Aim: This study aims to clarify the effectiveness of laparoscopic anatomical liver resections (ALRs) in surgical site infections (SSIs). Methods: We included 95 cases (44.0%) of laparoscopic ALRs (LALRs) and 121 (56.0%) of open ALRs (OALRs). Retrospective comparisons were performed between the two groups. Results: In preoperative factors, tumor size was significantly smaller in LALRs than in OALRs (34.4 ± 23.0 mm vs . 45.9 ± 35.7 mm, P = 0.007). The operative duration was longer in LALRs than in OALRs (523.0 ± 186.5 min vs . 356.3 ± 100.5 min, P < 0.001). However, the blood loss and the blood transfusion were fewer in LALRs than in OALRs (592.1 ± 911.7 mL vs . 1,240.6 ± 1,131.8 mL, P < 0.001, 26.3% vs . 48.8%, P = 0.001, respectively). Postoperative complications above the Clavien-Dindo grade IIIb were one case (1.1%) in LALRs and two in OALRs (P = 1.000). The postoperative hospital stay was shorter in LALRs than in OALRs (14.8 ± 16.5 days vs . 20.7 ± 18.9 days, P = 0.017). There was one (0.8%) postoperative death within 90 days in OALRs and none (0.0%) in LALRs (P = 1.000). Incisional SSIs (ISSIs) were significantly reduced in LALRs than in OALRs (1.1% vs . 7.4%, P = 0.045). Organ/space SSIs (OSSIs) were observed in five cases (5.3%) in LALRs and seven cases (5.8%) in OALRs (P = 1.000). A strong correlation between bile leakage and OSSIs was found. Although OSSIs (Odds ratio 31.200, P = 0.009) were the significant predictive factors for developing ISSIs in OALRs, no risk factors predicting ISSIs were found in LALRs using Multivariate logistic regression analyses. Conclusion: Although this is a limited study at a single institution, minimally invasive anatomical hepatectomy can reduce ISSIs.

Previous studies have reported low serum creatine kinase (s-CK) levels as a poor prognostic factor in various cancers. However, there have been no reports on its significance in hepatocellular carcinoma. The present study aimed to evaluate the association of the preoperative s-CK levels with clinicopathologic features and their prognostic impact on survival in patients with hepatocellular carcinoma. This retrospective study included 163 patients with hepatocellular carcinoma (127 male and 36 female patients; median age, 69 years) who underwent radical liver resection between January 2004 and December 2021. A cutoff preoperative s-CK level of 91 U/l determined by receiver operating characteristic curve analysis was used to evaluate the significance of s-CK in predicting overall and recurrence-free survival. In addition, the prognostic impact of s-CK was evaluated using univariate and multivariate analysis. s-CK level was not associated with clinicopathologic factors. Overall survival and recurrence-free survival of the low s-CK group were significantly worse compared with the high s-CK group (P=0.043 and P=0.029, respectively). By multivariate analysis, low s-CK was an independent risk factor for poor overall survival and recurrence-free survival (P=0.019 and P=0.014, respectively). This trend was the same for male patients, but no significant difference was observed for female patients. Low preoperative s-CK level might be a poor prognostic biomarker in patients with hepatocellular carcinoma.

Midkine (MK) is a soluble cytokine, and its serum levels strongly correspond to protein expression levels in tumors. The present study aimed to clarify the clinicopathological and prognostic significance of serum MK (s-MK) in patients with hepatocellular carcinoma (HCC). Serum samples were obtained before surgery from 123 patients with HCC who had undergone surgery between January 2012 and December 2020. The receiver operating characteristic curve revealed that the best cut-off value for s-MK in differentiating HCC from healthy cases was 426 pg/ml. The clinicopathological variables and overall survival of patients were compared between the s-MK-positive group and s-MK-negative group. The sensitivity, specificity and accuracy of s-MK were 82.1, 97.4 and 88.0%, respectively. An s-MK-positive status was significantly associated with the number of tumors (>= 2). The positivity rate of s-MK was significantly higher compared with that of alpha-fetoprotein and protein-induced by vitamin K absence-II. In total, only 28% of the patients were positive for s-MK. The s-MK-positive group showed significantly worse overall survival compared with the s-MK-negative group. Moreover, multivariate analysis revealed that an s-MK-positive status was independently associated with poor prognosis. s-MK was useful in detecting early HCC. The findings of this study indicated that the s-MK-positive status is associated with the number of tumors and can act as an independent prognostic risk factor.

