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Background: Although liver resection is the only potentially curative treatment for colorectal liver metastases, recurrence is frequent. We previously published the early results of a randomized controlled phase 3 trial showing that adjuvant therapy with uracil-tegafur and leucovorin significantly prolongs recurrence-free survival. This study sought to elucidate the impact of adjuvant chemotherapy on patient survival after an additional follow-up period, building upon the results of our previous study., Methods: After resection for colorectal liver metastases, patients were randomly assigned in a 1:1 ratio to receive adjuvant uracil-tegafur and leucovorin or surgery alone. Patients assigned to the uracil-tegafur and leucovorin group received 5 cycles of uracil-tegafur and leucovorin within 8 weeks after surgery., Results: Patients were assigned to an adjuvant uracil-tegafur and leucovorin (n = 90) or a surgery alone (n = 90) group; 3 patients were excluded because of protocol violations. After a median follow-up period of 7.36 years (95% confidence interval, 6.93-7.87), 60 (68.2%) patients in the uracil-tegafur and leucovorin group and 61 (68.5%) patients in the surgery alone group developed recurrences. The median recurrence-free survival was 1.45 years (95% confidence interval, 0.96-2.16) in the uracil-tegafur and leucovorin group and 0.70 years (95% confidence interval, 0.44-1.07) in the surgery alone group. The locations and treatments of the first recurrences did not differ between the groups, nor did the overall survival (hazard ratio, 0.86; 95% confidence interval, 0.54-1.38; P = .54). The overall survival was significantly longer in patients who underwent curative repeated resection than in patients who received non-surgical treatment (hazard ratio, 0.25; 95% confidence interval, 0.15-0.40; P < .0001)., Conclusion: Adjuvant uracil-tegafur and leucovorin significantly prolonged the recurrence-free survival but not the overall survival. The repeated resection was the most important factor influencing overall survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Liver stiffness measurement using magnetic resonance elastography can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection for hepatocellular carcinoma. The aim of this prospective study was to investigate whether preoperative liver stiffness measurement by magnetic resonance elastograhy can predict recurrence after curative resection for hepatocellular carcinoma., Methods: Patients who underwent preoperative liver stiffness measurement and curative resection for hepatocellular carcinoma were enrolled in this study. Potential associations between liver stiffness measurement, along with other clinical and pathologic variables, and intrahepatic hepatocellular carcinoma recurrence were analyzed., Results: In total, 156 patients were included in this study. During a median follow-up period of 25.1 months (range, 6.0-60.5 months), 72 (46.1%) patients with hepatocellular carcinoma had an intrahepatic recurrence. The median disease-free period after resection was 17.9 months (range, 1.0-60.5 months). In the multivariate analysis, liver stiffness measurement (hazard ratio, 1.27; 95% confidence interval, 1.11-1.43; P <.001) and vascular invasion (hazard ratio, 1.96; 95% confidence interval, 1.15-3.25; P = .013) were identified as independent predictors of recurrence. When the optimal cutoff point was set at 4.53 kPa using the minimal P value approach, the disease-free period after curative resection in 71 patients with a liver stiffness measurement value ≥4.53 kPa (11.3 months [range, 2.0-60.5 months]) was significantly shorter than that of 85 patients with a liver stiffness measurement value <4.53 kPa (22.5 months [range, 1.1-60.5 months]; P <.001)., Conclusion: Liver stiffness measurement using magnetic resonance elastography is a useful preoperative predictor of intrahepatic recurrence after curative resection for hepatocellular carcinoma., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To propose an algorithm for resecting hepatocellular carcinoma (HCC) in the caudate lobe., Background: Owing to a deep location, resection of HCC originating in the caudate lobe is challenging, but a plausible guideline enabling safe, curable resection remains unknown., Methods: We developed an algorithm based on sublocation or size of the tumor and liver function to guide the optimal procedure for resecting HCC in the caudate lobe, consisting of 3 portions (Spiegel, process, and caval). Partial resection was prioritized to remove Spiegel or process HCC, while total resection was aimed to remove caval HCC depending on liver function., Results: According to the algorithm, we performed total (n = 43) or partial (n = 158) resections of the caudate lobe for HCC in 174 of 201 patients (compliance rate, 86.6%), with a median blood loss of 400 (10-4530) mL. Postoperative morbidity (Clavien grade ≥III b) and mortality rates were 3.0% and 0%, respectively. After a median follow-up of 2.6 years (range, 0.5-14.3), the 5-year overall and recurrence-free survival rates were 57.3% and 15.3%, respectively. Total and partial resection showed no significant difference in overall survival (71.2% vs 54.0% at 5 yr; P = 0.213), but a significant factor in survival was surgical margin (58.0% vs 45.6%, P = 0.034). The major determinant for survival was vascular invasion (hazard ratio 1.7, 95% CI 1.0-3.1, P = 0.026)., Conclusions: Our algorithm-oriented strategy is appropriate for the resection of HCC originating in the caudate lobe because of the acceptable surgical safety and curability., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The surgical indications for liver metastasis from bile duct cancer remain contentious, because surgery is generally thought unlikely to improve survival. However, recent reports show that long-term survival has been achieved with liver resection of metastasis from recurrent bile duct cancer in selected patients., Methods: Liver resection for liver metastasis from bile duct cancer was proposed only when the following criteria were met: liver-only metastasis, a solitary tumor, and no increase in the number of lesions during 3 months of observation. This study aimed to validate our criteria and to analyze which factors impact on survival., Result: Between 2003 and 2017, 164 patients underwent pathologically curative resection for bile duct cancer. Recurrence developed in 98 of these patients, as liver-only metastasis in 25. Eleven of these 25 patients underwent liver resection (liver resection group), and 14 did not (non-liver resection group). The median overall survival was longer in the liver resection group than in all the patients (44 months vs. 17.8 months, respectively p = 0.040). The median overall survival was better in the liver resection group than in the non-liver resection group (44 months vs. 19.9 months, p = 0.012). The disease-free interval was also significantly longer in the liver resection group than in the non-liver resection group [22 months (range; 4-34 months) vs. 3 months (2-11), p < 0.001]., Conclusion: Potentially, metachronous solitary liver metastasis from bile duct cancer is an indication for liver resection when the patient has had a long disease-free interval. Observation for 3 months from first detection of metastasis may optimize the selection for this surgery.

Background: Non-curative (debulking) hepatic resection for hepatocellular carcinoma (HCC) is occasionally applied for selected cases with bulky tumors or for oncologic emergency cases; however, the clinical usefulness of this procedure has not yet been fully evaluated. The aim of the present study was to evaluate the patient outcomes of non-curative hepatic resections for HCC using data from bi-annual nationwide surveys conducted in Japan., Method: Data of 1084 non-curative hepatic resections for HCC were collected. The patient outcomes were compared with those of curative resections, transcatheter arterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy (HAIC)., Results: Patient survival after the non-curative resection was poorer than that after curative resection (P < 0.001) and was especially dismal in cases with extrahepatic tumor spread (lymph node metastasis, peritoneal seeding, or distant metastasis). As compared to cases receiving TACE without surgery, non-curative resections for multiple intrahepatic tumors were applied to cases with advanced tumors with good liver functional reserve. The survival outcomes were significantly more favorable in the TACE group, but the results became similar after propensity score matching of the patients. The survival outcome of patients receiving non-curative resections was better than that of cases treated by HAIC, with median survival times of 26.0 months and 10.0 months, respectively., Conclusion: The indications for non-curative hepatic resection in patients with HCC should be judged cautiously, especially in patients with extrahepatic tumor spread. This treatment approach may be beneficial for selected patients with intermediate- or advanced-stage HCC limited in liver and with good liver functional reserve.

