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We compared outcomes in patients with solitary colorectal liver metastases treated by either hepatic resection (HR) or radiofrequency ablation (RFA). A retrospective analysis from a prospective database was performed on 67 consecutive patients with solitary colorectal liver metastases treated by either HR or RFA. Forty-two patients underwent HR and 25 patients underwent RFA. The 5-year overall and local recurrence-free survival rates after HR (50.1% and 89.7%, respectively) were higher than after RFA (25.5% and 69.7%, respectively) ( P = .0263 and .028, respectively). In small tumors less than 3 cm (n = 38), the 5-year survival rates between HR and RFA were similar, including overall (56.1% vs 55.4%, P = .451) and local recurrence-free (95.7% vs 85.6%, P = .304) survival rates. On multivariate analysis, tumor size, metastases treatment, and primary node status were significant prognostic factors. HR had better outcomes than RFA for recurrence and survival after treatment of solitary colorectal liver metastases. However, in tumors smaller than 3 cm, RFA can be recommended as an alternative treatment to patients who are not candidates for surgery because the liver metastases is poorly located anatomically, the functional hepatic reserve after a resection would be insufficient, the patient's comorbidity inhibits a major surgery, or extrahepatic metastases are present.

The purpose of this study was to investigate the surgical outcomes in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). Clinicopathological features and surgical outcomes of 50 patients with huge HCC who underwent curative resection (group A) were compared with 447 patients with smaller tumors (group B). In group A, we investigated prognostic factors. Group A patients had a higher incidence of α-fetoprotein at more than 1,000 IU/mL, microscopic vascular invasion, and advanced stage tumors. The disease-free survival of group A was significantly worse than group B. The rates of initial extrahepatic recurrence and early recurrence were higher in group A. The 5 year-overall survival of group A was 40.2%, significantly lower than that of group B (65.9% at 5 years). In group A, multivariate analysis revealed that the presence of single nodular type tumors was the only good prognostic factor for survival. Huge HCCs exhibit a more aggressive clinical behavior and worse survival. However, because the outcome of surgical treatment is far better than that of nonsurgical treatment, resection should be actively considered for patients with huge HCC. A single nodular type tumor is the best candidate for surgical resection.

Background Intrahepatic recurrence is a major problem after curative resection of hepatocellular carcinoma. However, the most effective treatments for patients with intrahepatic recurrence still remain unclear. In addition, the selection of various treatment modalities such as repeat resection, local ablation therapy, and transarterial chemoembolization is only applicable to patients with intrahepatic nodular recurrence. Methods Of 353 patients who underwent curative resection, 97 patients with intrahepatic nodular recurrence were retrospectively studied. The prognostic factors for survival after recurrence and treatment modalities were analyzed. The patients were divided into two groups, a control group and a progression group, according to their response to initial treatment for recurrent tumors. Results The 1-, 3-, and 5-year overall survival rates after recurrence in patients with intrahepatic nodular recurrence were 91.0%, 71.0%, and 37.5%, respectively. Multivariate analysis revealed that early recurrence (≤12 months), Child-Pugh class B or C at diagnosis of recurrence, and serum albumin level of ≤3.5 g/dL at diagnosis of recurrence were poor prognostic factors for survival after recurrence. With regard to the response to the initial treatment, time to recurrence of ≤12 months was found to be the only statistically significant risk factor for progression of disease in multivariate analysis. Conclusions Time to recurrence, which usually corresponds with the cellular origin of recurrence, seems to be more important when determining the prognosis of patients with recurrent disease and treatment response than treatment modality. Therefore, different treatment methods should be selected according to the time to recurrence of intrahepatic nodular recurrence.

Background Whether preoperative transarterial chemoembolization (TACE) has the therapeutic benefits in patients with resectable hepatocellular carcinoma (HCC) remains uncertain. Materials and methods We retrospectively investigated the influence of preoperative TACE on both disease‐free survival and the pattern of recurrence after curative resection. From March 1998 to January 2005, a series of 273 patients who underwent curative resection for HCC were reviewed. Altogether, 120 patients underwent preoperative TACE, and 153 patients did not. We compared disease‐free survival and the recurrence patterns between TACE and non‐TACE groups, as well as between subgroups, stratified with regard to initial tumor size (≤3 cm, 3–5 cm, >5 cm) and pathologic tumor stage (stage I‐II and stage III‐IVa). We also compared disease‐free survival and the pattern of recurrence among the three groups: complete necrosis, incomplete necrosis, non‐TACE groups. Results The 1‐, 3‐, and 5‐year disease‐free survival rates were 76.0%, 57.7%, and 51.3%, respectively, in the TACE group and 70.9%, 53.8%, and 46.8%, respectively, in the non‐TACE group. No significant difference was observed in disease‐free survival or the pattern of recurrence between the TACE and non‐TACE groups. Further analysis of disease‐free survival and the pattern of recurrence between subgroups according to initial tumor size and tumor stage showed no significant differences. Complete necrosis of tumor was recognized in only 33 patients of the TACE group (p = 0.001). Among the three complete necrosis, incomplete necrosis, and non‐TACE groups, no significant difference was observed in disease‐free survival or the pattern of recurrence. Conclusions Preoperative TACE did not significantly improve the disease‐free survival or the pattern of recurrence after curative resection of HCC. Even though this study is a retrospective analysis, preoperative TACE cannot be recommended as a routine procedure before hepatectomy for a resectable HCC.