BACKGROUND:Hand-assisted laparoscopic surgery (HALS) is known as a useful option. However, the outcome and predictor of conversion to HALS in laparoscopic liver resection (LLR) are unclear.METHODS:Data from consecutive patients who planned pure LLR between 2011 and 2020 were retrospectively reviewed. Univariate and multivariate analyses were performed and compared pure LLR, HALS, and converted open liver resection (OLR).RESULTS:Among the 169 LLRs, conversion to HALS was performed in 19 (11.2%) and conversion to OLR in 16 (9.5%). The most frequent reasons for conversion to HALS were failure to progress (11 cases). Subsequently, bleeding (3 cases), severe adhesion (2 cases), and oncological factors (2 cases) were the reasons. In the multivariable analysis, the tumor located in segments 7 or 8 (p = 0.002) was evaluated as a predictor of conversion to HALS. Pure LLR and HALS were associated with less blood loss than conversion to OLR (p = 0.005 and p = 0.014, respectively). However, there was no significant difference in operation time, hospital stay, or severe complications.CONCLUSIONS:The predictor of conversion to HALS was a tumor located in segments 7 or 8. The outcome of conversion to HALS was not inferior to pure LLR in terms of bleeding, operation time, hospital stay, or severe complication.

We experienced a case of resection of a metastatic umbilical tumor(Sister Mary Joseph's nodule: SMJN)derived from a pancreatic tail carcinoma. The patient was a 70-year-old woman. She visited her previous doctor with a chief complaint of lower abdominal pain and came to our hospital due to suspicion of pancreatic tail cancer. She was found to have metastases to multiple organs which was unresectable by surgery. After chemotherapy up to the second-line of treatment, she was diagnosed to have progressive disease. The decision was made to provide the best supportive care for the patient. Thereafter, the patient developed SMJN. She had hemorrhage from the tumor accompanied by body movement, and her activity of daily living became impaired. She had difficulty controlling the bleeding despite repeated hemostatic treatment at the outpatient clinic and at her home. However, she required frequent blood transfusions for her severe anemia. Therefore, we performed a resection of the SMJN to control bleeding and to relieve her symptoms. She had a good postoperative course and was discharged on the fifth postoperative day. Due to deterioration of her general condition, she expired on the 59th day after surgery. However, the patient was able to live at home without bleeding or pain by the umbilical tumor. The local resection was considered to be useful as a palliative surgical treatment for SMJN.

FACT-G subscale by treatment group

Background/Purpose: To investigate the safety of laparoscopic liver resections (LLRs) for high-risk patients (HRs) with preoperative comorbidities affecting the heart, lungs, kidneys, glucose tolerance, and central nervous system.Methods: This retrospective study included 585 patients who had undergone total hepatectomies from 2006 to 2020. Among them, 239 patients underwent LLRs, and 349 underwent open liver resections (OLRs). The safety and validity of LLRs were analyzed by comparing outcomes and preoperative records between HRs and nonhigh-risk patients (nHRs). HRs were defined as patients with any type of chronic heart disease rated New York Heart Association II or higher, chronic obstructive pulmonary disease rated stage III or higher, chronic kidney disease rated stage III or higher, insulin-dependent diabetes mellitus, or cerebrovascular disease with neurological sequelae.Results: A total of 117 LLRs (49.0%) were performed in HRs, and there were more patients with ASA class III or higher than nHRs. Complications of Clavien-Dindo classification grade 3b or higher were not observed in HRs and in only one nHR. Furthermore, no postoperative exacerbations of the five HRs factors were observed in either group.Conclusions: Rigorous assessment of surgical indications and perioperative management can promote safe LLRs, even in HRs with comorbidities.