Background: Subcuticular sutures reduce wound complication rates only in clean surgeries. Repeat resection is frequently required in liver surgery, due to the high recurrence rate (30-50%) of liver cancers. The aim of this study is to assess that subcuticular sutures is superior to staples in liver surgery., Methods: This single-centre, single-blinded, randomised controlled trial was conducted at a university hospital between January 2015 and October 2018. Patients were randomly assigned (1:1) to receive either subcuticular sutures or staples for skin closure. Three risk factors (repeat resection, diabetes mellitus and liver function) were matched preoperatively for equal allocation. The primary endpoint was the wound complication rate, while secondary endpoints were surgical site infection (SSI), duration of postoperative hospitalisation and total medical cost. Subset analyses were performed only for the 3 factors allocated as secondary endpoints., Results: Of the 581 enrolled patients, 281 patients with subcuticular sutures and 283 patients with staples were analysed. As the primary outcome, the wound complication rate with subcuticular sutures (12.5%) did not differ from that with staples [15.9%; odds ratio (OR), 1.33; 95% confidence interval (CI), 0.83-2.15; p = 0.241]. As secondary outcomes, no significant differences were identified between the two procedures in the overall cohort while overall wound complications [7 patients (8.5%) vs. 17 patients (20.0%); OR, 2.68; 95% CI, 1.08-7.29; p = 0.035] with repeat incision were significantly less frequent with subcuticular sutures., Conclusion: Subcuticular sutures were not shown to reduce wound complications compared to staples in open liver resection, but appear beneficial for repeat incisions.

Liver cancer frequently requires repeated liver resections due to the high recurrence rate. The aim of this study was to clarify whether subcuticular sutures reduce wound complication rates following repeat incisions. Data from 382 repeated liver resections in 1,245 consecutive patients were assessed. Patients were divided into a Subcuticular sutures group and a Skin staples group on the basis of the wound-closure method. To avoid bias in analysing wound complications, data were matched to adjust for patient background and operation variables. After matching, 82 matched, paired patients with subcuticular sutures or skin staples were compared. Total wound complication rate was significantly lower with subcuticular sutures than with skin staples (8.5% vs. 20.7%, p = 0.027). Incisional surgical site infection was also lower with subcuticular sutures than with skin staples (6.1% vs. 17.1, p = 0.028). Univariate analysis revealed 4 factors associated with wound complications: body mass index; serum albumin concentration; wound length; and closure with skin staples. Multivariate analysis revealed closure with skin staples (odds ratio, 2.91; 95% confidence interval, 1.07-7.94; p = 0.037) as the only independent factor negatively associated with wound complications. Subcuticular sutures appear to reduce wound complications compared to skin staples following repeat incision for liver resection.

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.

Multiplicity is one of the characteristics of hepatocellular carcinoma (HCC), and patients with multiple HCC (≤ 3 nodules) are recommended as candidates for liver resection. To confirm the validity of resecting multiple HCC, we compared the surgical outcomes in patients with synchronous and metachronous multiple HCC. Patients who underwent resection for multiple HCC (2 or 3 nodules) were classified into the "synchronous multiple HCC" group, while those undergoing resection for solitary HCC and repeated resection for 1 or 2 recurrent nodules within 2 years after initial operation were classified into the "metachronous multiple HCC" group. After one-to-one matching, longer operation time and more bleeding were seen in the synchronous multiple HCC group (n = 98) than those in the metachronous multiple HCC group (n = 98); however, the complication rates were not different between the two groups. The median overall survival times were 4.0 years (95% CI, 3.0-5.9) and 5.9 years (4.0-NA) for the synchronous and metachronous multiple HCC (after second operation) groups, respectively (P = 0.041). The recurrence-free survival times were shorter in the synchronous multiple HCC group than in the metachronous multiple HCC group (median, 1.5 years [95% CI, 0.9-1.8] versus 1.8 years, [1.3-2.2]) (P = 0.039). On multivariate analysis, independent factors for overall survivals in the synchronous multiple HCC group were older age, cirrhosis, larger tumor, and tumor thrombus. Taken together, resection of metachronous multiple HCC still has good therapeutic effect, even better than synchronous multiple HCC, so resection is suggested for metachronous multiple HCC.

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.

Purpose: The surgical margin for liver resection to treat hepatocellular carcinoma (HCC) is occasionally < 1 mm. This study determined the impact of a surgical margin < 1 mm [marginal resection (MR)] on the types of recurrence and the prognosis in solitary HCC., Methods: The data of 454 patients undergoing curative liver resection for solitary HCC in our institution were analyzed. The patients were divided into the MR (n = 90) and non-MR (n = 364) groups. The clinicopathological data and outcomes after liver resection were compared. A case-matching analysis using a propensity scoring method was also performed., Results: The recurrence-free survival was significantly and overall survival was marginally significantly lower in the MR group than in the non-MR group (p = 0.012-0.051, respectively). According to a multivariate analysis, MR was not a significant independent factor for recurrence-free survival (p = 0.056). After propensity score matching, there were no significant differences in the recurrence-free and overall survival between the two groups (p = 0.375-0.496, respectively). Furthermore, there were no significant differences in the intrahepatic recurrence patterns between the two groups before and after matching., Conclusion: MR for solitary HCC might be sufficient in patients with a limited liver functional reserve.

Introduction: Lenvatinib (LEN) is a novel potent multi-tyrosine kinase inhibitor, approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Considering its high objective response rate, LEN therapy could be expected to achieve downstaging of tumors and lead to conversion therapy with hepatectomy or ablation. However, the feasibility of conversion therapy after LEN treatment in unresectable HCC remains largely unknown., Patient Concerns: Here, we reported 3 cases of unresectable HCC: case 1, a 69-year-old man diagnosed with ruptured HCC; case 2, a 72-year-old woman with nonalcoholic steatohepatitis-based HCC; and case 3, a 73-year-old man with a history of alcoholic cirrhosis-based HCC., Diagnosis: In all cases, cirrhosis was classified as Child-Pugh 5 and modified albumin-bilirubin grade 1 or 2a. HCC was diagnosed as Barcelona Clinic Liver Cancer (BCLC) stage B., Interventions: In all cases, LEN was initiated after conventional-transcatheter arterial embolization enforcement, while maintaining liver function., Outcomes: In all cases, the main tumor size decreased after 6 months of LEN treatment and no satellite nodes were detected, indicating downstaging of HCC to BCLC stage A. Subsequently, conversion hepatectomy or ablation was performed. After successful conversion therapy, the general condition of the patients was good, without tumor recurrence during the observation period (median 10 months)., Lessons: This study demonstrated that LEN enables downstaging of HCC and thus represents a bridge to successful surgery or ablation therapy. In particular, LEN treatment may facilitate the possibility for conversion therapy of initially unresectable HCC, while maintaining the hepatic functional reserve.

Objective: The aim of the study was to evaluate the survival benefits of liver resection (LR) compared with transarterial chemoembolization (TACE) for patients with multiple hepatocellular carcinomas (HCCs)., Background: Despite significant improvements in diagnostic imaging and the widespread application of screening programs, some patients with HCC continue to present with multiple tumors. The surgical indications for multiple HCCs remain controversial., Methods: Among 77,268 patients with HCC reported in a Japanese nationwide survey, 27,164 patients had multiple HCCs. The exclusion criteria were Child-Pugh B/C, treatment other than LR and TACE, >3 tumors, and insufficient available data. Ultimately, 3246 patients (LR: n = 1944, TACE: n = 1302) were included. The survival benefit of LR for patients multiple HCCs was evaluated by using propensity score matching analysis., Results: The study group of 2178 patients (LR: n = 1089, TACE: n = 1089) seemed to be well matched. The overall survival rate in the LR group was 60.0% at 5 years, which was higher than that in the TACE group (41.6%, P < 0.001). Among patients with a tumor size of 30 mm or more, LR showed a survival benefit over TACE at 5 years (53.0% vs 32.7%, P < 0.001). The multivariate analysis indicated that age, serum albumin level, serum alpha-fetoprotein (AFP) level, macrovascular invasion, tumor size, and TACE were independent predictors of poor prognosis in multiple HCCs., Conclusions: LR could offer better long-term survival than TACE for patients with multiple HCCs (up to 3 tumors). If patients have good liver function (Child-Pugh A), LR is recommended, even for those with multiple HCCs with tumor sizes of 30 mm or more.

