the identified risk factors for PHLF were the ratio of future remnant liver volume to total liver volume (FRLV/TLV) ≤ 42 % and indocyanine green clearance fraction of the future remnant liver (ICGK-F) ≤ 0.07. Patients with these two factors were significantly associated with PHLF compared with those with either one or none of the risk factors (60.0 % vs 15.1 % and 8.1 %, respectively). Conclusion: The combinational use of ICGK-F and FRLV/TLV is useful for preoperative liver function assessment with a safety margin to avoid PHLF and postoperative mortality in hepatectomy for hilar cholangiocarcinoma.

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Splenic Metastasis of Endometrial Carcinoma Manifesting as a Hemorrhagic Splenic Cyst 17 Years After Surgery

Kitago M., Kamiyama M., Abe Y., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Masugi Y., Ueno A., Sakai K., Yokota M., Yamagami W., Kitagawa Y.

Asian Journal of Endoscopic Surgery 18 ( 1 ) 2025.01

ISSN 17585902

Splenic metastases from solid tumors are rare, particularly when they occur after a long postsurgical interval. We report the case of a 69-year-old woman who developed a splenic metastasis from endometrial carcinoma, presenting as a hemorrhagic splenic cyst, 17 years after her initial surgery. Laparoscopic splenectomy achieving R0 resection was successfully performed; however, the patient subsequently developed multiple liver metastases. This case highlights the importance of periodic evaluation for recurrence, including monitoring for symptoms and elevated tumor markers, in patients with a history of endometrial carcinoma or other solid tumors.

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Laparoscopic Donor Left Lateral Sectionectomy Using the Glissonean Pedicle Approach: Technical Details With Video

Hasegawa Y., Abe Y., Obara H., Yamada Y., Kitago M., Fujino A., Kitagawa Y.

Asian Journal of Endoscopic Surgery 18 ( 1 ) 2025.01

ISSN 17585902

Introduction: Pure laparoscopy for living donor hepatectomy is gaining popularity due to its advantages. However, despite the long-standing application of laparoscopic donor left lateral sectionectomy, the dissection of the Glisson branch, portal vein, and biliary ducts, particularly those of the caudate lobe, remains insufficiently described. Although the Glissonean approach offers easy standardization for hilar dissection, clear landmarks for parenchymal transection, and reduces postoperative bile leakage, it has not been widely adopted in laparoscopic donor hepatectomy. Here, we introduce a modified Glissonean pedicle approach to address the movement restrictions in laparoscopic surgery. Surgical Technique: After liver mobilization, the Glisson of Spiegel lobe (G1L) was divided, followed by encircling the left Glissonean pedicle. A tape for the liver hanging maneuver was placed from the right edge of the left Glissonean pedicle, along the Arantius plate, to the left edge of the left hepatic vein. When the parenchymal transection was completed, the left hepatic vein was automatically taped. The left hepatic artery and left portal vein were exposed, and some branches of P1 were divided to lengthen for anastomosis. The left hepatic duct was taped by removing the left hepatic artery and left hepatic vein from the left Glissonean pedicle. The left hepatic duct was divided under intraoperative cholangiography. Next, the left hepatic artery, left portal vein, and left hepatic vein were sequentially divided, and the graft liver was retrieved. Discussion: Our Glissonean approach can help standardize donor left lateral sectionectomy, minimize the exposure of the left hepatic duct, and clarify B1 branch dissection.

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Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma

Kurebayashi Y., Sugimoto K., Tsujikawa H., Matsuda K., Nomura R., Ueno A., Masugi Y., Yamazaki K., Effendi K., Takeuchi H., Itoi T., Hasegawa Y., Abe Y., Kitago M., Ojima H., Sakamoto M.

