Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency.

Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes IDH1 and BAP1 mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland.

Combination of risk alleles of PNPLA3, TM6SF2, and HSD17B13 of donors can predict recurrence of steatotic liver disease after liver transplantation.

AIMS: This study aimed to identify the genetic risk factors from donors or recipients that contribute to postliver transplantation (LT) steatotic liver disease (SLD), focusing on the genetic risk score (GRS) based on single nucleotide polymorphisms (SNPs) in SLD patients. METHODS: This retrospective study included 55 Japanese SLD recipients and their respective donors. Genotyping of PNPLA3, TM6SF2, and HSD17B13 was undertaken, and the combined GRS was calculated. The relationship between the GRS and the incidence of posttransplant SLD was also evaluated. RESULTS: The SLD recipients had a high prevalence of post-LT graft steatosis/steatohepatitis (76.4% and 58.2%, respectively). Although the recipients had a high frequency of risk alleles, there was no relationship between the number of risk alleles for each SNP and the incidence of posttransplant SLD. In contrast, an increased number of risk alleles for any SNP in the donor was correlated with high incidence rates of both post-LT steatosis and steatohepatitis. A multivariable analysis showed that a high donor GRS was an independent risk factor for graft steatosis (odds ratio 8.77; 95% CI, 1.94-52.94; p = 0.009). Similarly, a high donor GRS was an independent risk factor (odds ratio 6.76; 95% CI, 1.84-30.78; p = 0.007) for post-LT graft steatohepatitis. CONCLUSIONS: Donor risk alleles of PNPLA3, TM6SF2, and HSD17B13, rather than recipient risk alleles, have been implicated in the development of posttransplant SLD. The combination of these donor risk alleles into a GRS could predict the development of posttransplant SLD.

Comprehensive analyses of the clinicopathological features and genomic mutations of combined hepatocellular-cholangiocarcinoma.

AIM: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer that has two different tumor phenotypes in a single tumor nodule. The relationship between genetic mutations and clinicopathological features of cHCC-CCA remains to be elucidated. METHODS: Whole-exome sequencing analyses were carried out in 13 primary and 2 recurrent cHCC-CCAs. The whole-exome analyses and clinicopathological information were integrated. RESULTS: TP53 was the most frequently mutated gene in this cohort, followed by BAP1, IDH1/2, and NFE2L2 mutations in multiple cases. All tumors with diameters <3 cm had TP53 mutations. In contrast, six of seven tumors with diameters ≥3 cm did not have TP53 mutations, but all seven tumors had mutations in genes associated with various pathways, including Wnt, RAS/PI3K, and epigenetic modulators. In the signature analysis, the pattern of mutations shown in the TP53 mutation group tended to be more similar to HCC than the TP53 nonmutation group. Mutations in recurrent cHCC-CCA tumors were frequently identical to those in the primary tumor, suggesting that those tumors originated from identical clones of the primary cHCC-CCA tumors. Recurrent and co-occurrent HCC tumors in the same patients with cHCC-CCA had either common or different mutation patterns from the primary cHCC-CCA tumors in each case. CONCLUSIONS: The study suggested that there were two subtypes of cHCC-CCA, one involving TP53 mutations in the early stage of the carcinogenic process and the other not involving such mutations. The comparison of the variants between primary and recurrent tumors suggested that cHCC-CCA was derived from an identical clone.

A Conceptual Classification of Resectability for Hepatocellular Carcinoma.

BACKGROUNDS: In the era of multidisciplinary treatment strategy, resectability for hepatocellular carcinoma (HCC) should be defined. This study aimed to propose and validate a resectability classification of HCC. METHODS: We proposed following the three groups; resectable-(R), borderline resectable-(BR), and unresectable (UR)-HCCs. Resectable two groups were sub-divided according to the value of indocyanine green clearance of remnant liver (ICG-Krem) and presence of macrovascular invasion (MVI); BR-HCC was defined as resectable HCCs with MVI and/or ICG-Krem≥0.03-<0.05, and R-HCC was the remaining. Consecutive patients with HCC who underwent liver resection (LR) and non-surgical treatment(s) (i.e., UR-HCC) between 2011 and 2017 were retrospectively analyzed to validate the proposed classification. RESULTS: A total of 361 patients were enrolled in the study. Of these, R-, BR- and UR-HCC were found in 251, 46, and 64 patients, respectively. In patients with resected HCC, ICG-Krem≥0.05 was associated with decreased risk of clinically relevant posthepatectomy liver failure (p=0.013) and the presence of MVI was associated with worse overall survival (OS) (p<0.001). The 3-5-years OS rates according to the proposed classification were 80.3, and 68.3% versus 51.4, and 35.6%, in the R and BR groups, respectively (both p<0.001). Multivariate analysis showed BR-HCC was independently associated with poorer OS (p<0.001) after adjusting for known tumor prognostic factors. Meanwhile, BR-HCC was associated with benefit in terms of OS compared with UR-HCC (p<0.001). CONCLUSION: Our proposal of resectability for HCC allows for stratifying survival outcomes of HCC and may help to determine treatment strategy.