Background: Despite curative resection, hepatocellular carcinoma (HCC) has a high probability of recurrence. We validated the potential role of liver resection (LR) for recurrent HCC., Methods: Patients with intrahepatic recurrence with up to three lesions were included. We compared survival times of patients undergoing their first LR to those of patients undergoing repeated LR. Then, survival times of the patients who had undergone LR and transcatheter chemoembolization (TACE) for recurrent HCC after propensity score matching were compared., Results: After a median follow-up period of 3.1 years (range, 0.2-16.3), median overall survival times were 6.5 years (95% CI 6.0-7.0), 5.7 years (5.2-6.2), and 5.1 years (4.9-7.3) for the first LR (n = 1234), second LR (n = 273), and third LR (n = 90) groups, respectively. Severe complications frequently occurred in the first LR group (p = 0.059). Operative times were significantly longer for the third LR group (p = 0.012). After the first recurrence, median survival times after one-to-one pair matching were 5.7 years (95% CI 4.5-6.5) and 3.1 years (2.1-3.8) for the second LR group (n = 146) and TACE group (n = 146), respectively (p < 0.001). The median survival time of the third LR group (n = 41) (6.2 years; 95% CI 3.7-NA) was also longer than that of TACE group (n = 41) (3.4 years; 1.8-4.5; p = 0.010) after the second recurrence., Conclusions: Repeated LR for recurrent HCC is the procedure of choice if there are three or fewer tumors.

Background: Prior hepatitis B virus infection (PBI) may increase the risk of developing hepatocellular carcinoma (HCC), but the impact of PBI on clinical outcomes following treatment for HCC remains unknown. The aim of this study was to clarify whether PBI affects clinical outcomes after liver resection for hepatitis C virus (HCV)-related HCC by retrospective cohort study., Methods: PBI patients were defined as those negative for hepatitis B surface antigen and positive for anti-hepatitis B core antibody. Surgical outcomes of HCV-related HCC patients with PBI were compared to those without PBI. Survival of patients with non-B non-C HCC with and without PBI were also compared., Results: In the HCV group, the median overall survival of 165 patients with PBI was 4.7 years (95% confidence interval [CI], 3.9-5.9), and was significantly shorter compared with 263 patients without PBI (6.6 years [5.3-9.8]; p = 0.015). Conversely, there was no significant difference in recurrence-free survival between the two groups (1.8 years [95% CI, 1.4-2.0] vs 2.0 years [1.7-2.3]; p = 0.205). On Cox proportional hazards regression model, independent factors for overall survival were PBI (hazard ratio 1.38 [95% CI, 1.02-1.87]; p = 0.033), multiple tumors (p = 0.007), tumor size (p = 0.002), and liver cirrhosis (p <  0.001). On the other hand, in the non-B non-C HCC group, both the median overall survival (6.5 years [95% CI, 4.8-7.1]) and recurrence-free survival (2.4 years, [95% CI, 1.5-3.3]) in 104 patients with PBI were not significantly different from those (7.5 years [5.5 - NA; p = 0.932]; and 2.2 years [1.7-2.7; p = 0.983]) in 213 patients without PBI., Conclusions: PBI and HCV in conjunction with each other affect the survival of patients that have undergone resection for HCC.

Objective: We reviewed nationwide follow-up data to determine outcomes of different treatments for early-stage hepatocellular carcinoma (HCC) in elderly patients., Summary Background Data: Outcomes of early-stage HCC treatments in elderly patients have not been prospectively compared., Methods: We included 6490 HCC patients, aged ≥75 years at treatment, who underwent curative hepatic resection (HR, n = 2020), radiofrequency ablation (RFA, n = 1888), microwave ablation (MWA, n = 193), or transcatheter arterial chemoembolization (TACE, n = 2389), and compared their characteristics and survival. We used matching propensity score analysis (PSA) between the HR and RFA subgroups with tumors ≤3 cm to overcome baseline bias., Results: The HR group had significantly longer recurrence-free survival (RFS) than the RFA, MWA, and TACE groups [RFA vs HR-hazard ratio: 1.22, 95% confidence interval (CI): 1.09-1.37, P < 0.001; MWA vs HR-hazard ratio: 1.51, 95% CI: 1.22-1.88, P < 0.001; TACE vs HR-hazard ratio: 2.70, 95% CI: 2.44-2.99, P < 0.001). HR and RFA patients had significantly longer overall survival (OS) than the TACE group (RFA vs HR-hazard ratio: 1.01, 95% CI: 0.87-1.17, P = 0.919, TACE vs HR-hazard ratio: 2.11, 95% CI: 1.86-2.40, P < 0.001). PSA successfully matched HR and RFA patients from with primary HCC tumors ≤3.0 cm and similar liver function and tumor characteristics; and showed significantly longer RFS (hazard ratio: 1.64, 95% CI: 1.29-2.10, P < 0.001) and OS (hazard ratio: 1.57, 95% CI: 1.12-2.20, P = 0.009) for HR than for RFA (including subgroup analyses). In Cox proportional hazard analysis, HR offered better prognosis than RFA., Conclusions: HR decreases recurrence risk and improves OS in patients aged ≥75 years with primary HCC tumors ≤3.0 cm.

Objective: The impact of age on survival after hepatic resection for hepatocellular carcinoma (HCC) has not been thoroughly examined. We reviewed the data of a nationwide follow-up survey to determine the outcomes of hepatectomy for HCC in elderly patients., Background: Management of malignant diseases in elderly patients has become a global clinical issue because of the increased life expectancy worldwide. Advancements in surgical techniques and perioperative management have reduced age-related contraindications for liver surgery., Methods: In all, 12,587 patients with HCC who underwent curative hepatic resection were included in this cohort study and classified according to age group [40-59 years (n = 2991), 60-74 years (n = 7576,), and ≥75 years (n = 2020)]. Clinicopathological features, long-term survival, and cumulative incidences of death after hepatic resection were compared among the groups. The cause-specific subdistribution hazard ratios for 3 types of death depending on age were also estimated., Results: Preoperative liver function tests showed that the prothrombin activity and platelet count were higher in the ≥75-year age group than in the other age groups. The overall survival was significantly lower in the elderly than younger patients. However, recurrence-free survival was almost identical among the 3 groups. The cumulative incidence of HCC-related or liver-related death was almost identical among the 3 groups; however, the cumulative incidence of other causes of death was significantly different. The 60-year subdistribution hazard ratio for other causes of death increased remarkably with increasing age., Conclusions: Elderly patients in this nationwide survey had significantly worse overall survival after hepatectomy than middle-aged and young patients. The cumulative incidence of other causes of death in elderly patients was significantly different from that of HCC-related or liver-related death among the 3 groups.