Clinical Cancer Research 30 ( 24 ) 5666 - 5680 2024.12

ISSN 10780432

Purpose: Immunotherapies have led to a paradigm shift in the treatment of hepatocellular carcinoma (HCC). Studies have revealed the single-cell catalogs of tumor-infiltrating immune cells and the trajectories of their differentiation. Nevertheless, the spatial distribution of these immune cells with distinct phenotypes in the tumor microenvironment and their clinicopathologic significance in resectable and unresectable HCCs are still largely unclear. Experimental Design: We analyzed the spatial dynamics of intratumoral CD4 and CD8 T cells and their association with B and plasma cells using 283 surgically resected HCC samples, 58 unresectable HCC samples before combined immunotherapy [atezolizumab plus bevacizumab (Atezo + Bev)], and autopsy specimens from 50 cases of advanced-stage HCC through multiplex IHC combined with transcriptomic and driver gene mutation analyses. Classification based on the spatial dynamics of T- and B-cell responses (refined immunosubtype) was developed, and its clinicopathologic significance was analyzed. Results: We found that stem-like CD4 and CD8 T cells were mainly observed in T-cell aggregates and T-cell zone of tertiary lymphoid structure (TLS). The differentiation of T follicular helper cells was associated with the development of TLS, whereas the differentiation of CXCL13-expressing CD4 T<inf>CXCL13</inf> cells with a phenotype resembling T peripheral helper cells was associated with the development of the lymphoplasmacytic microenvironment. The refined immunosubtype could predict clinical outcomes of resectable HCC after surgery and unresectable HCC after Atezo + Bev therapy. The immune microenvironment of metastatic lesions tended to reflect those of primary lesions. Conclusions: We revealed the spatial dynamics of T- and B-cell responses in HCC, which is closely associated with the clinical outcome after surgical resection or Atezo + Bev therapy.

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Vessels encapsulating tumor clusters contribute to the intratumor heterogeneity of HCC on Gd-EOB-DTPA-enhanced MRI

Matsuda K., Ueno A., Tsuzaki J., Kurebayashi Y., Masugi Y., Yamazaki K., Tamura M., Abe Y., Hasegawa Y., Kitago M., Jinzaki M., Sakamoto M.

Hepatology Communications 9 ( 1 ) 2024.12

Background: Vessels encapsulating tumor clusters (VETC) pattern is tumor vasculature of HCC and is a predictor of prognosis and therapeutic efficacy. Recent radiological studies have demonstrated the predictability of VETC from preoperative images, but the mechanisms of image formation are not elucidated. This study aims to determine the relationship between VETC and intratumor heterogeneity in Gd-EOB-DTPA-enhanced magnetic resonance imaging (EOB-MRI) and to provide its pathological evidence. Methods: Radiologists visually classified preoperative arterial- and hepatobiliary-phase EOB-MRI images of 204 surgically resected HCCs into patterns based on heterogeneity and signal intensity; these classifications were validated using texture analysis. Single and multiplex immunohistochemistry for CD34, h-caldesmon, and OATP1B3 were performed to evaluate VETC, arterial vessel density (AVD), and OATP1B3 expression. Recurrence-free survival was assessed using the generalized Wilcoxon test. The contribution of clinicoradiological factors to the prediction of VETC was evaluated by random forest and least absolute shrinkage and selection operator regression. Results: VETC was frequently found in tumors with arterial-phase heterogeneous hyper-enhancement patterns and in tumors with hepatobiliary-phase heterogeneous hyperintense/isointense patterns (HBP-Hetero). AVD and OATP1B3 expression positively correlated with signal intensity in the arterial and hepatobiliary phases, respectively. Intratumor spatial analysis revealed that AVD and OATP1B3 expression were lower in VETC regions than in tumor regions without VETC. Patients with HBP-Hetero tumors had shorter recurrence-free survival. Machine learning models highlighted the importance of serum PIVKA-II, tumor size, and enhancement pattern of arterial and hepatobiliary phase for VETC prediction. Conclusions: VETC is associated with local reductions of both AVD and OATP1B3 expression, likely contributing to heterogeneous enhancement patterns in EOB-MRI. Evaluation of the arterial and hepatobiliary phases of EOB-MRI would enhance the predictability of VETC.

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Molecular diagnosis for detecting KRAS mutation in peritoneal washing fluid of pancreatic ductal adenocarcinoma

Shimane G., Nakano Y., Matsuda S., Kitago M., Masugi Y., Nakamura K., Nakamura Y., Yagi H., Abe Y., Hasegawa Y., Hori S., Tanaka M., Takemura R., Nishihara H., Kitagawa Y.

