Intrahepatic Recurrence Research Articles

Hepatectomy Procedures with Awareness of Repeated Resection

Introduction: Repeat hepatectomy is often performed for intrahepatic recurrence of primary and metastatic liver cancers. However, repeat hepatectomy requires complicated procedures due to adhesion and deviation of anatomical position. We present surgical techniques for repeat hepatectomy and its results. Method: From January 2016 to November 2019, 317 cases of hepatectomy were performed at our hospital, and among them 50 cases of repeat hepatectomy were performed. At the initial hepatectomy, laparoscopic approach was preferably selected. The gallbladder was preserved if possible, and the round ligament and the falciform ligament of the liver were reconstructed. Adhesion barriers were placed around the hepatoduodenal ligament, the diaphragmatic surface of the liver, and at the left hepatectomy, the minor curvature of the stomach to prevent gastric rotation. At repeat hepatectomy, laparoscopic approach was attempted because pneumoperitoneum could be useful for the division of adhesion. To secure the hepatoduodenal ligament, we approached the hepatic hilum through the round ligament, and performed Kocherization if needed. Thoracotomy was used if adhesion was severe. Results: All the 50 cases included metastatic liver tumor (n=30), hepatocellular carcinoma (n=8), intrahepatic cholangiocarcinoma (n=2), and peritoneal dissemination (n=1). Laparoscopic surgery was performed in 27 cases (54%). Extent of liver resection included partial resection (n=30), segmentectomy (n=6), sectionectomy (n=8), and hemihepatectomy (n=6). Median operation time was 241 minutes (39-519) and the median blood loss was 100 ml (0-1400). Postoperative bile leakage (Clavien-Dindo classification Grade IIIa or higher) occurred in 2 cases(4.0%). Conclusions: Repeat hepatectomy can be performed safely by devising surgical techniques.

Indocyanine green fluorescence-guided laparoscopic left hemihepatectomy: efficacy of negative staining for precise parenchymal transection and bile duct resection

Purpose: ICG fluorescence imaging is useful to locate segmental boundaries for anatomical resection and to delineate biliary anatomy. Its application in laparoscopic liver surgery is being recently explored and perceived of usefulness given the lack of tactile sensation. This video documents the application of the negative ICG staining technique for an efficient fluorescence guide in pure laparoscopic left hemihepatectomy, for both precise parenchymal transection and bile duct resection. Method: The patient is affected by solitary intrahepatic recurrence of colorectal liver metastasis between Sg 3 and 4 with endobiliary thrombus dilating the left hemiliver biliary tree. The hilar approach is used to isolate the left hepatic artery and ipsilateral portal branch, and the inflow for the left hemiliver is selectively clamped. A solution of 10 mg of ICG diluted in 10 mL saline solution is administered i.v. and the camera switched to the near infrared light. Results: After 2 mins the right hemiliver becomes fluorescent and left hemiliver counterstained on the glissonian surface. The proper transection line is marked, and the transection started. Differently from the traditional vascular demarcation, the ICG fluorescence boundary remains highly visible along the deep transection planes which allows to follow a clear and clean dissection plane during all the transection time. The transection is continued up to the hilar plate until the left portal branch and ipsilateral hepatic artery are encountered, which are both secured with clips before bulldog removal it is ensured that the left hemiliver remains unperfused by ICG, and the two vessels are then interrupted. The left bile duct is identified intraparenchymally, with the endobiliary thrombus inside remaining counterstained, and it is encircled distally to its endobiliary bulging thus allowing precise bile duct section with sufficient free margin at first frozen section. The transection is carried forward up to the identification of the left hepatic vein, which is sectioned by vascular stapler, and the specimen then extracted after biliostatic and hemostatic check. Conclusion: ICG fluorescence imaging with negative staining is useful not only for segmental anatomical resections but safe and efficient technique for both precise parenchymal transection and bile duct resection during anatomical major hemihepatectomy.