Background: Despite curative resection of hepatocellular carcinoma, patients have a high probability of recurrence. We examined indications for liver resection in cases of recurrent hepatocellular carcinoma., Methods: Patients undergoing a second liver resection (n=210) or treatment by transcatheter arterial chemoembolization (n=184) for recurrent hepatocellular carcinoma of up to 3 lesions were included. We developed a prediction score based on prognostic factors and compared survival according to this prediction score., Results: The prediction score was based on 3 independent variables identified by survival analysis in 210 patients undergoing a second liver resection and included age ≥ 75 years, tumor size ≥ 3.0 cm, and multiple tumors. Each patient was assigned a total score. Median overall survival in patients undergoing a second liver resection with scores of 0, 1, and 2/3 were 7.9 years (95% confidence interval, 5.6-NA), 4.5 years (3.8-6.2), and 2.6 years (2.1-5.3), respectively (P < 0.001). Among patients with a score of 0, the survival in patients undergoing liver resection was greater than survival in those undergoing transcatheter arterial chemoembolization (median 7.9 [95% confidence interval, 5.6-NA] years versus 3.1 [2.1-3.7] years, P < 0.001), and resection was an independent factor for survival. In contrast, survival did not differ in patients with scores 2/3 (2.6 years [95% confidence interval, 1.9-5.3] versus 2.3 years [1.6-2.8], P = 0.176)., Conclusion: Liver resection is recommended as first-line therapy for recurrent hepatocellular carcinoma in patients with a score of 0, while those with score 2/3 should be considered candidates for transcatheter arterial chemoembolization., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Resection of hepatocellular carcinoma located in the caudate lobe is challenging because this anatomical location is difficult to approach, especially the caval portion., Methods: We performed resection of the caval portion of the caudate lobe using a ventral approach combined with the resection of segment IV, VII, or VIII for hepatocellular carcinoma in 41 patients (extended segmentectomy group). As a control group, 138 patients with hepatocellular carcinoma who underwent segmentectomy for IV, VII, or VIII (segmentectomy group) were studied. We compared surgical outcomes, including postoperative morbidity and survival, between the 2 groups., Results: When compared with the segmentectomy group, platelet count was lower (12.8 × 10 4 /µL [range, 2.4-33.8] vs 14.8 × 10 4 /µL [3.2-41.4], P = .085), operation time was significantly longer (442 minutes [range, 184-710] vs 333 minutes [131-810], P < .001), blood loss was significantly greater (579 mL [range, 25-2688] vs 301 mL [10-3887], P = .001), and the percentage of patients with cirrhosis was greater (19 [46.3%] vs 41 [29.7%], P = .059) in the extended segmentectomy group. However, the morbidity rate (48.7% and 33.3%, P = .096) and median overall survival period (5.2 years; [95% confidence interval, 4.6-6.6] vs 6.2 years, [5.4-9.7], P = .203) were not significantly different between the 2 groups., Conclusion: The ventral approach for the resection of hepatocellular carcinoma in the caval portion of the caudate lobe is a viable alternative to other approaches, especially in patients with insufficient liver function., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Aims: Small hypovascular hepatocellular carcinoma (HCC) ≤2 cm is biologically less aggressive than hypervascular one, however, the optimal treatment is still undetermined. The efficacy of surgical resection (SR), radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) was evaluated., Methods: The 853 (SR, 176; RFA, 491; PEI, 186) patients were enrolled who met Child-Pugh A/B, single hypovascular HCC ≤2 cm pathologically proven, available tumour differentiation and absence of macrovascular invasion and extrahepatic metastasis. Overall and recurrence-free survivals were compared in original and a propensity score weighted pseudo-population with 732 patients., Results: The median follow-up time and tumour size were 2.8 years and 1.47 cm respectively. In original population, multivariate Cox regression showed no significant difference for overall survival among three groups. In pseudo-population, Cox regression also revealed no significant difference for overall survival among them, although SR (HR, 0.56; 95% CI, 0.36-0.86) and RFA (HR, 0.75; 95% CI, 0.57-1.00) groups had significantly lower recurrence than PEI group. The overall survival rates at 3 and 5 years for the SR, RFA and PEI groups were 94%/70%, 90%/75% and 94%/73% respectively. Corresponding recurrence-free survival rates were 64%/54%, 59%/41% 48%/33% respectively. Subgroup analysis revealed no significant survival benefit of SR compared with non-SR. No treatment-related death occurred., Conclusions: For patients with single hypovascular HCC ≤2 cm, no significant difference for overall survival was first identified among 3 treatment groups. The SR or RFA could be recommended, and PEI would be alternative to RFA., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To clarify whether high transient elevation of serum transaminase predicts severe complications and is related to the ischemic area on CT. Postoperative laboratory data and ischemia area on CT were analyzed on the basis of the presence of high transaminase elevation (aspartate aminotransferase (AST) > 1,000 IU/L within postoperative day (POD) 2 after liver resection. In the high elevation group, volume of ischemic areas was assessed by CT on POD2. The 538 patients were divided into a high transaminase group (n = 51) and a control group (n = 487). Median operation time (527 min vs. 360 min, p < 0.01) and liver ischemia time (121 min vs. 70 min, p < 0.01) were significantly longer, and intraoperative blood loss (478 mL [85-1572 mL] vs. 269 mL [5-4491 mL], p < 0.01) was significantly greater in the high transaminase group. No significant differences observed in frequency of severe complications (Clavien-Dindo classification Grade III or more) or postoperative hospitalization. Operation time (> 500 min; odds ratio (OR), 4.86; 95% confidence interval (CI), 2.40-9.89; p < 0.01) and liver ischemia time (> 120 min; OR, 3.47; 95%CI, 1.67-7.17; p < 0.01) were independent predictors of high transaminase elevation. No relationship was observed between degree of transaminase elevation and ischemic area (correlation coefficients: AST, R 2 < 0.001; alanine aminotransferase, R 2 = 0.005) CT volumetry on POD2. In conclusions, high transaminase elevations do not predict severe complications or reflect remnant ischemic area.

Major portal vein invasion (MVI) by hepatocellular carcinoma (HCC) carries an extremely poor prognosis. Our aim was to clarify the indications of hepatic resection in the presence of MVI by HCC. Between 2001 and 2015, 1,306 patients undergoing primary treatment for HCC were analyzed (866 hepatic resections and 440 transarterial therapies). Significant prognostic factors were identified by retrospectively analyzing tumor status, liver function and treatment. Overall survival was compared in terms of the degree of vascular invasion and treatment. The 5-year survival rates according to the degree of vascular invasion (Vp) were Vp0: 51.9%, Vp1: 33.0%, Vp2: 16.7%, Vp3: 21.8%, and Vp4: 0%, respectively. Overall survival (OS) did not differ significantly between patients with Vp3 and Vp4 MVI (p = 0.153). Median survival following hepatic resection of Vp3 cases was significantly better than that for Vp4 cases (1,913 vs. 258 days, p = 0.014), while OS following transarterial therapy was not significantly different (164 vs. 254 days in Vp3 vs. Vp4, p = 0.137). Multivariate analysis revealed hepatic resection (Odds: 2.335 [95%CI: 1.236-4.718], p = 0.008) and multiple tumors (1.698 [1.029-2.826], p = 0.038) as independent predictors of survival. Hepatic resection in HCC patients with MVI should be indicate in patients with Vp3 invasion.

The precise assessment of both tumor factor and the liver function is of a crucial value the surgical treatment with the greatest guarantee of hepatocellular carcinoma (HCC), as the balance between the operative procedure and the remnant liver function is the most important concern in patients with chronic liver disease. The mortality rate in liver resection has decreased significantly worldwide, according to various surgical criteria for liver resection. Among countries where HCC is prevalent Japan is a leading country in doing liver resection. The Japanese evidence-based guidelines for the surgical treatment for HCC were generated in 2005, and the third revised version is now available. A strict evaluation policy for surgical indications and management based on such evidence helps to minimize the mortality rate in these patients. Herein, we report a series of unique approaches to the perioperative management of liver resection based on the available evidence with the goal of achieving 'no mortality' in liver resection for HCC., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Because of the rarity of hepatic vein tumor thrombus (HVTT) compared with portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma, little is known about this disease entity. The aim of this study was to evaluate the prognosis of each treatment modality for HVTT through an analysis of data collected in a Japanese nationwide survey. We analyzed data for 1,021 Child-Pugh A hepatocellular carcinoma patients with HVTT without inferior vena cava invasion registered between 2000 and 2007. Of these patients, 540 who underwent liver resection (LR) and 481 who received other treatments were compared. Propensity scores were calculated, and we successfully matched 223 patients (49.0% of the LR group). The median survival time in the LR group was 2.89 years longer than that in the non-LR group (4.47 versus 1.58 years, P < 0.001) and 1.61 years longer than that in the non-LR group (3.42 versus 1.81 years, P = 0.023) in a propensity score-matched cohort. After curative resection, median survival times were similar between patients with HVTT in the peripheral hepatic vein and those with HVTT in the major hepatic vein (4.85 versus 4.67 years, P = 0.974). In the LR group, the postoperative 90-day mortality rate was 3.4% (16 patients). In patients without PVTT, the median survival time was significantly better than that in patients with PVTT (5.67 versus 1.88 years, P < 0.001)., Conclusion: LR is associated with a good prognosis in hepatocellular carcinoma patients with HVTT, especially in patients without PVTT. (Hepatology 2017;66:510-517)., (© 2017 by the American Association for the Study of Liver Diseases.)

