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Abstract Aim Approximately 30 years have passed since the first experience of living donor liver transplantation. The time to evaluate the long‐term safety of living donors has been fulfilled. Meanwhile, nonalcoholic fatty liver disease is increasingly common and a critical problem. The aim of this study was to evaluate the safety of living donor, focusing on fatty liver postdonation hepatectomy. Methods Living donors (n = 212, 1997–2019) were evaluated by computed tomography (CT) at >1‐year postdonation. A liver to spleen (L/S) ratio of 1.3, which included a case with a Fib‐4 index of >2.67, no significant increased Fib‐4 index was observed in the subjects with fatty liver as compared to those without fatty liver (p = 0.66). The independent predictive risk factors for developing fatty liver were male sex, pediatric recipient, and higher body mass index (>25) at donation. Conclusion Living donors with risk factors for developing fatty liver should be carefully followed‐up for the prevention and management of metabolic syndrome.

Abstract Background Alveolar echinococcosis (AE) is a rare parasitic disease caused by the larva of Echinococcus multilocularis. It nearly always occurs in the liver, and cardiac involvement is extremely rare. Liver resection is the most effective intervention for AE because the only potentially curative treatment is removal of the lesion. Even when complete resection is not performed, long-term survival can be expected after surgical removal of most of the lesion with lifelong administration of albendazole (ABZ). Case presentation A 64-year-old man who lived in Hokkaido was referred to our hospital due to abnormalities in biliary enzymes. According to the findings from enhanced computed tomography and magnetic resource imaging of the abdomen, transthoracic echocardiography and serologic tests, he was diagnosed with hepatic AE with rupture into the pericardium. He underwent extended left hemi-hepatectomy with reconstruction of the inferior vena cava and opening of the pericardium with drainage as reduction surgery. Pathological examination revealed echinococcal infection in the pericardium as well as the liver. He started chemotherapy with 400 mg ABZ per Day 67 days after surgery. Although the surgical margin was positive in the pathological findings, he was alive 19 months later with no regrowth of the echinococcal lesion. Conclusion AE with cardiac involvement is extremely rare. Even if the complete removal of cardiac-involved AE is not possible, surgical debulking with lifelong ABZ treatment can successfully manage the disease.

Abstract Background Although there is no established treatment strategy for liver metastasis of leiomyosarcoma, liver resection has been reported to be effective in some cases. However, almost all liver resections performed for liver metastasis of primary leiomyosarcoma are reported to be open resections, and there are few reports of liver resection performed by laparoscopy. Here, we report a case of laparoscopic liver resection for liver metastasis of a leiomyosarcoma in the right thigh. Case presentation An 80-year-old man was diagnosed with leiomyosarcoma of the right thigh with liver metastasis. The primary tumor was first resected, and he was discharged on the 25th postoperative day. Four months after primary tumor resection, a laparoscopic right posterior sectionectomy was performed. There were no postoperative complications, and the patient was discharged on the 11th postoperative day with a histopathological diagnosis of liver metastasis of leiomyosarcoma and negative resection margins. Currently, 9 months have passed since the resection of the primary tumor, and 5 months have passed since the laparoscopic liver resection; there is no recurrence. Conclusions The liver metastasis of leiomyosarcoma was successfully removed, with good short-term outcomes after the laparoscopic liver resection. Laparoscopic liver resection seems to be effective for liver metastasis of leiomyosarcoma, which is characterized by a high recurrence rate after surgery. However, more case studies may be necessary to examine the effectiveness and long-term results of laparoscopic liver resection for the treatment of liver metastasis of leiomyosarcoma.