Aggressive local treatment for recurrent intrahepatic cholangiocarcinoma following hepatic resection

Purpose: Recurrence of intrahepatic cholangiocarcinoma (ICC)after hepatic resection (HR) is a frequent problem and treatment is challenging. To evaluate the efficacy, safety and overall clinical outcome of HR of ICC with preferably aggressive liver-directed treatment of recurrence. Method: Between 2007 and 2019 72 consecutive patients underwent HR for primary ICC. If amenable, recurrent tumors were aggressively treated by repeated liver-directed therapy with curative intent (RLDT), either HR or stereotactic radiofrequency ablation (SRFA). Endpoints consisted of i) morbidity and mortality, ii) local and distant recurrence, iii) survival after recurrence (SAR), iv) and overall survival (OS). Potential clinicopathological factors influencing recurrence, recurrence management and long-term survival were analyzed. Results: After a median follow-up of 28 months, intrahepatic recurrence of ICC was observed in 43 patients (60.3%) with bildbar involvement being identified as an independent risk factor (p=0.044). 5 patients were subsequently treated by HR and 11 patients by SRFA, respectively. The remaining 27 patients underwent palliative treatment (chemotherapy or best supportive care) for first recurrence. Median SAR was superior among patients who underwent RLDT (38 months) as compared to palliative treatment (17 months, p=0.010). OS of patients who underwent aggressive RLDT was comparable to patients without recurrence (p=0.938) and was significantly better compared to patients receiving palliative treatment (p=0.018). The 5-year OS rates for patients without recurrence, the RLDT group and the palliative treatment group were 54.3%, 47.7% and 12.3%, respectively. By combining different liver-directed treatment options, the rate of curative re-treatment increased from 11.9% to 37.2%. Conclusion: Repeated HR is often precluded due to patient morbidity or anatomical and functional limitations. SRFA with local curative intent is safe, feasible and effective for recurrent ICC following HR with low morbidity levels and favorable clinical outcome.

MRI-guided percutaneous thermoablation as first-line treatment of recurrent hepatic malignancies following hepatic resection: single center long-term experience

Purpose Hepatic recurrence of liver malignancies is a leading problem in patients after liver resection with curative intention. Thermoablation is a promising treatment approach for patients after hepatic resection, especially in liver-limited conditions. This study aimed to investigate safety, survival, and local tumor control rates of MRI-guided percutaneous thermoablation of recurrent hepatic malignancies following hepatic resection. Material and methods Data from patients with primary or secondary hepatic malignancies treated between 2004 and 2018 with MRI-guided percutaneous thermoablation of hepatic recurrence after prior hepatic resection were retrospectively analyzed. Disease-free survival and overall survival rates were calculated using the Kaplan-Meier method. Results A total of 57 patients with hepatic recurrence (mean tumor size = 18.9 ± 9.1 mm) of colorectal cancer liver metastases (n = 27), hepatocellular carcinoma (n = 17), intrahepatic recurrence of cholangiocellular carcinoma (n = 9), or other primary malignant tumor entities (n = 4) were treated once or several times with MR-guided percutaneous radiofrequency (n = 52) or microwave ablation (n = 5) (range: 1–4 times). Disease progression occurred due to local recurrence at the ablation site in nine patients (15.8%), non-local hepatic recurrence in 33 patients (57.9%), and distant malignancy in 18 patients (31.6%). The median overall survival for the total cohort was 40 months and 49 months for the colorectal cancer group, with a 5-year overall survival rate of 40.7 and 42.5%, respectively. The median disease-free survival was 10 months for both the total cohort and the colorectal cancer group with a 5-year disease-free survival rate of 15.1 and 14.8%, respectively. The mean follow-up time was 39.6 ± 35.7 months. Conclusion MR-guided thermoablation is an effective and safe approach in the treatment of hepatic recurrences in liver-limited conditions and can achieve long-term survival.

Small Steatotic HCC: A Radiological Variant Associated With Improved Outcome After Ablation.