Impact of liver volumetric regeneration on survival outcomes in patients with hepatocellular carcinoma after major hepatectomy.

PURPOSE: Prognostic value of liver volumetric regeneration (LVR) in patients with hepatocellular carcinoma (HCC) who undergo major hepatectomy remains unknown. The aim of this study was to investigate the impact of LVR on long-term outcomes in these patients. METHODS: Data of 399 consecutive patients with HCC who underwent major hepatectomy between 2000 to 2018 were retrieved from a prospectively maintained institutional database. The LVR-index was defined as the relative increase in liver volume from 7 days to 3 months (RLV3m/RLV7d, where RLV3m and RLV7d is the remnant liver volume around 3 months and postoperative 7 days after surgery). The optimal cut-off value was determined using the median value of LVR-index. RESULTS: A total of 131 patients were eligible in this study. The optimal cut off value of LVR-index was 1.194. The 1-, 3-, 5- and 10-year overall survival (OS) rate of patients in the high LVR-index group were significantly better compared to those in the low LVR-index group (95.5%, 84.8%, 75.4% and 49.1% vs. 95.4%, 70.2%, 56.4%, and 19.9%, p = 0.002). Meanwhile, there was no significant difference with regards to time to recurrence between the two groups (p = 0.607). Significance of LVR-index for OS was retained after adjusting for known prognostic factors (p = 0.002). CONCLUSION: In patients with HCC undergoing major hepatectomy, LVR-index may serve as a prognostic indicator for OS.

Impact of patient-specific three-dimensional printed liver models on hepatic surgery safety: a pilot study.

BACKGROUND: Simulation and navigation technologies in hepatobiliary surgery have been developed recently. In this prospective clinical trial, we evaluated the accuracy and utility of our patient-specific three dimensional (3D)-printed liver models as an intraoperative navigation system to ensure surgical safety. METHOD: Patients requiring advanced hepatobiliary surgeries during the study period were enrolled. Three cases were selected for comparison of the computed tomography (CT) scan data of the models with the patients' original data. Questionnaires were completed after surgeries to evaluate the utility of the models. Psychological stress was used as subjective data and operation time and blood loss as objective data. RESULTS: Thirteen patients underwent surgery using the patient-specific 3D liver models. The difference between patient-specific 3D liver models and the original data was less than 0.6 mm in the 90% area. The 3D model assisted with intra-liver hepatic vein recognition and the definition of the cutting line. According to the post-operative subjective evaluation, surgeons found the models improved safety and reduced psychological stress during operations. However, the models did not reduce operative time or blood loss. CONCLUSION: The patient-specific 3D-printed liver models accurately reflected patients' original data and were an effective intraoperative navigation tool for meticulously difficult liver surgeries. CLINICAL TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trial Registry (UMIN000025732).

[Simultaneous living donor liver transplantation and pancreatoduodenectomy for an extensive cholangiocarcinoma with primary sclerosing cholangitis: a case report].

The treatment of choice for a resectable hilar cholangiocarcinoma is hepatectomy. Alternative treatment for unresectable cases includes liver transplantation;however, curative surgery is hindered by a distal cholangiocarcinoma extension into the intrapancreatic duct. Herein, we present a case of simultaneous living donor liver transplantation and pancreaticoduodenectomy for an extensive cholangiocarcinoma that is associated with primary sclerosing cholangitis, involving the perihilar and intrapancreatic duct. The treatment strategy involved neoadjuvant chemotherapy and radiation therapy, an exploratory laparoscopy and laparotomy for accurate staging, en-bloc whole bile duct and hepatoduodenal ligament resection, portal vein reconstruction with an interposition graft, and arterial reconstruction with the middle colic artery. The patient was discharged 122 days postoperatively although she suffered from postoperative ascites and delayed gastric emptying. Simultaneous living donor liver transplantation and pancreatoduodenectomy should be considered as treatment options for advanced cholangiocarcinoma.