To evaluate the predictors of a difficult Pringle maneuver (PM) in laparoscopic liver resection (LLR) and to assess alternative procedures to PM. Data from patients undergoing LLR between 2013 and 2020 were reviewed retrospectively. Univariate and multivariate analyses were performed and the outcomes of patients who underwent PM or alternative procedures were compared. Among 106 patients who underwent LLR, PM could not be performed in 18 (17.0

BACKGROUND: Laparoscopic liver resection (LLR) has been spread as minimally invasive surgery for liver disease. Advances in surgical technique and devices enabled us to perform various procedures of LLR. Indocyanine green (ICG) fluorescence imaging has been suggested as useful tool to identify liver tumors, anatomical territory of liver parenchyma, and cholangiography in open liver surgery. Due to recent development, this technology can be applied in LLR. we describe safe and effective using of the ICG fluorescence imaging during LLR. METHODS: From September 2013 to August 2019, 34 patients were performed LLR using a total of 46 procedures by ICG fluorescence imaging system for purposes including identification of anatomic domain of the liver in 12 LLRs, detection of liver tumors in 30 nodules, or intraoperative cholangiography in 4 LLRs. RESULTS: During the detection of liver tumors, 25 nodules in 30 malignant to benign tumors were positively detected (83.3%). Although there has been no publication regarding information on ICG fluorescence imaging of low grade malignant or benign tumors, we found positive emission in focal nodular hyperplasia, an angiomyolipoma, and an intraductal papillary neoplasm of the bile duct. The identification of anatomic domain in the liver was successful in all 12 LLRs with negative and positive staining techniques. In the intraoperative cholangiography, all 4 tests were successfully performed. One of 4 patients were found to have biliary leakage which was repaired intraoperatively. CONCLUSIONS: The ICG fluorescence imaging could be useful in safe and precise performance of LLR.

Aim: Laparoscopic liver resection (LLR) has been recognized as a minimally invasive surgery offering disease curability for liver tumors. Moreover, recent publications suggest that the systematic liver resections including hemi-hepatectomies have been performed safely in high volume centers. We describe our indication, standardized technique, and surgical outcome for totally laparoscopic hemi-hepatectomy (TLHH). Moreover, we hypothesize that TLHHs can be performed feasibly, as well as discuss the technical correspondence of technically difficult cases which have marginal indication for TLHHs. Methods: From September 2008 to July 2020, in total, 488 cases of liver resections including 222 cases of LLR were performed in our institution. We invented the favorable indication of TLHHs of locally resectable tumors without involvement of tumor to hepatic hilus, confluence of hepatic veins, inferior vena cava, or extrahepatic organs, in patients with sufficient hepatic functional reserve for hemi-hepatectomies. Among 21 TLHHs for liver tumors performed during study period, there were cases which derogate favorable indications; however, they might have been able to undergo TLHHs. We divided these cases into "difficult indication group (DIG)" (10 of 21 cases) and "favorable indication group (FIG)"; compared them on perioperative background, surgical outcome; and discussed the technical correspondence of TLHHs on DIG. Results: There were no significant differences in patient's background and operative outcome. Operative duration, blood loss, and postoperative morbidity tended to be larger in DIG, mainly due to tumor factor, than in FIG. However, TLHHs were performed without any severe perioperative complications beyond Clavien-Dindo grade IIIb or mortality. Conclusion: We believe that hemi-hepatectomies can safely be stylized by totally laparoscopic fashion and correspondence for difficulty can be made through technical standardization.

Background: Several reports showed that high soluble programmed death-ligand 1(sPD-L1) level was a risk factor for poor prognosis in various tumors. To date, the clinicopathologic and prognostic impact of sPD-L1 level in patients with hepato-biliary-pancreatic cancer have not been determined. Methods: A total of 119 patients (66 patients with hepatocellular carcinoma, 23 patients with cholangiocarcinoma, 30 patients with pancreatic cancer) who were treated at the Toho University Omori Hospital (Tokyo, Japan) from 2008 to 2016 were retrospectively analyzed. sPD-L1 levels were measured using an enzyme-linked immunosorbent assay for PD-L1 to evaluate clinicopathologic and prognostic impact. Results: sPD-L1 levels were significantly higher in low-albumin group than normal albumin group. According to stages in hepatocellular carcinoma and cholangiocarcinoma, there were no significant differences in sPD-L1 levels, which gradually increased according to stage in pancreatic cancer. Using a cut-off value of 81.6pg/ml for sPD-L1level, the high sPD-L1 group showed significantly worse prognosis than the low sPD-L1 group in patients with pancreatic cancer. Multivariate analysis identified sPD-L1 level ≥ 81.6 mg/dl ( p = 0.047) as an independent predictor of poor overall survival in patients with pancreatic cancer. Conclusion: Using a cut-off value of 81.6pg/ml for sPD-L1level, high sPD-L1 levels were independently associated with poor prognosis in patients with pancreatic cancer. However, this association in hepatocellular carcinoma or cholangiocarcinoma was not clear.