Percutaneous thermal ablation is a validated treatment option for small hepatocellular carcinoma (HCC). Steatotic HCC can be reliably detected by magnetic resonance imaging. To determine the clinical relevance of this radiological variant, we included 235 patients (cirrhosis in 92.3%, classified Child‐Pugh A in 97%) from a prospective database on percutaneous thermal ablation for <3 cm HCC. Among these patients, 52 (22.1%) had at least one steatotic HCC nodule. Nonalcoholic steatohepatitis was more frequent in patients with than without steatotic HCC (P = 0.057), whereas body mass index, diabetes mellitus, liver steatosis, and liver fat content did not differ between groups. Liver disease was less advanced in patients with than without steatotic HCC: lower total bilirubin (‐2.1 µmol/L; P = 0.035), higher albumin (+0.8 g/L; P = 0.035), and lower Model for End‐Stage Liver Disease score (‐0.8; P = 0.014). Tumor phenotype was less aggressive in patients with steatotic HCC: lower alpha‐fetoprotein (AFP) concentration (P = 0.019), less frequent AFP > 100 ng/mL (P = 0.045), and multifocality (P = 0.015). During the follow‐up (median: 28.3 months), overall mortality (3.8% vs. 23.5%; P = 0.001) and HCC‐specific mortality (0.0% vs. 14.2%; P = 0.002) rates were lower in patients with steatotic HCC. Early (<2 years) recurrence was also less frequent (32.7% vs. 49.2%; P = 0.041). The mean time to intrahepatic distant recurrence (16.4 vs. 9 months, P = 0.006) and the median time to recurrence and recurrence‐free survival (32.4 vs. 18.6 months, P = 0.024 and 30.4 vs. 16.4 months, P = 0.018) were longer in patients with steatotic versus nonsteatotic HCC. The 3‐year overall survival was 94.4% and 70.9% in steatotic and nonsteatotic HCC (P = 0.008). In multivariate analysis, steatotic HCC (hazard ratio = 0.12; P = 0.039) and AFP (HR=1.002; P < 0.001) independently predicted overall survival. Conclusion: Small steatotic HCC detected by magnetic resonance imaging is associated with a less aggressive tumor phenotype. In patients with such radiological variant, percutaneous thermal ablation results in improved outcome.

Recurrence at surgical margin following hepatectomy for colorectal liver metastases is not associated with R1 resection and does not impact survival

BackgroundResection margin status has traditionally been associated with tumor recurrence and oncological outcome following liver resection for colorectal liver metastases. Previous studies, however, did not address the impact of resection margin on the site of tumor recurrence and did not differentiate between true local recurrence at the resection margin and recurrence elsewhere in the liver. This study aimed to determine whether positive resection margins determine local recurrence and whether recurrence at the surgical margin influences long-term survival. MethodsClinicopathological data and oncological outcomes of patients who underwent curative resection for colorectal liver metastases between 2012 and 2017 at 2 major hepatobiliary centers (Bern, Switzerland, and Berlin, Germany) were assessed. Cross-sectional imaging following hepatectomy was reviewed by radiologists in both centers to distinguish between recurrence at the resection margin, defined as hepatic local recurrence, and intrahepatic recurrence elsewhere. The association between surgical margin status and location of tumor recurrence was evaluated, and the impact on overall survival was determined. ResultsDuring the study period, 345 consecutive patients underwent hepatectomy for colorectal liver metastases. Histologic surgical margins were positive for tumor cells (R1) in 63 patients (18%). After a median follow-up time of 34 months, tumor recurrence was identified in 154 patients (45%). Hepatic local recurrence was not detected more frequently after R1 than after R0 resection (P = .555). Hepatic local recurrence was not associated with worse overall survival (P = .436), while R1 status significantly impaired overall survival (P = .025). Additionally, overall survival was equivalent between patients with hepatic local recurrence and patients with any intrahepatic and/or extrahepatic recurrence. In patients with intrahepatic recurrence only, oncological outcomes improved if local hepatic therapy was possible (resection or ablation) in comparison to patients treated only with chemotherapy or best supportive care (3-year overall survival: 85% vs 39%; P < .0001). ConclusionThe incidence of hepatic local recurrence after hepatectomy for colorectal liver metastases is independent of R1 resection margin status. Additionally, hepatic local recurrence at the resection margin is not associated with worse overall survival compared with any other intra- or extrahepatic recurrence. Therefore, R1 status at hepatectomy seems to be a surrogate factor for advanced disease without influencing location of recurrence and thereby oncological outcome. This finding may support decision-making when extending the indication for surgery in borderline resectable colorectal liver metastases.