Impact of Preoperative CEA Uptrend on Survival Outcomes in Patients with Colorectal Liver Metastasis After Hepatectomy.

BACKGROUND: Preoperative carcinoembryonic antigen (CEA) has been reported as a prognostic factor in patients with colorectal liver metastasis (CRLM) after hepatectomy. However, the impact of a preoperative "CEA uptrend" on prognosis after hepatectomy in these patients remains unknown. This study assessed the impact of CEA uptrend on prognosis in patients undergoing hepatectomy for CRLM. METHODS: Consecutive patients with CRLM who underwent hepatectomy between 2009 and 2018 were retrospectively analyzed. Patients with CRLM for whom CEA was measured both around 1 month before (CEA-1m) and within 3 days (CEA-3d) before hepatectomy were enrolled. A CEA-3d higher than both the upper limit of normal (5 ng/ml) and CEA-1m was defined as a CEA uptrend. RESULTS: Study participants comprised 212 patients with CRLM. Of these, 88 patients (41.5%) showed a CEA uptrend. CEA uptrend indicated better discriminatory ability (corrected Akaike information criteria, 733.72) and homogeneity (likelihood ratio chi-square value, 18.80) than CEA-3d or CEA-1m. Patients with CEA uptrend showed poorer overall survival than those without CEA uptrend (p < 0.001). After adjusting for known prognostic factors, the prognostic significance of CEA uptrend retained (hazard ratio 2.63, 95% confidence interval 1.63-4.26, p < 0.001). In subgroup analyses, the prognostic significance of CEA uptrend was retained irrespective of the status of RAS mutation or response to preoperative chemotherapy. CONCLUSIONS: CEA uptrend offers better prediction of survival outcomes than conventional CEA measurements in patients undergoing hepatectomy for CRLM.

Learning process of laparoscopic liver resection and postoperative outcomes: chronological analysis of single-center 15-years' experience.

BACKGROUND: Limited studies have reported the actual learning process of laparoscopic liver resection (LLR). This study aimed to chronologically evaluate our 15 years' experience of LLR. METHODS: All consecutive LLRs between 2006 to 2020 were retrospectively analyzed. The time period was divided into three groups; first (2006-2010), second (2011-2015), and third (2016-2020) period. The primary endpoint of this study was a composite of overall (Clavien-Dindo grade ≥ II) or major (grade ≥ IIIa) postoperative complications within 30 days. Using the IWATE criteria (four difficulty levels based on six indices), LLR was categorized as basic (< 7 points) and advanced (≥ 7 points) one. All analyses were performed based on the intention-to-treat principles. RESULTS: During the study period, a total of 382 LLRs were gradually performed (first period, n = 54; second period, n = 114, and third period, n = 214). Low incidences of overall and major complications were maintained (9.3, 10.5, and 7.0%, p = 0.514, and 1.9, 2.6, and 2.3%, p = 1.000). Meanwhile, pure LLRs (i.e., LLRs without hand-assisted or hybrid approach) and advanced LLRs were increasingly performed in 25 (46.3%), 71 (62.3%), and 205 (95.8%) patients (p < 0.001) and 3 (5.6%), 18 (15.8%), and 58 (27.1%) patients (p < 0.001), respectively. CONCLUSIONS: This study suggests that stepwise approach from basic to advanced procedures and use of hand-assisted or hybrid approach during the early phases for starting LLR practice may allow for maintaining low morbidity in specialized center.

Surgery for Recurrent Hepatocellular Carcinoma: Achieving Long-term Survival.