Background: Solid pseudopapillary neoplasm of the pancreas has been classified by the World Health Organization as a low-grade malignant tumor with potential to metastasize. The standard treatment for this neoplasm is complete surgical resection. However, it is not always feasible to perform a complex procedure such as pancreaticoduodenectomy or distal pancreatectomy, especially for patients with a history of hepato-biliary-pancreatic surgery. In such cases, the treatment strategy must consider the patient's postoperative quality of life. We herein report a case of solid pseudopapillary neoplasm of the pancreas following living-donor liver transplantation. Case presentation: The patient was a 13-year-old girl who had undergone the Kasai procedure for biliary atresia at 140 days of age. She thereafter underwent living-donor liver transplantation because of recurrent cholangitis and progressive jaundice. Her repeated history of cholangitis had caused narrowing of the portal vein. Therefore, the portal vein was reconstructed using the donor's ovarian vein as an interposition graft. At 13 years of age, a mass was identified at the head of the pancreas. Biopsy was performed and the patient was diagnosed with solid pseudopapillary neoplasm of the pancreas. Surgical resection was planned, and three options were considered: pancreaticoduodenectomy, duodenum-preserving pancreatic head resection, and enucleation. Considering the complications associated with radical surgery, tumor enucleation was performed. The patient developed a postoperative pancreatic fistula that required prolonged fasting and drainage. She began a low-fat diet on postoperative day 15. Because the pancreatic fistula was well controlled with a low-fat diet, the patient was discharged on postoperative day 51 after she and her parents had received dietary guidance. At the time of this writing, 1 year had passed since the enucleation with no evidence of recurrence. Conclusions: We have herein reported a case of solid pseudopapillary neoplasm of the pancreas after living-donor liver transplantation. Although a radical operation such as pancreaticoduodenectomy or distal pancreatectomy is preferable from an oncological perspective, enucleation should be considered for patients with high surgical risk.

Abstract Background Pancreaticoduodenal artery aneurysms (PDAAs) are rare visceral aneurysms, and prompt intervention/treatment of all PDAAs is recommended at the time of diagnosis to avoid rupture of aneurysms. Herein, we report two cases of PDAA caused by the median arcuate ligament syndrome, treated with surgical revascularization by aortosplenic bypass followed by coil embolization. Case presentation Case 1 A 54-year-old woman presented with a chief complaint of severe epigastralgia and was diagnosed with two large fusiform inferior PDAAs and celiac axis occlusion. To preserve the blood flow of the pancreatic head, duodenum, liver, and spleen, we performed elective surgery to release the MAL along with aortosplenic bypass. At 6 days postoperatively, transcatheter arterial embolization was performed. At the 8-year 6-month follow-up observation, no recurrent perfusion of the embolized PDAAs or rupture had occurred, including the non-embolized small PDAA, and the bypass graft had excellent patency. Case 2 A 39-year-old man who had been in good health was found to have a PDAA with celiac stenosis during a medical checkup. Computed tomography and superior mesenteric arteriography showed severe celiac axis stenosis and a markedly dilated pancreatic arcade with a large saccular PDAA. To preserve the blood flow of the pancreatic arcade, we performed elective surgery to release the MAL along with aortosplenic bypass. At 9 days postoperatively, transcatheter arterial embolization was performed. At the 6-year 7-month follow-up observation, no recurrent perfusion or rupture of the PDAA had occurred, and the bypass graft had excellent patency. Conclusion Combined treatment with bypass surgery and coil embolization can be an effective option for the treatment of PDAAs associated with celiac axis occlusion or severe stenosis.