Scientific Reports 14 ( 1 ) 2024.12

Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of KRAS mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (P < 0.001) and in patients with peritoneal dissemination than in those without peritoneal dissemination (P < 0.01). The optimal Ct cut-off to predict KRAS mutations in IPWF was 36.42 based on a receiver operating characteristic curve. The sensitivity, specificity, and accuracy for molecular diagnosis were 100%, 80.0%, and 85.2%, respectively. Peritoneal dissemination recurrence was significantly more frequent in patients with a positive molecular diagnosis than in those with a negative diagnosis (38.9 vs. 8.0%, P = 0.013). The genomic approach might be clinically valuable for a more precise tumor cell detection in IPWF.

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Multiple asynchronous recurrence as a predictive factor for refractoriness against locoregional and surgical therapy in patients with intermediate-stage hepatocellular carcinoma

Kasuga R., Taniki N., Chu P.S., Tamura M., Tabuchi T., Yamaguchi A., Hayatsu S., Koizumi J., Ojiro K., Hoshi H., Kaneko F., Morikawa R., Noguchi F., Yamataka K., Usui S., Ebinuma H., Itano O., Hasegawa Y., Abe Y., Kitago M., Inoue M., Nakatsuka S., Jinzaki M., Kitagawa Y., Kanai T., Nakamoto N.

Scientific Reports 14 ( 1 ) 2024.12

Development of subclassification of intermediate-stage hepatocellular carcinoma (HCC) by treatment suitability is in demand. We aimed to identify predictors that define treatment refractoriness against locoregional(transarterial chemoembolization(TACE) or thermal ablation) and surgical therapy. This multicenter retrospective study enrolled 1167 HCC patients between 2015 and 2021. Of those, 209 patients were initially diagnosed with intermediate-stage HCC. Treatment refractoriness was defined as clinical settings that meets the following untreatable progressive conditions by TACE (1) 25% increase of intrahepatic tumor, (2) transient deterioration to Child–Pugh class C, (3) macrovascular invasion or extrahepatic spread, within one year. We then analyzed factors contributing to treatment refractoriness. The Child–Pugh score/class, number of tumors, infiltrative radiological type, and recurrence were significant factors. Focusing on recurrence as a predictor, median time to untreatable progression (TTUP) was 17.2 months in the recurrence subgroup whereas 35.5 months in the initial occurrence subgroup (HR, 2.06; 95% CI, 1.44–2.96; P = 0.001). Median TTUP decreased in cases with more later times of recurrence (3–5 recurrences, 17.3 months; ≥ 6 recurrences, 7.7 months). Recurrence, even more at later times, leads to increased treatment refractoriness. Early introduction of multidisciplinary treatment should be considered against HCC patients after multiple recurrent episodes.

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Efficacy and safety of neoadjuvant S-1-based chemoradiotherapy in resectable and borderline-resectable pancreatic cancer: a long-term follow-up study

Shimane G., Kitago M., Endo Y., Aiura K., Yagi H., Abe Y., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Fukada J., Masugi Y., Kitagawa Y.

World Journal of Surgical Oncology 22 ( 1 ) 2024.12

Background/objectives: This study aimed to evaluate the safety, efficacy, and long-term outcomes of S-1-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable or borderline-resectable pancreatic ductal adenocarcinoma (PDAC). Methods: This retrospective study included patients with PDAC who underwent S-1-based NACRT at our institute between 2010 and 2017. Results: Forty patients were included in the study, including 15 (37.5%) with resectable PDAC and 25 (62.5%) with borderline-resectable PDAC. The NACRT completion and resection rates were 85.0% (n = 34) and 67.5% (n = 27), respectively. Several grade 3 adverse events were observed, including leukopenia (25.0%), anorexia (17.5%), neutropenia (10.0%), thrombocytopenia (7.5%), febrile neutropenia (2.5%), elevated aspartate aminotransferase/alanine aminotransferase (2.5%) levels, and hyponatremia (2.5%). The R0 resection rate was 70.4% (n = 19/27) in patients who underwent pancreatectomy. Grades 1, 2, and 3 according to the College of American Pathologists grading system were observed in 1 (3.7%), 12 (44.4%), and 14 (51.9%) patients, respectively. Over a median follow-up period of 32.9 months (interquartile range, 9.1–68.0), the 1-, 3-, and 5-year OS rates were 81.4%, 45.5%, and 30.3%, respectively, in the intention-to-treat analysis. In the curative-intent surgery cohort (n = 27), the 1-, 3-, and 5-year OS rates were 88.9%, 48.2%, and 37.0%, respectively. Conclusions: S-1-based NACRT is safe and yields acceptable long-term outcomes for patients with resectable or borderline-resectable PDAC.