OBJECTIVE: To evaluate the long-term outcomes of surgery for recurrent hepatocellular carcinoma (HCC). BACKGROUND: HCC recurs with high incidence after liver resection. Little is known about long-term outcomes of patients undergoing surgery for recurrent HCC. METHODS: Among 989 patients who underwent R0/R1 liver resection for HCC between 1995 and 2014, 676 patients who exhibited recurrence were included. Repeat surgery was performed in 128 patients (RS group), and not in the remaining 548 patients (NS group). Prognostic value after repeat surgery was evaluated by comparing survival after recurrence (SAR) between the RS and NS groups. Subgroup analyses according to the 3 recurrence patterns [intrahepatic recurrence (IHR), extrahepatic recurrence (EHR), and intra plus extrahepatic recurrence (IHR + EHR)] were performed. RESULTS: Seventy-three of 430 patients (17.0%) with IHR, 17 of 57 patients (29.8%) with EHR, and 38 of 189 patients (20.1%) with IH + EHR underwent repeat surgery. Compared with the NS group, the RS group had better liver function and their time to recurrence was significantly longer (16.5 vs 11.4 months; P < 0.001). In the overall and 3 recurrence patterns, the 5-year SAR rate was better in the RS group compared with the NS group (RS vs NS group; overall, 53.0% vs 25.7%; IHR, 73.8% vs 37.2%; EHR, 30.0% vs 0%; IHR + EHR, 34.1% vs 10.6%; all P < 0.001, respectively). On multivariate analysis, repeat surgery was identified as an independent factor for better SAR (P < 0.001). CONCLUSION: Surgery for recurrent HCC may yield long-term survival for not only IHR but also for EHR in selected patients.

Utility of Mac-2 Binding Protein Glycosylation Isomer to Evaluate Graft Status After Liver Transplantation.

Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel liver fibrosis biomarker, but there are few studies on M2BPGi in liver transplantation (LT) recipients. This study aimed to evaluate the utility of M2BPGi measurement in LT recipients. We collected the clinicopathological data of 233 patients who underwent a liver biopsy at Kyoto University Hospital after LT between August 2015 and June 2019. The median values of M2BPGi in patients with METAVIR fibrosis stages F0, F1, F2, and ≥F3 were 0.61, 0.76, 1.16, and 1.47, respectively, whereas those in patients with METAVIR necroinflammatory indexes A0, A1, and ≥A2 were 0.53, 1.145, and 2.24, respectively. Spearman rank correlation test suggested that the necroinflammatory index had a stronger correlation to the M2BPGi value than the fibrosis stage. The area under the receiver operating characteristic curve of M2BPGi to predict ≥A1 was 0.75, which was significantly higher than that of any other liver fibrosis and inflammation marker. Patients with a rejection activity index (RAI) of ≥3 had a higher M2BPGi value than those with RAI ≤ 2 (P = 0.001). Patients with hepatitis C virus viremia had a higher M2BPGi value than sustained virological responders or those with other etiologies. In conclusion, the present study demonstrated that M2BPGi values are more strongly influenced by necroinflammatory activity and revealed M2BPGi, which has been thought to be a so-called fibrosis marker, as a disease activity marker in transplant recipients. M2BPGi measurement may be useful to detect early stage liver inflammation that cannot be detected by routine blood examination of LT recipients.

Liver Transection-First Approach in Hepatopancreatoduodenectomy for Hilar Cholangiocarcinoma: A Safe and Secure Technique for the Early Assessment of Curable Resection and Vascular Reconstruction.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is often indicated in the resection of cholangiocarcinoma but is associated with high mortality.1-3 From a risk-benefit perspective, HPD can be justified only when curative resection is achievable.4-6 METHODS: A liver transection-first approach is a surgical technique in which liver transection precedes pancreatoduodenectomy (PD) and skeletonization of the hepatoduodenal ligament in HPD. This approach enables an early assessment of resectability and curability. RESULTS: A 64-year-old with jaundice had a tumor located mainly in the proximal bile duct, spreading from the confluence of hepatic ducts (dominant in the left hepatic duct) to the intrapancreatic bile duct. The right hepatic artery and portal vein existed in close proximity to the tumor. HPD (left hemi-hepatectomy and subtotal stomach-preserving PD) with vascular resection was performed. After liver transection along the Cantlie line, the right Glissonean pedicle was collectively secured inside the liver. The right hepatic artery, right portal vein, and right hepatic duct (RHD) were isolated, and the feasibility of vascular reconstruction was confirmed. After the RHD was divided and the negative margin was confirmed, we proceeded to perform PD. The portal vein was reconstructed between the right portal vein and the portal vein trunk. The right hepatic artery was anastomosed to the second jejunal artery of the jejunal loop with the right gastroepiploic artery as an interposition graft. CONCLUSION: The liver transection-first technique in HPD facilitates early assessment of curability and resectability as well as a safe and secure manipulation and reconstruction of the hepatic artery and portal vein.