Abstract Background Hepatic angiomyolipoma (HAML) is a rare liver tumor, and hepatectomy is the only effective treatment. Due to the difficulty of correct diagnosis of HAML before surgery by image studies, more than 36.6% of reported HAMLs are misdiagnosed as other malignant liver tumors before surgery. As there are only few reported cases in which HAMLs were removed using laparoscopic hepatectomy, the effectiveness of laparoscopic hepatectomy for such HAMLs in which are diagnosed as other malignant liver tumor before surgery has not been reported. Case presentation Case 1: a 58-year-old female with a history of treatment for autoimmune hepatitis was preoperatively diagnosed with hepatocellular carcinoma (size: 20 mm) in segment 7 (S7) of the liver. The tumor was removed by laparoscopic partial resection and was diagnosed as a HAML through a pathological examination. The patient’s postoperative course was good, and she was recurrence-free at 37 months after the hepatectomy. Case 2: a 29-year-old female with a history of surgery for a right mature cystic teratoma was referred to our department to receive treatment for a growing 20-mm liver tumor with some calcification, which arose in S3 of the liver. A metastatic liver tumor derived from the mature cystic teratoma was suspected, and laparoscopic left lateral sectionectomy was performed. The liver tumor was diagnosed as a HAML after a pathological examination. The patient’s postoperative course was unremarkable, and more than 54 months have passed since the hepatectomy without any recurrence. Conclusions Two cases in which HAMLs were preoperatively diagnosed as other malignant liver tumor were successfully removed by laparoscopic hepatectomy with a correct postoperative diagnosis. Laparoscopic hepatectomy for the present 2 cases of HAML seemed to be effective for providing a correct diagnosis after the curative removement of liver tumor with a smaller invasion compared to open hepatectomy, and for denying risk of dissemination of the malignant tumor by needle biopsy that had to be considered before ruling out malignant tumor.

Abstract Background and Aim Gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (EOB‐MRI) has been recognized as a useful imaging technique to distinguish the biological behavior of hepatocellular carcinoma (HCC). Methods We analyzed 217 hepatectomy recipients with HCCs measuring 10 cm or less. We divided the patients into a decreased intensity (DI) group (n = 189, 87%) and an increased or neutral intensity (INI) group (n = 28, 13%) according to the ratio of tumor intensity to liver intensity during the hepatobiliary phase (HBP). According to the ratio of the maximum tumor diameter (including peritumoral hypointensity) between HBP images and precontrast T1‐weighted images (RHBPP), we divided the patients as follows: The group whose RHBPP was ≥1.036 was the high RHBPP group (n = 60, 28%), and the group whose RHBPP was

Abstract Background Hepatic cavernous hemangioma (CH) is the most common hepatic benign tumor. Most cases are solitary, asymptomatic, and found incidentally. In symptomatic cases with rapidly growing tumors and coagulopathy, surgical treatment is considered. In rare cases, diffuse hepatic hemangiomatosis (DHH) is reported as a comorbidity. The etiology of DHH is unknown. Case presentation A 29-year-old female patient had a history of endometriosis treated with oral contraceptives. Hepatic CH was incidentally detected in the segment IVa of the liver according to the Couinaud classification. Follow-up computed tomography (CT) and ultrasound sonography showed the growth of the lesion and formation of multiple new lesions near the first. Enhanced CT and magnetic resonance imaging (MRI) revealed that the new lesions were different from CH. Although oral contraceptives were stopped, all lesions grew in size. Malignancy and possibility of rupture of these tumors were considered due to the clinical course, and we opted for surgical removal of the tumors. Left liver lobectomy and cholecystectomy were performed. Surgical findings were small red spot spreading and a mass in segment IV of the liver. Pathological examination revealed a circumscribed sponge-like tumor with diffuse irregular extension to the adjacent area. Both of the lesions consisted of blood-filled dilated vascular spaces lined by flat endothelium without atypia. The diagnosis was hepatic CH with DHH. The patient was discharged on postoperative day 12 uneventfully. Conclusion We report the successful resection of CH with DHH. The case findings suggest a relationship between oral contraceptive use and enlargement of CH and DHH. Although DHH has been poorly understood, a few previously published cases reported DHH occurrence in patients using oral contraceptives. In such cases, the decision to perform surgical resection should be made after careful examination.