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Prognosis prediction of PDAC via detection of O-glycan altered extracellular vesicles in perioperative sera

Uemura S., Kabe Y., Kitago M., Matsuda S., Abe Y., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Sato Y., Itonaga M., Ono M., Kawakami T., Suematsu M., Kitagawa Y.

Cancer Science 115 ( 11 ) 3718 - 3728 2024.11

ISSN 13479032

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy due to the difficulty in diagnosis and poor prognosis because of the high recurrence rate, necessitating reliable biomarkers to improve the diagnosis and prognosis. However, the existing markers have limitations. We previously identified extracellular vesicles (EVs) recognized by O-glycan-binding lectins (Amaranthus caudatus agglutinin [ACA]) as a novel diagnostic biomarker for PDAC using an EV-counting system (ExoCounter). This retrospective study analyzed changes in ACA-positive EVs in perioperative PDAC serum and its association with prognosis using ExoCounter. Absolute EV levels in the pre- and postoperative sera of 44 patients who underwent curative pancreatectomy for PDAC were quantified using ExoCounter. The carbohydrate antigen 19-9 levels declined in most samples postoperatively, and presented no correlation with poor prognosis. In contrast, ACA-positive EVs increased in serum at 7 days postoperatively in 27 of 44 patients (61.4%). We therefore divided participants with ACA-positive EVs before and after surgery into elevation and decline groups. The overall survival (OS) and recurrence-free survival (RFS) of patients with higher ACA-positive EVs were significantly shorter than those with lower ACA-positive EVs (26.1 months vs. not reached, P = 0.018; 11.9 vs. 38.6 months, P = 0.013). Multivariable analysis revealed that ACA-positive EV elevation in postoperative serum was an independent prognostic factor for poor OS (hazard ratio [HR] = 3.891, P = 0.023) and RFS (HR = 2.650, P = 0.024). The detection of ACA-positive EVs in perioperative serum may be used to predict the prognosis of PDAC in the early postoperative period.

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Improved survival of pediatric deceased donor liver transplantation recipients after introduction of the pediatric prioritization system: Analysis of data from a Japanese national survey

Takemura Y., Shinoda M., Kasahara M., Sakamoto S., Hatano E., Okamoto T., Ogura Y., Sanada Y., Matsuura T., Ueno T., Obara H., Soejima Y., Umeshita K., Eguchi S., Kitagawa Y., Egawa H., Ohdan H., Ogawa E., Ito T., Sakuma Y., Yoshizumi T., Eguchi H., Shimamura T., Mita A., Hibi T., Fukumoto T., Hasegawa K., Marubashi S., Umeda Y., Nobori S., Hasegawa Y., Yamada Y., Kitago M.

