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Tumor stiffness measurement using magnetic resonance elastography can assess tumor mechanical properties and predict hepatocellular carcinoma recurrence. This study aimed to investigate preoperative tumor stiffness on magnetic resonance elastography as a predictor of overall survival and recurrence-free survival in patients with solitary nodular hepatocellular carcinoma who underwent curative resection.Seventy-eight patients with solitary nodular hepatocellular carcinoma who underwent preoperative magnetic resonance elastography and curative resection were retrospectively analyzed. Potential associations of tumor stiffness and other clinicopathological variables with overall survival and recurrence-free survival were analyzed in both univariate and multivariate Cox proportional hazards analyses. The optimal tumor stiffness cutoff value was determined using the minimal P value approach.In multivariate analysis, tumor stiffness (hazard ratio 1.31; 95% confidence interval, 1.07-1.59; P = .008) and vascular invasion (hazard ratio 2.62; 95% confidence interval, 1.27-5.17; P = .010) were independent predictors of recurrence-free survival. For overall survival, tumor stiffness (hazard ratio, 1.33; 95% confidence interval, 1.02-1.76; P = .037) was the only independent predictor. The optimal tumor stiffness cutoff value was 5.81 kPa for both overall survival and recurrence-free survival. Patients with tumor stiffness ≥5.81 kPa had a significantly greater risk of death (hazard ratio 6.10; 95% confidence interval, 2.11-21.90; P.001) than those with tumor stiffness5.81 kPa.Preoperative tumor stiffness as measured by magnetic resonance elastography was a predictor of overall survival and recurrence-free survival in hepatocellular carcinoma patients who underwent curative resection. Higher tumor stiffness was associated with higher risk of recurrence and death.

Gemcitabine/cisplatin (GC) combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). No randomized clinical trials have been able to demonstrate the survival benefit over GC during the past decade. In our previous phase II trial, adding S-1 to GC (GCS) showed promising efficacy and we aimed to determine whether GCS could improve overall survival compared with GC for patients with advanced BTC.We performed a mulitcenter, randomized phase III trial across 39 centers. Enrolled patients were randomly allocated (1:1) to either the GCS or GC arm. The GCS regimen comprised gemcitabine (1000 mg/mBetween July 2014 and February 2016, 246 patients were enrolled. The median OS and 1-year OS rate were 13.5 months and 59.4% in the GCS arm and 12.6 months and 53.7% in the GC arm, respectively (hazard ratio [HR] 0.79, 90% confidence interval [CI]: 0.628-0.996; P = .046 [stratified log-rank test]). Median PFS was 7.4 months in the GCS arm and 5.5 months in the GC arm (HR 0.75, 95% CI: 0.577-0.970; P = .015). RR was 41.5% in the GCS arm and 15.0% in the GC arm. Grade 3 or worse AEs did not show significant differences between the two arms.GCS is the first regimen which demonstrated survival benefits as well as higher RR over GC in a randomized phase III trial and could be the new first-line standard chemotherapy for advanced BTC. To exploit the advantage of its high RR, GCS is now tested in the neoadjuvant setting in a randomized phase III trial for potentially resectable BTC.

The effect of bevacizumab plus mFOLFOX6 on downsizing of liver metastases for curative resection has not been well assessed for patients with advanced colorectal liver metastases (CRLMs). This multicenter phase II trial aimed to examine the efficacy and safety of bevacizumab plus mFOLFOX6 for advanced CRLMs harboring mutant-type KRAS.Patients with advanced CRLMs (tumor number of ≥5 and/or technically unresectable) harboring mutant-type KRAS were included. Surgical indication was evaluated every 4 cycles of bevacizumab plus mFOLFOX6. Liver resection was planned if the CRLMs were resectable. The primary endpoint was R0 resection rate. The secondary endpoints included overall survival (OS), recurrence-free survival, progression-free survival, and safety.Between 2013 and 2017, 29 patients from six centers were registered. The rates of complete and partial responses were 0% and 62.1%, respectively. R0 and R1 resections were performed in 19 and 1 patient, respectively (R0 resection rate: 65.5%). No mortality occurred. During the median follow-up of 30.7 months, the 3-year OS rate for all the patients was 64.4% with the median survival of 49.1 months.For advanced CRLMs harboring mutant-type KRAS, bevacizumab plus mFOLFOX6 achieved a high R0 resection rate, leading to favorable survival.