Background: Cirrhosis is associated with blood loss during liver resection and postoperative complications. The liver stiffness measurement has recently become available for assessment of liver fibrosis., Methods: This prospective study was performed to predict postoperative outcomes of liver resection. The liver stiffness measurement was measured prospectively using magnetic resonance elastography for patients who had undergone liver resection for malignancy. We investigated whether the liver stiffness measurement by magnetic resonance elastography is correlated with liver fibrosis and postoperative outcomes., Results: The median liver stiffness measurement by magnetic resonance elastography in 175 patients was 3.4 (range: 1.5-11.3) kPa, and the pathologic grade of liver fibrosis was significantly correlated with the liver stiffness measurement (r = 0.68, P < .001). The median blood loss during transection per unit area was 4.1 mL/cm 2 (range: 0.1-37.0 mL/cm 2 ), and the frequency of major complications was 16.0%. The liver stiffness measurement was the only independent prognostic factor for both blood loss (regression coefficient: 1.14, 95% confidence interval: 0.45-1.83, P = .001) and major complications (odds ratio: 2.14, 95% confidence interval: 1.63-2.93, P < .001). Receiver operating characteristic curve analysis indicated a significant correlation between the liver stiffness measurement and major complications with calculated area under the curve of 0.81 (P < .001), and the sensitivity and specificity for prediction of major complications (cutoff value: 5.3 kPa) were 64.3% and 87.8%, respectively. On the other hand, the amount of blood loss was significantly correlated with the frequency of major complications (P = .003)., Conclusion: The liver stiffness measurement by magnetic resonance elastography could be used as a predictive marker for the risk of major complications due to blood loss during liver resection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Previous RCTs have failed to demonstrate the usefulness of combining energy devices with the conventional clamp crushing method to reduce blood loss during liver transection. Here, the combination of an ultrasonically activated device (UAD) and a bipolar vessel-sealing device (BVSD) with crush clamping was investigated., Methods: Patients scheduled to undergo hepatectomy at the University of Tokyo Hospital or Nihon University Itabashi Hospital were eligible for this parallel-group, single-blinded randomized study. Patients were assigned to a control group (no energy device used), an UAD group or a BVSD group. The primary endpoint was the volume of blood loss during liver transection. Outcomes of the control group and the combined energy device groups (UAD plus BVSD) were first compared. Pairwise comparisons among the three groups were made for outcomes for which the combined energy device group was superior to the control group., Results: A total of 380 patients were enrolled between July 2012 and May 2014; 116 patients in the control group, 122 in the UAD group and 123 in the BVSD group were included in the final analysis. Median blood loss during liver transection was lower in the combined energy device group (245 patients) than in the control group (116 patients): median 190 (range 0-3575) versus 230 (range 3-1570) ml (P = 0·048). Pairwise comparison revealed that blood loss was lower in the BVSD group than in the control group (P = 0·043)., Conclusion: The use of energy devices combined with crush clamping reduced blood loss during liver transection. Registration number: C000008372 (www.umin.ac.jp/ctr/index.htm)., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: We previously established an optimal postoperative drain management rule after liver resection (i.e., drain removal on postoperative day 3 if the drain fluid bilirubin concentration is <3 mg/dl) from the results of 514 drains of 316 consecutive patients. This test set predicts that 274 of 316 patients (87.0 %) will be safely managed without adverse events when drain management is performed without deviation from the rule., Objective: To validate the feasibility of our rule in recent time period., Methods: The data from 493 drains of 274 consecutive patients were prospectively collected. Drain fluid volumes, bilirubin levels, and bacteriological cultures were measured on postoperative days (POD) 1, 3, 5, and 7. The drains were removed according to the management rule. The achievement rate of the rule, postoperative adverse events, hospital stay, medical costs, and predictive value for reoperation according to the rule were validated., Results: The rule was achieved in 255 of 274 (93.1 %) patients. The drain removal time was significantly shorter [3 days (1-30) vs. 7 (2-105), p < 0.01], drain fluid infection was less frequent [4 patients (1.5 %) vs. 58 (18.4 %), p < 0.01], postoperative hospital stay was shorter [11 days (6-73) vs. 16 (9-59), p = 0.04], and medical costs were decreased [1453 USD (968-6859) vs. 1847 (4667-9498), p < 0.01] in the validation set compared with the test set. Five patients who required reoperation were predicted by the drain-based information and treated within 2 days after operation., Conclusions: Our 3 × 3 rule is clinically feasible and allows for the early removal of the drain tube with minimum infection risk after liver resection.

Introductions: Different staging systems have been devised for patients undergoing resection for hepatocellular carcinoma (HCC) with disparate results. The aim of this study was to create a new nomogram to predict individual survival after hepatectomy for HCC., Methods: Based on the "Hepatocellular Carcinoma: Eastern & Western Experiences Network," data from 2046 patients who underwent HCC resections at ten centers were reviewed. Patient survival was analyzed with Cox-regression analysis to construct a unique nomogram and contour plots to predict survival., Results: The nomograms built on the multivariate analyses, which showed that the independent predictors were tumor size, tumor number, vascular invasion, cirrhosis, preoperative bilirubin value, and esophageal varices, showed good calibration and discriminatory abilities with C-index value of 0.62 (95 % CI, 0.59-0.69) and 0.61 (95 % CI, 0.56-0.64) for overall and disease-free survival, respectively. The 5-year survival contour plots showed that the presence of vascular invasion was associated with decreased survival, regardless of the tumor number or size. Cirrhosis and varices were equally associated with decreased survival, according to the tumor number or size., Conclusions: These nomograms accurately predict individual prognosis after HCC resection and support an expansion of the selection criteria for resection. They offer useful guidance to clinicians for individual survival prediction.

Background: In liver resection, bile leakage remains the most common cause of operative morbidity. In order to predict the risk of this complication on the basis of various factors, we developed a clinical score system to predict the potential risk of bile leakage after liver resection., Methods: We analyzed the postoperative course in 518 patients who underwent liver resection for malignancy to identify independent predictors of bile leakage, which was defined as "a drain fluid bilirubin concentration at least three times the serum bilirubin concentration on or after postoperative day 3," as proposed by the International Study Group of Liver Surgery. To confirm the robustness of the risk score system for bile leakage, we analyzed the independent series of 289 patients undergoing liver resection for malignancy., Results: Among 81 (15.6 %) patients with bile leakage, 76 had grade A bile leakage, and five had grade C leakage and underwent reoperation. The median postoperative hospital stay was significantly longer in patients with bile leakage (median, 14 days; range, 8 to 34) than in those without bile leakage (11 days; 5 to 62; P = 0.001). There was no hepatic insufficiency or in-hospital death. The risk score model was based on the four independent predictors of postoperative bile leakage: non-anatomical resection (odds ratio, 3.16; 95 % confidence interval [CI], 1.72 to 6.07; P < 0.001), indocyanine green clearance rate (2.43; 1.32 to 7.76; P = 0.004), albumin level (2.29; 1.23 to 4.22; P = 0.01), and weight of resected specimen (1.97; 1.11 to 3.51; P = 0.02). When this risk score system was used to assign patients to low-, middle-, and high-risk groups, the frequency of bile leakage in the high-risk group was 2.64 (95 % CI, 1.12 to 6.41; P = 0.04) than that in the low-risk group. Among the independent series for validation, 4 (5.7 %), 16 (10.0 %), and 10 (16.6 %) patients in low-, middle, and high-risk groups were given a diagnosis of bile leakage after operation, respectively (P = 0.144)., Conclusions: Our risk score model can be used to predict the risk of bile leakage after liver resection.

The treatment of recurrences that occur after radical resection of intractable hepatobiliary pancreatic cancers such as intrahepatic cholangiocarcinoma, pancreatic carcinoma, and biliary tract carcinoma is more difficult than the treatment of primary lesions. In our institute, chest and abdominal CT examinations after radical resection of intractable hepatobiliary pancreatic cancers are performed about 3 times a year in order to evaluate for the possible emergence of small nodules in the liver. Instead of performing hepatectomy immediately after detecting small nodules, we conduct observations essentially for 3 to 6 months. Meanwhile, if the number of metastatic lesions tends to increase and absence of spread to other organs is confirmed, we decide to perform hepatectomy. In particular, when the detected nodule is solitary and larger than 1 cm, immediate hepatectomy is considered. We present the following 4 cases of hepatectomy for liver metastases after radical resection of intractable hepatobiliary pancreatic cancers: intrahepatic cholangiocarcinoma (n=1), gallbladder carcinoma (n=1), and pancreatic carcinoma (n=2). Liver metastases were detected at 3 to 17 months after radical resection of the primary lesion. Hepatectomy for the liver metastases was performed 14 to 18 months after the primary resection. Survival after hepatectomy was 22 to 45 months. The median survival was more than 25 months. By carefully selecting the indication for surgery, good results were obtained after hepatectomy even in cases of intractable cancers.