PROGNOSTIC IMPACT OF PRETREATMENT FIB-4 INDEX AFTER RADIOFREQUENCY ABLATION FOR HEPATOCELLULAR CARCINOMA

Intrahepatic distant recurrence, after successful radiofrequency ablation for hepatocellularcarcinoma, is related to many factors. Underlying liver fibrosis/cirrhosis severity thought to beone of these contributors. FIB-4 index is a non-invasive marker which reflects the severity ofliver fibrosis. The aim of this study was to evaluate the prognostic value of FIB-4 index afterradiofrequency ablation for hepatocellular carcinoma with curative intent. This retrospectivestudy included 121 HCV related hepatocellular carcinoma patients with Child class A who underwentradiofrequency ablation between 1/2010 & 12/2014. The study assessed the overallsurvival and denovo intrahepatic distant recurrence using pretreatment FIB-4 index.The result showed that pretreatment FIB-4 index of ≤3.25 patients had significant better freeintrahepatic distant recurrence and overall survival rates after radiofrequency ablation when comparedto those with pretreatment FIB-4 index of > 3.25, even in subsets of patients with Childscore 5, single lesion or lesions< 3cm. Also, FIB-4 index was useful prognostic predictor of intrahepaticdistant recurrence and overall survival after radiofrequency ablation in Child class Apatients in uni and multivraite analysis.

Prognosis after intrahepatic recurrence in the patients who underwent curative resection for hepatocellular carcinoma.

Backgrounds/AimsIntrahepatic recurrence is frequent result after hepatectomy for hepatocellular carcinoma (HCC). We analyzed the clinical results of patients who had the intrahepatic recurrences of HCC after curative surgical resections.MethodsFrom January 2009 to December 2016, 320 patients underwent curative surgical resection for HCC in department of Surgery, Korea Cancer Center Hospital. After surgical resection, 155 patients had suffered HCC recurrence during follow-up period. Among them, 122 patients had only intrahepatic recurrence initially, who were included in this retrospective study. We analyzed about the period of the recurrence after surgery, treatment methods for the recurred tumors, and poor prognostic factors for survival after intrahepatic recurrences.ResultsAmong the 122 patients, 83 patients had recurrence within 24 months after surgery. Thirty-eight patients underwent curative treatment for the recurred tumors (re-resection in 18, radiofrequency ablation in 20 patients). Non-curative treatments were performed in 77 patients (TACE in 68 patients, radiotherapy in 9 patients) and conservative management in 7 patients. Five-year survival rate of patients who underwent curative treatment is 86.4% (p≤0.001). Five-year survival rate of non-curative treatment is 55.7% (p≤0.001), conservative management is 0% (p=0.021). Among the clinical factors, non-curative treatment for recurred tumor, AFP level at the time of recurrence, size of recurred tumor were independent poor prognostic factors for survival after intrahepatic recurrences (p<0.001).ConclusionsFor the patients who had intrahepatic recurrent HCC after surgery, aggressive local treatment can improve the prognosis in selective cases. Further study is necessary to validate this retrospective investigation.

Prognostic value of γ-glutamyl transpeptidase to albumin ratio combined with aspartate aminotransferase to lymphocyte ratio in patients with hepatocellular carcinoma after hepatectomy.

Hepatocellular carcinoma (HCC) is a malignant tumor associated with a high recurrence rate after hepatectomy. Recently, preoperative inflammatory and liver function reserve indices were found to predict increased risk of recurrence and decreased survival in HCC patients. This study aims to evaluate the ability of the γ-glutamyl transpeptidase-to-albumin ratio (GAR) and aspartate aminotransferase-to-lymphocyte ratio (ALRI), individually and in combination, to predict the prognosis of HCC patients after hepatectomy.We retrospectively reviewed 206 HCC patients who underwent radical resection at the General Hospital of Ningxia Medical University from January 2011 to November 2016. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value for GAR and ALRI. The Pearson Chi-Squared test was used to analyze the correlations between GAR, ALRI and clinicopathological characteristics. Univariate and multivariate analyses were used to determine the predictive value of these factors for disease-free survival (DFS) and overall survival (OS). Survival rates were drawn according to the Kaplan-Meier method and differences between subgroups were compared by the log-rank statistics.GAR and ALRI were significantly correlated with gender, history of smoking, prothrombin time, tumor diameter, T stage and early intrahepatic recurrence by the Pearson Chi-Squared test (all P < .05). Univariate analysis indicated that T stage, GAR and ALRI were significantly correlated with DFS and OS in HCC patients after hepatectomy. Multivariate analysis illustrated that GAR and ALRI were independently related to DFS and OS in HCC patients. Preoperative GAR > 0.946 or ALRI > 18.734 predicted poor prognosis in HCC patients after hepatectomy. Additionally, the predictive scope of GAR combined with ALRI was more sensitive than that of either individual measurement alone.Our data indicate that there is a close association between the clinicopathological characteristics in HCC patients and increased GAR or ALRI. Higher levels of GAR and ALRI could sensitively and specifically predict a poor prognosis in HCC patients after hepatectomy. Furthermore, combined usage of GAR and ALRI could improve the accuracy of this prediction.