Portal vein thrombosis (PVT) after liver resection is rare but can lead to life-threatening liver failure. This prospective study evaluated patients using contrast-enhanced computed tomography (E-CT) on the first day after liver resection for early PVT detection and management.To evaluate patients by E-CT on the first day after liver resection for early PVT detection and immediate management.Patients who underwent liver resection for primary liver cancer from January 2015 were enrolled. E-CT was performed on the first day after surgery in patients undergoing anatomical resection, multiple resections, or with postoperative bile leakage in the high-risk group for PVT. When PVT was detected, anticoagulant therapy including heparin, warfarin, and edoxaban was administered. E-CT was performed monthly until PVT resolved.The overall incidence of PVT was 1.57% (8/508). E-CT was performed on the first day after surgery in 235 consecutive high-risk patients (165 anatomical resections, 74 multiple resections, and 28 bile leakages), with a PVT incidence of 3.4% (8/235). Symptomatic PVT was not observed in the excluded cohort. Multivariate analyses revealed that sectionectomy was the only independent predictor of PVT [odds ratio (OR) = 12.20; 95% confidence interval (CI): 2.22-115.97;Sectionectomy on the left side should be chosen with caution as it showed the highest risk of PVT. E-CT followed by anticoagulant therapy was effective in managing early-phase PVT for 2 mo without adverse events.

We aimed to validate our algorithm for resecting Hepatocellular carcinoma (HCC) in the caudate lobe based on tumor location, tumor size, and indocyanine green clearance rate.Patients who underwent curative resections for solitary HCC in the caudate lobe were included. The surgical outcomes of patients with HCC in the caudate lobe were compared with those of patients with HCC in other sites of the liver.After one-to-one matching, the caudate-lobe group (n = 150) had longer operation time, greater amount of bleeding, lower weight of resected specimens, and shorter distance between tumor and resection line than the other-sites group (n = 150), but the complication rates were not different between the groups (38.0% vs. 34.1%, P = 0.719). After a median follow-up period of 3.0 years (range, 0.3-16.2 years), the median overall survivals were 6.5 (95% confidence interval [CI], 5.3-7.9) and 7.5 years (95% CI, 6.3-9.7) in the caudate-lobe and other-site groups, respectively (P = 0.430). Median recurrence-free survivals in the caudate-lobe group (1.9 years; 95% CI, 1.4-2.7) had a tendency to be shorter than those in the other-sites group (2.3 years; 1.7-3.4) (P = 0.052).Patients' survival and complication rates in the caudate-lobe group were comparable to those in the other-sites group; therefore, our algorithm for resecting HCC in the caudate lobe is of clinical use.

In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21 155 newly registered patients and 43 041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from January 1, 2012 to December 31, 2013. Basic statistics compiled for patients newly registered in the 22nd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathologic diagnosis, recurrence status and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, more patients with non-B non-C HCC, smaller tumor diameter and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer worldwide.

PDF file, 36KB, A 30 mg dose of peptide caused stronger local skin reactions (blushing, induration) at the injection site than did a 3.0 mg dose.

Table S1 shows Clinical features. Table S2 shows Patient/sample information and NGS statistics. Table S3 shows Methylation status of CpG sites of WNT targets with CTNNB1 mutation. Table S4 shows Chromosomal aberrations.