Background: There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation., Methods: We undertook this phase 3, double-blind, placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection (n=900) or local ablation (n=214) in 202 sites (hospitals and research centres) in 28 countries. Patients were randomly assigned (1:1) to receive 400 mg oral sorafenib or placebo twice a day, for a maximum of 4 years, according to a block randomisation scheme (block size of four) using an interactive voice-response system. Patients were stratified by curative treatment, geography, Child-Pugh status, and recurrence risk. The primary outcome was recurrence-free survival assessed after database cut-off on Nov 29, 2013. We analysed efficacy in the intention-to-treat population and safety in randomly assigned patients receiving at least one study dose. The final analysis is reported. This study is registered with ClinicalTrials.gov, number NCT00692770., Findings: We screened 1602 patients between Aug 15, 2008, and Nov 17, 2010, and randomly assigned 1114 patients. Of 556 patients in the sorafenib group, 553 (>99%) received the study treatment and 471 (85%) terminated treatment. Of 558 patients in the placebo group, 554 (99%) received the study treatment and 447 (80%) terminated treatment. Median duration of treatment and mean daily dose were 12·5 months (IQR 2·6-35·8) and 577 mg per day (SD 212·8) for sorafenib, compared with 22·2 months (8·1-38·8) and 778·0 mg per day (79·8) for placebo. Dose modification was reported for 497 (89%) of 559 patients in the sorafenib group and 206 (38%) of 548 patients in the placebo group. At final analysis, 464 recurrence-free survival events had occurred (270 in the placebo group and 194 in the sorafenib group). Median follow-up for recurrence-free survival was 8·5 months (IQR 2·9-19·5) in the sorafenib group and 8·4 months (2·9-19·8) in the placebo group. We noted no difference in median recurrence-free survival between the two groups (33·3 months in the sorafenib group vs 33·7 months in the placebo group; hazard ratio [HR] 0·940; 95% CI 0·780-1·134; one-sided p=0·26). The most common grade 3 or 4 adverse events were hand-foot skin reaction (154 [28%] of 559 patients in the sorafenib group vs four [<1%] of 548 patients in the placebo group) and diarrhoea (36 [6%] vs five [<1%] in the placebo group). Sorafenib-related serious adverse events included hand-foot skin reaction (ten [2%]), abnormal hepatic function (four [<1%]), and fatigue (three [<1%]). There were four (<1%) drug-related deaths in the sorafenib group and two (<1%) in the placebo group., Interpretation: Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study aims to investigate the safety of inferior right hepatic vein (IRHV)-conserving surgery by comparing the surgical data and postoperative complications between IRHV-conserving segments 7 to 8 (S7 to S8) resection and conventional right hemihepatectomy (RH). Five patients who underwent IRHV-conserving S7 to S8 segmentectomy between 2007 and 2011 (IRHV group) and 25 liver cancer patients who underwent RH without biliary tract reconstruction during the same period (RH group) were investigated. The surgical data, postoperative complications, and duration of hospital stay were compared. The IRHV and RH groups included 2 (40%) and 13 (52%) hepatocellular carcinoma patients, respectively. There were no significant differences in liver function before surgery between the groups. The presence of the IRHV did not adversely affect the processing of the short hepatic vein or frontal dissection of the inferior vena cava. The operative time was shorter (median, 366 minutes versus 501 minutes; P = 0.0001), the postoperative bilirubin level was lower (12 mg/dL versus 1.8 mg/dL; P = 0.037), and the duration of hospital stay was shorter (10 days versus 14 days; P = 0.002) in the IRHV group. No significant differences were noted in the intraoperative blood loss, postoperative transaminase levels, or the incidence of severe complications (Clavien grade IIIb or higher) between the groups. IRHV-conserving resection of the liver is a safe surgical procedure that is useful in preventing postoperative elevation of bilirubin level and in shortening the duration of hospital stay.

Background: Only a few papers have focused on the surgical outcomes of patients with hepatocellular carcinoma (HCC) associated with the metabolic syndrome. We compared the outcomes of patients with metabolic HCC with those of patients with non-B, non-C HCC associated with other etiologies., Methods: Metabolic HCC was defined as HCC arising in patients with at least three of the following metabolic disorders: central obesity, dyslipidemia, hypertension, and diabetes mellitus. A total of 246 patients with non-B, non-C HCC were divided into three groups: metabolic HCC (n = 35), alcoholic HCC (n = 114), and cryptogenic HCC (n = 97). Clinical characteristics, surgical data, and survival were compared among the three groups., Results: Metabolic HCC was diagnosed at a significantly higher age than alcoholic (75 vs. 68 years, P = 0.004) and cryptogenic HCCs (75 vs. 71 years, P = 0.027). Postoperative complications occurred significantly higher in patients with metabolic HCC compared with those with cryptogenic HCC (40.0 vs. 22.7 %, P = 0.049). Especially, pulmonary complications were significant in metabolic HCC compared with cryptogenic HCC (22.9 vs. 8.2 %, P = 0.023). The overall survival rates in the metabolic, alcoholic, and cryptogenic HCC groups were 96.7 % (95 % CI, 90.5-100), 96.3 % (95 % CI, 92.8-99.9), and 95.6 % (95 % CI, 91.5-99.9) at 1 year, respectively, and 87.2 % (95 % CI, 74.5-100), 82.9 % (95 % CI, 74.6-92.2), and 84.5 % (95 % CI, 75.7-94.3) at 3 years, respectively (P = 0.84). The disease-free survival rates in each group were 74.4 % (95 % CI, 60.5-91.5), 76.9 % (95 % CI, 69.2-85.5), and 74.3 % (95 % CI, 65.0-84.8) at 1 year, respectively, and 29.3 % (95 % CI, 16.6-51.8), 39.0 % (95 % CI, 29.7-51.2), and 41.1 % (95 % CI, 29.7-56.8) at 3 years, respectively, (P = 0.90)., Conclusions: Metabolic HCC patients have specific risks of postoperative complication related to the metabolic syndrome.

Background: Subcutaneous drainage is considered effective for preventing wound infections, but only anecdotal evidence supports its clinical benefit. The present study evaluated the benefit of subcutaneous drainage in preventing wound infections in patients undergoing liver resection., Methods: Patients scheduled for liver resection were randomly assigned to receive or not receive subcutaneous drains. After suture of the peritoneum and fascia, a 10 Fr drain was placed subcutaneously and connected to a low pressure (under 80 cmH2 O) aspiration reservoir to allow drainage of the full length of the wound. The primary endpoint was wound infection development within 30 days of the liver resection., Results: We performed liver resections in 260 patients with hepatobiliary malignancies. Between the subcutaneous-drainage group (n = 131) and non-drainage group (n = 129), there were no significant differences in the operative variables. Wound infection occurred in 10 drainage group patients (8%) and 12 patients (9%) in the non-drainage group (P = 0.629); there was no significant difference in the probability of wound infection (P = 0.624). No significant differences were found between the groups for the hospital stay duration (P = 0.363), postoperative complications (P = 0.725) or medical expenses (P = 0.360)., Conclusions: Subcutaneous drainage does not prevent wound infections in patients undergoing liver resection; therefore, its routine use is not justified., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

The use of adjuvant systemic chemotherapy for resectable liver metastases from colorectal cancer (CRC) is controversial because no trial demonstrated its benefit. We conducted the phase III trial to evaluate UFT/leucovorin (LV) for colorectal liver metastases (CRLM). The primary endpoint has not been available until 2014, we first report the feasibility and safety data of UFT/LV arm. In this multicenter trial, patients who underwent curative resection of liver metastases from colorectal cancer were randomly assigned to receive surgery alone or surgery followed by adjuvant chemotherapy with UFT/LV. The primary endpoint was relapse-free survival. Secondary endpoints included overall survival and safety. A total of 180 patients were enrolled, 90 were randomly assigned to receive UFT/LV therapy. Eighty two of whom were included in safety analyses. In the UFT/LV group, the completion rate of UFT/LV was 54.9%, the relative dose intensity was 70.8% and grade 3 or higher adverse events occurred in 12.2% of the patients. Elevated bilirubin levels, decreased hemoglobin levels, elevated alanine aminotransferase levels, diarrhea, anorexia were common. Most other adverse events were grade 2 or lower and tolerable. In conclusions, UFT/LV is a safe regimen for postoperative adjuvant chemotherapy in patients who have undergone resection of liver metastases from colorectal cancer. Further studies are warranted to improve completion rate, but UFT/LV is found to be a promising treatment in this setting.

