Sarcomatoid change in combined hepatocellular carcinoma and cholangiocarcinoma as a poor prognostic factor.

Background: Sarcomatoid change is rarely seen in epithelial malignancy that can be observed in diverse organs. Although a sarcomatoid change in combined hepatocellular-cholangiocarcinoma (cHCC-CC) is assumed to be a poor prognostic factor, this issue has not been studied due to its rare incidence. In this study, we aimed to identify the oncological impact of sarcomatoid change in patients with cHCC-CC and verify that sarcomatoid change is a poor prognostic factor for resected cHCC-CC. Methods: Between January 2006 and December 2020, 102 patients who underwent surgical resection for cHCC-CC were retrospectively reviewed. The hazard ratio (HR) according to sarcomatoid change was calculated using other known prognostic factors for cHCC-CC. In addition, the patients were divided into two groups according to the sarcomatoid change, and their survival was compared. Results: The multivariate analysis demonstrated that sarcomatoid change in cHCC-CC is a poor prognostic factor {disease-free survival (DFS), HR =3.84 [95% confidence interval (CI): 1.63-9.10], P=0.002; overall survival (OS), HR =3.94 (95% CI: 1.67-9.31), P=0.002}. In the survival analysis, the sarcomatoid change group displayed a worse prognosis compared to the non-sarcomatoid change group {DFS: 4.0 [interquartile range (IQR): 1.2-6.8] vs. 23.0 (IQR: 9.3-36.7) months, P=0.001; OS: 19.0 (IQR: 7.2-30.8) vs. 85.0 (IQR: 31.8-138.2) months, P=0.004}. Conclusions: Sarcomatoid change is a poor prognostic factor for resected cHCC-CC.

Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue.

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.

Preoperative Prediction of Microvascular Invasion with Gadoxetic Acid-Enhanced Magnetic Resonance Imaging in Patients with Single Hepatocellular Carcinoma: The Implication of Surgical Decision on the Extent of Liver Resection.

Introduction: Microvascular invasion (MVI) is one of the most important prognostic factors for hepatocellular carcinoma (HCC) recurrence, but its application in preoperative clinical decisions is limited. This study aimed to identify preoperative predictive factors for MVI in HCC and further evaluate oncologic outcomes of different types and extents of hepatectomy according to stratified risk of MVI. Methods: Patients with surgically resected single HCC (≤5 cm) who underwent preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI) were included in a single-center retrospective study. Two radiologists reviewed the images with no clinical, pathological, or prognostic information. Significant predictive factors for MVI were identified using logistic regression analysis against pathologic MVI and used to stratify patients. In the subgroup analysis, long-term outcomes of the stratified patients were analyzed using the Kaplan-Meier method with log-rank test and compared between anatomical and nonanatomical or major and minor resection. Results: A total of 408 patients, 318 men and 90 women, with a mean age of 56.7 years were included. Elevated levels of tumor markers (alpha-fetoprotein [α-FP] ≥25 ng/mL and PIVKA-II ≥40 mAU/mL) and three MRI features (tumor size ≥3 cm, non-smooth tumor margin, and arterial peritumoral enhancement) were independent predictive factors for MVI. As the MVI risk increased from low (no predictive factor) and intermediate (1-2 factors) to high-risk (3-4 factors), recurrence-free and overall survival of each group significantly decreased (p = 0.001). In the high MVI risk group, 5-year cumulative recurrence rate was significantly lower in patients who underwent major compared to minor hepatectomy (26.6 vs. 59.8%, p = 0.027). Conclusion: Tumor markers and MRI features can predict the risk of MVI and prognosis after hepatectomy. Patients with high MVI risk had the worst prognosis among the three groups, and major hepatectomy improved long-term outcomes in these high-risk patients.

Surgical strategy for incidental intrahepatic cholangiocarcinoma in terms of lymph node dissection.

BACKGROUND: Although many guidelines recommend performing lymph node dissection (LND) during surgery for intrahepatic cholangiocarcinoma (ICC), there is no evidence for patients with incidentally detected ICC who did not undergo LND. This study aimed to identify the role of LND in patients with incidental ICC. METHODS: The data from 284 patients who had undergone radical surgery for ICC from 2000 to 2020 were retrospectively reviewed. The enrolled patients were divided into 3 groups according to their T stage (T1 vs T2 vs T3 + 4). Moreover, the patients of each T group were divided into 3 groups according to their nodal status (N0 vs N1 vs Nx) and their survival outcomes were compared. RESULTS: Survival outcomes of Nx group were statistically similar to that of N0 group in T1 stage (Nx vs N0: disease-free survival [DFS] [months], 129.0 [75.6-182.4] vs 125.0 [65.7-184.3], P = .948; overall survival [OS] [months], 175.0 [153.9-196.1] vs 173.0 [109.0-237.0], P = .443). In contrast, survival outcomes of Nx group in the other T stage (T2 and T3 + 4) were poorer than that of N0 group and were better than that of N1 group. In addition, in the Nx subgroup analysis according to T stage, T1 group showed significantly better survival outcomes than the other groups (T1 vs T2 vs T3 + 4: DFS [months], 129.0 [75.9-182.1] vs 16.0 [9.8-22.2] vs 13.0 [0.3-25.7], P < .001; OS [months], 175.0 [153.9-196.1] vs 53.0 [30.8-75.2] vs 37.0 [17.6-56.4], P < .001). CONCLUSION: Patients with ICC incidentally diagnosed as having T2 or above T stage may consider additional LND.

Additional nodules detected using EOB-MRI in patients with resectable single hepatocellular carcinoma: an implication for active treatment strategy.