Supplementary Figure legends

Purpose:Hepatitis B viral (HBV) DNA is frequently integrated into the genomes of hepatocellular carcinoma (HCC) in patients with chronic HBV infection (chronic HBV, hereafter), whereas the frequency of HBV integration in patients after the disappearance of HBV (prior HBV, hereafter) has yet to be determined. This study aimed to detect integration of HBV and adeno-associated virus type 2 (AAV2) into the human genome as a possible oncogenic event.Experimental Design:Virome capture sequencing was performed, using HCC and liver samples obtained from 243 patients, including 73 with prior HBV without hepatitis C viral (HCV) infection and 81 with chronic HBV.Results:Clonal HBV integration events were identified in 11 (15.0%) cases of prior HBV without HCV and 61 (75.3%) cases of chronic HBV (P < 0.001). Several driver genes were commonly targeted by HBV, leading to transcriptional activation of these genes; TERT [four (5.4%) vs. 15 (18.5%)], KMT2B [two (2.7%) vs. five (6.1%)], CCNE1 [zero vs. one (1.2%)], CCNA2 [zero vs. one (1.2%)]. Conversely, CCNE1 and CCNA2 were, respectively, targeted by AAV2 only in prior HBV. In liver samples, HBV genome recurrently integrated into fibrosis-related genes FN1, HS6ST3, KNG1, and ROCK1 in chronic HBV. There was not history of alcohol abuse and 3 patients with a history of nucleoside analogue treatment for HBV in 8 prior HBV with driver gene integration.Conclusions:Despite the seroclearance of hepatitis B surface antigen, HBV or AAV2 integration in prior HBV was not rare; therefore, such patients are at risk of developing HCC.

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Purpose: The carcinoembryonic antigen glypican-3 (GPC3) is an ideal target of anticancer immunotherapy against hepatocellular carcinoma (HCC). In this nonrandomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3 peptide vaccination in patients with advanced HCC.Experimental Design: Thirty-three patients with advanced HCC underwent GPC3 peptide vaccination (intradermal injections on days 1, 15, and 29 with dose escalation). The primary endpoint was the safety of GPC3 peptide vaccination. The secondary endpoints were immune response, as measured by IFN-γ ELISPOT assay, and the clinical outcomes tumor response, time to tumor progression, and overall survival (OS).Results: GPC3 vaccination was well-tolerated. One patient showed a partial response, and 19 patients showed stable disease 2 months after initiation of treatment. Four of the 19 patients with stable disease had tumor necrosis or regression that did not meet the criteria for a partial response. Levels of the tumor markers α-fetoprotein and/or des-γ-carboxy prothrombin temporarily decreased in nine patients. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 30 patients. Furthermore, GPC3-specific CTL frequency after vaccination correlated with OS. OS was significantly longer in patients with high GPC3-specific CTL frequencies (N = 15) than in those with low frequencies (N = 18; P = 0.033).Conclusions: GPC3-derived peptide vaccination was well-tolerated, and measurable immune responses and antitumor efficacy were noted. This is the first study to show that peptide-specific CTL frequency can be a predictive marker of OS in patients with HCC receiving peptide vaccination. Clin Cancer Res; 18(13); 3686–96. ©2012 AACR.

PDF file, 60KB, Expression of GPC3 and HLA class I in cases 8 and 25 was determined by immunohistochemistry. Magnification = 200�.

PDF file, 28KB, The levels of AFP or DCP decreased temporarily at least once in nine of the 33 patients. In seven of these nine patients, the levels of DCP fell to < 30% of baseline values.

PDF file, 47KB, There was no significant difference in the clinical background of patients with GPC3-specific CTL frequencies ≥ 50 and those with < 50. A peptide dose of greater than 1.0 mg was required for adequate induction of GPC3-specific CTL frequences ≥ 50.

Figure S1 shows Histological findings of stepwise hepatocarcinogenesis and somatic substitution patterns. Figure S2 shows Activation of WNT targets. Figure S3 shows Homozygous deletion in 4q and 16q. Figure S4 shows Circos plot and transcription of the 5' portion of fusion genes that included TERT sequences. Figure S5 shows Upregulation mechanisms of TERT gene. Figure S6 shows Classification of HCC samples based on the methylation data.