Objective: The aim of this study was to investigate in a retrospective setting the patients' profile and results of those undergoing surgery for hepatocellular carcinoma (HCC) in high-volume surgical centers throughout the world., Background: Whether surgery for HCC is a suitable approach and for which subset of patients is still controversial. The EASL/AASLD (European Association for the Study of Liver Disease/American Association for the Study of Liver Disease) guidelines, based on the Barcelona Clinic Liver Cancer (BCLC) classification, leave little room for hepatic resection; inversely, other reports promote its wider application., Methods: On the basis of the network "Hepatocellular Carcinoma: Eastern & Western Experiences," data for 2046 consecutive patients resected for HCC in 10 centers were collected. According to the BCLC classification, 1012 (50%) were BCLC 0-A, 737 (36%) BCLC B, and 297 (14%) BCLC C. Analysis of overall survival and disease-free survival and multivariate analysis of prognostic factors were performed., Findings: The 90-day mortality rate was 2.7%. Overall morbidity was 42%. After a median follow-up of 25 months (range, 1-209 months), the 1-, 3-, and 5-year overall survival rates were 95%, 80%, and 61% for BCLC 0-A; 88%, 71%, and 57% for BCLC B; and 76%, 49%, and 38% for BCLC C (P = 0.000). The 1-, 3-, and 5-year disease-free survival rates were as follows: 77%, 41%, and 21% for BCLC 0-A; 63%, 38%, and 27% for BCLC B; and 46%, 28%, and 18% for BCLC C (P = 0.000). The multivariate analysis identified bilirubin, cirrhosis, esophageal varices, tumor size, and macrovascular invasion to be statistical and independent prognostic factors for overall survival., Conclusions: This large multicentric survey shows that surgery is in current practice widely applied among patients with multinodular, large, and macrovascular invasive HCC, providing acceptable short- and long-term results and justifying an update of the EASL/AASLD therapeutic guidelines in this sense.

Background: Having three liver resections for colorectal metastases has long been considered to be associated with a high risk of postoperative complications. The present study was designed to assess the feasibility and survival benefits of three liver resections., Methods: Between 2004 and 2011, data for 273 consecutive patients with colorectal metastases were analyzed. The patient characteristics, tumor status, operation-related variables, degree of liver steatosis, and short- and long-term outcomes were compared according to the number of liver resections., Results: The history of preoperative chemotherapy was higher for patients who had had three liver resections as compared with other resections: i.e., one resection 41.0 %, versus two resections 56.8 %, versus three resections 81.8 %; p = 0.04. Patients receiving three liver resections had a high rate of liver steatosis (17.9 vs. 32.4 vs. 59.1 %; p = 0.03). The median operative time for three resections was significantly longer than for the other resections (359 min [range: 115-579 min] vs. 395 min [range: 178-740 min], vs. 482 min [range: 195-616 min]; p = 0.04). However, the complication rate and the postoperative hospital stay did not differ among the three groups. The 1-, 3- and 5-year survival rates did not differ significantly among the three groups (83.3, 57.5, and 44.6 % for one resection vs. 92.3, 52.1, and 35.7 % for two resections vs. 93.3, 49.0, and 34.1 % for three resections). Patients who had <5 tumors at a third liver resection and a recurrence interval of ≥ 500 days from the second resection were good candidates for three resections., Conclusions: Undergoing three resections of colorectal metastasis is feasible and provides a similar survival benefit as one or two resections, without increasing morbidity or mortality.

Background & Aims: Early treatment has been recommended for hepatocellular carcinoma (HCC) due to its high cure rate. However, the reported survival benefits of treating early HCC may be affected by lead time., Methods: Early HCC was defined as a well-differentiated cancer containing Glisson's triad (carcinoma in situ). We applied the concept of lead time to chronic liver disease, which is originally the length of time between screen-detected and symptom-detected disease. To evaluate prolongation of survival with treatment of early HCC, survivals of patients with early and overt HCCs smaller than 2.0 cm treated with liver resection were compared. To calculate lead time and survival benefit of liver resection, survivals of untreated early and overt HCC patients were compared., Results: After liver resection, median overall survival of 46 patients with early HCC (8.8 years; 95% CI, 7.2-11.2) was significantly longer than that of the 202 with overt HCC (6.8 years; 95% CI, 6.2-8.3, p = 0.0257). The prolongation in survival time with liver resection for early HCC was 34.7 (95% CI, 22.1-46.5) months. On the other hand, comparing liver resection and natural history, the survival benefits of surgery for 12 patients with early and 16 with overt HCC were 74.7 (95% CI, 51.9-97.4) and 73.4 (95% CI, 57.9-88.9) months, respectively. Consequently, the lead time and survival benefit with resection for early HCC were estimated as 33.4 (95% CI, 18.9-47.8) and 1.3 (95% CI, -22.1-24.7) months, respectively., Conclusions: Survival benefit of resection for early HCC is marginal because of a long lead time, and early HCC is therefore not a target lesion for surgery., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Surgeons have attempted to prevent early cancer-related death after resection of hepatocellular carcinoma to identify risk factors associated with early death from hepatocellular carcinoma recurrence after liver resection., Methods: The study group comprised 350 patients who had undergone liver resection for hepatocellular carcinoma between 1997 and 2007. The preoperative risk factors for early death from intrahepatic recurrence (within 1 year after resection) were evaluated., Results: Fourteen (4%) patients died of intrahepatic recurrence in the first year after resection. Multivariate analyses identified the following risk factors for early cancer-related death: multiple tumors (odds ratio 10.4; 95% confidence interval, 2.42-44.3; P = .002), vascular invasion (odds ratio 10.1; 95% confidence interval 2.07-50; P = .004), serum alpha-fetoprotein level >20 ng/mL (odds ratio 9.52; 95% confidence interval 1.0--84.2; P = .043), and tumor size ≥50 mm (odds ratio 4.80; 95% confidence interval 1.06-21.9; P = .042). Each of these factors was assigned a score of 1 point, and an algorithm was developed to predict the risk of early death. Outcomes did not differ significantly between patients with 3 or 4 points (P = .48) or between those with 1 or 2 points (P = .49). Patients who underwent liver resection could be stratified into the following distinct groups according to the point score and the associated 1-year survival rate and median survival (shown respectively): 0 points, 99%, and not yet; 1 or 2 points, 96%, and 68 months; and 3 or 4 points, 50%, and 12 months) (P < .0001)., Conclusion: Even if hepatocellular carcinoma is resectable, patients with a score of 3 or 4 points may not be good candidates for liver resection., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: The caudate lobe of the liver is located behind both major lobes and is surrounded by the inferior vena cava, three main hepatic veins, and the hepatic hilum. Despite a hard-to-approach anatomic location, isolated complete removal of the caudate lobe is recommended to improve curability in hepatocellular carcinoma (HCC). This is because most patients with HCC cannot undergo caudate lobectomy (segmentectomy 1) with resection of adjacent liver regions due to their poor liver function., Methods: We performed an anatomic isolated caudate lobectomy using a high dorsal resection technique in patients with HCC involving the paracaval portion of the liver. In this procedure, the caudate lobe is dissected, the boundary of the caudate lobe is identified using counterstaining and tattooing techniques, and the liver is transected along landmarks. The caudate lobe can be removed completely, without loss of the parenchyma of the major lobes, thereby preserving liver function., Conclusions: Given that most patients with HCC concurrently have chronic liver disease, those with HCC in the caudate lobe are good candidates for high dorsal resection of the liver, which is safe, potentially curative procedure.