CMTM6 Stabilizes PD-L1 Expression and Is a New Prognostic Impact Factor in Hepatocellular Carcinoma.

CKLF‐like MARVEL transmembrane domain containing 6 (CMTM6) was identified as a regulator of programmed death ligand 1 (PD‐L1), which induces antitumor immunity in several cancers. This study aimed to clarify the relationship between CMTM6 and PD‐L1 expression and clinical outcomes in patients with hepatocellular carcinoma (HCC). In total, 259 patients with HCC who had undergone hepatic resection were enrolled. Immunohistochemical staining for CMTM6 and PD‐L1 was performed. The relationships between CMTM6 expression and the clinicopathological characteristics and outcomes were analyzed. Additionally, the stabilization of PD‐L1 expression and regulation of malignant activities by CMTM6 were examined in vitro. Our patients were divided into high (n = 65, 25.1%) and low (n = 194, 74.9%) CMTM6 expression groups. High CMTM6 expression was significantly associated with malignant aggregates, including poor differentiation (P < 0.0001), microscopic intrahepatic metastasis (P = 0.0369), and multiple intrahepatic recurrences (P = 0.0211). CMTM6 expression was significantly correlated with PD‐L1 expression in HCC tissues (P < 0.0001). The patients were classified into three groups: high CMTM6/PD‐L1 positive (n = 21), high CMTM6/ PD‐L1 negative (n = 44), and low CMTM6 (n = 194) expression pattern groups. Overall survival was significantly different among the three groups (P < 0.0001). Additionally, immunohistochemical double staining revealed that CMTM6 and PD‐L1 were co‐expressed on HCC cells. In vitro, PD‐L1 expression was enhanced at late time points in the presence of CMTM6 expression. CMTM6 also regulated epithelial‐to‐mesenchymal transition and stemness phenotypes in HCC cells. Conclusion: Our large cohort study found that CMTM6 co‐expressed with PD‐L1 was strongly associated with the clinical outcome in patients with HCC. The evaluation of CMTM6 combined with PD‐L1 in HCC might be useful for patient selection in immune checkpoint therapy.

Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma

BackgroundExtrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection. MethodsThe participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping. ResultsExtrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively. ConclusionWe have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.

Late recurrence of hepatocellular carcinoma after radiofrequency ablation: a multicenter study of risk factors, patterns, and survival.

This study aims to determine the risk factors, patterns, and long-term survival outcomes of late recurrence after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within the Milan criteria and develop a nomogram to predict the recurrence-free survival (RFS). This retrospective study included patients with HCC within the Milan criteria, who received RFA at three hospitals in China from January 2011 to December 2016. The clinical variables were assessed by univariate and multivariate Cox regression analyses. A total of 398 patients were included. The median follow-up was 58.7months (range: 24.1-96.0). Ninety-eight patients had late recurrence. Furthermore, 14 patients (14.29%) had local tumor progression (LTP) alone, 43 patients (43.88%) had intrahepatic distant recurrence (IDR) alone, 15 patients (15.31%) had extrahepatic recurrence (ER) alone, three patients (3.06%) had both LTP and IDR, six patients (6.12%) had both LTP and ER, and 17 patients (17.35%) had both IDR and ER. Patients without late recurrence had better long-term overall survival (OS) compared to those with late recurrence (p < 0.001). Male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence. A well-discriminated and calibrated nomogram was constructed to predict the probability of RFS. Male gender, multiple tumors, and cirrhosis are the independent risk factors of late recurrence after RFA for HCC within the Milan criteria. Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. An individualized surveillance and prevention strategy for HCC patients after RFA should be developed. • In the present retrospective study of 398 patients, male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence (> 2years) of HCC after RFA. • The most common pattern of late recurrence was intrahepatic distant recurrence alone (n = 43, 43.88%). Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. • A prognostic nomogram was built to predict the individualized recurrence-free survival after RFA, which achieved good calibration and discriminatory ability with a concordance index of 0.763.