Cancer develops through the accumulation of genetic and epigenetic aberrations. To identify sequential molecular alterations that occur during the development of hepatocellular carcinoma (HCC), we compared 52 early and 108 overt HCC samples by genome sequencing. Gene mutations in the p53/RB1 pathway, WNT pathway, MLL protein family, SWI/SNF complexes, and AKT/PI3K pathway were common in HCC. In the early phase of all entities, TERT was the most frequently upregulated gene owing to diverse mechanisms. Despite frequent somatic mutations in driver genes, including CTNNB1 and TP53, early HCC was a separate molecular entity from overt HCC, as each had a distinct expression profile. Notably, WNT target genes were not activated in early HCC regardless of CTNNB1 mutation status because β-catenin did not translocate into the nucleus due to the E-cadherin/β-catenin complex at the membrane. Conversely, WNT targets were definitively upregulated in overt HCC, with CTNNB1 mutation associated with downregulation of CDH1 and hypomethylation of CpG islands in target genes. Similarly, cell-cycle genes downstream of the p53/RB pathway were upregulated only in overt HCC, with TP53 or RB1 gene mutations associated with chromosomal deletion of 4q or 16q. HCC was epigenetically distinguished into four subclasses: normal-like methylation, global-hypomethylation (favorable prognosis), stem-like methylation (poor prognosis), and CpG island methylation. These methylation statuses were globally maintained through HCC progression. Collectively, these data show that as HCC progresses, additional molecular events exclusive of driver gene mutations cooperatively contribute to transcriptional activation of downstream targets according to methylation status.Significance:In addition to driver gene mutations in the WNT and p53 pathways, further molecular events are required for aberrant transcriptional activation of these pathways as HCC progresses.

Background Transarterial chemoembolisation (TACE) is a treatment option for hepatocellular carcinoma (HCC), but the optimum agent for TACE remains unclear. We compared the efficacy of TACE with cisplatin versus with epirubicin in patients with unresectable HCC. Methods This multicentre, randomised, phase 2/3 trial was performed at 21 hospitals in Japan. Patients with liver-confined HCC, performance status 0–2, and Child-Pugh class A/B were randomised to receive TACE with cisplatin or epirubicin. Patients were stratified in accordance with the institution, Child-Pugh class, tumour size, tumour thrombosis, α-fetoprotein and prior treatment. The primary end-point was overall survival in the intention-to-treat population. Tumour response was evaluated in accordance with the Response evaluation criteria in solid tumours criteria. Findings Between 2008 and 2012, 455 patients were randomly assigned to undergo TACE with cisplatin (n = 228) or epirubicin (n = 227). Eleven patients were ineligible, and 444 patients were included in the full analysis. Twelve patients not receiving TACE were excluded, and 432 patients were included in the safety analysis set. In phase 2, disease control rates in cisplatin (91·7%) and epirubicin (91·8%) groups exceeded the predefined threshold of 70%, and the study proceeded to phase 3. After a median follow-up of 32·7 months (IQR = 15·3–49·3), median overall survival periods were 2·93 years (95% CI 2·60–3·79) and 2·74 years (95%CI 2·26–3·21), respectively (hazard ratio 0·90 [95% CI 0·71–1·15], p = 0·22). Median times to treatment failure were 1·38 and 1·46 years (hazard ratio 1·09 [95% CI 0·88–1·35], p = 0·88), response rates were 65·3% and 60·6% (p = 0·31), and serious adverse event rates were 49·8% and 48·3% (p = 0·56), respectively. No treatment-related deaths occurred in either group. Interpretation In our phase 2/3 randomised trial, cisplatin is not significantly superior to epirubicin in TACE for patients with HCC.

High dorsal resection (HDR) of the liver is a systematic resection technique for hepatocellular carcinoma (HCC) arising in the caudate lobe. HDR is rarely performed, as the procedure requires a high level of operative skill, knowledge of liver anatomy and is performed in patients with limited hepatic function. Between 2002 and 2012, we performed HDR on 9 patients. The median operation time was 534 min (range, 349–903 min), and the median blood loss volume was 430 mL (range, 94–4,530 mL). The severe morbidity rate was 11.1%, but there was no operative mortality, and the median hospitalization was 13 days (range, 8–93 days). The overall survival was 49.7 months (range, 3.1–89.0 months). Despite the hard-to-approach anatomic location, HDR can be carried out safely with good survival compared to other segments.