Introduction: Staining technique in order to remove portal inflow territory are performed in conventional anatomical liver resection. Due to magnified caudal view, Laparoscopic liver resection (LLR)can provide better exposure on hepatic hilum than open surgery. Therefore, isolation and transection of Glissonean vessels which ramify close to hepatic hilum can be performed. However, for vessels which ramify far from hilum, it could be difficult to isolate them in hilum prior to parenchymal transection. We describe our application of staining technique in LLR, depending on the variation of portal ramification. Method: Until January 2019, we performed 14 cases of anatomical LLRs using dye staining technique. Negative staining (NS) using near-infrared fluorescence scope were made by systemic administration of Indocyanine green (ICG) after ischemia by selective inflow occlusion. Positive staining (PS) using dye injection is made by direct needle puncture into portal vein under guidance of laparoscopic ultrasonography. Result: All LLRs were successfully performed anatomically. In NS, selective inflow occlusion can be standardized for Glissonean vessels which ramify close to hepatic hilum. ICG near-infrared fluorescence scope can help to detect the ischemic area even in patients with liver cirrhosis or post-adhesiolysis, in which have unclear demarcation under usual white light of endoscope. Although, PS have been considered technically difficult under the pneumoperitoneum, we experienced successful application of PS for vessels which ramify far from hilum, using our original modification tool under guidance of laparoscopic ultrasonography. Conclusion: Staining technique of portal inflow territory could contribute to perform precise anatomical laparoscopic liver resection.

肝囊胞に対するインドシアニングリーン（indocyanine green；以下，ICGと略記）蛍光法を用いた腹腔鏡下天蓋切除術を6例に施行した．全例女性で年齢の平均値は63歳（52～82），手術時間は152.3分（103～232），出血量14.6 ml（1～70）で，周術期合併症は認めなかった．手術開始時のICG蛍光法による観察では，全例で囊胞内容液は蛍光を発していなかった．囊胞内容液を吸引後に囊胞壁を切開し囊胞内壁を観察すると，白色光では視認できなかった胆管が明瞭に描出された．切離線にかかる視認された胆管は，クリップまたは結紮後に切離した．残存囊胞内壁に対する凝固において，視認できる脈管や描出される胆管を避けるためには，凝固が可能な範囲は極めて狭く，限局的であった．本法では，肝離断面からの胆汁漏の有無，囊胞内壁に存在する胆管走行の評価などが可能になり，より安全な腹腔鏡下天蓋切除術の施行に貢献しうると考えられた．

Abstract We investigated the efficacy of a Wilms' tumor gene 1 (WT1) vaccine combined with gemcitabine (GEMWT1) and compared it with gemcitabine (GEM) monotherapy for advanced pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II study. We randomly assigned HLA-A*02:01– or HLA-A*24:02–positive patients with advanced PDAC to receive GEMWT1 or GEM. We assessed WT1-specific immune responses via delayed-type hypersensitivity (DTH) to the WT1 peptide and a tetramer assay to detect WT1-specific cytotoxic T lymphocytes (WT1-CTL). Of 91 patients enrolled, 85 were evaluable (GEMWT1: n = 42; GEM: n = 43). GEMWT1 prolonged progression-free survival [PFS; hazard ratio (HR), 0.66; P = 0.084] and improved overall survival rate at 1 year (1-year OS%; GEMWT1: 35.7%; GEM: 20.9%). However, the difference in OS was not significant (HR: 0.82; P = 0.363). These effects were particularly evident in metastatic PDAC (PFS: HR 0.51, P = 0.0017; 1-year OS%: GEMWT1 27.3%; GEM 11.8%). The combination was well tolerated, with no unexpected serious adverse events. In patients with metastatic PDAC, PFS in the DTH-positive GEMWT1 group was significantly prolonged, with a better HR of 0.27 compared with the GEM group, whereas PFS in the DTH-negative GEMWT1 group was similar to that in the GEM group (HR 0.86; P = 0.001). DTH positivity was associated with an increase in WT1-CTLs induced by the WT1 vaccine. GEM plus the WT1 vaccine prolonged PFS and may improve 1-year OS% in advanced PDAC. These clinical effects were associated with the induction of WT1-specific immune responses. Cancer Immunol Res; 6(3); 320–31. ©2018 AACR.