Parenchyma-sparing hepatectomy improves salvageability and survival for solitary small intrahepatic cholangiocarcinoma

BackgroundThis study aimed to investigate the prognostic impact of parenchyma-sparing hepatectomy (PSH) on solitary small intrahepatic cholangiocarcinoma (ICC). MethodsA total of 184 patients with solitary small ICC (≤ 5 cm) from 2009 to 2017 were included. Short- and long-term outcomes were compared between PSH and Non-PSH approach. Results95 (51.6%) patients underwent PSH and 89 (48.4%) patients underwent Non-PSH for solitary small ICC. PSH was associated with less intraoperative blood loss (212.9 mL versus 363.5 mL, P=0.038), lower transfusion rate (7.4% versus 16.9%, P=0.048), without increasing the frequency of tumor recurrence (60.0% versus 58.4%). No significant differences were observed in overall survival (OS), recurrence-free survival (RFS) and liver RFS (P = 0.627, 0.769 and 0.538, respectively). 109 (59.2%) patients experienced recurrence, of these, 67 (36.4%) were intrahepatic recurrence. Subgroup analysis of patients with liver-only recurrence demonstrated an increased likelihood of repeat hepatectomy for PSH compared to Non-PSH (21.2% versus 2.9%, P = 0.031), thus resulting in improved liver OS (P = 0.016). ConclusionPSH was associated with improved perioperative outcomes but it did not increase liver recurrence rates. PSH offered an increased rate of salvage hepatectomy for recurrent tumor, thus improving long-term survival in cases in which liver recurrence occurred.

A Case of Intrahepatic Cholangiocarcinoma with Recurrence-Free Survival for Twelve Years after Five Resections for Intrahepatic Recurrence after Initial Hepatectomy

A Case of Intrahepatic Cholangiocarcinoma with Recurrence-Free Survival for Twelve Years after Five Resections for Intrahepatic Recurrence after Initial Hepatectomy

Ten-Year Outcomes of Percutaneous Radiofrequency Ablation for Colorectal Cancer Liver Metastases in Perivascular vs. Non-Perivascular Locations: A Propensity-Score Matched Study.

PurposeTo compare long-term outcomes of percutaneous radiofrequency ablation for colorectal liver metastases in perivascular versus non-perivascular locations.MethodsThis retrospective study included 388 consecutive patients with colorectal liver metastases (246 men, 142 women; age range 27–86 years) who underwent percutaneous radiofrequency ablation between January 2006 and December 2018. Propensity-score matching was performed for groups with perivascular and non-perivascular colorectal liver metastases. Rates of accumulative local tumor progression, overall survival, intra/extrahepatic recurrence, and complications were compared between the two groups.ResultsWe successfully matched 104 patients each in the perivascular and non-perivascular groups (mean age: 60.1 ± 11.5 and 60.1 ± 11.3 years, respectively). Cumulative local tumor progression rates at 6 months, 1 years, 3 years, and 5 years, respectively, were 8.8%,14.8%, 18.9%, and 18.9% in the perivascular group and 8.8%, 13.1%, 15.5%, and 15.5% in the non-perivascular group. The 1-, 3-, 5-, and 10-year overall survival rates, respectively, were 91.3%, 45.6%, 23.9%, and 18.7% in the perivascular group and 88.0%, 47.2%, 27.2%, and 22.6% in the non-perivascular group. No significant between-group differences were detected in cumulative local tumor progression (p=0.567, hazard ratio: 1.224) or overall survival (p = 0.801, hazard ratio: 1.047). The major complication rate was 1.0% (1/104, p > 0.999) in both groups. Tumor size was the only independent prognostic factor for local tumor progression (hazard ratio: 2.314; p = 0.002). On multivariate analysis for overall colorectal liver metastases, tumor diameter >3 cm, tumor location in the right colon, multiple tumors, and extrahepatic metastases before radiofrequency ablation (hazard ratios: 2.046, 1.920, 1.706, and 1.892, respectively; all p < 0.001) and intrahepatic recurrence (hazard ratio: 1.564; p = 0.002) were associated with poor overall survival.ConclusionCumulative local tumor progression, overall survival, and major complications rates did not differ significantly between perivascular and non-perivascular colorectal liver metastases after percutaneous radiofrequency ablation. For perivascular colorectal liver metastases, percutaneous radiofrequency ablation is a safe and effective treatment option.