Although Makuuchi's criteria are widely used to determine the cut-off for safe liver resection, there have been few reports of concrete data supporting their validity. Here, we verified the utility of Makuuchi's criteria by comparing the operative mortality rates associated with liver resection between hepatocellular carcinoma (HCC) patients meeting or exceeding the criteria.A database was built using data from 15 597 patients treated between 2000 and 2007 for whom values for all three variables included in Makuuchi's criteria for liver resection (clinical ascites, serum bilirubin, and indocyanine green clearance) were available. The patients were divided into those fulfilling (n = 12 175) or exceeding (n = 3422) the criteria. The postoperative mortality (death for any reason within 30 days) and long-term survival were compared between the two groups.The operative mortality rate was significantly lower in patients meeting the criteria than in those exceeding the criteria (1.07% vs. 2.01%, respectively; p 0.001). On multivariate analysis, exceeded the criteria was significantly associated with the risk for operative mortality (relative risk 2.08; 95% confidence interval (CI), 1.23-3.52; p = 0.007). Surgical indication meeting or exceeding the criteria was an independent factor for overall survival (hazard ratio 1.27; 95% CI, 1.18-1.36; p 0.001).Makuuchi's criteria are suitable for determining the indication for resection of HCC due to the reduction in risk of operative mortality.

To retrospectively compare the predictive value of computed tomography volumetry (CTV), magnetic resonance elastography (MRE) of the liver, and their combination for major complications after liver resection. We enrolled 108 consecutive patients who underwent anatomical liver resection for liver tumors and preoperative contrast-enhanced CT and MRE. The future liver remnant (FLR) ratio was calculated by CTV, while the liver stiffness measurement (LSM) was obtained by MRE. FLR ratio alone, LSM alone, and combined FLR ratio and LSM were evaluated to predict major complications (Clavien–Dindo grade ≥ IIIa). Univariate and multivariate analyses of hepatic biochemical parameters and imaging data were performed to identify predictors of major complications. Receiver operating characteristic analyses of FLR ratio, LSM, and their combination were performed, and the sensitivity and specificity were calculated. Twenty-two (20.4%) of the 108 patients experienced major complications. According to multiple regression analysis, the FLR ratio (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.91–0.99, p = 0.040) and LSM (OR 1.72, 95% CI 1.01–2.94, p = 0.047) were independent predictors of major complications. The combined FLR ratio and LSM were predictive of major complications, with an area under the curve (AUC) of 0.818, sensitivity of 68.2%, and specificity of 84.9%. The AUC and specificity for combined FLR ratio and LSM were larger than those for FLR ratio (AUC: 0.711, specificity: 80.2%) and LSM (AUC: 0.793, specificity: 80.2%). Combined CTV and MRE analysis can improve the AUC and specificity for predicting major complications after anatomical liver resection.

Objective The effect of postoperative complications including red blood cell transfusion (BT) on long-term survival for hepatocellular carcinoma (HCC) is unknown. The purpose of this study was to define the relationship between postoperative complications and long-term survival in patients with HCC. Methods Postoperative complications of 1251 patients who underwent curative liver resection for HCC were classified, and their recurrence-free survival (RFS) and cumulative overall survival (OS) were investigated. Results Any complications occurred in 503 patients (40%). Five-year RFS and 5-year OS in the complication group were 21% and 56%, respectively, significantly lower than the respective values of 32% (P < 0.001) and 68% (P < 0.001) in the no-complication group (n = 748). Complications related to RFS were postoperative BT [hazard ratio (HR): 1.726, 95% confidence interval (CI): 1.338–2.228, P < 0.001], pleural effusion (HR: 1.434, 95% CI: 1.200–1.713, P < 0.001) using Cox proportional-hazard model. Complications related to OS were postoperative BT (HR: 1.843, 95% CI: 1.380–2.462, P < 0.001), ascites (HR: 1.562, 95% CI: 1.066–2.290, P = 0.022), and pleural effusion (HR: 1.421, 95% CI: 1.150–1.755, P = 0.001). Conclusions Postoperative complications were factors associated with poor long-term survival. Postoperative BT and pleural effusion were noticeable complications that were prognostic factors for both RFS and OS.