Background Intrahepatic cholangiocarcinoma is a malignancy of the intrahepatic biliary tree. Although surgical resection is the mainstay of treatment for this tumor, the impact of lymph node dissection during hepatectomy is controversial. In this study, we evaluated the impact of lymph node dissection during surgical resection for intrahepatic cholangiocarcinoma. Methods Records from 170 patients who underwent radical hepatectomy for intrahepatic cholangiocarcinoma from January 2000 to December 2014 were retrospectively reviewed. Twenty-two patients who underwent R1 resection or had distant metastasis at the time of surgery were excluded. Using propensity score matching (matched factors: differentiation, lymphovascular invasion, perineural invasion, and T stage), the patients were divided into two groups: no dissection ( n  = 34) or lymph node dissection ( n  = 34). Disease-free survival and overall survival were compared between groups. Results There was a marginally significant difference between the two groups with respect to the disease-free survival (no dissection vs. lymph node dissection: 20.0 [4.2–35.8] months vs. 64.0 [27.3–120.8] months, p  = 0.077). Overall survival was significantly longer in the lymph node dissection group (no dissection vs. lymph node dissection: 44.0 [31.1–56.9] months vs. 90.0 [51.1–158.9] months, p  = 0.027). Conclusion Radical surgery including an adequate lymph node dissection area and suitable harvested lymph nodes appears to improve oncologic outcomes for intrahepatic cholangiocarcinoma.

Background Robotic surgery can enhance a surgeon’s laparoscopic skills through a magnified three-dimensional view and instruments with seven degrees of freedom compared to conventional laparoscopy. Methods This study reviewed a single surgeon’s experience of robotic liver resections in 30 consecutive patients, focusing on major hepatectomy. Clinicopathological characteristics and perioperative and short-term outcomes were analyzed. Results The mean age of the patients was 52.4 years and 14 were male. There were 21 malignant tumors and 9 benign lesions. There were 6 right hepatectomies, 14 left hepatectomies, 4 left lateral sectionectomies, 2 segmentectomies, and 4 wedge resections. The average operating time for the right and left hepatectomies was 724 min (range 648–812) and 518 min (range 315–763), respectively. The average estimated blood loss in the right and left hepatectomies was 629 ml (range 100–1500) and 328 ml (range 150–900), respectively. Four patients (14.8%) received perioperative transfusion. There were two conversions to open surgery (one right hepatectomy and one left hepatectomy). The overall complication rate was 43.3% (grade I, 5; grade II, 2; grade III, 6; grade IV, 0) and 40% in 20 patients who underwent major hepatectomy. Among the six (20.0%) grade III complications, a liver resection–related complication (bile leakage) occurred in two patients. The mean length of hospital stay was 11.7 days (range 5–46). There was no recurrence in the 13 patients with hepatocellular carcinoma during the median follow-up of 11 months (range 5–29). Conclusions From our experience, robotic liver resection seems to be a feasible and safe procedure, even for major hepatectomy. Robotic surgery can be considered a new advanced option for minimally invasive liver surgery.

Background/Aims: This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC).Methods: The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated.Results: The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001).Conclusions: Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.

Purpose Unusual grafts, including extended left liver plus caudate lobe, right anterior section, and right posterior section grafts, are alternatives to left and right lobe grafts for living-donor liver transplantation. This study aimed to investigate unusual grafts from the perspectives of recipients and donors. Methods From 2016 to 2021, 497 patients received living-donor liver transplantation at Severance Hospital. Among them, 10 patients received unusual grafts. Three patients received extended left liver plus caudate lobe grafts, two patients received right anterior section grafts, and five patients received right posterior section grafts. Liver volumetrics and anatomy were analyzed for all recipients and donors. We collected data on laboratory examinations (alanine aminotransferase, total bilirubin, international normalized ratio), imaging studies, graft survival, and complications. A 1:2 ratio propensity-score matching method was used to reduce selection bias and balance variables between the unusual and conventional graft groups. Results The median of Model for End-stage Liver Disease score of unusual graft recipients was 13.5 (interquartile range 11.5–19.3) and that of graft–recipient weight ratio was 0.767 (0.7–0.9). ABO incompatibility was observed in four cases. The alanine aminotransferase level, total bilirubin level, and international normalized ratio decreased in both recipients and donors. Unusual and conventional grafts had similar survival rates ( p  = 0.492). The right and left subgroups did not differ from each counter-conventional subgroup ( p  = 0.339 and p  = 0.695, respectively). The incidence of major complications was not significantly different between unusual and conventional graft recipients ( p  = 0.513). Wound seromas were reported by unusual graft donors; the complication ratio was similar to that in conventional graft donors ( p  = 0.169). Conclusion Although unusual grafts require a complex indication, they may show feasible surgical outcomes for recipients with an acceptable donor complication.

Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions. Hepatocellular carcinoma is the most common type of primary liver cancer. Here the authors show an oxygen gradient chip that separates aggressive hepatocellular carcinoma cells from a heterogeneous tumor mass, mirroring the conditions of the portal vein, hepatic artery, and liver.

Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs). The expression of α-smooth muscle actin (α-SMA), p21Waf1/Cif1, γ-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P <0.05, all). The numbers of α-SMA-positive cancer-associated fibroblasts (CAFs) (P = 0.049) and α-SMA-positive CAFs co-expressing p21Waf1/Cif1 (P = 0.038), γ-H2AX (P = 0.065), and IL-6 (P = 0.048) were greater for SH-HCCs than C-HCCs. Additionally, non-tumoral liver from SH-HCCs showed a higher incidence of non-alcoholic fatty liver disease and a higher number of α-SMA-positive stellate cells expressing γ-H2AX and p21Waf1/Cif1 than that from C-HCCs (P <0.05, all). In conclusion, SH-HCCs are considered to occur more frequently in metabolic syndrome patients. Therein, senescent and damaged CAFs, as well as non-tumoral stellate cells, expressing SASP including IL-6 may contribute to the development of SH-HCC.