Identifying Patients Who May Benefit from Liver Resection Compared to Living Donor Liver Transplantation for Hepatocellular Carcinoma Using 18F-FDG PET.

BACKGROUND: This study aimed to assess an oncologic setting where patients with hepatocellular carcinoma (HCC) could benefit from liver resection (LR) compared to living donor liver transplantation (LDLT) using 18F-fluorodeoxyglucose (FDG) positron emission tomography. METHODS: The consecutive data of patients with HCC who underwent 18F-FDG PET before LR (LR group, n = 314) and LDLT (LDLT group, n = 65) between 2003 and 2015 were retrospectively analyzed. Tumor 18F-FDG avidity was quantified as the tumor to liver standardized uptake value ratio (TLR, cut-off value was defined at 2). Multivariate analysis was performed to assess significant preoperative tumor factors in the LR group. Survival outcomes between the two groups were stratified by these factors. RESULTS: The 5-year overall survival (OS: 56.9% vs. 73.8%, LR vs. LDLT, p < 0.001) and recurrence-free survival rate (RFS: 27.4% vs. 70.7%, p < 0.001) were significantly better in the LDLT group compared to the LR group. In the LR study, multivariate analysis identified TLR and tumor multiplicity as significant preoperative tumor factors for OS. In patients with solitary and TLR < 2 HCC, the 5-year OS rate was not significantly different between the LR and LDLT groups (70.3% vs. 71.8%, p = 0.352); meanwhile, RFS rate was better in the LDLT group (34.3% vs. 71.8%, p = 0.001). CONCLUSIONS: LDLT is associated with better long-term outcomes than LR in patients with HCC; however, selected patients with solitary and TLR < 2 HCC may benefit from LR.

Laparoscopic Versus Open Liver Resection for Hepatocellular Carcinoma: A Case Controlled Study with Propensity Score Matching.

BACKGROUND: Several studies have suggested that laparoscopic liver resection (LLR) is associated with fewer postoperative complications than open liver resection (OLR) for hepatocellular carcinoma (HCC). However, this issue remains controversial since the data may have been attributable to an imbalance in patients' background. METHODS: We retrospectively analyzed 290 hepatectomies for HCC undertaken between 2011 and 2019. Liver resection difficulty was based on the 3 levels of the Institut Mutualiste Montsouris classification. Resection ratio was calculated using computed tomography volumetry. Patient characteristics were compared between the LLR and OLR groups. Propensity score matching (PSM) was adopted to adjust the imbalance between the cohorts, and the incidence of postoperative complications was compared. RESULTS: The difficulty and resection ratio were significantly lower in LLR (n = 112) than in OLR (n = 178) (difficulty grade I/II/III: 84/10/18 vs. 43/39/96, p < 0.001; resection ratio: 11.4 ± 12.7 vs. 22.7 ± 17.2%, p < 0.001). The incidence of postoperative complications (Clavien-Dindo grade III or more) was lower in LLR (2.7% vs. 21.9%, p < 0.001), which was mainly attributable to fewer incidences of ascites and pleural effusion. PSM generated 68 well-matched patients in each group. The lower incidence of postoperative complications in LLR was also maintained in the PSM cohort (2.9% vs. 16.2%, p = 0.017). On multivariate analysis, LLR was the independent predictor of postoperative complications (OR 0.184, 95% CI 0.051-0.672, p = 0.010). CONCLUSION: The present study demonstrated that a laparoscopic approach reduces the incidence of postoperative complications in liver resection for HCC.

Low level of postoperative plasma antithrombin III is associated with portal vein thrombosis after liver surgery.