Hepatectomy, the most common treatment for hepatocellular carcinoma, is associated with greater intraoperative blood loss than is resection of other malignancies. The effect of blood product transfusion (red blood cell [RBC], platelet, fresh frozen plasma [FFP], 5 and 25% albumin) on prognosis remains unclear. This study examined effects of blood product transfusion on prognoses of patients who underwent hepatectomy for hepatocellular carcinoma.We included 2015 patients with pathologically confirmed hepatocellular carcinoma who underwent hepatectomy at our institution during 1990-2019. Patients (n = 534) who underwent repeat hepatectomy, non-curative hepatectomy, those with synchronous cancer in other organs, those who died within 1 month of surgery, and those with missing data were excluded. Finally, 1481 patients (1142 males, 339 females; median age: 68 years) with curability A or B were included.Intraoperative blood loss ( 500 mL) was an independent predictor of RBC transfusion (odds ratio, 8.482; P 0.001). All transfusion groups had poorer recurrence-free survival (RFS) and overall survival (OS) than non-transfusion groups. After propensity score matching, the 5 year RFS rate was 13.4 and 16.3% in the RBC and no-RBC groups, respectively (P = 0.020). The RBC group had a significantly lower 5 year OS rate than the no-RBC group (42.1 vs. 48.8%, respectively; P = 0.035) and the FFP group (57.0%) than the no-FFP group (63.9%) (p = 0.047). No significant between-subgroup differences were found for other blood transfusion types.RBC transfusion promotes hepatocellular carcinoma recurrence and RBC/FFP transfusions reduced long-term survival and RFS and OS in patients who underwent radical liver resection of HCC.

Aims: We aimed to develop a computer-assisted system for the gross classification of resected hepatocellular carcinoma (HCC) and to evaluate whether this objective classification can be used to predict patient outcomes.Methods: This study included 236 patients diagnosed with solitary HCC who underwent initial resection. We analyzed photographed images of the cut surface of HCCs using a new software to establish a novel gross classification system. Survival curves in each of the classified groups were compared. Results: The median (range) values for the equivalent diameter, circularity, and complexity of tumors were 2.63 cm (0.72–14.49), 0.49 (0.00–0.84), and 0.51 (0.16–1.00), respectively. HCCs were classified into three groups using hierarchical cluster analysis: Type I (circular type, n=130), Type II (rough type, n=92), and Type III (disordered type, n=14). Microscopic portal invasion was observed in 14.6%, 23.9%, 71.4% patients in the Type I, II, and III groups, respectively. The 5-year recurrence-free survival rates of patients with Type I, II, and III HCC were 31.5%, 24.7%, and 14.3%, respectively. The 5-year overall survival rates of patients with Types I, II, and III HCC were 65.4%, 54.7%, and 28.6%, respectively. Type II or III HCC were independently associated with death and an increased risk of recurrence. The conventional classification was not adopted due to its weaker power than the above-mentioned contributors.Conclusion: Our computer-assisted gross classification system for HCC indicated that this classification is closely associated with microscopic portal invasion, suggesting aid in predicting patient outcomes than that of conventional subjective classification.

The presence of esophageal varices (EV) is a phenotype of portal hypertension, and the indications of liver resection for hepatocellular carcinoma (HCC) in patients with concomitant EV are conflicting. This retrospective study aimed to elucidate if there is justification for liver resection in patients with EV. The surgical outcomes were compared between the patients who underwent resection for HCC with EV (EV group) and those without EV (non-EV group) after propensity-score matching. More bleeding was prevalent (P < 0.001) and refractory ascites was more frequently observed (P = 0.031) in the EV group (n = 277) compared with the non-EV group (n = 277); however, the numbers of patients with morbidities (P = 0.740) and re-operation (P = 0.235) were not significantly different between the two groups. After a median follow-up period of 3.0 years, the median overall and recurrencefree survival periods of patients with EV were 4.8 years (95% confidence interval [CI], 4.1-5.9) and 1.7 years (1.5-2.0), respectively, and were significantly shorter than those of patients without EV (7.6 years [95% CI, 6.3.9.7], P < 0.001, and 2.2 years [1.9-2.5], P = 0.016). On multivariate analysis, the independent factors for overall survival in the EV group were indocyanine green clearance rate at 15 minutes, des-gamma carboxyprothrombin, and the presence of multiple tumors. Considering that liver resection for patients with EV can be safely performed, it should not be contraindicated. However, surgical outcomes of these patients were unsatisfactory, suggesting that candidates for resection for HCC should be carefully selected.