Abstract Objectives The aim was to evaluate the prognostic factors, clinicopathological characteristics, and surgical outcomes after hepatectomy in very elderly patients with hepatocellular carcinoma (HCC). Methods We analyzed 796 patients with HCC from 2000 to 2017. Patients aged 80 years or older were classified into the very elderly group (group VE; n = 49); patients younger than 80 years old and aged 65 years or older were classified into the elderly group (group E; n = 363), and patients younger than 65 years old were classified into the young group (group Y; n = 384). We investigated the prognoses, clinicopathological characteristics, and surgical outcomes after hepatectomy. Results The number of surgical procedures and outcomes, including morbidities, was not significantly different. Groups VE, E, and Y showed similar prognoses in terms of both survival and recurrence. In group VE, prothrombin activity (PA) < 80% and PIVKA-II ≥ 400 mAU/ml were unfavorable factors for survival, and PIVKA-II ≥ 400 mAU/ml and the presence of portal venous invasion (PVI), hepatic venous invasion, and fibrosis were unfavorable factors for recurrence. In group E, ChE < 180 IU/l, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and hepatic venous invasion (HVI) were unfavorable factors for survival, and ChE < 180 IU/l, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and HVI were unfavorable factors for recurrence. In group Y, AFP ≥ 20 ng/ml, the presence of multiple tumors, poor differentiation, PVI, HVI, and blood loss ≥ 400 ml were unfavorable factors for survival, and PA < 80%, albumin < 3.5 g/dl, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, poor differentiation, and PVI were unfavorable factors for recurrence. Conclusions Tumor factors might have limited influence on the prognosis of very elderly patients, and liver function reserve might be important for the long-term survival of very elderly patients. Hepatectomy can be performed safely, even in very elderly patients. Hepatectomy should not be avoided in very elderly patients with HCC if patients have a good general status because these patients have the same prognoses as nonelderly individuals.

Abstract Introduction The roles of preformed anti‐HLA donor‐specific antibodies (DSAs) in liver transplantation remain controversial. We evaluated the impact of preformed DSAs in living donor liver transplantation. Methods Adults who underwent living donor liver transplantation (n = 175) in our institute were included in this study. Lymphocyte cytotoxicity test (LCT), flow cytometric crossmatch (FCXM), and single‐antigen bead assays were performed. Results Among adult living donor liver transplantation recipients, 27 (16.5%) and 14 (8.5%) had pretransplant FCXM‐positive findings and LCT‐positive findings, respectively. FCXM‐positive patients displayed a significantly worse 5‐year graft survival rate (77.3%; vs. DSA‐negative, 91.6%). Six of 14 LCT‐positive patients exhibited graft loss shortly after transplantation (5‐year survival rate: 57.1%). All LCT‐positive patients with graft loss underwent left lobe living donor liver transplantation. Significantly lower ratio of graft volume relative to standard liver volume (32.9 ± 5.7%) and smaller graft size (365.3 ± 57.9 g) were observed in patients with graft loss (p

Purpose: Active hexose-correlated compound (AHCC), a standardized extract of cultured Lentinula edodes mycelia, exerts antitumor effects through anti-inflammatory and immune-modulatory functions. Adjuvant therapy for patients with hepatocellular carcinoma (HCC) who have undergone curative hepatectomy has not been established. The purpose of this study was to evaluate the efficacy and safety of AHCC as adjuvant therapy in patients with advanced HCC after curative hepatectomy. Patients and methods: The study design was single-armed, non-randomized, open (no one was blinded), and uncontrolled. Patients with HCC who underwent curative hepatectomy were treated with AHCC (1 g) 3 times daily orally for 2 years. The inclusion criteria were HCC diagnosed preoperatively as stages A and B of the Barcelona clinic liver cancer (BCLC) classification and alpha-fetoprotein × protein induced by vitamin K absence or antagonist II (PIVKA-II) ≥ 10 5 for stage A. Results: A total of 29 patients were treated with AHCC, of which 25 (4 patients discontinued) were followed up. The 2-year recurrence-free survival rate after resection was 48% for those without discontinuations and 55.2% for all patients with a history of treatment. Serum albumin levels decreased to a minimum in the first postoperative month and gradually recovered to the preoperative level at 6 months. Almost no change in lymphocyte percentage was observed during follow-up. Inflammation-based prognostic scores were maintained at favorable levels after hepatectomy. Toxicity and adverse events were not observed in any patient. Conclusion: AHCC may be safe and effective in preventing HCC recurrence after curative hepatectomy, and further randomized trials of AHCC for its use in this setting are warranted. This clinical trial was registered in UMIN Clinical Trials Registry (ID UMIN000024396).