Background: The transthoracic approach in liver resection is a useful option for improving the clearance of and access to the operation field. However, this approach remains controversial due to the threat of increased respiratory complications. The aim of this study was to evaluate the clinical outcomes and biological responses of patients who underwent the transthoracic versus the transabdominal approach in liver resection., Methods: This case-matched cohort study included a total of 127 patients who underwent treatment for hepatocellular carcinoma from June 2006 to December 2007 at the Nihon University Itabashi Hospital. Forty-four (34.6%) patients had the transthoracic approach of liver resection, and the patients were matched on three variables: (1) scale of liver resection, (2) perioperative steroid administration, and (3) pathologically proven liver cirrhosis. The patients were divided into two groups according to the transthoracic (n = 36) or transabdominal (n = 36) approaches. Clinical outcomes (including respiratory and overall complications) and biological responses (including acute-phase cytokine production and oxygenation) were compared between the two different approaches., Results: The preoperative variables were well matched. However, for the transthoracic group relative to the transabdominal group, the median operative time was significantly longer (median = 402 min [range = 236-661] vs. 330 min [range = 178-697], P ≤ 0.001), the ischemia time was shorter (65 min [range = 12-223] vs. 76 min [range = 28-247], P = 0.04), the level of AaDO(2) on POD 1 was higher (66.1 vs. 33.5 Torr, P = 0.04), and the IL-6 level in pleural effusions on POD 2 was higher (21,900 pg/ml [range = 6,020-123,000] vs. 866 pg/ml [range = 389-2,210], P < 0.001). There was no postoperative mortality and no significant difference between groups in overall morbidity (P = 0.81), overall respiratory complications (P = 0.11), atelectasis (P = 0.10), pleural effusion (P = 0.06), pneumonia (P = 1.00), and length of postoperative hospital stay (P = 0.23)., Conclusion: Because of there was no significant difference between transthoracic and transabdominal approaches. We recommend using the transthoracic approach in liver resection.

Objective: To establish transfusion criteria for use of fresh frozen plasma (FFP) in liver resection., Background: Fresh frozen plasma has been transfused in liver resection without adequate supporting evidence, leading to unnecessary use., Design: Prospective study using a phase 1 dose-escalation, 3 + 3 cohort expansion design, modified for FFP transfusion. We designated a serum albumin level of 3.0 g/dL (step 1) as the starting limit for no transfusion and reduced the level in 0.2-g/dL steps. Advancement to the next step was permitted when the albumin level equaled the target value for the previous step in 3 patients. If the albumin value on postoperative day 2 fell below the target value, 100 mL of albumin, 25%, was transfused on that day and on postoperative day 3. The study continued until high-grade postoperative complications occurred without transfusion. If 1 of 3 patients developed Clavien-Dindo grade II or higher complications, 3 more patients (3 + 3 cohort) were added to the same step., Setting: Hepatobiliary pancreatic surgery center of a university hospital., Patients: Patients with hepatocellular carcinoma who had had Child-Pugh class A liver function and an intraoperative blood loss of less than 1000 mL., Intervention: Transfusion or no transfusion of FFP. Main Outcome Measure Reduction of transfusion rate in liver resection., Results: Of the 213 consecutive patients with liver cancer enrolled, 172 patients (80.8%) fulfilled the inclusion criteria. Step progression proceeded until step 5 (albumin level, 2.2 g/dL) without high-grade complications, but step 2 (albumin level, 2.8 g/dL) required 63 patients to complete because 1 patient developed grade II complications (massive ascites). Step progression was broken off at step 5 in the 172nd patient because the postoperative day 2 albumin value did not fall below the step 4 level (2.4 g/dL), defined as the goal limit. The overall operative morbidity rate was 27.9%; the mortality rate was 0%. The FFP transfusion rate was significantly reduced from 48.6% in a previous series involving 222 patients (unpublished historical data from our institution) to 0.6% (1 of 172 patients) in the present study (P < .001). The postoperative hospital stay in the present study was significantly shorter than that in our previous series (13 vs 16 days; P = .01). Total medical costs were significantly reduced from a median of $21 061 (range, 10 032-59 410) to $17 267 (11 823-35 785; P = .04)., Conclusion: In liver resection, FFP transfusion is not necessary in patients with serum albumin levels higher than 2.4 g/dL on postoperative day 2.

Surgery is the most important therapeutic approach for patients with hepatocellular carcinoma. We have reviewed patients' survival after resection for hepatocellular carcinoma in 17 series since 2000, each including more than 100 patients. Median survival rates were 80% (range 63-97%) at 1 year, 70% (34-78%) at 3 years and 50% (17-69%) at 5 years. Such wide ranges of survival rates are attributed mainly to differences in the hepatocellular carcinoma stage among studies, but the survival rate is obviously much better for early hepatocellular carcinomas. Today, liver resection is an established treatment for hepatocellular carcinoma owing to minimal surgical mortality and improved survival. Liver transplantation is one of the best treatments for hepatocellular carcinoma in patients who meet the selection criteria. Further studies are needed to establish suitable criteria for transplantation in patients with hepatocellular carcinoma. For patients who are not candidates for liver resection or transplantation, percutaneous ablation is the best treatment option. However, no randomized controlled clinical trial has compared the results of ablation with those of surgical therapy for hepatocellular carcinoma, and none of the ablation techniques have been shown to offer a definitive survival advantage. A treatment algorithm based on published evidence is now available, which helps us to select the most suitable therapeutic option for individual patients, depending on tumor characteristics and liver functional reserve. This review paper summarizes the current status of the surgical management of hepatocellular carcinoma.

Objective: We performed a randomized controlled trial to investigate the clinical benefits of perioperative treatment with steroids in patients undergoing liver resection., Background: Perioperative steroids are considered to reduce surgical stress, but evidence supporting proposed clinical benefits is largely anecdotal., Patients and Methods: The 210 patients scheduled to undergo liver resection were randomly assigned to a steroids group (n = 105) or a control group (n = 105). The steroids group received 500 mg hydrocortisone immediately before hepatic-pedicle clamping, followed by 300 mg hydrocortisone on postoperative day (POD) 1, 200 mg on POD 2, and 100 mg on POD 3. Serum levels of total bilirubin, aminotransferases coagulation factors, and inflammatory-related cytokines, and the clinical course were compared between the 2 groups. The primary end point was the postoperative bilirubin level., Results: All 210 patients underwent radical liver resection with no operative mortality. The median bilirubin level on POD 2 was significantly lower in the steroids group [0.71 mg/dL (0.33-2.17)] than in the control group [1.03 mg/dl (0.39-3.57); P = 0.01]. The postoperative time courses of the bilirubin level (P = 0.01), the interleukin-6 level (P = 0.01) and the C-reactive protein level (P = 0.01) were significantly lower whereas the the prothrombin level (P = 0.01) and interleukin-10 level (P = 0.01) were significantly higher in the steroids group. There was no difference between the groups in the proportion of patients with complications (40% vs 43%; P = 0.66) or the length of the hospital stay (14 days vs 13 days; P = 0.68)., Conclusions: Perioperative treatment with steroids has a positive impact on the liver function of patients who undergo liver resection, without increasing the risk of complications.

A 64-year-old male was referred to our hospital from another hospital for acute abdomen. Emergency laparotomy was performed to confirm an upper gastrointestinal tract perforation. He was diagnosed as a gastric perforation and peritonitis due to a suspected gastric cancer. He underwent omental implantation and peritoneal drainage for peritonitis. Histopathological examination revealed a perforated gastric carcinoma. After the surgery, a liver metastasis was found on the findings of the enhanced abdominal CT scan. Twenty-one days after the emergency surgery, he underwent total gastrectomy with lymphatic dissection and hepatectomy. Eighteen days after the curative surgery, he started to receive postoperative adjuvant chemotherapy. He has been well without recurrence for 2 years and half following the start of chemotherapy.

Purpose: For hepatocellular carcinoma (HCC), surgical resection and radiofrequency ablation (RFA) are accepted as effective treatments. To clarify the long-term outcome in patients with small HCC, we analyzed data from a nationwide survey of Japan., Methods: Between 2000 and 2003, a total of 2,550 patients who had undergone resection (n = 1,235) or RFA (n = 1,315) for single small HCC (