Journal of Hepato Biliary Pancreatic Sciences 31 ( 11 ) 782 - 797 2024.11

ISSN 18686974

Background: In Japan, there has never been a national analysis of pediatric deceased donor liver transplantation (pDDLT) based on donor and recipient factors. We constructed a Japanese nationwide database and assessed outcomes of pDDLT focusing on the pediatric prioritization system introduced in 2018. Methods: We collected data on pDDLTs (<18 years) performed between 1999 and 2021 from the Japan Organ Transplant Network and Japanese Liver Transplantation Society, identified risk factors for graft survival and compared the characteristics and graft survival in pDDLTs conducted before and after the introduction of the pediatric prioritization system. Results: Overall, 112 cases of pDDLT were included, with a 1-year graft survival rate of 86.6%. Four poor prognostic factors were identified: recipient intensive care unit stay, model for end-stage liver disease/pediatric end-stage liver disease score, donor cause of death, and donor total bilirubin. After the introduction of the system, allografts from pediatric donors were more reliably allocated to pediatric recipients and the annual number of pDDLTs increased. The 1-year graft survival rate improved significantly as did pDDLT conditions indicated by the risk factors. Conclusions: Under the revised allocation system, opportunities for pDDLT increased, resulting in favorable recipient and donor conditions and improved survival.

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A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure

Shimata K., Yoon Y.I., Hibi T., Morinaga J., Narayanan A.K., Toshima T., Ito T., Akamatsu N., Kotera Y., Hong S.K., Hasegawa Y., Umeda Y., Reddy M.S., Ong A.D.L., Sivaprasadan S., Varghese J., Sugawara Y., Chen C.L., Nakayama N., Mochida S., Tanaka A., Suh K.S., Ikegami T., Lee K.W., Lee S.G., Sudhindran S., Yoshizumi T., Hatano E., Okumura S., Hasegawa K., Egawa H., Obara H., Yasui K., Ogura Y., Jobara K., Nitta H., Katagiri H., Otsuka M., Kuboki S., Eguchi S., Hara T., Eguchi H., Sasaki K., Aoki T., Ohdan H., Ohira M., Takada Y., Ogawa K., Fukumoto T., Kuramitsu K., Saiura A., Ichida H., Hashimoto T., Marubashi S., Sato N., Ushigome H., Harada S., Soejima Y., Masuda Y., Shimada M., Saitou Y., Taketomi A., Goto R., Shimamura T., Mizuno S., Tanemura A., Endo I., Unno M., Miyagi S., Okamura Y., Aramaki O., Hakamada K., Ishido K., Kato Y., Takahara T., Takatsuki M., Ono S.

American Journal of Transplantation 24 ( 10 ) 1857 - 1867 2024.10

ISSN 16006135

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection.

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Japanese living donor liver transplantation criteria for hepatocellular carcinoma: nationwide cohort study

Ohira M., Aoki G., Orihashi Y., Yoshimura K., Toshima T., Hatano E., Eguchi S., Hibi T., Hasegawa K., Umeda Y., Hashimoto T., Hasegawa Y., Nobori S., Ogura Y., Nitta H., Egawa H., Eguchi H., Takada Y., Ueda Y., Kasahara M., Kawachi S., Soejima Y., Tokushige K., Nagano H., Haga H., Fukumoto T., Mochida S., Umeshita K., Ohdan H., Mizuno S., Kuboki S., Otsuka M., Kobayashi T., Wakai T., Ishigame T., Marubashi S., Watanabe M., Taketomi A., Nakamuma S., Yagi S., Wakiya T., Ishido K., Sawada Y., Endo I., Goto Y., Hisaka T., Uryuhara K., Sakuma Y., Ichida H., Saiura A., Haruki K., Ikegami T., Iso Y., Aoki T., Takahara T., Yokoo H., Beck Y., Miyagi S., Tokodai K.

Bjs Open 8 ( 4 ) 2024.08

Background: Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set. Methods: The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model. Results: Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors. Conclusion: This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy.

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Anatomic, isolated complete caudate lobectomy using an anterior transhepatic approach with glissonian pedicle approach and indocyanine green fluorescence guidance: a case report

Endo Y., Abe Y., Kitago M., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Shimazu M., Kitagawa Y.