PURPOSE: Although decreased antithrombin-III (AT-III) is a risk factor for portal vein thrombosis (PVT) in patients with liver cirrhosis, the association between postoperative PVT and postoperative AT-III levels is unknown in patients undergoing hepatectomy. METHODS: Patients who underwent hepatectomy between 2015 and 2018 were retrospectively analyzed. Postoperative PVT was assessed on CT at days 6-9 after hepatectomy. One-to-one propensity score (PS) matching was used to match the baseline characteristics. RESULTS: Of the 295 patients included in this analysis, 19 patients (6.4%) were diagnosed with postoperative PVT. The AT-III level on postoperative day (POD) 3 predicted postoperative PVT with a sensitivity/specificity of 74%/59% (AUC, 0.644; cut-off value, 60%; p = 0.032). Multivariate analysis revealed that AT-III levels ≤ 60% on POD3 (OR, 3.01; 95% CI 1.02-8.89; p = 0.046), cirrhosis (OR, 5.88; 95% CI 1.92-18.0; p = 0.002) and right-sided hepatectomy (OR, 4.16; 95% CI 1.45-11.9; p = 0.0079) were significant risk factors for postoperative PVT. After PS matching, 56 patients with and without AT-III supplementation were analyzed. The two groups had a similar incidence of PVT (p = 0.489). CONCLUSIONS: Patients with AT-III levels ≤ 60% on POD3 should be carefully followed up regarding postoperative PVT. Our results did not support the efficacy of routine AT-III supplementation for the prophylaxis of postoperative PVT.

Quantitative assessment of microvascular invasion in hepatocellular carcinoma using preoperative serological and imaging markers.

BACKGROUND: The aim of this study was to establish a quantitative equation to predict microvascular invasion (MVI) for patients with resectable hepatocellular carcinoma (HCC). METHODS: This retrospective study included 219 patients with resected HCC from 2004 to 2015. All had available three pre-operative serological markers (alfa-feto protein (AFP), fucosylated AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP)), and one imaging marker (tumor to liver ratio of SUVmax (TLR) by 18F-FDG-PET). A multiple linear regression model for predicting MVI was developed (2004-2009, n = 111) and then validated (2010-2015, n = 108). Further, impact on the obtained model on survival outcomes was assessed. RESULTS: Using the derivation cohort, following equation was developed; MVI probability (%) = 14.2 × log10DCP + 9.9 × TLR - 22.0. This model resulted in an area under receiver operating characteristic curve (ROC) of 0.806 and 0.751, in the derivation and validation cohort, respectively. Furthermore, MVI probability ≥40% determined by ROC analysis was associated with worse overall survival and recurrence-free survival in the derivation and the validation cohort (all p < 0.05). CONCLUSION: A quantitative model, using DCP and TLR, was able to preoperatively predict with good performance MVI and long-term outcomes in patients with HCC after liver resection.

Fluid dynamics analyses of the intrahepatic portal vein tributaries using 7-T MRI.

BACKGROUND: Assessing portal vein (PV) hemodynamics is an essential part of liver disease management/liver surgery, yet the optimal methods of assessing intrahepatic PV flow have not yet been established. This study investigated the usefulness of 7-Tesla MRI with hemodynamic analysis for detecting small flow changes within narrow intrahepatic PV branches. METHODS: Flow data in the main PV was obtained by two methods, two-dimensional cine phase contrast-MRI (2D cine PC-MRI) and three-dimensional non-cine phase contrast-MRI (3D PC-MRI). Hemodynamic parameters, such as flow volume rate, flow velocity, and wall shear stress in intrahepatic PV branches were calculated before and after a meal challenge using 3D PC-MRI and hemodynamic analysis. RESULTS: The hemodynamic parameters obtained using 3D PC-MRI and 2D cine PC-MRI were similar. All intrahepatic PV branches were clearly depicted in eight planes, and significant changes in flow volume rate were seen in three planes. Average and maximum velocities, cross-sectional area, and wall shear stress were similar between before and after a meal challenge in all planes. CONCLUSION: 7-Tesla 3D PC-MRI combined with hemodynamic analysis is a promising tool for assessing intrahepatic PV flow and enables future studies in small animals to investigate PV hemodynamics associated with liver disease/postoperative liver recovery.

Laparoscopic liver resection versus percutaneous radiofrequency ablation for small hepatocellular carcinoma.