Features of extrahepatic metastasis after radiofrequency ablation for hepatocellular carcinoma.

BACKGROUNDExtrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) is associated with poor outcomes. However, the clinical features and risk factors of EHM of HCC after radiofrequency ablation (RFA) remain unclear.AIMTo elucidate the characteristics and risk factors of EHM after RFA for HCC.METHODSFrom January 2008 to December 2017, we retrospectively enrolled 661 patients who underwent RFA as first-line treatment for HCC at 2 tertiary hospitals. The inclusion criteria were age ≥ 18 years, a diagnosis of HCC, and treatment-naivety. Abdominal computed tomography (CT) or magnetic resonance imaging (MRI) and alpha-fetoprotein measurements were routinely performed at 1 mo after RFA and followed-up at intervals of 3-6 mo. Univariate analyses were performed using the chi-squared test or Student’s t-test, and univariate and multivariate analyses were performed via logistic regression, as appropriate.RESULTSEHM was diagnosed in 44 patients (6.7%) during a median follow-up period of 1204 days. The 10-year cumulative rate of HCC recurrence and EHM was 92.7% and 33.7%, respectively. Initial recurrence was most often intrahepatic, and the rate of extrahepatic recurrence at initial recurrence was only 1.2%. The median time to the diagnosis of EHM was 2.68 years, and 68.2% of patients developed EHM within 2 years of the first recurrence, regardless of recurrence-free survival and 75.0% of patients developed EHM within 5 years after first recurrence. EHM was mostly diagnosed via abdominal CT/MRI in 33 (75.0%) and 38 of 44 patients (86.4%) with EHM had either positive abdominal CT scan results or serum AFP level elevation. In multivariate analysis, recurrence-free survival < 2 years, ablation zone/tumor size < 2, and alpha-fetoprotein level > 400 IU/mL were associated with a high EHM risk.CONCLUSIONEHM occurs following multiple intrahepatic recurrences after RFA and combined contrast-enhanced abdominal CT and serum AFP were useful for surveillance. Patients especially with high-risk factors require close follow-up for EHM.

Management of Recurrent HCC After Liver Transplantation.

Liver transplantation is the best treatment option for hepatocellular carcinoma (HCC). Although centers use strict selection criteria, there is a risk of recurrence, reaching up to 20% which are mostly observed within two years following the procedure. The survival after the recurrence is poor and it has been reported to be between 7-16 months. This poor prognosis is due to the systemic course of the recurrence even its presentation is local initially. The clinical management and treatment algorithm of recurrence is challenging and there is no guideline regarding the situation. Staging of the disease and multi-disciplinary approach are important. The decision for choice of treatment is given depending on the localization and spread of the recurrence. Adjusting and switching the immunosuppressive therapy should be the first attempt. When the recurrence is limited or confined to resectable regions, surgery should be the choice of treatment. Multiple recurrence sites such as adrenal glands, lung, lymph nodes are not contraindication for curative surgery. Resection of the graft for intrahepatic recurrence is the most beneficial procedure for survival. If resection is not possible due to advanced hepatic disease, loco-regional therapies such as TACE, RF, microwave ablation should be considered. SBRT may be an alternative both for hepatic and extra-hepatic recurrence. In case of systemic disease, sorafenib should be the drug choice.

Stereotactic Body Radiation Therapy for Recurrent, Isolated Hepatocellular Carcinoma Lymph Node Metastasis With or Without Prior Liver Transplantation.