Journal of Surgical Case Reports 2024 ( 8 ) 2024.08

Hepatocellular carcinoma (HCC) in the caudate lobe presents surgical challenges due to the lack of distinct anatomical landmarks. This case report introduces a novel surgical approach combining Takasaki’s classification and indocyanine green negative counterstaining for precise anatomical caudate lobectomy. A 78-year-old patient with hepatocellular carcinoma in the caudate lobe underwent surgery following preoperative volumetric assessment. The method involved a glissonian approach for both left and right pedicles, coupled with meticulous dissection of hepatic pedicles of the caudate lobe guided by taping of left and right glissonian pedicles, followed by indocyanine green administration for improved visualization of caudate lobe boundaries. The procedure enabled complete tumor resection with minimal blood loss. At 50 months postsurgery, the patient maintains favorable liver function and performance status. This innovative approach offers a promising solution for precise resection of caudate lobe hepatocellular carcinoma, potentially improving surgical outcomes and long-term prognosis.

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Excess mortality in COVID-19-affected solid organ transplant recipients across the pandemic

Yamanaga S., Shimata K., Ohfuji S., Yoshikawa M., Natori Y., Hibi T., Yuzawa K., Egawa H., Unagami K., Ishida H., Omoto K., Kasahara M., Uchida H., Sakamoto S., Futamura K., Nishikawa K., Imamura R., Nakazawa S., Hatano E., Ito T., Masano Y., Nishihira M., Hirata Y., Sakuma Y., Onishi Y., Yokoyama N., Yamamoto S., Yamada Y., Ogura Y., Kurata N., Uchida J., Kabei K., Iwamoto H., Ikeda C., Shinoda K., Yoshiike M., Hotta K., Hidaka Y., Iwami D., Ishii Y., Kamiyama M., Yoshizumi T., Kosai-Fujimoto Y., Kobayashi T., Motoyama K., Yamamoto M., Asai T., Tasaki M., Kenmochi T., Ito T., Tokodai K., Fujio A., Tsukamoto Y., Watanabe T., Akamatsu N., Yamashina S., Ishii D., Kitajima K., Yamada Y., Mitsuke A., Sakaguchi T., Nakamura M., Tomita Y., Nakamura Y., Ishimoto T., Ohdan H., Tanimine N., Fujiwara T., Yanagihara M., Hatakeyama S., Takai M., Nose K., Kikuchi T., Mori Y., Araki M., Sekito T., Nishimura S., Tanabe T., Igarashi Y., Hidaka S., Watanabe M., Ariyoshi Y., Hasegawa Y., Kamiyama M., Yoneda T., Shimizu T., Nishikawa K., Fukumoto T., Kuramitsu K., Kato M., Saito M., Shinkai M., Usui H., Sato M., Eguchi H., Imamura H., Kobayashi S., Soejima Y., Mita A., Kobayashi T.

American Journal of Transplantation 24 ( 8 ) 1495 - 1508 2024.08

ISSN 16006135

The excess mortality of coronavirus disease 2019 (COVID-19) solid organ transplant recipients (SOTRs) throughout the pandemic remains unclear. This prospective cohort study based on the Japanese nationwide registry included 1632 SOTRs diagnosed with COVID-19 between February 1, 2020, and July 31, 2022, categorized based on dominant phases of variants of concern (VOCs): Waves 1 to 3 (Beta), 4 (Alpha), 5 (Delta), 6 (Omicron BA.1/BA.2), and 7 (Omicron BA.5). Excess mortality of COVID-19-affected SOTRs was analyzed by calculating standardized mortality ratios (SMRs). Overall, 1632 COVID-19-confirmed SOTRs included 1170 kidney, 408 liver, 25 lung, 20 heart, 1 small intestine, and 8 multiorgan recipients. Although disease severity and all-cause mortality decreased as VOCs transitioned, SMRs of SOTRs were consistently higher than those of the general population throughout the pandemic, showing a U-shaped gap that peaked toward the Omicron BA.5 phase; SMR (95% CI): 6.2 (3.1-12.5), 4.0 (1.5-10.6), 3.0 (1.3-6.7), 8.8 (5.3-14.5), and 21.9 (5.5-87.6) for Waves 1 to 3 (Beta), Wave 4 (Alpha), Wave 5 (Delta), Wave 6 (Omicron BA.1/2), and Wave 7 (Omicron BA.5), respectively. In conclusion, COVID-19 SOTRs had greater SMRs than the general population across the pandemic. Vaccine boosters, immunosuppression optimization, and other protective measures, particularly for older SOTRs, are paramount.

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