There is no literature that mainly searched for rectal neuroendocrine tumor (rNET) using transanal minimal invasive surgery (TAMIS). We report our clinical experiences of TAMIS for rectal neuroendocrine tumors to evaluate the feasibility and safety. Between December 2010 and March 2020, the 25 consecutive patients with rectal neoplasma underwent the TAMIS procedure performed by single laparoscopic surgeon at the two hospitals. Of these, ten patients with rectal neuroendocrine tumors were reviewed retrospectively. The full-thickness excision down to the outer fatty tissues was completed using TAMIS technique. Clinicopathological findings, perioperative and postoperative complications were recorded. TAMIS for small rNET was successfully completed in all cases. There were seven cases with a tumor size of less than 10 mm, and three cases with a tumor size between 10 and 15 mm. Six patients underwent the primary tumor excision; the remaining four patients underwent resection for the scar after endoscopic procedure. The median surgical duration was 80.5 (53–124) minutes and the median blood loss was 1 (1–12) ml. All removed tumors in the 6 primary excisions were diagnosed as neuroendocrine tumor G1. The margins of specimens were completely free in all cases. Among the four patients after endoscopic procedure, all had no histological evidence of residual tumor. The median length of hospital stay was 7 days postoperatively. There was no post-operative mortality or severe complication. The median length of observation was 54 months. No recurrence, no local or distant metastasis and no mortality of all patients were observed. TAMIS is safety and feasible procedure for small rNET. Further experience and clinical trials are needed to fully define the advantages, disadvantages, and indications of TAMIS for rNET.

Background Surgical indications for liver metastases from pancreatic ductal adenocarcinoma (PDAC) are lacking because outcomes are usually poor. However, liver resection and the recent progress in perioperative chemotherapy have been observed to improve survival. Methods We performed liver resection for liver metastases from PDAC only under the following criteria: (1) liver-only metastasis, (2) up to three tumors, and (3) no increase in the number of metastases during the 3-month observation period. No limitations were placed on the location or size of liver metastasis. In this study, we aimed to validate our surgical criteria and analyze factors affecting survival in patients with PDAC. Results Seventy-nine patients underwent curative resection for PDAC between 2005 and 2015. Seventy-one patients experienced recurrence, with liver-only recurrence in 17 patients. Among these, nine patients underwent liver resection and eight did not. The median survival time was significantly better for patients who underwent liver resection (55 months) than for those with other recurrences (17.5 months, p = 0.016). The median survival after liver recurrence was significantly better in the liver resection group (31 months) than in the non-liver resection group (7 months, p = 0.0008). The median disease-free interval (DFI) after pancreatectomy was significantly longer in the liver resection group (21 months; range, 3–44 months) than in the non-liver resection group (3 months; range, 2–7 months; p = 0.02). Conclusion Good indications for liver metastases from PDAC include solitary metachronous tumors and longer DFIs.

Blood loss is associated with the degree of damage in liver stiffness. Severe liver steatosis is a matter of concern in liver surgery, but does not correlate with liver stiffness. This study aimed to assess the relationship between blood perfusion of the liver and blood loss in liver pathologies. Data from elective liver resection for liver cancer were analyzed. All patients underwent preoperative assessments including perfusion CT. Patients were divided into 4 groups in accordance with the pathological background of liver parenchyma. Relationships between portal flow as assessed by perfusion CT and perioperative variables were compared. Factors correlating with blood loss were analyzed. In 166 patients, portal flow from perfusion CT correlated positively with platelet count and negatively with indocyanine green retention rate at 15 min. Background liver pathology was normal liver (NL) in 43 cases, chronic hepatitis (CH) in 56, liver cirrhosis (LC) in 42, and liver steatosis (LS) in 25. Rates of hepatitis viral infection and pathological hepatocellular carcinoma were more frequent in LC and CH groups than in the other groups (p < 0.05). LC and LS showed significantly worse liver function than the NL and CH groups. Portal flow from perfusion CT correlated positively with damage to liver parenchyma and negatively with blood loss at liver transection. Low portal flow on perfusion CT predicts blood loss during liver transection.