Lymph node metastases from hepatocellular carcinoma (HCC) represents a challenging clinical scenario with a poor prognosis, especially in the setting of prior liver transplant. Long-term survival is achievable in select patients with isolated lymph node metastases who undergo surgical resection, but little data exist regarding non-surgical options. For intrahepatic HCC, stereotactic body radiation therapy (SBRT) has emerged as a standard and effective nonsurgical treatment option. Here, we present three patients (two with prior liver transplant) with isolated lymph node metastases treated with curative intent using SBRT to doses of 30-45 Gy in three to five fractions. Two patients (with follow-up of 27 and 31 months) had a complete or near-complete response and remain cancer-free. One patient had intrahepatic HCC recurrence shortly after SBRT but stable disease in the treated lymph node metastasis at 20 months. Liver function remained excellent after radiation in all three patients, but one patient developed a grade 3 duodenal ulcer at 20 months that resolved with medical management. These cases illustrate the potential utility of SBRT as a non-invasive, definitive treatment option for patients with isolated lymph node metastases from HCC.

Current management of intrahepatic cholangiocarcinoma: from resection to palliative treatments.

BackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common liver primary tumour after hepatocellular carcinoma and represents 20% of all the cholangiocarcinomas. Its incidence is increasing and mortality rates are rising. Surgical resection is the only option to cure the disease, despite the high recurrence rates reported to be up to 80%. Intrahepatic recurrences may be still treated with curative intent in a small percentage of the patients. Unfortunately, due to lack of specific symptoms, most patients are diagnosed in a late stage of disease and often unsuitable for resection. Liver transplantation for ICC is still controversial. After the first published poor results, improving outcomes have been reported in highly selected cases, including locally advanced ICC treated with neoadjuvant chemotherapy, when successful in controlling tumour progression. Thus, liver transplantation should be considered a possible option within study protocols. When surgical management is not possible, palliative treatments include chemotherapy, radiotherapy and loco-regional treatments such as radiofrequency ablation, trans-arterial chemoembolization or radioembolization.ConclusionsThis update on the management of ICC focusses on surgical treatments. Known and potential prognostic factors are highlighted in order to assist in treatment selection.

A Multi-Institutional Retrospective Study of Repeated Stereotactic Body Radiation Therapy for Intrahepatic Recurrent Hepatocellular Carcinoma

Through this multi-institutional study, we aimed to retrospectively evaluate the safety and efficacy of repeated stereotactic body radiation therapy (SBRT) for intrahepatic recurrent hepatocellular carcinoma (HCC). Between 2005 and 2017, 709 patients with 835 HCCs underwent SBRT; those treated with repeated SBRT were eligible. The median prescribed dose was 40 Gy in 5 fractions. Eighty-one patients with 189 tumors underwent repeated SBRT (≥ 2 courses [median 2 times; range, 2-5 times]). The median follow-up periods from the first to the second SBRT were 41.5 (range, 12-99) and 20 (range, 1-81) months, respectively. The median interval between the first and second SBRT was 18 (range, 3-74) months. The 5-year local recurrence rate was 6.3% (95% confidence interval [CI], 2.3%-13.4%). The 5-year overall survival (OS) and liver-related death rates from the first SBRT were 60.4% (95% CI, 47.0%-73.8%) and 32.9% (95% CI, 20.3%-46.0%), respectively, and the 3-year rates from the second SBRT were 61.0% (95% CI, 49.9%-75.2%) and 34.5% (95% CI, 20.6%-48.9%), respectively. The frequency of grade 3 toxicity was not significantly different between the first and second SBRT (first: 11% [95% CI, 5.2%-20%]; second: 15% [95% CI, 7.9%-24%]; P = .48). Among 39 patients with no intrahepatic recurrence for 1 year after the first and second SBRT, the deterioration in liver function after the first and second SBRT was not significantly different; the albumin-bilirubin score increased 1 year after the first versus second SBRT (first, 0.143 ± 0.23; second, 0.195 ± 0.38; P = .48). Multivariate analysis revealed that the intrahepatic recurrence-free interval was the only significant factor for OS. Repeated SBRT for intrahepatic recurrent HCC resulted in high local control with safety and a satisfactory OS comparable with that of other curative local treatments for patients with well-preserved liver function.