BACKGROUND: Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) play central roles to treat early-stage hepatocellular carcinoma (HCC, ≤3 cm, 1-3 nodules, and no macrovascular involvement), although data are lacking regarding whether LLR or RFA is preferable. This study aimed to compare outcomes of both treatments for small HCCs. METHODS: Treatment outcomes of small HCCs were compared between all the minor LLRs performed between 2005 and 2016 and RFAs performed between 2011 and 2016 at Kyoto University. RESULTS: A total of 85 and 136 patients underwent LLR and RFA, respectively. Patients that underwent LLR had higher incidence of blood transfusions, complications, and longer hospital stay. Overall and disease-specific survival rates were similar between LLR and RFA; however, recurrence-free (49.2% vs. 22.1% at 3-year) and local recurrence-free survival rates (94.9% vs. 63.6% at 3-year) were higher after LLR. Multivariate analyses identified that multiple nodules and 65-year-old and above are predictors of disease-specific survival, and that RFA is a predictor of recurrence and local recurrence. CONCLUSION: RFA is less invasive, although both LLR and RFA are safe and effective. LLR provides better local control with superior recurrence-free and local-recurrence free survival. These results help optimize treatment selection based on patient-specific factors.

Proposed Definition for Oligometastatic Recurrence in Biliary Tract Cancer Based on Results of Locoregional Treatment: A Propensity-Score-Stratified Analysis.

BACKGROUND: Oligometastatic recurrence involves relapsed tumors for which locoregional treatment (LT) may yield a survival benefit. However, there are no clear criteria for selecting patients for LT or determining the effects of LT in recurrent biliary tract cancer (BTC). The aim of this retrospective study is to assess the effects of LT on survival outcomes and to identify potential criteria for selecting LT in recurrent BTC. PATIENTS AND METHODS: In the present work, 232 consecutive patients with recurrent BTC who initially underwent curative surgery between 1996 and 2015 were evaluated. The primary outcome was length of survival after recurrence (SAR). Propensity score stratification with various tumor-related factors was used to identify patients who would likely benefit from LT. RESULTS: Among the cohort, 60 (25.9%) patients underwent LT, whereas 172 (74.1%) patients did not. The multivariate Cox model identified carbohydrate antigen 19-9 levels of > 50 U/mL, multiorgan recurrence, tumor number > 3, tumor size > 30 mm, and early recurrence (≤ 1 year) as independent predictors of poor SAR (P < 0.001 for each factor). In the propensity-score-stratified analysis, LT was associated with survival benefits for patients representing single-organ recurrence with at most three tumors and late-onset recurrence (> 1 year) (median SAR: 48.6 vs. 14.2 months, n = 33 vs. n = 34, hazard ratio: 0.10, 95% confidence interval: 0.04-0.20, P < 0.001). CONCLUSIONS: Patients with recurrent BTC may benefit from LT if they have single-organ recurrence with at most three tumors and late-onset recurrence. We propose that these patients may have clinically relevant "oligometastatic recurrence" of BTC.

Pretransplantation splenomegaly frequently persists after liver transplantation and can manifest as hypersplenism and graft fibrosis - a retrospective study.

The risk factors and clinical impact of post-transplantation splenomegaly (SM) are poorly understood. We investigated the predictors and impacts of post-transplantation SM in 415 LT patients at Kyoto University Hospital from April 2006 to December 2015. First, the predictors and clinical consequences of SM three years post-transplantation were analyzed among spleen-preserved recipients. Second, the clinical data of surviving recipients three years post-transplantation were compared between splenectomized and spleen-preserved recipients. There was no difference in indication for liver transplantation between these two groups. Third, survival outcomes were compared between splenectomized and spleen-preserved recipients. SM was determined as a SV/body surface area (BSA) higher than 152 ml/m2 . In the first analysis, preoperative SM occurred in 79.9% recipients and SM persisted three years post-transplantation in 72.6% recipients among them. Preoperative SV/BSA was the only independent predictor of three year post-transplantation SM, which was associated with lower platelet (PLT), white blood cell (WBC) counts and significant graft fibrosis (21.4% vs. 2.8%). In the second analysis, spleen-preservation was related to lower PLT, WBC counts and a higher proportion of significant graft fibrosis (26.7% vs. 7.1%) three years post-transplantation. In the third analysis, spleen-preserved recipients showed worse survival than splenectomized recipients. In conclusion, preoperative SM frequently persists more than three years post-transplantation and is associated with subclinical hypersplenism, graft fibrosis, graft loss, and even death.