BACKGROUND/AIM: Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOBMRI) further enhances the identification of additional hepatic nodules compared with computed tomography (CT) alone; however, the optimal treatment for such additional nodules remains unclear. We investigated the long-term oncological effect of aggressive treatment strategies for additional lesions identified using EOB-MRI in patients with hepatocellular carcinoma (HCC). METHODS: Data from 522 patients diagnosed with solitary HCC using CT between January 2008 and December 2012 were retrospectively reviewed. Propensity score-matched (PSM) analysis was used to compare the oncologic outcomes between patients with solitary HCC and those with additional nodules on EOB-MRI after aggressive treatment (resection or radiofrequency ablation [RFA]). RESULTS: Among the 383 patients included, 59 had additional nodules identified using EOB-MRI. Compared with patients with solitary HCC, those with additional nodules on EOB-MRI had elevated total bilirubin, aspartate transaminase, and alanine transaminase; had a lower platelet count, higher MELD score, and highly associated with liver cirrhosis (P<0.05). Regarding long-term outcomes, 59 patients with solitary HCC and those with additional nodules after PSM were compared. Disease-free survival (DFS) and overall survival (OS) were comparable between the two groups (DFS, 60.4 vs. 44.3 months, P=0.071; OS, 82.8 vs. 84.8 months, P=0.986). CONCLUSION: The aggressive treatment approach, either resection or RFA, for patients with additional nodules identified on EOBMRI was associated with long-term survival comparable with that for solitary HCC. However, further studies are required to confirm these findings.

Unusual grafts for living-donor liver transplantation.

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.

Prognostic impact of R1 resection margin in synchronous and simultaneous colorectal liver metastasis resection: a retrospective cohort study.

BACKGROUND: A margin ≥ 1 mm is considered a standard resection margin for colorectal liver metastasis (CRLM). However, microscopic incomplete resection (R1) is not rare since aggressive surgical resection has been attempted in multiple and bilobar CRLM. This study aimed to investigate the prognostic impact of resection margins and perioperative chemotherapy in patients with CRLM. METHODS: A total of 368 of 371 patients who underwent simultaneous colorectal and liver resection for synchronous CRLM between 2006 and June 2017, excluding three R2 resections, were included in this study. R1 resection was defined as either abutting tumor on the resection line or involved margin in the pathological report. The patients were divided into R0 (n = 304) and R1 (n = 64) groups. The clinicopathological characteristics, overall survival, and intrahepatic recurrence-free survival were compared between the two groups using propensity score matching. RESULTS: The R1 group had more patients with ≥ 4 liver lesions (27.3 vs. 50.0%, P < 0.001), higher mean tumor burden score (4.4 vs. 5.8%, P = 0.003), and more bilobar disease (38.8 vs. 67.2%, P < 0.001) than the R0 group. Both R0 and R1 groups showed similar long-term outcomes in the total cohort (OS, P = 0.149; RFS, P = 0.414) and after matching (OS, P = 0.097, RFS: P = 0.924). However, the marginal recurrence rate was higher in the R1 group than in the R0 group (26.6 vs. 16.1%, P = 0.048). Furthermore, the resection margin did not have a significant impact on OS and RFS, regardless of preoperative chemotherapy. Poorly differentiated, N-positive stage colorectal cancer, liver lesion number ≥ 4, and size ≥ 5 cm were poor prognostic factors, and adjuvant chemotherapy had a positive impact on survival. CONCLUSIONS: The R1 group was associated with aggressive tumor characteristics; however, no effect on the OS and intrahepatic RFS with or without preoperative chemotherapy was observed in this study. Tumor biological characteristics, rather than resection margin status, determine long-term prognosis. Therefore, aggressive surgical resection should be considered in patients with CRLM expected to undergo R1 resection in this multidisciplinary approach era.

Left-sided Hepatectomy Leads to Less Postoperative Liver Failure and Comparable Overall Survival to Right-sided Hepatectomy in Type II or IV Perihilar Cholangiocarcinoma.

INTRODUCTION: Right-side hepatectomy (RH) is used in oncological resection for perihilar cholangiocarcinoma (PHC); however, the decision between performing left-side hepatectomy (LH) or RH is still controversial. We compared surgical and oncologic outcomes of LH and RH in PHC type II or IV where either hepatectomy was expected to have a negative margin. METHODS: From 2001 to 2020, 99 patients underwent major liver resection for type II or IV PHC. Patients with unilateral vascular invasion, unilateral tumor growth, and atrophy of unilateral liver were excluded. Preoperative characteristics, perioperative, and long-term outcomes were compared between the remaining RH and LH patients. RESULTS: After excluding 47 cases with side predominance, the RH group (n = 29) and LH group (n = 23) were compared. Clinical characteristics and disease severity did not differ between the groups. Portal vein embolization (RH: 48.3% vs. LH: 0.0%, p < 0.001) and days from diagnosis to operation (RH: 31.0 ± 16.2 vs. LH: 18.8 ± 13.4, p = 0.006) were significantly higher in the RH group. The RH group had statistically higher rate of postoperative hepatic failure (RH: 55.2% vs. LH: 21.7%, p = 0.015) and a higher mortality rate that was not significant (RH: 13.8% vs. LH: 0%, p = 0.120). The R0 resection rate (RH: 72.4% vs. LH: 78.3%, p = 0.629), median disease-free (p = 0.620), and overall (p = 0.487) survival did not differ between groups. R1 resection and lymph node metastasis were significant risk factors for disease-free survival in multivariate analysis. CONCLUSIONS: In type II or type IV PHC where either LH or RH was feasible, LH provided a shorter period of preoperative preparation, lower postoperative hepatic failure rate, similar R0 rate, and comparable long-term outcomes. LH should be considered a reasonable option in type II or IV PHC.