Only a few studies have evaluated the clinicopathological significance of the p53 protein expression and s-p53-Abs level in patients with cholangiocarcinoma. We therefore analyzed the clinicopathological and prognostic significance of s-p53-Abs in patients with extrahepatic cholangiocarcinoma.

Introduction: Laparoscopic liver resection (LLR) is now widely used as a minimally invasive surgical option for benign and malignant liver disease. However, the endoscopic approach is limited by absence of tactile sense and the difficulty in establishing anatomic orientation. Indocyanine green (ICG) fluorescence imaging system has been developed as a tool for diagnosis and real-time surgical navigation. It has also been available for laparoscopic setting. We describe the usefulness of ICG fluorescence imaging in LLR. Methods: A high-end full high-definition laparoscopic camera system equipped with integrated filters for optimal detection of near-infrared fluorescence was used in 10 patients received LLR. In identifying portal parenchymal territory with contrast emission, ICG was administered intravenously after the selective occlusion of the portal pedicles prior to anatomically oriented hepatic transection. In detecting the localization of liver tumors, ICG was administered intravenously within the 2 weeks before surgery for preoperative evaluation of hepatic functional reserve. Emitted liver tumors by uptake of ICG were inspected during the surgery. In detecting bile leakage, trans-catheter cholangiography by intrabiliary injection of ICG was performed after the completion of hepatectomy. Emitted leakage from the bile duct was inspected, and was repaired by suturing. Results: All of 10 LLRs were successfully performed. This system was helpful in terms of identification of the portal territory, liver tumors and the bile leakage. Conclusions: The ICG fluorescence imaging system will be clinically useful for diagnostic and navigation tool, as a surgical "third eye" in ensuring safe and precise LLR.

3085 Background: Wilms’ tumor gene (WT1) is overexpressed in almost all malignancies including PDAC, and is supposed to be most promising tumor-associated antigen in cancer immunotherapies. To investigate superiority of WT1 vaccine in combination with gemcitabine (GEMWT1) compared to GEM alone (GEM) for patients (pts) with advanced PDAC, we designed the randomized phase II trial. Methods: HLA-A*02:01 and/or A*24:02-positive pts with locally advanced or metastatic PDAC without prior treatment, or recurrence after surgery were enrolled. Pts were randomly assigned at a ratio of 1:1 to GEMWT1 or GEM. Pts in GEM were allowed to receive GEM + WT1 vaccine after disease progression. The primary end point was overall survival (OS) rate at 1 year. Secondary end points were progression free survival (PFS), WT1-specific immunogenic response, and safety. WT1 vaccine, which was composed of HLA-restricted 9-mer WT1 peptide (3mg/body) and Montanide ISA51 adjuvant, was intradermally injected on days 1 and 15, and GEM was administrated at 1,000 mg/m2 on days 1, 8, and 15 in a 28-day cycle until disease progression. Results: A total of 91 pts were enrolled and 85 evaluable finally (GEMWT1, n = 42; GEM, n = 43). GEMWT1 improved 1-yr OS rate and prolonged PFS compared to GEM (Table). These were remarkable in pts with metastatic PDAC. WT1-specific immunity was assessed with delayed-typed hypersensitivity (DTH) to WT1 peptide and tetramer assay of WT1-specific cytotoxic lymphocytes (WT1-CTLs). Median PFS was 195, 102, and 100 days for DTH(+), DTH(-), and GEM, respectively [HR (90% CI), 0.51 (0.31 to 0.85), 0.80 (0.50 to 1.28), and 1]. WT1-CTLs increased in almost all DTH(+) pts. Conclusions: GEM + WT1 vaccine prolonged PFS in pts with advanced PDAC. Clinical efficacy of this combination therapy was associated with the induction of WT1-CTL responses. Clinical trial information: UMIN000005248. Total Metastatic GEM+WT1 n = 42 GEM n = 43 GEM+WT1 n = 35 GEM n = 34 1-yr OS, % [90% CI] 34.2 [22.4-46.3] 21.5 [12.2-32.6] 26.5 [15.1-39.4] 12.2 [4.8-23.3] PFS, median (days) [90% CI] 157 [102-193] 100 [57-141] 133 [87-166] 76 [54-106] PFS, HR [90% CI] 0.66 [0.44 – 0.99] p = 0.089 0.48 [0.30 – 0.77] p = 0.008

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.