Background and Aim Lenvatinib has been recently approved as a first‐line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child‐Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real‐world setting. Methods Among patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis. Results A total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups. Conclusion Lenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria.

Abstract Background Percutaneous transhepatic portal embolization (PTPE) is useful for safe major hepatectomy. This study investigated the correlation between hepatic hypertrophy and hemodynamics of portal venous flow by ultrasound sonography after PTPE. Methods We analyzed 58 patients with PTPE, excluding those who underwent recanalization (n = 10). Using CT volumetry results 2 weeks after PTPE, the patients were stratified into a considerable hypertrophy group (CH; n = 15) with an increase rate of remnant liver volume (IR-RLV) ≥ 40% and a minimal hypertrophy group (MH; n = 33) with an IR-RLV

This study was performed to determine the clinical significance of adenomatous polyposis coli (APC)-binding protein end-binding 1 (EB1) in hepatocellular carcinoma (HCC) and to characterize its biochemical role in comparison with previous reports. We performed immunohistochemical staining to detect EB1 expression in tissues from 235 patients with HCC and investigated its correlations with clinicopathological features and prognosis. We also investigated the roles of EB1 in cell proliferation, migration, and tumorigenesis in vitro and in vivo by siRNA- and CRISPR/Cas9-mediated modulation of EB1 expression in human HCC cell lines. The results showed that EB1 expression was significantly correlated with several important factors associated with tumor malignancy, including histological differentiation, portal vein invasion status, and intrahepatic metastasis. Patients with high EB1 expression in HCC tissue had poorer overall survival and higher recurrence rates than patients with low EB1 expression. EB1 knockdown and knockout in HCC cells reduced cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Further, genes encoding Dlk1, HAMP, and SLCO1B3 that were differentially expressed in association with EB1 were identified using RNA microarray analysis. In conclusion, elevated expression of EB1 promotes tumor growth and metastasis of HCC. EB1 may serve as a new biomarker for HCC, and genes coexpressed with EB1 may represent potential targets for therapy.

BackgroundMost glycomics studies have focused on understanding disease mechanisms and proposing serum markers for various diseases, yet the influence of ethnic variation on the identified glyco-biomarker remains poorly addressed. This study aimed to investigate the inter-ethnic serum N-glycan variation among US origin control, Japanese, Indian, and Ethiopian healthy volunteers.MethodsHuman serum from 54 healthy subjects of various ethnicity and 11 Japanese hepatocellular carcinoma (HCC) patients were included in the study. We employed a comprehensive glycoblotting-assisted MALDI-TOF/MS-based quantitative analysis of serum N-glycome and fluorescence HPLC-based quantification of sialic acid species. Data representing serum N-glycan or sialic acid levels were compared among the ethnic groups using SPSS software.ResultsTotal of 51 N-glycans released from whole serum glycoproteins could be reproducibly quantified within which 33 glycoforms were detected in all ethnicities. The remaining N-glycans were detected weakly but exclusively either in the Ethiopians (13 glycans) or in all the other ethnic groups (5 glycans). Highest abundance (p < 0.001) of high mannose, core-fucosylated, hyperbranched/hypersialylated N-glycans was demonstrated in Ethiopians. In contrast, only one glycan (m/z 2118) significantly differed among all ethnicities being highest in Indians and lowest in Ethiopians. Glycan abundance trend in Ethiopians was generally close to that of Japanese HCC patients. Glycotyping analysis further revealed ethnic-based disparities mainly in the branched and sialylated structures. Surprisingly, some of the glycoforms greatly elevated in the Ethiopian subjects have been identified as serum biomarkers of various cancers. Sialic acid level was significantly increased primarily in Ethiopians, compared to the other ethnicities.ConclusionThe study revealed ethnic-specific differences in healthy human serum N-glycome with highest abundance of most glycoforms in the Ethiopian ethnicity. The results strongly emphasized the need to consider ethnicity matching for accurate glyco-biomarker identification. Further large-scale study employing various ethnic compositions is needed to verify the current result.